CHICAGO – A combination of the investigational agent PLX9486 with another novel tyrosine kinase inhibitor (TKI) showed some efficacy against a range of primary and secondary KIT mutations in patients with gastrointestinal stromal tumor (GIST), the results of a phase 1 dose escalation study have suggested.

Among 39 patients with GIST who had progressed on imatinib and other TKIs, the rates of clinical benefit at 16 weeks were 64% for 11 patients treated with PLX8486 monotherapy at a dose of 1,000 mg daily and 67% for 9 patients treated with PLX9486 and the investigational TKI pexidartinib.

One patient in the 1,000 mg monotherapy group had a partial response on interim analysis. The median progression-free survival in this dose group was 6 months, which was “significantly better than at lower doses,” reported Andrew J. Wagner, MD, PhD, from the Dana-Farber Cancer Institute in Boston and his colleagues.

“The combination of PLX9486 with either pexidartinib or sunitinib is generally well tolerated and toxicities are typically grade 1 or 2 in nature and reversible,” they wrote in a poster presented at the annual meeting of the American Society of Clinical Oncology.

PLX9486 is an inhibitor of KIT primary mutations in exons 9 and 11 and secondary resistance mutations in exons 17 and 18. Compared with other KIT-targeted TKIs, PLX9486 has complementary selectivity for mutant forms of KIT with a greater than 150-fold selectivity for mutant versus wild-type KIT, the investigators explained.

“Combinations of PLX9486 with either pexidartinib (PLX3397) or sunitinib potentially inhibit and address all common primary and secondary KIT mutations,” they wrote.

The investigators conducted a phase 1, open-label, dose-escalation study with two parts. The first part was designed to study the safety and pharmacokinetics of single-agent PLX9486 and established a maximum tolerated dose (MTD) for phase 2 studies. The second part was designed to study the drug as a single agent at the recommended phase 2 dose in GIST and other solid tumors with KIT mutations and also in combination with either pexidartinib or sunitinib in patients with GIST.

They found that single-agent PLX9486 was well tolerated at all doses tested (250, 300, 350, 500, and 1,000 mg daily) and that it selectively inhibited a spectrum of KIT mutations, “including difficult to treat exon 17/18 activation loop variants.”

The combination of PLX9486 at 500 mg and pexidartinib 600 mg was associated with three partial responses and a clinical benefit rate of 67%, with a PFS on interim analysis of 6 months.

The efficacy of single agent PLX9486 was suggested by circulating tumor DNA studies, which showed reductions in circulating tumor DNA levels of exons 11 and 17/18, which reflected the selectivity profile of the TKI.

In the PLX9486 dose escalation phase, there were three cases of grade 3 or 4 toxicities, including one case each of fatigue, creatinine phosphokinase increase, and hypophosphatemia.

The combination of PLX9486 and pexidartinib was associated with grade 1 or 2 adverse events, including hair color changes in five patients; fatigue and decreased appetite in four patients each; anemia, diarrhea, nausea, alanine aminotransferase increase, and aspartate aminotransferase increase in three patients each; and weight loss, maculopapular rash, and hypertension in two patients each.

At the time of the poster presentation, the sunitinib cohort was still accruing, and interim efficacy data were not available.

“Given these interim results, it is anticipated that the selectivity profile and potency of PLX9486 + sunitinib combination will achieve broader and more durable coverage of primary and secondary KIT mutations,” Dr. Wagner and his associates wrote.

SOURCE: Wagner AJ et al. ASCO 2018, Abstract 11509.
 

CHICAGO – A combination of the investigational agent PLX9486 with another novel tyrosine kinase inhibitor (TKI) showed some efficacy against a range of primary and secondary KIT mutations in patients with gastrointestinal stromal tumor (GIST), the results of a phase 1 dose escalation study have suggested.

Among 39 patients with GIST who had progressed on imatinib and other TKIs, the rates of clinical benefit at 16 weeks were 64% for 11 patients treated with PLX8486 monotherapy at a dose of 1,000 mg daily and 67% for 9 patients treated with PLX9486 and the investigational TKI pexidartinib.

One patient in the 1,000 mg monotherapy group had a partial response on interim analysis. The median progression-free survival in this dose group was 6 months, which was “significantly better than at lower doses,” reported Andrew J. Wagner, MD, PhD, from the Dana-Farber Cancer Institute in Boston and his colleagues.

“The combination of PLX9486 with either pexidartinib or sunitinib is generally well tolerated and toxicities are typically grade 1 or 2 in nature and reversible,” they wrote in a poster presented at the annual meeting of the American Society of Clinical Oncology.

PLX9486 is an inhibitor of KIT primary mutations in exons 9 and 11 and secondary resistance mutations in exons 17 and 18. Compared with other KIT-targeted TKIs, PLX9486 has complementary selectivity for mutant forms of KIT with a greater than 150-fold selectivity for mutant versus wild-type KIT, the investigators explained.

“Combinations of PLX9486 with either pexidartinib (PLX3397) or sunitinib potentially inhibit and address all common primary and secondary KIT mutations,” they wrote.

The investigators conducted a phase 1, open-label, dose-escalation study with two parts. The first part was designed to study the safety and pharmacokinetics of single-agent PLX9486 and established a maximum tolerated dose (MTD) for phase 2 studies. The second part was designed to study the drug as a single agent at the recommended phase 2 dose in GIST and other solid tumors with KIT mutations and also in combination with either pexidartinib or sunitinib in patients with GIST.

They found that single-agent PLX9486 was well tolerated at all doses tested (250, 300, 350, 500, and 1,000 mg daily) and that it selectively inhibited a spectrum of KIT mutations, “including difficult to treat exon 17/18 activation loop variants.”

The combination of PLX9486 at 500 mg and pexidartinib 600 mg was associated with three partial responses and a clinical benefit rate of 67%, with a PFS on interim analysis of 6 months.

The efficacy of single agent PLX9486 was suggested by circulating tumor DNA studies, which showed reductions in circulating tumor DNA levels of exons 11 and 17/18, which reflected the selectivity profile of the TKI.

In the PLX9486 dose escalation phase, there were three cases of grade 3 or 4 toxicities, including one case each of fatigue, creatinine phosphokinase increase, and hypophosphatemia.

The combination of PLX9486 and pexidartinib was associated with grade 1 or 2 adverse events, including hair color changes in five patients; fatigue and decreased appetite in four patients each; anemia, diarrhea, nausea, alanine aminotransferase increase, and aspartate aminotransferase increase in three patients each; and weight loss, maculopapular rash, and hypertension in two patients each.

At the time of the poster presentation, the sunitinib cohort was still accruing, and interim efficacy data were not available.

“Given these interim results, it is anticipated that the selectivity profile and potency of PLX9486 + sunitinib combination will achieve broader and more durable coverage of primary and secondary KIT mutations,” Dr. Wagner and his associates wrote.

SOURCE: Wagner AJ et al. ASCO 2018, Abstract 11509.
 

CHICAGO – A combination of the investigational agent PLX9486 with another novel tyrosine kinase inhibitor (TKI) showed some efficacy against a range of primary and secondary KIT mutations in patients with gastrointestinal stromal tumor (GIST), the results of a phase 1 dose escalation study have suggested.

Among 39 patients with GIST who had progressed on imatinib and other TKIs, the rates of clinical benefit at 16 weeks were 64% for 11 patients treated with PLX8486 monotherapy at a dose of 1,000 mg daily and 67% for 9 patients treated with PLX9486 and the investigational TKI pexidartinib.

One patient in the 1,000 mg monotherapy group had a partial response on interim analysis. The median progression-free survival in this dose group was 6 months, which was “significantly better than at lower doses,” reported Andrew J. Wagner, MD, PhD, from the Dana-Farber Cancer Institute in Boston and his colleagues.

“The combination of PLX9486 with either pexidartinib or sunitinib is generally well tolerated and toxicities are typically grade 1 or 2 in nature and reversible,” they wrote in a poster presented at the annual meeting of the American Society of Clinical Oncology.

PLX9486 is an inhibitor of KIT primary mutations in exons 9 and 11 and secondary resistance mutations in exons 17 and 18. Compared with other KIT-targeted TKIs, PLX9486 has complementary selectivity for mutant forms of KIT with a greater than 150-fold selectivity for mutant versus wild-type KIT, the investigators explained.

“Combinations of PLX9486 with either pexidartinib (PLX3397) or sunitinib potentially inhibit and address all common primary and secondary KIT mutations,” they wrote.

The investigators conducted a phase 1, open-label, dose-escalation study with two parts. The first part was designed to study the safety and pharmacokinetics of single-agent PLX9486 and established a maximum tolerated dose (MTD) for phase 2 studies. The second part was designed to study the drug as a single agent at the recommended phase 2 dose in GIST and other solid tumors with KIT mutations and also in combination with either pexidartinib or sunitinib in patients with GIST.

They found that single-agent PLX9486 was well tolerated at all doses tested (250, 300, 350, 500, and 1,000 mg daily) and that it selectively inhibited a spectrum of KIT mutations, “including difficult to treat exon 17/18 activation loop variants.”

The combination of PLX9486 at 500 mg and pexidartinib 600 mg was associated with three partial responses and a clinical benefit rate of 67%, with a PFS on interim analysis of 6 months.

The efficacy of single agent PLX9486 was suggested by circulating tumor DNA studies, which showed reductions in circulating tumor DNA levels of exons 11 and 17/18, which reflected the selectivity profile of the TKI.

In the PLX9486 dose escalation phase, there were three cases of grade 3 or 4 toxicities, including one case each of fatigue, creatinine phosphokinase increase, and hypophosphatemia.

The combination of PLX9486 and pexidartinib was associated with grade 1 or 2 adverse events, including hair color changes in five patients; fatigue and decreased appetite in four patients each; anemia, diarrhea, nausea, alanine aminotransferase increase, and aspartate aminotransferase increase in three patients each; and weight loss, maculopapular rash, and hypertension in two patients each.

At the time of the poster presentation, the sunitinib cohort was still accruing, and interim efficacy data were not available.

“Given these interim results, it is anticipated that the selectivity profile and potency of PLX9486 + sunitinib combination will achieve broader and more durable coverage of primary and secondary KIT mutations,” Dr. Wagner and his associates wrote.

SOURCE: Wagner AJ et al. ASCO 2018, Abstract 11509.
 

AMSTERDAM – Preexposure prophylaxis (PrEP) against HIV infection by U.S. residents appears to be paying off: The number of new U.S. HIV infections among those at least 13 years old dropped during 2012-2016, and this decline showed a statistically significant link with growth in drug prophylaxis among U.S. residents during the same time.

Mitchel L. Zoler/MDedge News

Uptake of HIV PrEP “was significantly associated with declines in HIV diagnoses in the United States, independent of levels of viral suppression,” Patrick S. Sullivan, Ph.D., and his associates said in a poster presented at the 22nd International AIDS Conference.

Their analysis of nationwide U.S. data showed that during 2012-2016 new HIV diagnoses in residents at least 13 years old fell by an estimated annual percent change of 4.65 among the 10 states with the greatest rate of PrEP use by residents, compared with increases in the estimated annual percent change in new HIV diagnoses of about 1-1.5 in the 14 states with the lowest PrEP use. This statistically significant link remained after adjusting for variations in levels of viral suppression among HIV-infected residents in each state, another factor driving reduced infection rates, Dr. Sullivan and his associates reported..

In the ten-state subgroup with the greatest PrEP uptake, use of PrEP in people at risk for HIV rose from 12/1,000 people in 2012, the year that the Food and Drug Administration first approved a PrEP regimen, to 110/1,000 at-risk people in 2016, a ninefold increase. PrEP use jumped by about the same relative amount in the seven states with the lowest PrEP use, but because it was only 3/1,000 people in 2012 it reached only 35/1,000 in 2016, less than a third of the rate in the states that administered the most PrEP.

In absolute, unadjusted numbers the rate of new HIV diagnoses in the 10 states with the greatest PrEP use fell from 19.4 cases/100,000 population to 13.6/100,000 in 2016. Total U.S. HIV diagnosis rates in people at least 13 years old fell from 15.7/100,000 in 2012 to 14.5/100,000 in 2016, reported Dr. Sullivan, a professor of epidemiology at Emory University in Atlanta.

Dr. Sullivan and his coauthors cautioned that these associations do not allow inference of a causal relationship, and their data did not allow them to estimate the relative contributions of PrEP uptake and HIV suppression to the declining trend in diagnosed HIV infections. However PrEP and suppressive HIV treatment act in a complimentary way to potentially drop the rate of new HIV transmissions, he said.

In the years since 2012, when the Food and Drug Administration approved PrEP as an indication for 200-mg emtricitabine (Emtriva) and 300 mg tenofovir (Viread) – formulated into a single pill and marketed as Truvada, the idea of PrEP for people at increased risk for HIV exposure has gained traction.

Awareness of, knowledge about, and uptake of PrEP have all increased among U.S. residents since a PrEP formulation became available, Dr. Sullivan said. It’s become a cultural norm in at least some communities, he said in an interview. The cost for daily PrEP has posed a barrier to some potential users, but in many U.S. settings people can find ways to at least partially subsidize the cost even when lacking insurance coverage for the drug, he noted.

To determine rates of new U.S. HIV diagnoses Dr. Sullivan and his associates used data collected by the National HIV Surveillance System. To estimate rates of PrEP uptake they used data from prescriptions filled for the emtricitabine and tenofovir formulation that they then adjusted to rule out use for indications other than PrEP (Ann Epidemiol. 2018 Jun 22. doi: 10.1016/j.annepidem.2018.06.009).

