Follicular lymphoma: Quantitative PET/CT measures for detecting bone marrow involvement

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Follicular lymphoma: Quantitative PET/CT measures for detecting bone marrow involvement

Quantifying bone marrow uptake of FDG (18fluorodeoxyglucose) improved the diagnostic accuracy of PET/CT for predicting bone marrow involvement in patients with follicular lymphoma, based on the results of a retrospective study.

Visual evidence of focal increased uptake on PET/CT indicates marrow involvement in follicular lymphoma; however, diffuse uptake is a nonspecific finding. Measuring the mean bone marrow standardized uptake value (BM SUV mean) improves PET/CT diagnostic accuracy, Dr. Chava Perry and his colleagues at Tel Aviv Sourasky Medical Center reported in Medicine [(Baltimore). 2016 Mar;95(9):e2910].

The researchers evaluated 68 consecutive patients with follicular lymphoma; 16 had bone marrow involvement – 13 had biopsy-proven involvement and 3 had a negative biopsy with increased medullary uptake that normalized after treatment. BM FDG uptake was diffuse in 8 of them and focal in the other 8.

While focal increased uptake is indicative of bone marrow involvement, diffuse uptake can be associated with false-positive results, as it was in the case of 17 patients (32.7% of those with diffuse uptake). Overall, visual assessment of scan results had a negative predictive value of 100% and a positive predictive value (PPV) of 48.5%.

On a quantitative assessment, however, BM SUV mean was significantly higher in patients with bone marrow involvement (SUV mean of 3.7 [1.7-6] vs. 1.4 [0.4-2.65]; P  less than .001). On the receiver operator curve (ROC) analysis, a BM SUV mean  exceeding  2.7 had a positive predictive value of 100% for bone marrow involvement (sensitivity of 68%). A BM SUV mean  less than 1.7 had an negative predictive value of 100% (specificity of 73%).

A mean standardized uptake value (BM SUV mean) below 1.7 may spare the need for bone marrow biopsy while a BM SUV mean above 2.7 is compatible with bone marrow involvement, although biopsy may still be recommended to exclude large cell transformation, the researchers concluded.

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Quantifying bone marrow uptake of FDG (18fluorodeoxyglucose) improved the diagnostic accuracy of PET/CT for predicting bone marrow involvement in patients with follicular lymphoma, based on the results of a retrospective study.

Visual evidence of focal increased uptake on PET/CT indicates marrow involvement in follicular lymphoma; however, diffuse uptake is a nonspecific finding. Measuring the mean bone marrow standardized uptake value (BM SUV mean) improves PET/CT diagnostic accuracy, Dr. Chava Perry and his colleagues at Tel Aviv Sourasky Medical Center reported in Medicine [(Baltimore). 2016 Mar;95(9):e2910].

The researchers evaluated 68 consecutive patients with follicular lymphoma; 16 had bone marrow involvement – 13 had biopsy-proven involvement and 3 had a negative biopsy with increased medullary uptake that normalized after treatment. BM FDG uptake was diffuse in 8 of them and focal in the other 8.

While focal increased uptake is indicative of bone marrow involvement, diffuse uptake can be associated with false-positive results, as it was in the case of 17 patients (32.7% of those with diffuse uptake). Overall, visual assessment of scan results had a negative predictive value of 100% and a positive predictive value (PPV) of 48.5%.

On a quantitative assessment, however, BM SUV mean was significantly higher in patients with bone marrow involvement (SUV mean of 3.7 [1.7-6] vs. 1.4 [0.4-2.65]; P  less than .001). On the receiver operator curve (ROC) analysis, a BM SUV mean  exceeding  2.7 had a positive predictive value of 100% for bone marrow involvement (sensitivity of 68%). A BM SUV mean  less than 1.7 had an negative predictive value of 100% (specificity of 73%).

A mean standardized uptake value (BM SUV mean) below 1.7 may spare the need for bone marrow biopsy while a BM SUV mean above 2.7 is compatible with bone marrow involvement, although biopsy may still be recommended to exclude large cell transformation, the researchers concluded.