[email protected]

SOURCE: Sullivan PS et al. AIDS 2018, Abstract 13004.

AMSTERDAM – Preexposure prophylaxis (PrEP) against HIV infection by U.S. residents appears to be paying off: The number of new U.S. HIV infections among those at least 13 years old dropped during 2012-2016, and this decline showed a statistically significant link with growth in drug prophylaxis among U.S. residents during the same time.

Mitchel L. Zoler/MDedge News

Uptake of HIV PrEP “was significantly associated with declines in HIV diagnoses in the United States, independent of levels of viral suppression,” Patrick S. Sullivan, Ph.D., and his associates said in a poster presented at the 22nd International AIDS Conference.

Their analysis of nationwide U.S. data showed that during 2012-2016 new HIV diagnoses in residents at least 13 years old fell by an estimated annual percent change of 4.65 among the 10 states with the greatest rate of PrEP use by residents, compared with increases in the estimated annual percent change in new HIV diagnoses of about 1-1.5 in the 14 states with the lowest PrEP use. This statistically significant link remained after adjusting for variations in levels of viral suppression among HIV-infected residents in each state, another factor driving reduced infection rates, Dr. Sullivan and his associates reported..

In the ten-state subgroup with the greatest PrEP uptake, use of PrEP in people at risk for HIV rose from 12/1,000 people in 2012, the year that the Food and Drug Administration first approved a PrEP regimen, to 110/1,000 at-risk people in 2016, a ninefold increase. PrEP use jumped by about the same relative amount in the seven states with the lowest PrEP use, but because it was only 3/1,000 people in 2012 it reached only 35/1,000 in 2016, less than a third of the rate in the states that administered the most PrEP.

In absolute, unadjusted numbers the rate of new HIV diagnoses in the 10 states with the greatest PrEP use fell from 19.4 cases/100,000 population to 13.6/100,000 in 2016. Total U.S. HIV diagnosis rates in people at least 13 years old fell from 15.7/100,000 in 2012 to 14.5/100,000 in 2016, reported Dr. Sullivan, a professor of epidemiology at Emory University in Atlanta.

Dr. Sullivan and his coauthors cautioned that these associations do not allow inference of a causal relationship, and their data did not allow them to estimate the relative contributions of PrEP uptake and HIV suppression to the declining trend in diagnosed HIV infections. However PrEP and suppressive HIV treatment act in a complimentary way to potentially drop the rate of new HIV transmissions, he said.

In the years since 2012, when the Food and Drug Administration approved PrEP as an indication for 200-mg emtricitabine (Emtriva) and 300 mg tenofovir (Viread) – formulated into a single pill and marketed as Truvada, the idea of PrEP for people at increased risk for HIV exposure has gained traction.

Awareness of, knowledge about, and uptake of PrEP have all increased among U.S. residents since a PrEP formulation became available, Dr. Sullivan said. It’s become a cultural norm in at least some communities, he said in an interview. The cost for daily PrEP has posed a barrier to some potential users, but in many U.S. settings people can find ways to at least partially subsidize the cost even when lacking insurance coverage for the drug, he noted.

To determine rates of new U.S. HIV diagnoses Dr. Sullivan and his associates used data collected by the National HIV Surveillance System. To estimate rates of PrEP uptake they used data from prescriptions filled for the emtricitabine and tenofovir formulation that they then adjusted to rule out use for indications other than PrEP (Ann Epidemiol. 2018 Jun 22. doi: 10.1016/j.annepidem.2018.06.009).

[email protected]

SOURCE: Sullivan PS et al. AIDS 2018, Abstract 13004.

AMSTERDAM – Preexposure prophylaxis (PrEP) against HIV infection by U.S. residents appears to be paying off: The number of new U.S. HIV infections among those at least 13 years old dropped during 2012-2016, and this decline showed a statistically significant link with growth in drug prophylaxis among U.S. residents during the same time.

Mitchel L. Zoler/MDedge News

Uptake of HIV PrEP “was significantly associated with declines in HIV diagnoses in the United States, independent of levels of viral suppression,” Patrick S. Sullivan, Ph.D., and his associates said in a poster presented at the 22nd International AIDS Conference.

Their analysis of nationwide U.S. data showed that during 2012-2016 new HIV diagnoses in residents at least 13 years old fell by an estimated annual percent change of 4.65 among the 10 states with the greatest rate of PrEP use by residents, compared with increases in the estimated annual percent change in new HIV diagnoses of about 1-1.5 in the 14 states with the lowest PrEP use. This statistically significant link remained after adjusting for variations in levels of viral suppression among HIV-infected residents in each state, another factor driving reduced infection rates, Dr. Sullivan and his associates reported..

In the ten-state subgroup with the greatest PrEP uptake, use of PrEP in people at risk for HIV rose from 12/1,000 people in 2012, the year that the Food and Drug Administration first approved a PrEP regimen, to 110/1,000 at-risk people in 2016, a ninefold increase. PrEP use jumped by about the same relative amount in the seven states with the lowest PrEP use, but because it was only 3/1,000 people in 2012 it reached only 35/1,000 in 2016, less than a third of the rate in the states that administered the most PrEP.

In absolute, unadjusted numbers the rate of new HIV diagnoses in the 10 states with the greatest PrEP use fell from 19.4 cases/100,000 population to 13.6/100,000 in 2016. Total U.S. HIV diagnosis rates in people at least 13 years old fell from 15.7/100,000 in 2012 to 14.5/100,000 in 2016, reported Dr. Sullivan, a professor of epidemiology at Emory University in Atlanta.

Dr. Sullivan and his coauthors cautioned that these associations do not allow inference of a causal relationship, and their data did not allow them to estimate the relative contributions of PrEP uptake and HIV suppression to the declining trend in diagnosed HIV infections. However PrEP and suppressive HIV treatment act in a complimentary way to potentially drop the rate of new HIV transmissions, he said.

In the years since 2012, when the Food and Drug Administration approved PrEP as an indication for 200-mg emtricitabine (Emtriva) and 300 mg tenofovir (Viread) – formulated into a single pill and marketed as Truvada, the idea of PrEP for people at increased risk for HIV exposure has gained traction.

Awareness of, knowledge about, and uptake of PrEP have all increased among U.S. residents since a PrEP formulation became available, Dr. Sullivan said. It’s become a cultural norm in at least some communities, he said in an interview. The cost for daily PrEP has posed a barrier to some potential users, but in many U.S. settings people can find ways to at least partially subsidize the cost even when lacking insurance coverage for the drug, he noted.

To determine rates of new U.S. HIV diagnoses Dr. Sullivan and his associates used data collected by the National HIV Surveillance System. To estimate rates of PrEP uptake they used data from prescriptions filled for the emtricitabine and tenofovir formulation that they then adjusted to rule out use for indications other than PrEP (Ann Epidemiol. 2018 Jun 22. doi: 10.1016/j.annepidem.2018.06.009).

[email protected]

SOURCE: Sullivan PS et al. AIDS 2018, Abstract 13004.

CHICAGO – In elderly patients with previously untreated metastatic soft-tissue sarcomas (STSs), the oral alkylating agent trofosfamide was associated with a lower overall response rate but long-lasting remissions among patients who had complete responses, investigators reported.

In a randomized phase 2 trial that compared trofosfamide with doxorubicin (Adriamycin), the 6-month progression-free survival (PFS) rate with trofosfamide, the primary endpoint, was 27. 6% versus 35.9% in the doxorubicin arm, said Joerg Thomas Hartmann, MD, from Franziskus Hospital in Bielefeld, Germany.

“Median age was 70 years, which means that the population included [patients] 10-15 years older as compared to other trials in metastatic adult sarcoma. The trial met its predefined endpoint, demonstrating that patients treated with trofosfamide attained a 6-month progression-free rate of more than 20%,” he said at the annual meeting of the American Society of Clinical Oncology.

Trofosfamide is an oral alkylating agent chemically related to cyclophosphamide and ifosfamide. It has been evaluated in a variety of hematologic and solid malignancies and has shown particular activity in patients with chemotherapy-naive and treatment-refractory adult STSs.

Dr. Hartmann and his colleagues conducted the phase 2 study to determine whether oral continuous or “metronomic” therapy with trofosfamide could produce a 6-month PFS rate of at least 20% in patients older than 60 years with previously untreated STSs. They selected this rate of 20% or higher based on the European Organisation for Research and Treatment of Cancer (EORTC) target criterion for doxorubicin of 25%.

They also compared grade 3 or greater toxicities of the two regimens, as well as overall response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) 1,0, and overall survival.

A total of 120 patients with histologically confirmed STSs with no prior first-line chemotherapy and with adequate bone marrow, renal, and liver function were enrolled. The histologies included pleomorphic sarcoma not otherwise specified, leiomyosarcoma, liposarcoma, and others not specified by Dr. Hartmann.

The patients were randomly assigned on a 1:2 basis to receive either intravenous doxorubicin 60 mg/m² on day 1 of each 21-day cycle for a total of 6 cycles (40 patients) or oral trofosfamide 300 mg/day for days 1 through 7 followed by 150 mg/day until disease progression or unacceptable toxicities (80 patients).

The median patient age in each arm was 70 years.

After a median follow-up of 18.4 months, the trial met its primary endpoint of a 6-months PFS with trofosfamide exceeding 20% (27.6%).

Overall response rates were 7.7% in the doxorubicin arm and 6.6% in the trofosfamide arm.

All three responses in the doxorubicin arm were partial. In the trofosfamide arm there were five responses, including two complete responses and three PR.

The duration of responses in the patients treated with trofosfamide who achieved a complete response were 8.8 and 46.6 months (median, 27.7 months). The median duration of response for trofosfamide-treated patients with a partial response was 8.2 months (range, 1.4-14.9 months).

In contrast, the median duration of response in the patients treated with doxorubicin who achieved a partial response was 4.3 months (range, 2.2-5.6 months).

SOURCE: Hartman JT et al. ASCO 2018, Abstract 11507.

CHICAGO – In elderly patients with previously untreated metastatic soft-tissue sarcomas (STSs), the oral alkylating agent trofosfamide was associated with a lower overall response rate but long-lasting remissions among patients who had complete responses, investigators reported.

In a randomized phase 2 trial that compared trofosfamide with doxorubicin (Adriamycin), the 6-month progression-free survival (PFS) rate with trofosfamide, the primary endpoint, was 27. 6% versus 35.9% in the doxorubicin arm, said Joerg Thomas Hartmann, MD, from Franziskus Hospital in Bielefeld, Germany.

“Median age was 70 years, which means that the population included [patients] 10-15 years older as compared to other trials in metastatic adult sarcoma. The trial met its predefined endpoint, demonstrating that patients treated with trofosfamide attained a 6-month progression-free rate of more than 20%,” he said at the annual meeting of the American Society of Clinical Oncology.

Trofosfamide is an oral alkylating agent chemically related to cyclophosphamide and ifosfamide. It has been evaluated in a variety of hematologic and solid malignancies and has shown particular activity in patients with chemotherapy-naive and treatment-refractory adult STSs.

Dr. Hartmann and his colleagues conducted the phase 2 study to determine whether oral continuous or “metronomic” therapy with trofosfamide could produce a 6-month PFS rate of at least 20% in patients older than 60 years with previously untreated STSs. They selected this rate of 20% or higher based on the European Organisation for Research and Treatment of Cancer (EORTC) target criterion for doxorubicin of 25%.

They also compared grade 3 or greater toxicities of the two regimens, as well as overall response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) 1,0, and overall survival.

A total of 120 patients with histologically confirmed STSs with no prior first-line chemotherapy and with adequate bone marrow, renal, and liver function were enrolled. The histologies included pleomorphic sarcoma not otherwise specified, leiomyosarcoma, liposarcoma, and others not specified by Dr. Hartmann.

The patients were randomly assigned on a 1:2 basis to receive either intravenous doxorubicin 60 mg/m² on day 1 of each 21-day cycle for a total of 6 cycles (40 patients) or oral trofosfamide 300 mg/day for days 1 through 7 followed by 150 mg/day until disease progression or unacceptable toxicities (80 patients).

The median patient age in each arm was 70 years.

After a median follow-up of 18.4 months, the trial met its primary endpoint of a 6-months PFS with trofosfamide exceeding 20% (27.6%).

Overall response rates were 7.7% in the doxorubicin arm and 6.6% in the trofosfamide arm.

All three responses in the doxorubicin arm were partial. In the trofosfamide arm there were five responses, including two complete responses and three PR.

The duration of responses in the patients treated with trofosfamide who achieved a complete response were 8.8 and 46.6 months (median, 27.7 months). The median duration of response for trofosfamide-treated patients with a partial response was 8.2 months (range, 1.4-14.9 months).

In contrast, the median duration of response in the patients treated with doxorubicin who achieved a partial response was 4.3 months (range, 2.2-5.6 months).

SOURCE: Hartman JT et al. ASCO 2018, Abstract 11507.

CHICAGO – In elderly patients with previously untreated metastatic soft-tissue sarcomas (STSs), the oral alkylating agent trofosfamide was associated with a lower overall response rate but long-lasting remissions among patients who had complete responses, investigators reported.

In a randomized phase 2 trial that compared trofosfamide with doxorubicin (Adriamycin), the 6-month progression-free survival (PFS) rate with trofosfamide, the primary endpoint, was 27. 6% versus 35.9% in the doxorubicin arm, said Joerg Thomas Hartmann, MD, from Franziskus Hospital in Bielefeld, Germany.

“Median age was 70 years, which means that the population included [patients] 10-15 years older as compared to other trials in metastatic adult sarcoma. The trial met its predefined endpoint, demonstrating that patients treated with trofosfamide attained a 6-month progression-free rate of more than 20%,” he said at the annual meeting of the American Society of Clinical Oncology.

Trofosfamide is an oral alkylating agent chemically related to cyclophosphamide and ifosfamide. It has been evaluated in a variety of hematologic and solid malignancies and has shown particular activity in patients with chemotherapy-naive and treatment-refractory adult STSs.

Dr. Hartmann and his colleagues conducted the phase 2 study to determine whether oral continuous or “metronomic” therapy with trofosfamide could produce a 6-month PFS rate of at least 20% in patients older than 60 years with previously untreated STSs. They selected this rate of 20% or higher based on the European Organisation for Research and Treatment of Cancer (EORTC) target criterion for doxorubicin of 25%.

They also compared grade 3 or greater toxicities of the two regimens, as well as overall response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) 1,0, and overall survival.

A total of 120 patients with histologically confirmed STSs with no prior first-line chemotherapy and with adequate bone marrow, renal, and liver function were enrolled. The histologies included pleomorphic sarcoma not otherwise specified, leiomyosarcoma, liposarcoma, and others not specified by Dr. Hartmann.

The patients were randomly assigned on a 1:2 basis to receive either intravenous doxorubicin 60 mg/m² on day 1 of each 21-day cycle for a total of 6 cycles (40 patients) or oral trofosfamide 300 mg/day for days 1 through 7 followed by 150 mg/day until disease progression or unacceptable toxicities (80 patients).

The median patient age in each arm was 70 years.

After a median follow-up of 18.4 months, the trial met its primary endpoint of a 6-months PFS with trofosfamide exceeding 20% (27.6%).

Overall response rates were 7.7% in the doxorubicin arm and 6.6% in the trofosfamide arm.

All three responses in the doxorubicin arm were partial. In the trofosfamide arm there were five responses, including two complete responses and three PR.

The duration of responses in the patients treated with trofosfamide who achieved a complete response were 8.8 and 46.6 months (median, 27.7 months). The median duration of response for trofosfamide-treated patients with a partial response was 8.2 months (range, 1.4-14.9 months).

In contrast, the median duration of response in the patients treated with doxorubicin who achieved a partial response was 4.3 months (range, 2.2-5.6 months).

SOURCE: Hartman JT et al. ASCO 2018, Abstract 11507.

The Food and Drug Administration has approved mogamulizumab-kpkc (Poteligeo) for the treatment of adults with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) who have received at least one prior systemic therapy.

Mogamulizumab is a humanized monoclonal antibody directed against CC chemokine receptor 4 (CCR4). It is the first biologic agent targeting CCR4 to be approved for patients in the United States.

Mogamulizumab is expected to be commercially available in the fourth quarter of 2018.

The FDA previously granted mogamulizumab breakthrough therapy and orphan drug designations, as well as priority review.

The approval is supported by the phase 3 MAVORIC trial. Results from this trial were presented at the 10th Annual T-cell Lymphoma Forum in February 2018.

MAVORIC enrolled 372 adults with histologically confirmed MF or SS who had failed at least one systemic therapy. They were randomized to receive mogamulizumab at 1.0 mg/kg (weekly for the first 4-week cycle and then every 2 weeks) or vorinostat at 400 mg daily. Patients were treated until disease progression or unacceptable toxicity. Those receiving vorinostat could cross over to mogamulizumab if they progressed or experienced intolerable toxicity. Baseline characteristics were similar between the treatment arms. The study’s primary endpoint was progression-free survival. The median progression-free survival was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio, 0.53; P less than .0001).

The global overall response rate was 28% (52/189) in the mogamulizumab arm and 5% (9/186) in the vorinostat arm (P less than .0001). For patients with MF, the ORR was 21% with mogamulizumab and 7% with vorinostat; for patients with SS, the ORR was 37% and 2%, respectively. After crossover, the ORR in the mogamulizumab arm was 30% (41/136).

The median duration of response (DOR) was 14 months in the mogamulizumab arm and 9 months in the vorinostat arm. For MF patients, the median DOR was 13 months with mogamulizumab and 9 months with vorinostat; for SS patients, the median DOR was 17 months and 7 months, respectively.

The most common treatment-emergent adverse events (AEs), which occurred in at least 20% of patients in either arm (mogamulizumab and vorinostat, respectively), included the following:

• Infusion-related reactions (33.2% vs. 0.5%).
• Drug eruptions (23.9% vs. 0.5%).
• Diarrhea (23.4% vs. 61.8%).
• Nausea (15.2% vs. 42.5%).
• Thrombocytopenia (11.4% vs. 30.6%).
• Dysgeusia (3.3% vs. 28.0%).
• Increased blood creatinine (3.3% vs. 28.0%).
• Decreased appetite (7.6% vs. 24.7%).

There were no grade 4 AEs in the mogamulizumab arm. Grade 3 AEs in mogamulizumab recipients included drug eruptions (n = 8), infusion-related reactions (n = 3), fatigue (n = 3), decreased appetite (n = 2), nausea (n = 1), pyrexia (n = 1), and diarrhea (n = 1).

The drug is marketed by Kyowa Kirin.

The Food and Drug Administration has approved mogamulizumab-kpkc (Poteligeo) for the treatment of adults with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) who have received at least one prior systemic therapy.

Mogamulizumab is a humanized monoclonal antibody directed against CC chemokine receptor 4 (CCR4). It is the first biologic agent targeting CCR4 to be approved for patients in the United States.

Mogamulizumab is expected to be commercially available in the fourth quarter of 2018.

The FDA previously granted mogamulizumab breakthrough therapy and orphan drug designations, as well as priority review.

The approval is supported by the phase 3 MAVORIC trial. Results from this trial were presented at the 10th Annual T-cell Lymphoma Forum in February 2018.

MAVORIC enrolled 372 adults with histologically confirmed MF or SS who had failed at least one systemic therapy. They were randomized to receive mogamulizumab at 1.0 mg/kg (weekly for the first 4-week cycle and then every 2 weeks) or vorinostat at 400 mg daily. Patients were treated until disease progression or unacceptable toxicity. Those receiving vorinostat could cross over to mogamulizumab if they progressed or experienced intolerable toxicity. Baseline characteristics were similar between the treatment arms. The study’s primary endpoint was progression-free survival. The median progression-free survival was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio, 0.53; P less than .0001).

The global overall response rate was 28% (52/189) in the mogamulizumab arm and 5% (9/186) in the vorinostat arm (P less than .0001). For patients with MF, the ORR was 21% with mogamulizumab and 7% with vorinostat; for patients with SS, the ORR was 37% and 2%, respectively. After crossover, the ORR in the mogamulizumab arm was 30% (41/136).

The median duration of response (DOR) was 14 months in the mogamulizumab arm and 9 months in the vorinostat arm. For MF patients, the median DOR was 13 months with mogamulizumab and 9 months with vorinostat; for SS patients, the median DOR was 17 months and 7 months, respectively.

The most common treatment-emergent adverse events (AEs), which occurred in at least 20% of patients in either arm (mogamulizumab and vorinostat, respectively), included the following:

• Infusion-related reactions (33.2% vs. 0.5%).
• Drug eruptions (23.9% vs. 0.5%).
• Diarrhea (23.4% vs. 61.8%).
• Nausea (15.2% vs. 42.5%).
• Thrombocytopenia (11.4% vs. 30.6%).
• Dysgeusia (3.3% vs. 28.0%).
• Increased blood creatinine (3.3% vs. 28.0%).
• Decreased appetite (7.6% vs. 24.7%).

There were no grade 4 AEs in the mogamulizumab arm. Grade 3 AEs in mogamulizumab recipients included drug eruptions (n = 8), infusion-related reactions (n = 3), fatigue (n = 3), decreased appetite (n = 2), nausea (n = 1), pyrexia (n = 1), and diarrhea (n = 1).

The drug is marketed by Kyowa Kirin.

The Food and Drug Administration has approved mogamulizumab-kpkc (Poteligeo) for the treatment of adults with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) who have received at least one prior systemic therapy.

Mogamulizumab is a humanized monoclonal antibody directed against CC chemokine receptor 4 (CCR4). It is the first biologic agent targeting CCR4 to be approved for patients in the United States.

Mogamulizumab is expected to be commercially available in the fourth quarter of 2018.

The FDA previously granted mogamulizumab breakthrough therapy and orphan drug designations, as well as priority review.

The approval is supported by the phase 3 MAVORIC trial. Results from this trial were presented at the 10th Annual T-cell Lymphoma Forum in February 2018.

MAVORIC enrolled 372 adults with histologically confirmed MF or SS who had failed at least one systemic therapy. They were randomized to receive mogamulizumab at 1.0 mg/kg (weekly for the first 4-week cycle and then every 2 weeks) or vorinostat at 400 mg daily. Patients were treated until disease progression or unacceptable toxicity. Those receiving vorinostat could cross over to mogamulizumab if they progressed or experienced intolerable toxicity. Baseline characteristics were similar between the treatment arms. The study’s primary endpoint was progression-free survival. The median progression-free survival was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio, 0.53; P less than .0001).

The global overall response rate was 28% (52/189) in the mogamulizumab arm and 5% (9/186) in the vorinostat arm (P less than .0001). For patients with MF, the ORR was 21% with mogamulizumab and 7% with vorinostat; for patients with SS, the ORR was 37% and 2%, respectively. After crossover, the ORR in the mogamulizumab arm was 30% (41/136).

The median duration of response (DOR) was 14 months in the mogamulizumab arm and 9 months in the vorinostat arm. For MF patients, the median DOR was 13 months with mogamulizumab and 9 months with vorinostat; for SS patients, the median DOR was 17 months and 7 months, respectively.

The most common treatment-emergent adverse events (AEs), which occurred in at least 20% of patients in either arm (mogamulizumab and vorinostat, respectively), included the following:

• Infusion-related reactions (33.2% vs. 0.5%).
• Drug eruptions (23.9% vs. 0.5%).
• Diarrhea (23.4% vs. 61.8%).
• Nausea (15.2% vs. 42.5%).
• Thrombocytopenia (11.4% vs. 30.6%).
• Dysgeusia (3.3% vs. 28.0%).
• Increased blood creatinine (3.3% vs. 28.0%).
• Decreased appetite (7.6% vs. 24.7%).

There were no grade 4 AEs in the mogamulizumab arm. Grade 3 AEs in mogamulizumab recipients included drug eruptions (n = 8), infusion-related reactions (n = 3), fatigue (n = 3), decreased appetite (n = 2), nausea (n = 1), pyrexia (n = 1), and diarrhea (n = 1).

The drug is marketed by Kyowa Kirin.

A public figure who chooses to share his or her private burdens can help others cope with a similar circumstance. Or, such actions might inspire feelings of annoyance and ridicule over the human foibles of someone who is rich and successful – and get airtime for something that many others struggle with alone.

A public figure who chooses to share his or her private burdens can help others cope with a similar circumstance. Or, such actions might inspire feelings of annoyance and ridicule over the human foibles of someone who is rich and successful – and get airtime for something that many others struggle with alone.

A public figure who chooses to share his or her private burdens can help others cope with a similar circumstance. Or, such actions might inspire feelings of annoyance and ridicule over the human foibles of someone who is rich and successful – and get airtime for something that many others struggle with alone.

Patients with myeloproliferative neoplasms treated with Janus-kinase (JAK) 1/2 inhibitors may be at significantly increased risk of aggressive B cell non-Hodgkin lymphomas, according to a study published in Blood.

A retrospective cohort study of 626 Viennese patients with myeloproliferative neoplasms – 69 of whom were treated with JAK1/2 inhibitors – found that 4 of the 69 patients (5.8%) developed aggressive B-cell lymphoma, compared with just 2 patients (0.36%) in the rest of the group. This represented a significant, 16-fold higher risk of aggressive B cell lymphoma associated with JAK1/2 inhibitor therapy (P = .0017).

The lymphoma was diagnosed within 13-35 months of starting JAK1/2 inhibitors. In three patients, the disease was in the bone marrow and peripheral blood, one patient had it in mammary tissue, and another had it in mucosal tissue. All four lymphomas showed positive MYC and p53 staining.

All four patients had been treated with ruxolitinib, one was also treated with fedratinib, and three of the four had been pretreated with alkylating agents.

Meanwhile, a second retrospective cohort study in Paris of 929 patients with myeloproliferative neoplasms, reported in the same paper, found that 3.51% of those treated with ruxolitinib developed lymphoma, compared with 0.23% of conventionally-treated patients.

Using archived bone marrow samples from 54 of the 69 patients treated with JAK1/2 inhibitors, researchers discovered that 15.9% of them – including three of the B-cell lymphoma patients (the fourth was not tested) – had a preexisting B cell clone. This was present as early as 47-70 months before the lymphoma diagnosis.

“In patients, the clonal B-cell population was present as long as 6 years before overt lymphoma and preceded JAK1/2 inhibition which offers the opportunity to determine patients at risk,” wrote Edit Porpaczy, MD, of the Comprehensive Cancer Center at the Medical University of Vienna, and her coauthors. “Targeted inhibition of JAK-STAT signaling appears to be required to trigger the appearance of the B-cell clone as other treatments eliminating the myeloid cell load in men do not exert a comparable effect.”

In the Viennese cohort, three of the lymphomas were aggressive CD19⁺ B-cell type, and the fourth was a nonspecified high-grade B-cell lymphoma.

Researchers also looked at the effects of JAK1/2 inhibition in STAT1^-/- mice, and found that two-thirds developed a spontaneous myeloid hyperplasia with the concomitant presence of aberrant B-cells.