[email protected]

On Twitter @maryjodales

Quantifying bone marrow uptake of FDG (18fluorodeoxyglucose) improved the diagnostic accuracy of PET/CT for predicting bone marrow involvement in patients with follicular lymphoma, based on the results of a retrospective study.

Visual evidence of focal increased uptake on PET/CT indicates marrow involvement in follicular lymphoma; however, diffuse uptake is a nonspecific finding. Measuring the mean bone marrow standardized uptake value (BM SUV mean) improves PET/CT diagnostic accuracy, Dr. Chava Perry and his colleagues at Tel Aviv Sourasky Medical Center reported in Medicine [(Baltimore). 2016 Mar;95(9):e2910].

The researchers evaluated 68 consecutive patients with follicular lymphoma; 16 had bone marrow involvement – 13 had biopsy-proven involvement and 3 had a negative biopsy with increased medullary uptake that normalized after treatment. BM FDG uptake was diffuse in 8 of them and focal in the other 8.

While focal increased uptake is indicative of bone marrow involvement, diffuse uptake can be associated with false-positive results, as it was in the case of 17 patients (32.7% of those with diffuse uptake). Overall, visual assessment of scan results had a negative predictive value of 100% and a positive predictive value (PPV) of 48.5%.

On a quantitative assessment, however, BM SUV mean was significantly higher in patients with bone marrow involvement (SUV mean of 3.7 [1.7-6] vs. 1.4 [0.4-2.65]; P  less than .001). On the receiver operator curve (ROC) analysis, a BM SUV mean  exceeding  2.7 had a positive predictive value of 100% for bone marrow involvement (sensitivity of 68%). A BM SUV mean  less than 1.7 had an negative predictive value of 100% (specificity of 73%).

A mean standardized uptake value (BM SUV mean) below 1.7 may spare the need for bone marrow biopsy while a BM SUV mean above 2.7 is compatible with bone marrow involvement, although biopsy may still be recommended to exclude large cell transformation, the researchers concluded.

[email protected]

On Twitter @maryjodales

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Key clinical point: Measuring the mean standardized uptake value of 18fluorodeoxyglucose in the bone marrow of patients with follicular lymphoma improves the diagnostic accuracy of PET/CT.

Major finding: In this study, diffuse uptake was associated with 17 (32.7%) false positive cases.

Data source: Retrospective study of 68 consecutive patients with follicular lymphoma.

Disclosures: The authors had no funding and conflicts of interest to disclose.

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Infant egg introduction can prevent sensitization at 12 months

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Infant egg introduction can prevent sensitization at 12 months

LOS ANGELES – Among infants at risk for allergic disease, egg introduction at 4 months cuts the risk of egg sensitization at 12 months by about half, according a randomized, placebo-controlled, double blind trial from Australia.

“This is what we hoped to find.” Introducing egg early “is certainly safe, and it may promote tolerance,” said senior investigator Dr. Dianne Campbell, professor and chair of pediatric allergy and clinical immunology at the Children’s Hospital at Westmead, which is affiliated with the University of Sydney.

Dr. Dianne Campbell

Four-month-old children were randomized to 350 mg of pasteurized raw whole egg powder or – as a control – rice powder sprinkled once daily on their weaning food until month 8, at which time parents in both groups were encouraged to add eggs to their children’s diets. At least one of each child’s parents had a history of atopic disease, including asthma, eczema, hay fever, or food allergy. Even so, all of the infants had negative (less than 2 mm) skin prick tests (SPTs) at baseline. Compliance by parent diary was 89% in the rice and 81% in the egg groups.

At 12 months, SPTs were positive (3 mm or more) for whole egg in 25 of 122 (20%) children in the rice group, but only 13 of 122 (11%) in the egg group (odds ratio, 0.46; 95% confidence interval, 0.22-0.95; P = .03). Whole egg IgG4 and IgG4/IgE ratios to egg, ovalbumin, and ovomucoid were also higher in the egg group, indicating developing tolerance (P less than .0001 for each).