“Upon STAT1-deficiency myeloid hyperplasia is paralleled by the occurrence of a malignant B-cell clone, which evolves into disease upon bone-marrow transplantation and gives rise to a leukemic lymphoma phenotype,” the authors wrote.

The study was supported by the Austrian Science Fund, the Anniversary Fund of the Austrian National Bank and the WWTF Precision Medicine Program. Several authors reported support, funding or advisory board positions with the pharmaceutical industry.

SOURCE: Porpaczy E et al. Blood. 2018 Jun 14. doi: 10.1182/blood-2017-10-810739.

Patients with myeloproliferative neoplasms treated with Janus-kinase (JAK) 1/2 inhibitors may be at significantly increased risk of aggressive B cell non-Hodgkin lymphomas, according to a study published in Blood.

A retrospective cohort study of 626 Viennese patients with myeloproliferative neoplasms – 69 of whom were treated with JAK1/2 inhibitors – found that 4 of the 69 patients (5.8%) developed aggressive B-cell lymphoma, compared with just 2 patients (0.36%) in the rest of the group. This represented a significant, 16-fold higher risk of aggressive B cell lymphoma associated with JAK1/2 inhibitor therapy (P = .0017).

The lymphoma was diagnosed within 13-35 months of starting JAK1/2 inhibitors. In three patients, the disease was in the bone marrow and peripheral blood, one patient had it in mammary tissue, and another had it in mucosal tissue. All four lymphomas showed positive MYC and p53 staining.

All four patients had been treated with ruxolitinib, one was also treated with fedratinib, and three of the four had been pretreated with alkylating agents.

Meanwhile, a second retrospective cohort study in Paris of 929 patients with myeloproliferative neoplasms, reported in the same paper, found that 3.51% of those treated with ruxolitinib developed lymphoma, compared with 0.23% of conventionally-treated patients.

Using archived bone marrow samples from 54 of the 69 patients treated with JAK1/2 inhibitors, researchers discovered that 15.9% of them – including three of the B-cell lymphoma patients (the fourth was not tested) – had a preexisting B cell clone. This was present as early as 47-70 months before the lymphoma diagnosis.

“In patients, the clonal B-cell population was present as long as 6 years before overt lymphoma and preceded JAK1/2 inhibition which offers the opportunity to determine patients at risk,” wrote Edit Porpaczy, MD, of the Comprehensive Cancer Center at the Medical University of Vienna, and her coauthors. “Targeted inhibition of JAK-STAT signaling appears to be required to trigger the appearance of the B-cell clone as other treatments eliminating the myeloid cell load in men do not exert a comparable effect.”

In the Viennese cohort, three of the lymphomas were aggressive CD19⁺ B-cell type, and the fourth was a nonspecified high-grade B-cell lymphoma.

Researchers also looked at the effects of JAK1/2 inhibition in STAT1^-/- mice, and found that two-thirds developed a spontaneous myeloid hyperplasia with the concomitant presence of aberrant B-cells.

“Upon STAT1-deficiency myeloid hyperplasia is paralleled by the occurrence of a malignant B-cell clone, which evolves into disease upon bone-marrow transplantation and gives rise to a leukemic lymphoma phenotype,” the authors wrote.

The study was supported by the Austrian Science Fund, the Anniversary Fund of the Austrian National Bank and the WWTF Precision Medicine Program. Several authors reported support, funding or advisory board positions with the pharmaceutical industry.

SOURCE: Porpaczy E et al. Blood. 2018 Jun 14. doi: 10.1182/blood-2017-10-810739.

Patients with myeloproliferative neoplasms treated with Janus-kinase (JAK) 1/2 inhibitors may be at significantly increased risk of aggressive B cell non-Hodgkin lymphomas, according to a study published in Blood.

A retrospective cohort study of 626 Viennese patients with myeloproliferative neoplasms – 69 of whom were treated with JAK1/2 inhibitors – found that 4 of the 69 patients (5.8%) developed aggressive B-cell lymphoma, compared with just 2 patients (0.36%) in the rest of the group. This represented a significant, 16-fold higher risk of aggressive B cell lymphoma associated with JAK1/2 inhibitor therapy (P = .0017).

The lymphoma was diagnosed within 13-35 months of starting JAK1/2 inhibitors. In three patients, the disease was in the bone marrow and peripheral blood, one patient had it in mammary tissue, and another had it in mucosal tissue. All four lymphomas showed positive MYC and p53 staining.

All four patients had been treated with ruxolitinib, one was also treated with fedratinib, and three of the four had been pretreated with alkylating agents.

Meanwhile, a second retrospective cohort study in Paris of 929 patients with myeloproliferative neoplasms, reported in the same paper, found that 3.51% of those treated with ruxolitinib developed lymphoma, compared with 0.23% of conventionally-treated patients.

Using archived bone marrow samples from 54 of the 69 patients treated with JAK1/2 inhibitors, researchers discovered that 15.9% of them – including three of the B-cell lymphoma patients (the fourth was not tested) – had a preexisting B cell clone. This was present as early as 47-70 months before the lymphoma diagnosis.

“In patients, the clonal B-cell population was present as long as 6 years before overt lymphoma and preceded JAK1/2 inhibition which offers the opportunity to determine patients at risk,” wrote Edit Porpaczy, MD, of the Comprehensive Cancer Center at the Medical University of Vienna, and her coauthors. “Targeted inhibition of JAK-STAT signaling appears to be required to trigger the appearance of the B-cell clone as other treatments eliminating the myeloid cell load in men do not exert a comparable effect.”

In the Viennese cohort, three of the lymphomas were aggressive CD19⁺ B-cell type, and the fourth was a nonspecified high-grade B-cell lymphoma.

Researchers also looked at the effects of JAK1/2 inhibition in STAT1^-/- mice, and found that two-thirds developed a spontaneous myeloid hyperplasia with the concomitant presence of aberrant B-cells.

“Upon STAT1-deficiency myeloid hyperplasia is paralleled by the occurrence of a malignant B-cell clone, which evolves into disease upon bone-marrow transplantation and gives rise to a leukemic lymphoma phenotype,” the authors wrote.

The study was supported by the Austrian Science Fund, the Anniversary Fund of the Austrian National Bank and the WWTF Precision Medicine Program. Several authors reported support, funding or advisory board positions with the pharmaceutical industry.

SOURCE: Porpaczy E et al. Blood. 2018 Jun 14. doi: 10.1182/blood-2017-10-810739.

AMSTERDAM – One maxim of current HIV management is U=U; Undetectable equals Untransmissible, and it received new backing for the specific question of whether HIV treated to an undetectable level can transmit from a man who engages in condomless anal sex to an uninfected man. The answer was it effectively could not.

Mitchel L. Zoler/MDedge News

Based on the number of sex events studies Dr. Rodger and her associates calculated the 95% confidence interval around the zero transmissions they observed during gay male sex events with undetectable HIV in both PARTNER-2 and PARTNER-1. The upper bound of this confidence interval was a rate of 0.23 transmissions per 100 person years of follow-up,

In other words, the scope of the two combined studies cannot statistically rule out a worst-case scenario of one transmission for every 435 person years of follow-up, or for every 18,696 sex events of the type studied. However, “we’ve made the confidence much more robust. We can’t say it’s zero risk, but it’s effectively zero,” Dr. Rodger said in an interview. “You could keep studying this forever” to further rule out the risk for transmission of undetectable HIV, “but I think the question is now settled,” she declared. She also stressed that condom use remained important to prevent other sexually transmitted diseases.

[email protected]

SOURCE: Rodger A et al. AIDS 2018, Abstract 13470.

AMSTERDAM – One maxim of current HIV management is U=U; Undetectable equals Untransmissible, and it received new backing for the specific question of whether HIV treated to an undetectable level can transmit from a man who engages in condomless anal sex to an uninfected man. The answer was it effectively could not.

Mitchel L. Zoler/MDedge News

Based on the number of sex events studies Dr. Rodger and her associates calculated the 95% confidence interval around the zero transmissions they observed during gay male sex events with undetectable HIV in both PARTNER-2 and PARTNER-1. The upper bound of this confidence interval was a rate of 0.23 transmissions per 100 person years of follow-up,

In other words, the scope of the two combined studies cannot statistically rule out a worst-case scenario of one transmission for every 435 person years of follow-up, or for every 18,696 sex events of the type studied. However, “we’ve made the confidence much more robust. We can’t say it’s zero risk, but it’s effectively zero,” Dr. Rodger said in an interview. “You could keep studying this forever” to further rule out the risk for transmission of undetectable HIV, “but I think the question is now settled,” she declared. She also stressed that condom use remained important to prevent other sexually transmitted diseases.

[email protected]

SOURCE: Rodger A et al. AIDS 2018, Abstract 13470.

AMSTERDAM – One maxim of current HIV management is U=U; Undetectable equals Untransmissible, and it received new backing for the specific question of whether HIV treated to an undetectable level can transmit from a man who engages in condomless anal sex to an uninfected man. The answer was it effectively could not.

Mitchel L. Zoler/MDedge News

Based on the number of sex events studies Dr. Rodger and her associates calculated the 95% confidence interval around the zero transmissions they observed during gay male sex events with undetectable HIV in both PARTNER-2 and PARTNER-1. The upper bound of this confidence interval was a rate of 0.23 transmissions per 100 person years of follow-up,

In other words, the scope of the two combined studies cannot statistically rule out a worst-case scenario of one transmission for every 435 person years of follow-up, or for every 18,696 sex events of the type studied. However, “we’ve made the confidence much more robust. We can’t say it’s zero risk, but it’s effectively zero,” Dr. Rodger said in an interview. “You could keep studying this forever” to further rule out the risk for transmission of undetectable HIV, “but I think the question is now settled,” she declared. She also stressed that condom use remained important to prevent other sexually transmitted diseases.

[email protected]

SOURCE: Rodger A et al. AIDS 2018, Abstract 13470.

The Food and Drug Administration has expanded the indication for Orkambi (lumacaftor/ivacaftor) to include patients who are aged as young as 2 years with cystic fibrosis (CF), according to its manufacturer, Vertex Pharmaceuticals. Specifically, the drug is meant to treat the most common underlying cause of CF – having two copies of the F508del-CFTR mutation – and is the first drug to treat it.

The approval is based on a phase 3, two-part, open-label, multicenter study that assessed various doses in patents aged 2-5 years. The study demonstrated safety and tolerability in that age group equivalent to that seen in older patients. The drug is expected to be available for this age group within 2-4 weeks of this approval.

Available as oral granules in two doses for weight-based dosing (either lumacaftor 100 mg/ivacaftor 125 mg or lumacaftor 150 mg/ivacaftor 188 mg), the compound targets the defective chloride channels responsible for CF; the two halves work together to increase the number of chloride channels on cell surfaces and also improve their function.

Orkambi should be prescribed only for patients with CF who have the dual F508del-CFTR mutation; it is not indicated for other types of CF. Patients should not take this drug if they are taking drugs such as rifampin, phenytoin, triazolam, or cyclosporine because of possible drug interactions. It can also lead to worsening liver function and elevated blood liver enzymes, increased blood pressure, or cataracts. The most common side effects include breathing problems, nausea, fatigue, and rash. Full prescribing information is available on the FDA website.
 

[email protected]

The Food and Drug Administration has expanded the indication for Orkambi (lumacaftor/ivacaftor) to include patients who are aged as young as 2 years with cystic fibrosis (CF), according to its manufacturer, Vertex Pharmaceuticals. Specifically, the drug is meant to treat the most common underlying cause of CF – having two copies of the F508del-CFTR mutation – and is the first drug to treat it.

The approval is based on a phase 3, two-part, open-label, multicenter study that assessed various doses in patents aged 2-5 years. The study demonstrated safety and tolerability in that age group equivalent to that seen in older patients. The drug is expected to be available for this age group within 2-4 weeks of this approval.

Available as oral granules in two doses for weight-based dosing (either lumacaftor 100 mg/ivacaftor 125 mg or lumacaftor 150 mg/ivacaftor 188 mg), the compound targets the defective chloride channels responsible for CF; the two halves work together to increase the number of chloride channels on cell surfaces and also improve their function.

Orkambi should be prescribed only for patients with CF who have the dual F508del-CFTR mutation; it is not indicated for other types of CF. Patients should not take this drug if they are taking drugs such as rifampin, phenytoin, triazolam, or cyclosporine because of possible drug interactions. It can also lead to worsening liver function and elevated blood liver enzymes, increased blood pressure, or cataracts. The most common side effects include breathing problems, nausea, fatigue, and rash. Full prescribing information is available on the FDA website.
 

[email protected]

The Food and Drug Administration has expanded the indication for Orkambi (lumacaftor/ivacaftor) to include patients who are aged as young as 2 years with cystic fibrosis (CF), according to its manufacturer, Vertex Pharmaceuticals. Specifically, the drug is meant to treat the most common underlying cause of CF – having two copies of the F508del-CFTR mutation – and is the first drug to treat it.

The approval is based on a phase 3, two-part, open-label, multicenter study that assessed various doses in patents aged 2-5 years. The study demonstrated safety and tolerability in that age group equivalent to that seen in older patients. The drug is expected to be available for this age group within 2-4 weeks of this approval.

Available as oral granules in two doses for weight-based dosing (either lumacaftor 100 mg/ivacaftor 125 mg or lumacaftor 150 mg/ivacaftor 188 mg), the compound targets the defective chloride channels responsible for CF; the two halves work together to increase the number of chloride channels on cell surfaces and also improve their function.

Orkambi should be prescribed only for patients with CF who have the dual F508del-CFTR mutation; it is not indicated for other types of CF. Patients should not take this drug if they are taking drugs such as rifampin, phenytoin, triazolam, or cyclosporine because of possible drug interactions. It can also lead to worsening liver function and elevated blood liver enzymes, increased blood pressure, or cataracts. The most common side effects include breathing problems, nausea, fatigue, and rash. Full prescribing information is available on the FDA website.
 

[email protected]

Click here to read Hot Topics in Primary Care.

This supplement includes 5.0 CME credits (scroll down for more information).

Topics include:

• Hepatitis C
• Migraine 
• Orally Inhaled Human Insulin 
• Gout
• Orthostatic Hypotension
• Irritable Bowel Syndrome with Diarrhea
• SGLT-2 Inhibitors
• Statin Therapy 
• Basal Insulin/GLP-1RA Combination
• RCTs to the Real World
• Weight Management for Patients with T2DM
• NSAID OTC Formulations
• Colorectal Cancer Screening

This supplement offers the opportunity to earn a total of 5 CME credits.

Credit is awarded for successful completion of the online evaluations at the links below. These links may also be found within the supplement on the first page of each article. 

• On the Front Lines: Hepatitis C Infection in Primary Care 
  • To complete the online evaluation and receive 1 CME credit for this article: please click on the link at the end of the article or go to www.pceconsortium.org/hepC.

• Long-term Treatment of Gout: New Opportunities for Improved Outcomes 
  • To complete the online evaluation and receive 1 CME credit for this article: please click on the link at the end of the article or go to www.pceconsortium.org/gout.

• Recognition and Management of Orthostatic Hypotension in Primary Care 
  • To complete the online evaluation and receive 1 CME credit for this article: please click on the link at the end of the article or go to www.pceconsortium.org/orthostatic.

• Practical Evaluation and Management of Irritable Bowel Syndrome with Diarrhea: A Case Study Approach  
  • To complete the online evaluation and receive 1 CME credit for this article: please click on the link at the end of the article or go to www.pceconsortium.org/ibs.

• Differentiating Among the SGLT-2 Inhibitors: Considering Cardiovascular and Other Safety Outcomes
  •  To complete the online evaluation and receive 1 CME credit for this article: please click on the link at the end of the article or go www.pceconsortium.org/sglt2.

Click here to read Hot Topics in Primary Care.

This supplement includes 5.0 CME credits (scroll down for more information).

Topics include:

• Hepatitis C
• Migraine 
• Orally Inhaled Human Insulin 
• Gout
• Orthostatic Hypotension
• Irritable Bowel Syndrome with Diarrhea
• SGLT-2 Inhibitors
• Statin Therapy 
• Basal Insulin/GLP-1RA Combination
• RCTs to the Real World
• Weight Management for Patients with T2DM
• NSAID OTC Formulations
• Colorectal Cancer Screening

This supplement offers the opportunity to earn a total of 5 CME credits.

Credit is awarded for successful completion of the online evaluations at the links below. These links may also be found within the supplement on the first page of each article. 

• On the Front Lines: Hepatitis C Infection in Primary Care 
  • To complete the online evaluation and receive 1 CME credit for this article: please click on the link at the end of the article or go to www.pceconsortium.org/hepC.

• Long-term Treatment of Gout: New Opportunities for Improved Outcomes 
  • To complete the online evaluation and receive 1 CME credit for this article: please click on the link at the end of the article or go to www.pceconsortium.org/gout.

• Recognition and Management of Orthostatic Hypotension in Primary Care 
  • To complete the online evaluation and receive 1 CME credit for this article: please click on the link at the end of the article or go to www.pceconsortium.org/orthostatic.

• Practical Evaluation and Management of Irritable Bowel Syndrome with Diarrhea: A Case Study Approach  
  • To complete the online evaluation and receive 1 CME credit for this article: please click on the link at the end of the article or go to www.pceconsortium.org/ibs.

• Differentiating Among the SGLT-2 Inhibitors: Considering Cardiovascular and Other Safety Outcomes
  •  To complete the online evaluation and receive 1 CME credit for this article: please click on the link at the end of the article or go www.pceconsortium.org/sglt2.

Click here to read Hot Topics in Primary Care.

This supplement includes 5.0 CME credits (scroll down for more information).

Topics include:

• Hepatitis C
• Migraine 
• Orally Inhaled Human Insulin 
• Gout
• Orthostatic Hypotension
• Irritable Bowel Syndrome with Diarrhea
• SGLT-2 Inhibitors
• Statin Therapy 
• Basal Insulin/GLP-1RA Combination
• RCTs to the Real World
• Weight Management for Patients with T2DM
• NSAID OTC Formulations
• Colorectal Cancer Screening

This supplement offers the opportunity to earn a total of 5 CME credits.

Credit is awarded for successful completion of the online evaluations at the links below. These links may also be found within the supplement on the first page of each article. 

• On the Front Lines: Hepatitis C Infection in Primary Care 
  • To complete the online evaluation and receive 1 CME credit for this article: please click on the link at the end of the article or go to www.pceconsortium.org/hepC.

• Long-term Treatment of Gout: New Opportunities for Improved Outcomes 
  • To complete the online evaluation and receive 1 CME credit for this article: please click on the link at the end of the article or go to www.pceconsortium.org/gout.

• Recognition and Management of Orthostatic Hypotension in Primary Care 
  • To complete the online evaluation and receive 1 CME credit for this article: please click on the link at the end of the article or go to www.pceconsortium.org/orthostatic.

• Practical Evaluation and Management of Irritable Bowel Syndrome with Diarrhea: A Case Study Approach  
  • To complete the online evaluation and receive 1 CME credit for this article: please click on the link at the end of the article or go to www.pceconsortium.org/ibs.

• Differentiating Among the SGLT-2 Inhibitors: Considering Cardiovascular and Other Safety Outcomes
  •  To complete the online evaluation and receive 1 CME credit for this article: please click on the link at the end of the article or go www.pceconsortium.org/sglt2.

ABSTRACT

The purpose of this study is to determine the relationship of body mass index (BMI), age, smoking status, and other comorbid conditions to the rate and type of complications occurring in the perioperative period following periacetabular osteotomy. A retrospective review was performed on 80 hips to determine demographic information as well as pre- and postoperative pain scores, center-edge angle, Tönnis angle, intraoperative blood loss, and perioperative complications within 90 days of surgery. Patients were placed into high- (>30) and low- (<30) BMI groups to determine any correlation between complications and BMI. The high-BMI group had a significantly greater rate of perioperative complications than the low-BMI group (30% vs 8%) and, correspondingly, patients with complications had significantly higher BMI than those without (30.9 ± 9.5, 26.2 ± 5.6) (P = .03). Center-edge angle and Tönnis angle were corrected in both groups. Improvement in postoperative pain scores and radiographically measured acetabular correction can be achieved in high- and low-BMI patients. High-BMI patients have a higher rate of perioperative wound complications.

Continue to: The Bernese periacetabular osteotomy...

The Bernese periacetabular osteotomy (PAO) has become a widely used procedure for hip preservation in adolescent and young adult patients with symptomatic anatomic aberrancies of the acetabulum due to developmental hip dysplasia, trauma, infection, femoroacetabular impingement, and other causes.^1-6 Acetabular dysplasia is one of the most common causes of secondary osteoarthritis, and the goal of PAO is to slow or halt the progression of arthrosis to prolong or potentially eliminate the need for total hip arthroplasty while relieving pain and increasing function and activity.^1,7,8

The PAO involves realigning the acetabulum to improve anterior and lateral coverage of the femoral head, acetabular anteversion, and medicalization of the joint.^5,6 It is preferred over other described acetabular osteotomies due to its inherent stability given that the posterior column is not violated.^3,5,6,9 Since its initial description in 1988,⁵ short-, medium- and long-term outcomes have been reported with excellent patient satisfaction and function.^2,7,10-15 The radiographic, functional, and patient satisfaction outcomes are excellent; therefore, this has become an accepted form of treatment for acetabular dysplasia.¹⁶ Additional procedures, such as hip arthroscopy, have also been combined with PAO to treat intra-articular pathologies without open arthrotomy.¹⁷ Several studies have evaluated preoperative radiographic factors, such as Tönnis grade, previous surgeries, and morphology of the hip; as well as demographic factors, such as age, body mass index (BMI), comorbid diseases, and activity level, which seem to play a role in the final outcome.^11,18,19 This work has advanced our understanding and allowed surgeons to apply selection criteria to improve patient outcomes.

There are multiple reported complications of the PAO procedure, including infection,² wound dehiscence,²⁰ periacetabular fracture,²¹ intra-articular extension of the osteotomy,²² excessive acetabular retroversion,^23,24 hardware failure, femoral or sciatic nerve palsy,²⁵ heterotopic ossification, prominent hardware, deep vein thrombosis or pulmonary embolism,²⁶ osteonecrosis of the femoral head or acetabulum,²⁴ non-union,²⁴ intrapelvic bleeding,²⁴ incisional hernia,²⁷ lateral femoral cutaneous nerve palsy,^20,28 and reflex sympathetic dystrophy.^1,2,29 There are also several studies reporting a learning curve phenomenon, in which the proportion of complications is higher in the initial series of surgeries performed by each specific surgeon.^22,20,29

Despite the widely reported short-, medium-, and long-term results of this treatment, no study thus far has attempted to correlate preoperative patient factors with early perioperative outcomes and complications. This information would be useful in patient counseling and decision making in the early postoperative period. Therefore, the purpose of this study is to analyze data from the perioperative period in patients who have undergone the PAO performed by a single surgeon at our institution to determine any correlation between patient characteristics such as age, comorbid disease, hip pathologic diagnosis, BMI, or previous procedures and perioperative complications occurring within the first 90 days.

Continue to: MATERIALS AND METHODS...

MATERIALS AND METHODS

After Institutional Review Board approval was obtained, a search was performed on the basis of operative report Current Procedural Terminology (CPT) codes for all patients who underwent PAO performed by a single surgeon between 2005 and 2013. Patients were included if they had PAO surgery with at least 90 days of follow-up. There was no exclusion for age, previous surgery, or underlying hip or medical diagnosis. A retrospective review of electronic medical records and radiographic imaging was undertaken to determine pre- and postoperative demographic information, pain scores, center-edge angle of Weiberg and Tönnis angles, intraoperative estimated blood loss, and all perioperative complications. Weight and height were recorded from the immediate preoperative visit and measured in kilograms (kg) and meters (m), respectively. BMI was derived from these measurements. Pain was assessed via visual analog scale at the preoperative visit as well as at 12 weeks postoperatively. Preoperative and 12-week postoperative Tönnis and center-edge angles were measured by a single orthopedic surgeon. All radiographs were deemed adequate in position and penetration for measurement of these parameters. Evidence of osteonecrosis of the femoral head was evaluated on all postoperative radiographs within this perioperative period. Estimated blood loss was established by review of operative records and anesthesia notes.

Perioperative complications were classified using the Clavien-Dindo system, which has previously been validated for use in hip preservation surgery.³⁰ This includes 5 grades of complications based on the treatment needed and severity of resulting long-term disability. Grade I complications do not require any change in the postoperative course and were therefore left out of our statistical analysis. Examples include symptomatic hardware, mild heterotopic ossification, and iliopsoas tendonitis. Grade II complications are those that require a change in outpatient management, such as delayed wound healing, superficial infection, transient nerve palsy, violation of the posterior column, and intra-articular osteotomy. Grade III complications require invasive or surgical treatment but leave the patient with no long-term disability. Examples include wound dehiscence, hematoma or infection necessitating surgical débridement and irrigation, and revision of the osteotomy due to hardware malposition or hip instability. Grade IV complications involve both surgery and long-term disability. Grade IV complications applicable to hip preservation surgery are osteonecrosis, permanent nerve injury, major vascular injury, or pulmonary embolism. A grade V complication is death.

For analysis and correlation between demographics and perioperative outcomes and complications, patients were grouped into several groups for comparison. Low (<30) vs high (>30) BMI, smokers vs non-smokers, diabetic vs non-diabetic patients, and those who had previous surgery vs those who did not were compared. A two-tailed t test was used for normally distributed continuous variables and a Mann-Whitney U test, for non-parametric data to compare postoperative radiographic correction, pain scores, and complication rates between each of these groups.

The operative technique for PAO as described by Ganz and colleagues⁵ in 1988 was utilized in all patients. When preoperative imaging showed evidence of labral pathology, a Cam lesion of the femoral head and neck junction, abnormal proximal femoral anatomy, osteonecrosis of the femoral head, or an os acetabulum, a concomitant procedure was performed. Seventeen patients underwent débridement of a Cam lesion noted to be impinging following PAO. Seventeen patients underwent labral débridement and 4 underwent labral repair. Four patients underwent intertrochanteric osteotomy and 1 underwent greater trochanteric slide. Two patients underwent free-vascularized fibular grafting to the ipsilateral femoral head and 5 underwent fixation of an os acetabulum.

Continue to: RESULTS...