About 10% of the children originally in the egg group broke out in hives after their first few doses, and were withdrawn from the study. “This intervention may not be for everybody. There will be individuals who react” and it’s impossible, at this point, to predict who they will be. “We cannot prevent allergy in everyone,” said lead investigator Dr. John Tan, a pediatric immunologist at the hospital.

Dr. John Tan

Overall, however, early introduction was safe. There was no anaphylaxis in the trial, and no cardiovascular or respiratory complications. Rates of eczema and peanut allergy were similar at 12 months between the two groups, meaning that early egg introduction did not increase the risk of atopy.

The findings echo results from several recent pediatric egg allergy studies, as well as findings from recent peanut trials. Slowly, it’s becoming clear that delaying the introduction of at least some allergenic foods – a common practice for years – doesn’t prevent allergies and may, in fact, promote them.

Despite those findings, there remains “a big disconnect between the [new] research and what we [still] recommend” in Australia, the United States, and elsewhere. Delaying food introductions was medical “dogma for 20 years, from highly esteemed societies,” and it corresponded with a marked increase in food allergies, but “it’s very hard to turn these things around,” Dr. Campbell said at the American Academy of Allergy, Asthma, and Immunology annual meeting.

The Australian government is reworking its infant feeding guidelines to incorporate the new evidence. “Our revised guidelines will say that there’s strong evidence for peanut and moderate evidence for egg” in favor of early introduction in children who are not sensitized by 4 or so months old, she said.

The trial was powered to detect differences in SPT, not actual egg allergies, which were diagnosed in 13 children (11%) in the rice group and eight (7%) in the egg group; the difference was not statistically significant. “Not all kids who are sensitized will be allergic,” she noted.

The study groups were well matched; there were about equal numbers of boys and girls in each, and, in both groups, about 15% of children were exposed to second hand smoke at home and almost all were breastfed.

The work was funded by the Australian government, among others. The investigators have no disclosures.

[email protected]

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LOS ANGELES – Among infants at risk for allergic disease, egg introduction at 4 months cuts the risk of egg sensitization at 12 months by about half, according a randomized, placebo-controlled, double blind trial from Australia.

“This is what we hoped to find.” Introducing egg early “is certainly safe, and it may promote tolerance,” said senior investigator Dr. Dianne Campbell, professor and chair of pediatric allergy and clinical immunology at the Children’s Hospital at Westmead, which is affiliated with the University of Sydney.

Dr. Dianne Campbell

Four-month-old children were randomized to 350 mg of pasteurized raw whole egg powder or – as a control – rice powder sprinkled once daily on their weaning food until month 8, at which time parents in both groups were encouraged to add eggs to their children’s diets. At least one of each child’s parents had a history of atopic disease, including asthma, eczema, hay fever, or food allergy. Even so, all of the infants had negative (less than 2 mm) skin prick tests (SPTs) at baseline. Compliance by parent diary was 89% in the rice and 81% in the egg groups.

At 12 months, SPTs were positive (3 mm or more) for whole egg in 25 of 122 (20%) children in the rice group, but only 13 of 122 (11%) in the egg group (odds ratio, 0.46; 95% confidence interval, 0.22-0.95; P = .03). Whole egg IgG4 and IgG4/IgE ratios to egg, ovalbumin, and ovomucoid were also higher in the egg group, indicating developing tolerance (P less than .0001 for each).

About 10% of the children originally in the egg group broke out in hives after their first few doses, and were withdrawn from the study. “This intervention may not be for everybody. There will be individuals who react” and it’s impossible, at this point, to predict who they will be. “We cannot prevent allergy in everyone,” said lead investigator Dr. John Tan, a pediatric immunologist at the hospital.

Dr. John Tan

Overall, however, early introduction was safe. There was no anaphylaxis in the trial, and no cardiovascular or respiratory complications. Rates of eczema and peanut allergy were similar at 12 months between the two groups, meaning that early egg introduction did not increase the risk of atopy.

The findings echo results from several recent pediatric egg allergy studies, as well as findings from recent peanut trials. Slowly, it’s becoming clear that delaying the introduction of at least some allergenic foods – a common practice for years – doesn’t prevent allergies and may, in fact, promote them.