RESULTS

A total of 80 hips in 73 patients underwent PAO with adequate perioperative follow-up and records in the inclusion period. Figures A-E represent a patient pre-procedure, immediately post procedure, and 6 months after successful PAO. The average age was 27.5 years (12.8-43.6 years), and the average BMI was 26.8 (18.7-52.2). Four patients had diabetes, 8 were smokers, and 10 had undergone previous surgeries including arthroscopic labral débridement, 3 open reduction with Salter osteotomy, 3 open reduction with internal fixation of a femoral neck fracture, 1 core decompression for femoral head osteonecrosis, 3 subtrochanteric osteotomy and subsequent non-union treated with cephalomedullary nailing, and 1 previous PAO requiring revision.¹

There were 11 perioperative complications in 10 patients (12.5%). The majority of these were infection (n = 10). Overall complications categorized by BMI are summarized in Table 1. Age was similar in patients with complications (27.4 ± 8.8 years) and those without (27.5 ± 8.2 years) (P = .99). Patients with complications had significantly higher BMI than those without (30.9.3 ± 9.5, 26.2 ± 5.6) (P = .03). There was no effect of concomitant procedures on the complication rate. Of the patients who had complications, 60% (6/10) had concomitant procedures, vs 63% (44/70) of those who had no complications (P = .86) Two of 4 patients with diabetes mellitus developed complications, both of which were wound infections. One of these required incision and débridement. There were no perioperative complications in any of the 7 smokers.  

Abbreviation: BMI, body mass index.

Twenty hips were in the high-BMI (>30) and 60 were in the low-BMI (<30) patient groups. There were 6 total perioperative complications in the high-BMI group (30%) and 5 in the low-BMI group (8%). The most common complications in the low-BMI group were superficial infections.⁴ There were 6 total complications in the high-BMI group: 2 deep and 4 superficial infections. There were 3 reoperations (5%) in the low-BMI group during the perioperative period. Two patients underwent successful débridement and irrigation of a superficial wound, and 1 patient required removal of a prominent screw. There were 3 reoperations in the high-BMI group, all of which were débridement and irrigations for wound infections. The rate of wound dehiscence and wound infection was significantly higher in high-BMI patients (30% [6/20]) than in low-BMI patients (8.3% [4/60]) (P = .006). The mean estimated blood loss in the high-BMI group was greater at 923.75 mL vs 779.25 mL in the low-BMI patients; however, this did not reach statistical significance (P = .350). Seventy percent (14/20) of patients who were obese had concomitant procedures vs 60% (36/60) of those who had normal BMI (P = .42 by chi-square analysis). There was no difference in estimated blood loss in patients who underwent concomitant procedures (Table 2).

Abbreviations: BMI, body mass index; EBL, estimated blood loss.

Preoperative pain scores improved from 4.9 (range, 0-10) to 1.9 (range, 0-6) in the high-BMI group and 4.2 (range, 0-10) to 1.2 (range, 0-6) in the low-BMI group (P = .260). The preoperative center-edge angle in the high-BMI group improved from 6.63° ± 6.5° to 28.53° ± 6.7°, and the Tönnis angle from 24.96° ± 6.3° to 10.06° ± 7.7°. In the low-BMI group the center-edge angle improved from 10.53° ± 11.77° to 27.07° ± 13.9°, and the Tönnis angle from 19.00° ± 10.3° to 2.79° ± 8.3°. There was no difference in postoperative center-edge angle between the high-BMI and low-BMI groups (P = .66). There was a trend toward significance in the postoperative Tönnis angle between the high-BMI and low-BMI groups (P = .051).

Continue to: DISCUSSION...

DISCUSSION

There have been 4 previously published articles specifically on complications following PAO. Each of these encompassed follow-up visits including both the perioperative period and at least 2 years of follow-up.^20,22,24,29 Davey and Santore²⁹ reported an overall rate of complications of 10% in a series of 70 patients. These authors classified complications into minor, moderate, and major for purposes of research and discussion, and this classification system has been utilized or modified within the literature to discuss complications in most other articles. Complications within the perioperative period included 2 cases of excessive intraoperative bleeding, 2 cases of reflex sympathetic dystrophy, and 1 case each of unresolved sciatic nerve palsy and deep vein thrombosis.²⁹ Hussell and colleagues²² reported on a large series of 508 PAOs and analyzed the technical complications that occurred during the procedure and caused either immediate or longer-term problems for the patients. Notably, they concluded that 85% of the technical complications occurred with the initial 50 PAOs performed, signifying a steep learning curve for this technically demanding procedure. Perioperative complications reported were intra-articular osteotomy in 2.2%, femoral nerve palsy in 0.6%, sciatic nerve palsy in 1.0%, posterior column insufficiency in 1.2%, and symptomatic hardware in 3.0%.²² Biedermann and colleagues²⁰ found that 47 out of 60 PAOs in their series had at least 1 minor complication. The most common perioperative complications were lateral femoral cutaneous nerve dysesthesia in 33%, delayed wound healing infection in 15%, major blood loss in 8.3%, sciatic or peroneal nerve palsy in 10%, posterior column discontinuity in 6.7%, and intra-articular osteotomy in 1.6%.²⁰ Most recently, complications of PAO in an adolescent population were evaluated.²⁴ The overall rate of complications was 37%. Major perioperative complications included 1 patient with excessive bleeding due to an aberrant artery at the medial wall of the pelvis thought to be due to revascularization following a previous Dega osteotomy. Two patients required immediate revision of the osteotomy due to excessive anterior coverage noted on postoperative radiographs. There were 5% with superficial stitch abscess causing minor infection, 5% with transient lateral femoral cutaneous nerve palsy, and 15 patients with symptomatic hardware.²⁴

At 12.5%, our overall complication rate is slightly lower than that previously reported in the literature. This may be due to the difference in the scope of this study, which reported only perioperative complications. We also chose to utilize the modified Clavien-Dindo classification system for reporting our complications rather than classifying them as minor or major as in the above studies. This classification system has been validated for use in reporting complications of hip preservation surgery. We considered only Grade II complications and higher for statistical analysis as these required a change in postoperative management, which may have artificially lowered our complication rate.

The data in this study indicate that, compared with patients with a BMI of <30, obese patients have a higher rate of perioperative complications and reoperations. Additionally, the proportion of Grade II and higher complications, importantly deep infection, was higher in obese patients. We did not have any reported incidence of deep vein thrombosis or pulmonary embolism, urinary tract infection, intra-articular osteotomy, acetabular or pelvic fracture, femoral or sciatic nerve palsy, or long-term lateral femoral cutaneous nerve palsy in this series of patients. The most common complication in the low-BMI group was symptomatic hardware. Sixteen patients had this complaint; however, this was not considered a Grade II complication as there would be no change in management during the study period, including the perioperative time frame. Two out of 4 patients with diabetes mellitus developed wound infections, both of which required reoperation. However, the number of patients with diabetes mellitus was not large enough to draw any conclusions from this information. There were no perioperative complications in smokers. We hypothesized that there may be a higher rate of wound complications in this population, and although the data in our patients did not support this hypothesis, a larger cohort of smokers is needed to make this determination. Another potential complication in smokers is non-union, which was not reported in this study on perioperative complications. Although it did not reach statistical significance, the intraoperative blood loss was almost 150 mL greater in high-BMI patients (924 mL vs 779 mL). Additionally, there appears to be no effect of concomitant procedure on estimated blood loss in either low- or high-BMI groups. Age was not a risk factor for the development of perioperative complications in this cohort. Pain was reliably improved in both the high- and low-BMI groups at the 12-week follow-up visit. The center-edge angle could be normalized in both groups to 28.53° in the high-BMI group and 27.07° in the low-BMI group, with a similar final correction between groups. The Tönnis angle was also improved in both groups, but the final Tönnis angle strongly trended toward statistical significance (2.79° in the low-BMI group vs 10.06° in the high-BMI group).

This study has limitations in that it is a retrospective review of patient information based on medical records and therefore relied on documentation performed at the time of service. There also may have been a difference in the intraoperative or postoperative protocol for wound monitoring or rehabilitation among patients based on body habitus, which we are not able to detect from the medical records. Although the overall number of patients in this cohort is comparable to other studies on the outcomes of patients after PAO, the number of patients in each BMI group was not evenly matched. Without randomization, selection bias occurred at the time of the procedure as some obese patients were not offered this procedure based on the senior surgeon’s discretion. Additionally, when subgroups such as patients with diabetes mellitus or smokers were analyzed, the number of subjects was too small for statistical analysis; therefore, no conclusions could be made as to the risk of perioperative complications in these populations.

CONCLUSION

Despite the limitations in this study, based on the data from this cohort, we concluded that the goal of PAO of restoring more normal hip joint anatomy can be achieved in both low- and high-BMI patients. However, patients with a BMI >30 should be counseled on their increased risk of major perioperative complications, specifically wound dehiscence and infection, and the higher likelihood of reoperation for treatment of these complications. Diabetic patients can be counseled that they may have a higher risk of infection as well, but future studies with larger numbers will be needed to confirm this. Patients with low BMI should be counseled about the potential for prominent or symptomatic hardware, which may necessitate removal following osteotomy union.

ABSTRACT

The purpose of this study is to determine the relationship of body mass index (BMI), age, smoking status, and other comorbid conditions to the rate and type of complications occurring in the perioperative period following periacetabular osteotomy. A retrospective review was performed on 80 hips to determine demographic information as well as pre- and postoperative pain scores, center-edge angle, Tönnis angle, intraoperative blood loss, and perioperative complications within 90 days of surgery. Patients were placed into high- (>30) and low- (<30) BMI groups to determine any correlation between complications and BMI. The high-BMI group had a significantly greater rate of perioperative complications than the low-BMI group (30% vs 8%) and, correspondingly, patients with complications had significantly higher BMI than those without (30.9 ± 9.5, 26.2 ± 5.6) (P = .03). Center-edge angle and Tönnis angle were corrected in both groups. Improvement in postoperative pain scores and radiographically measured acetabular correction can be achieved in high- and low-BMI patients. High-BMI patients have a higher rate of perioperative wound complications.

Continue to: The Bernese periacetabular osteotomy...

The Bernese periacetabular osteotomy (PAO) has become a widely used procedure for hip preservation in adolescent and young adult patients with symptomatic anatomic aberrancies of the acetabulum due to developmental hip dysplasia, trauma, infection, femoroacetabular impingement, and other causes.^1-6 Acetabular dysplasia is one of the most common causes of secondary osteoarthritis, and the goal of PAO is to slow or halt the progression of arthrosis to prolong or potentially eliminate the need for total hip arthroplasty while relieving pain and increasing function and activity.^1,7,8

The PAO involves realigning the acetabulum to improve anterior and lateral coverage of the femoral head, acetabular anteversion, and medicalization of the joint.^5,6 It is preferred over other described acetabular osteotomies due to its inherent stability given that the posterior column is not violated.^3,5,6,9 Since its initial description in 1988,⁵ short-, medium- and long-term outcomes have been reported with excellent patient satisfaction and function.^2,7,10-15 The radiographic, functional, and patient satisfaction outcomes are excellent; therefore, this has become an accepted form of treatment for acetabular dysplasia.¹⁶ Additional procedures, such as hip arthroscopy, have also been combined with PAO to treat intra-articular pathologies without open arthrotomy.¹⁷ Several studies have evaluated preoperative radiographic factors, such as Tönnis grade, previous surgeries, and morphology of the hip; as well as demographic factors, such as age, body mass index (BMI), comorbid diseases, and activity level, which seem to play a role in the final outcome.^11,18,19 This work has advanced our understanding and allowed surgeons to apply selection criteria to improve patient outcomes.

There are multiple reported complications of the PAO procedure, including infection,² wound dehiscence,²⁰ periacetabular fracture,²¹ intra-articular extension of the osteotomy,²² excessive acetabular retroversion,^23,24 hardware failure, femoral or sciatic nerve palsy,²⁵ heterotopic ossification, prominent hardware, deep vein thrombosis or pulmonary embolism,²⁶ osteonecrosis of the femoral head or acetabulum,²⁴ non-union,²⁴ intrapelvic bleeding,²⁴ incisional hernia,²⁷ lateral femoral cutaneous nerve palsy,^20,28 and reflex sympathetic dystrophy.^1,2,29 There are also several studies reporting a learning curve phenomenon, in which the proportion of complications is higher in the initial series of surgeries performed by each specific surgeon.^22,20,29

Despite the widely reported short-, medium-, and long-term results of this treatment, no study thus far has attempted to correlate preoperative patient factors with early perioperative outcomes and complications. This information would be useful in patient counseling and decision making in the early postoperative period. Therefore, the purpose of this study is to analyze data from the perioperative period in patients who have undergone the PAO performed by a single surgeon at our institution to determine any correlation between patient characteristics such as age, comorbid disease, hip pathologic diagnosis, BMI, or previous procedures and perioperative complications occurring within the first 90 days.

Continue to: MATERIALS AND METHODS...

MATERIALS AND METHODS

After Institutional Review Board approval was obtained, a search was performed on the basis of operative report Current Procedural Terminology (CPT) codes for all patients who underwent PAO performed by a single surgeon between 2005 and 2013. Patients were included if they had PAO surgery with at least 90 days of follow-up. There was no exclusion for age, previous surgery, or underlying hip or medical diagnosis. A retrospective review of electronic medical records and radiographic imaging was undertaken to determine pre- and postoperative demographic information, pain scores, center-edge angle of Weiberg and Tönnis angles, intraoperative estimated blood loss, and all perioperative complications. Weight and height were recorded from the immediate preoperative visit and measured in kilograms (kg) and meters (m), respectively. BMI was derived from these measurements. Pain was assessed via visual analog scale at the preoperative visit as well as at 12 weeks postoperatively. Preoperative and 12-week postoperative Tönnis and center-edge angles were measured by a single orthopedic surgeon. All radiographs were deemed adequate in position and penetration for measurement of these parameters. Evidence of osteonecrosis of the femoral head was evaluated on all postoperative radiographs within this perioperative period. Estimated blood loss was established by review of operative records and anesthesia notes.

Perioperative complications were classified using the Clavien-Dindo system, which has previously been validated for use in hip preservation surgery.³⁰ This includes 5 grades of complications based on the treatment needed and severity of resulting long-term disability. Grade I complications do not require any change in the postoperative course and were therefore left out of our statistical analysis. Examples include symptomatic hardware, mild heterotopic ossification, and iliopsoas tendonitis. Grade II complications are those that require a change in outpatient management, such as delayed wound healing, superficial infection, transient nerve palsy, violation of the posterior column, and intra-articular osteotomy. Grade III complications require invasive or surgical treatment but leave the patient with no long-term disability. Examples include wound dehiscence, hematoma or infection necessitating surgical débridement and irrigation, and revision of the osteotomy due to hardware malposition or hip instability. Grade IV complications involve both surgery and long-term disability. Grade IV complications applicable to hip preservation surgery are osteonecrosis, permanent nerve injury, major vascular injury, or pulmonary embolism. A grade V complication is death.

For analysis and correlation between demographics and perioperative outcomes and complications, patients were grouped into several groups for comparison. Low (<30) vs high (>30) BMI, smokers vs non-smokers, diabetic vs non-diabetic patients, and those who had previous surgery vs those who did not were compared. A two-tailed t test was used for normally distributed continuous variables and a Mann-Whitney U test, for non-parametric data to compare postoperative radiographic correction, pain scores, and complication rates between each of these groups.

The operative technique for PAO as described by Ganz and colleagues⁵ in 1988 was utilized in all patients. When preoperative imaging showed evidence of labral pathology, a Cam lesion of the femoral head and neck junction, abnormal proximal femoral anatomy, osteonecrosis of the femoral head, or an os acetabulum, a concomitant procedure was performed. Seventeen patients underwent débridement of a Cam lesion noted to be impinging following PAO. Seventeen patients underwent labral débridement and 4 underwent labral repair. Four patients underwent intertrochanteric osteotomy and 1 underwent greater trochanteric slide. Two patients underwent free-vascularized fibular grafting to the ipsilateral femoral head and 5 underwent fixation of an os acetabulum.

Continue to: RESULTS...

RESULTS

A total of 80 hips in 73 patients underwent PAO with adequate perioperative follow-up and records in the inclusion period. Figures A-E represent a patient pre-procedure, immediately post procedure, and 6 months after successful PAO. The average age was 27.5 years (12.8-43.6 years), and the average BMI was 26.8 (18.7-52.2). Four patients had diabetes, 8 were smokers, and 10 had undergone previous surgeries including arthroscopic labral débridement, 3 open reduction with Salter osteotomy, 3 open reduction with internal fixation of a femoral neck fracture, 1 core decompression for femoral head osteonecrosis, 3 subtrochanteric osteotomy and subsequent non-union treated with cephalomedullary nailing, and 1 previous PAO requiring revision.¹

There were 11 perioperative complications in 10 patients (12.5%). The majority of these were infection (n = 10). Overall complications categorized by BMI are summarized in Table 1. Age was similar in patients with complications (27.4 ± 8.8 years) and those without (27.5 ± 8.2 years) (P = .99). Patients with complications had significantly higher BMI than those without (30.9.3 ± 9.5, 26.2 ± 5.6) (P = .03). There was no effect of concomitant procedures on the complication rate. Of the patients who had complications, 60% (6/10) had concomitant procedures, vs 63% (44/70) of those who had no complications (P = .86) Two of 4 patients with diabetes mellitus developed complications, both of which were wound infections. One of these required incision and débridement. There were no perioperative complications in any of the 7 smokers.  

Abbreviation: BMI, body mass index.

Twenty hips were in the high-BMI (>30) and 60 were in the low-BMI (<30) patient groups. There were 6 total perioperative complications in the high-BMI group (30%) and 5 in the low-BMI group (8%). The most common complications in the low-BMI group were superficial infections.⁴ There were 6 total complications in the high-BMI group: 2 deep and 4 superficial infections. There were 3 reoperations (5%) in the low-BMI group during the perioperative period. Two patients underwent successful débridement and irrigation of a superficial wound, and 1 patient required removal of a prominent screw. There were 3 reoperations in the high-BMI group, all of which were débridement and irrigations for wound infections. The rate of wound dehiscence and wound infection was significantly higher in high-BMI patients (30% [6/20]) than in low-BMI patients (8.3% [4/60]) (P = .006). The mean estimated blood loss in the high-BMI group was greater at 923.75 mL vs 779.25 mL in the low-BMI patients; however, this did not reach statistical significance (P = .350). Seventy percent (14/20) of patients who were obese had concomitant procedures vs 60% (36/60) of those who had normal BMI (P = .42 by chi-square analysis). There was no difference in estimated blood loss in patients who underwent concomitant procedures (Table 2).

Abbreviations: BMI, body mass index; EBL, estimated blood loss.

Preoperative pain scores improved from 4.9 (range, 0-10) to 1.9 (range, 0-6) in the high-BMI group and 4.2 (range, 0-10) to 1.2 (range, 0-6) in the low-BMI group (P = .260). The preoperative center-edge angle in the high-BMI group improved from 6.63° ± 6.5° to 28.53° ± 6.7°, and the Tönnis angle from 24.96° ± 6.3° to 10.06° ± 7.7°. In the low-BMI group the center-edge angle improved from 10.53° ± 11.77° to 27.07° ± 13.9°, and the Tönnis angle from 19.00° ± 10.3° to 2.79° ± 8.3°. There was no difference in postoperative center-edge angle between the high-BMI and low-BMI groups (P = .66). There was a trend toward significance in the postoperative Tönnis angle between the high-BMI and low-BMI groups (P = .051).

Continue to: DISCUSSION...

DISCUSSION

There have been 4 previously published articles specifically on complications following PAO. Each of these encompassed follow-up visits including both the perioperative period and at least 2 years of follow-up.^20,22,24,29 Davey and Santore²⁹ reported an overall rate of complications of 10% in a series of 70 patients. These authors classified complications into minor, moderate, and major for purposes of research and discussion, and this classification system has been utilized or modified within the literature to discuss complications in most other articles. Complications within the perioperative period included 2 cases of excessive intraoperative bleeding, 2 cases of reflex sympathetic dystrophy, and 1 case each of unresolved sciatic nerve palsy and deep vein thrombosis.²⁹ Hussell and colleagues²² reported on a large series of 508 PAOs and analyzed the technical complications that occurred during the procedure and caused either immediate or longer-term problems for the patients. Notably, they concluded that 85% of the technical complications occurred with the initial 50 PAOs performed, signifying a steep learning curve for this technically demanding procedure. Perioperative complications reported were intra-articular osteotomy in 2.2%, femoral nerve palsy in 0.6%, sciatic nerve palsy in 1.0%, posterior column insufficiency in 1.2%, and symptomatic hardware in 3.0%.²² Biedermann and colleagues²⁰ found that 47 out of 60 PAOs in their series had at least 1 minor complication. The most common perioperative complications were lateral femoral cutaneous nerve dysesthesia in 33%, delayed wound healing infection in 15%, major blood loss in 8.3%, sciatic or peroneal nerve palsy in 10%, posterior column discontinuity in 6.7%, and intra-articular osteotomy in 1.6%.²⁰ Most recently, complications of PAO in an adolescent population were evaluated.²⁴ The overall rate of complications was 37%. Major perioperative complications included 1 patient with excessive bleeding due to an aberrant artery at the medial wall of the pelvis thought to be due to revascularization following a previous Dega osteotomy. Two patients required immediate revision of the osteotomy due to excessive anterior coverage noted on postoperative radiographs. There were 5% with superficial stitch abscess causing minor infection, 5% with transient lateral femoral cutaneous nerve palsy, and 15 patients with symptomatic hardware.²⁴

At 12.5%, our overall complication rate is slightly lower than that previously reported in the literature. This may be due to the difference in the scope of this study, which reported only perioperative complications. We also chose to utilize the modified Clavien-Dindo classification system for reporting our complications rather than classifying them as minor or major as in the above studies. This classification system has been validated for use in reporting complications of hip preservation surgery. We considered only Grade II complications and higher for statistical analysis as these required a change in postoperative management, which may have artificially lowered our complication rate.

The data in this study indicate that, compared with patients with a BMI of <30, obese patients have a higher rate of perioperative complications and reoperations. Additionally, the proportion of Grade II and higher complications, importantly deep infection, was higher in obese patients. We did not have any reported incidence of deep vein thrombosis or pulmonary embolism, urinary tract infection, intra-articular osteotomy, acetabular or pelvic fracture, femoral or sciatic nerve palsy, or long-term lateral femoral cutaneous nerve palsy in this series of patients. The most common complication in the low-BMI group was symptomatic hardware. Sixteen patients had this complaint; however, this was not considered a Grade II complication as there would be no change in management during the study period, including the perioperative time frame. Two out of 4 patients with diabetes mellitus developed wound infections, both of which required reoperation. However, the number of patients with diabetes mellitus was not large enough to draw any conclusions from this information. There were no perioperative complications in smokers. We hypothesized that there may be a higher rate of wound complications in this population, and although the data in our patients did not support this hypothesis, a larger cohort of smokers is needed to make this determination. Another potential complication in smokers is non-union, which was not reported in this study on perioperative complications. Although it did not reach statistical significance, the intraoperative blood loss was almost 150 mL greater in high-BMI patients (924 mL vs 779 mL). Additionally, there appears to be no effect of concomitant procedure on estimated blood loss in either low- or high-BMI groups. Age was not a risk factor for the development of perioperative complications in this cohort. Pain was reliably improved in both the high- and low-BMI groups at the 12-week follow-up visit. The center-edge angle could be normalized in both groups to 28.53° in the high-BMI group and 27.07° in the low-BMI group, with a similar final correction between groups. The Tönnis angle was also improved in both groups, but the final Tönnis angle strongly trended toward statistical significance (2.79° in the low-BMI group vs 10.06° in the high-BMI group).

This study has limitations in that it is a retrospective review of patient information based on medical records and therefore relied on documentation performed at the time of service. There also may have been a difference in the intraoperative or postoperative protocol for wound monitoring or rehabilitation among patients based on body habitus, which we are not able to detect from the medical records. Although the overall number of patients in this cohort is comparable to other studies on the outcomes of patients after PAO, the number of patients in each BMI group was not evenly matched. Without randomization, selection bias occurred at the time of the procedure as some obese patients were not offered this procedure based on the senior surgeon’s discretion. Additionally, when subgroups such as patients with diabetes mellitus or smokers were analyzed, the number of subjects was too small for statistical analysis; therefore, no conclusions could be made as to the risk of perioperative complications in these populations.

CONCLUSION

Despite the limitations in this study, based on the data from this cohort, we concluded that the goal of PAO of restoring more normal hip joint anatomy can be achieved in both low- and high-BMI patients. However, patients with a BMI >30 should be counseled on their increased risk of major perioperative complications, specifically wound dehiscence and infection, and the higher likelihood of reoperation for treatment of these complications. Diabetic patients can be counseled that they may have a higher risk of infection as well, but future studies with larger numbers will be needed to confirm this. Patients with low BMI should be counseled about the potential for prominent or symptomatic hardware, which may necessitate removal following osteotomy union.

ABSTRACT

The purpose of this study is to determine the relationship of body mass index (BMI), age, smoking status, and other comorbid conditions to the rate and type of complications occurring in the perioperative period following periacetabular osteotomy. A retrospective review was performed on 80 hips to determine demographic information as well as pre- and postoperative pain scores, center-edge angle, Tönnis angle, intraoperative blood loss, and perioperative complications within 90 days of surgery. Patients were placed into high- (>30) and low- (<30) BMI groups to determine any correlation between complications and BMI. The high-BMI group had a significantly greater rate of perioperative complications than the low-BMI group (30% vs 8%) and, correspondingly, patients with complications had significantly higher BMI than those without (30.9 ± 9.5, 26.2 ± 5.6) (P = .03). Center-edge angle and Tönnis angle were corrected in both groups. Improvement in postoperative pain scores and radiographically measured acetabular correction can be achieved in high- and low-BMI patients. High-BMI patients have a higher rate of perioperative wound complications.

Continue to: The Bernese periacetabular osteotomy...

The Bernese periacetabular osteotomy (PAO) has become a widely used procedure for hip preservation in adolescent and young adult patients with symptomatic anatomic aberrancies of the acetabulum due to developmental hip dysplasia, trauma, infection, femoroacetabular impingement, and other causes.^1-6 Acetabular dysplasia is one of the most common causes of secondary osteoarthritis, and the goal of PAO is to slow or halt the progression of arthrosis to prolong or potentially eliminate the need for total hip arthroplasty while relieving pain and increasing function and activity.^1,7,8

The PAO involves realigning the acetabulum to improve anterior and lateral coverage of the femoral head, acetabular anteversion, and medicalization of the joint.^5,6 It is preferred over other described acetabular osteotomies due to its inherent stability given that the posterior column is not violated.^3,5,6,9 Since its initial description in 1988,⁵ short-, medium- and long-term outcomes have been reported with excellent patient satisfaction and function.^2,7,10-15 The radiographic, functional, and patient satisfaction outcomes are excellent; therefore, this has become an accepted form of treatment for acetabular dysplasia.¹⁶ Additional procedures, such as hip arthroscopy, have also been combined with PAO to treat intra-articular pathologies without open arthrotomy.¹⁷ Several studies have evaluated preoperative radiographic factors, such as Tönnis grade, previous surgeries, and morphology of the hip; as well as demographic factors, such as age, body mass index (BMI), comorbid diseases, and activity level, which seem to play a role in the final outcome.^11,18,19 This work has advanced our understanding and allowed surgeons to apply selection criteria to improve patient outcomes.

There are multiple reported complications of the PAO procedure, including infection,² wound dehiscence,²⁰ periacetabular fracture,²¹ intra-articular extension of the osteotomy,²² excessive acetabular retroversion,^23,24 hardware failure, femoral or sciatic nerve palsy,²⁵ heterotopic ossification, prominent hardware, deep vein thrombosis or pulmonary embolism,²⁶ osteonecrosis of the femoral head or acetabulum,²⁴ non-union,²⁴ intrapelvic bleeding,²⁴ incisional hernia,²⁷ lateral femoral cutaneous nerve palsy,^20,28 and reflex sympathetic dystrophy.^1,2,29 There are also several studies reporting a learning curve phenomenon, in which the proportion of complications is higher in the initial series of surgeries performed by each specific surgeon.^22,20,29

Despite the widely reported short-, medium-, and long-term results of this treatment, no study thus far has attempted to correlate preoperative patient factors with early perioperative outcomes and complications. This information would be useful in patient counseling and decision making in the early postoperative period. Therefore, the purpose of this study is to analyze data from the perioperative period in patients who have undergone the PAO performed by a single surgeon at our institution to determine any correlation between patient characteristics such as age, comorbid disease, hip pathologic diagnosis, BMI, or previous procedures and perioperative complications occurring within the first 90 days.

Continue to: MATERIALS AND METHODS...

MATERIALS AND METHODS

After Institutional Review Board approval was obtained, a search was performed on the basis of operative report Current Procedural Terminology (CPT) codes for all patients who underwent PAO performed by a single surgeon between 2005 and 2013. Patients were included if they had PAO surgery with at least 90 days of follow-up. There was no exclusion for age, previous surgery, or underlying hip or medical diagnosis. A retrospective review of electronic medical records and radiographic imaging was undertaken to determine pre- and postoperative demographic information, pain scores, center-edge angle of Weiberg and Tönnis angles, intraoperative estimated blood loss, and all perioperative complications. Weight and height were recorded from the immediate preoperative visit and measured in kilograms (kg) and meters (m), respectively. BMI was derived from these measurements. Pain was assessed via visual analog scale at the preoperative visit as well as at 12 weeks postoperatively. Preoperative and 12-week postoperative Tönnis and center-edge angles were measured by a single orthopedic surgeon. All radiographs were deemed adequate in position and penetration for measurement of these parameters. Evidence of osteonecrosis of the femoral head was evaluated on all postoperative radiographs within this perioperative period. Estimated blood loss was established by review of operative records and anesthesia notes.

Perioperative complications were classified using the Clavien-Dindo system, which has previously been validated for use in hip preservation surgery.³⁰ This includes 5 grades of complications based on the treatment needed and severity of resulting long-term disability. Grade I complications do not require any change in the postoperative course and were therefore left out of our statistical analysis. Examples include symptomatic hardware, mild heterotopic ossification, and iliopsoas tendonitis. Grade II complications are those that require a change in outpatient management, such as delayed wound healing, superficial infection, transient nerve palsy, violation of the posterior column, and intra-articular osteotomy. Grade III complications require invasive or surgical treatment but leave the patient with no long-term disability. Examples include wound dehiscence, hematoma or infection necessitating surgical débridement and irrigation, and revision of the osteotomy due to hardware malposition or hip instability. Grade IV complications involve both surgery and long-term disability. Grade IV complications applicable to hip preservation surgery are osteonecrosis, permanent nerve injury, major vascular injury, or pulmonary embolism. A grade V complication is death.

For analysis and correlation between demographics and perioperative outcomes and complications, patients were grouped into several groups for comparison. Low (<30) vs high (>30) BMI, smokers vs non-smokers, diabetic vs non-diabetic patients, and those who had previous surgery vs those who did not were compared. A two-tailed t test was used for normally distributed continuous variables and a Mann-Whitney U test, for non-parametric data to compare postoperative radiographic correction, pain scores, and complication rates between each of these groups.

The operative technique for PAO as described by Ganz and colleagues⁵ in 1988 was utilized in all patients. When preoperative imaging showed evidence of labral pathology, a Cam lesion of the femoral head and neck junction, abnormal proximal femoral anatomy, osteonecrosis of the femoral head, or an os acetabulum, a concomitant procedure was performed. Seventeen patients underwent débridement of a Cam lesion noted to be impinging following PAO. Seventeen patients underwent labral débridement and 4 underwent labral repair. Four patients underwent intertrochanteric osteotomy and 1 underwent greater trochanteric slide. Two patients underwent free-vascularized fibular grafting to the ipsilateral femoral head and 5 underwent fixation of an os acetabulum.

Continue to: RESULTS...

RESULTS

A total of 80 hips in 73 patients underwent PAO with adequate perioperative follow-up and records in the inclusion period. Figures A-E represent a patient pre-procedure, immediately post procedure, and 6 months after successful PAO. The average age was 27.5 years (12.8-43.6 years), and the average BMI was 26.8 (18.7-52.2). Four patients had diabetes, 8 were smokers, and 10 had undergone previous surgeries including arthroscopic labral débridement, 3 open reduction with Salter osteotomy, 3 open reduction with internal fixation of a femoral neck fracture, 1 core decompression for femoral head osteonecrosis, 3 subtrochanteric osteotomy and subsequent non-union treated with cephalomedullary nailing, and 1 previous PAO requiring revision.¹

There were 11 perioperative complications in 10 patients (12.5%). The majority of these were infection (n = 10). Overall complications categorized by BMI are summarized in Table 1. Age was similar in patients with complications (27.4 ± 8.8 years) and those without (27.5 ± 8.2 years) (P = .99). Patients with complications had significantly higher BMI than those without (30.9.3 ± 9.5, 26.2 ± 5.6) (P = .03). There was no effect of concomitant procedures on the complication rate. Of the patients who had complications, 60% (6/10) had concomitant procedures, vs 63% (44/70) of those who had no complications (P = .86) Two of 4 patients with diabetes mellitus developed complications, both of which were wound infections. One of these required incision and débridement. There were no perioperative complications in any of the 7 smokers.  

Abbreviation: BMI, body mass index.

Twenty hips were in the high-BMI (>30) and 60 were in the low-BMI (<30) patient groups. There were 6 total perioperative complications in the high-BMI group (30%) and 5 in the low-BMI group (8%). The most common complications in the low-BMI group were superficial infections.⁴ There were 6 total complications in the high-BMI group: 2 deep and 4 superficial infections. There were 3 reoperations (5%) in the low-BMI group during the perioperative period. Two patients underwent successful débridement and irrigation of a superficial wound, and 1 patient required removal of a prominent screw. There were 3 reoperations in the high-BMI group, all of which were débridement and irrigations for wound infections. The rate of wound dehiscence and wound infection was significantly higher in high-BMI patients (30% [6/20]) than in low-BMI patients (8.3% [4/60]) (P = .006). The mean estimated blood loss in the high-BMI group was greater at 923.75 mL vs 779.25 mL in the low-BMI patients; however, this did not reach statistical significance (P = .350). Seventy percent (14/20) of patients who were obese had concomitant procedures vs 60% (36/60) of those who had normal BMI (P = .42 by chi-square analysis). There was no difference in estimated blood loss in patients who underwent concomitant procedures (Table 2).

Abbreviations: BMI, body mass index; EBL, estimated blood loss.

Preoperative pain scores improved from 4.9 (range, 0-10) to 1.9 (range, 0-6) in the high-BMI group and 4.2 (range, 0-10) to 1.2 (range, 0-6) in the low-BMI group (P = .260). The preoperative center-edge angle in the high-BMI group improved from 6.63° ± 6.5° to 28.53° ± 6.7°, and the Tönnis angle from 24.96° ± 6.3° to 10.06° ± 7.7°. In the low-BMI group the center-edge angle improved from 10.53° ± 11.77° to 27.07° ± 13.9°, and the Tönnis angle from 19.00° ± 10.3° to 2.79° ± 8.3°. There was no difference in postoperative center-edge angle between the high-BMI and low-BMI groups (P = .66). There was a trend toward significance in the postoperative Tönnis angle between the high-BMI and low-BMI groups (P = .051).

Continue to: DISCUSSION...

DISCUSSION

There have been 4 previously published articles specifically on complications following PAO. Each of these encompassed follow-up visits including both the perioperative period and at least 2 years of follow-up.^20,22,24,29 Davey and Santore²⁹ reported an overall rate of complications of 10% in a series of 70 patients. These authors classified complications into minor, moderate, and major for purposes of research and discussion, and this classification system has been utilized or modified within the literature to discuss complications in most other articles. Complications within the perioperative period included 2 cases of excessive intraoperative bleeding, 2 cases of reflex sympathetic dystrophy, and 1 case each of unresolved sciatic nerve palsy and deep vein thrombosis.²⁹ Hussell and colleagues²² reported on a large series of 508 PAOs and analyzed the technical complications that occurred during the procedure and caused either immediate or longer-term problems for the patients. Notably, they concluded that 85% of the technical complications occurred with the initial 50 PAOs performed, signifying a steep learning curve for this technically demanding procedure. Perioperative complications reported were intra-articular osteotomy in 2.2%, femoral nerve palsy in 0.6%, sciatic nerve palsy in 1.0%, posterior column insufficiency in 1.2%, and symptomatic hardware in 3.0%.²² Biedermann and colleagues²⁰ found that 47 out of 60 PAOs in their series had at least 1 minor complication. The most common perioperative complications were lateral femoral cutaneous nerve dysesthesia in 33%, delayed wound healing infection in 15%, major blood loss in 8.3%, sciatic or peroneal nerve palsy in 10%, posterior column discontinuity in 6.7%, and intra-articular osteotomy in 1.6%.²⁰ Most recently, complications of PAO in an adolescent population were evaluated.²⁴ The overall rate of complications was 37%. Major perioperative complications included 1 patient with excessive bleeding due to an aberrant artery at the medial wall of the pelvis thought to be due to revascularization following a previous Dega osteotomy. Two patients required immediate revision of the osteotomy due to excessive anterior coverage noted on postoperative radiographs. There were 5% with superficial stitch abscess causing minor infection, 5% with transient lateral femoral cutaneous nerve palsy, and 15 patients with symptomatic hardware.²⁴

At 12.5%, our overall complication rate is slightly lower than that previously reported in the literature. This may be due to the difference in the scope of this study, which reported only perioperative complications. We also chose to utilize the modified Clavien-Dindo classification system for reporting our complications rather than classifying them as minor or major as in the above studies. This classification system has been validated for use in reporting complications of hip preservation surgery. We considered only Grade II complications and higher for statistical analysis as these required a change in postoperative management, which may have artificially lowered our complication rate.

The data in this study indicate that, compared with patients with a BMI of <30, obese patients have a higher rate of perioperative complications and reoperations. Additionally, the proportion of Grade II and higher complications, importantly deep infection, was higher in obese patients. We did not have any reported incidence of deep vein thrombosis or pulmonary embolism, urinary tract infection, intra-articular osteotomy, acetabular or pelvic fracture, femoral or sciatic nerve palsy, or long-term lateral femoral cutaneous nerve palsy in this series of patients. The most common complication in the low-BMI group was symptomatic hardware. Sixteen patients had this complaint; however, this was not considered a Grade II complication as there would be no change in management during the study period, including the perioperative time frame. Two out of 4 patients with diabetes mellitus developed wound infections, both of which required reoperation. However, the number of patients with diabetes mellitus was not large enough to draw any conclusions from this information. There were no perioperative complications in smokers. We hypothesized that there may be a higher rate of wound complications in this population, and although the data in our patients did not support this hypothesis, a larger cohort of smokers is needed to make this determination. Another potential complication in smokers is non-union, which was not reported in this study on perioperative complications. Although it did not reach statistical significance, the intraoperative blood loss was almost 150 mL greater in high-BMI patients (924 mL vs 779 mL). Additionally, there appears to be no effect of concomitant procedure on estimated blood loss in either low- or high-BMI groups. Age was not a risk factor for the development of perioperative complications in this cohort. Pain was reliably improved in both the high- and low-BMI groups at the 12-week follow-up visit. The center-edge angle could be normalized in both groups to 28.53° in the high-BMI group and 27.07° in the low-BMI group, with a similar final correction between groups. The Tönnis angle was also improved in both groups, but the final Tönnis angle strongly trended toward statistical significance (2.79° in the low-BMI group vs 10.06° in the high-BMI group).

This study has limitations in that it is a retrospective review of patient information based on medical records and therefore relied on documentation performed at the time of service. There also may have been a difference in the intraoperative or postoperative protocol for wound monitoring or rehabilitation among patients based on body habitus, which we are not able to detect from the medical records. Although the overall number of patients in this cohort is comparable to other studies on the outcomes of patients after PAO, the number of patients in each BMI group was not evenly matched. Without randomization, selection bias occurred at the time of the procedure as some obese patients were not offered this procedure based on the senior surgeon’s discretion. Additionally, when subgroups such as patients with diabetes mellitus or smokers were analyzed, the number of subjects was too small for statistical analysis; therefore, no conclusions could be made as to the risk of perioperative complications in these populations.

CONCLUSION

Despite the limitations in this study, based on the data from this cohort, we concluded that the goal of PAO of restoring more normal hip joint anatomy can be achieved in both low- and high-BMI patients. However, patients with a BMI >30 should be counseled on their increased risk of major perioperative complications, specifically wound dehiscence and infection, and the higher likelihood of reoperation for treatment of these complications. Diabetic patients can be counseled that they may have a higher risk of infection as well, but future studies with larger numbers will be needed to confirm this. Patients with low BMI should be counseled about the potential for prominent or symptomatic hardware, which may necessitate removal following osteotomy union.