Despite those findings, there remains “a big disconnect between the [new] research and what we [still] recommend” in Australia, the United States, and elsewhere. Delaying food introductions was medical “dogma for 20 years, from highly esteemed societies,” and it corresponded with a marked increase in food allergies, but “it’s very hard to turn these things around,” Dr. Campbell said at the American Academy of Allergy, Asthma, and Immunology annual meeting.

The Australian government is reworking its infant feeding guidelines to incorporate the new evidence. “Our revised guidelines will say that there’s strong evidence for peanut and moderate evidence for egg” in favor of early introduction in children who are not sensitized by 4 or so months old, she said.

The trial was powered to detect differences in SPT, not actual egg allergies, which were diagnosed in 13 children (11%) in the rice group and eight (7%) in the egg group; the difference was not statistically significant. “Not all kids who are sensitized will be allergic,” she noted.

The study groups were well matched; there were about equal numbers of boys and girls in each, and, in both groups, about 15% of children were exposed to second hand smoke at home and almost all were breastfed.

The work was funded by the Australian government, among others. The investigators have no disclosures.

[email protected]

LOS ANGELES – Among infants at risk for allergic disease, egg introduction at 4 months cuts the risk of egg sensitization at 12 months by about half, according a randomized, placebo-controlled, double blind trial from Australia.

“This is what we hoped to find.” Introducing egg early “is certainly safe, and it may promote tolerance,” said senior investigator Dr. Dianne Campbell, professor and chair of pediatric allergy and clinical immunology at the Children’s Hospital at Westmead, which is affiliated with the University of Sydney.

Dr. Dianne Campbell

Four-month-old children were randomized to 350 mg of pasteurized raw whole egg powder or – as a control – rice powder sprinkled once daily on their weaning food until month 8, at which time parents in both groups were encouraged to add eggs to their children’s diets. At least one of each child’s parents had a history of atopic disease, including asthma, eczema, hay fever, or food allergy. Even so, all of the infants had negative (less than 2 mm) skin prick tests (SPTs) at baseline. Compliance by parent diary was 89% in the rice and 81% in the egg groups.

At 12 months, SPTs were positive (3 mm or more) for whole egg in 25 of 122 (20%) children in the rice group, but only 13 of 122 (11%) in the egg group (odds ratio, 0.46; 95% confidence interval, 0.22-0.95; P = .03). Whole egg IgG4 and IgG4/IgE ratios to egg, ovalbumin, and ovomucoid were also higher in the egg group, indicating developing tolerance (P less than .0001 for each).

About 10% of the children originally in the egg group broke out in hives after their first few doses, and were withdrawn from the study. “This intervention may not be for everybody. There will be individuals who react” and it’s impossible, at this point, to predict who they will be. “We cannot prevent allergy in everyone,” said lead investigator Dr. John Tan, a pediatric immunologist at the hospital.

Dr. John Tan

Overall, however, early introduction was safe. There was no anaphylaxis in the trial, and no cardiovascular or respiratory complications. Rates of eczema and peanut allergy were similar at 12 months between the two groups, meaning that early egg introduction did not increase the risk of atopy.

The findings echo results from several recent pediatric egg allergy studies, as well as findings from recent peanut trials. Slowly, it’s becoming clear that delaying the introduction of at least some allergenic foods – a common practice for years – doesn’t prevent allergies and may, in fact, promote them.

Despite those findings, there remains “a big disconnect between the [new] research and what we [still] recommend” in Australia, the United States, and elsewhere. Delaying food introductions was medical “dogma for 20 years, from highly esteemed societies,” and it corresponded with a marked increase in food allergies, but “it’s very hard to turn these things around,” Dr. Campbell said at the American Academy of Allergy, Asthma, and Immunology annual meeting.

The Australian government is reworking its infant feeding guidelines to incorporate the new evidence. “Our revised guidelines will say that there’s strong evidence for peanut and moderate evidence for egg” in favor of early introduction in children who are not sensitized by 4 or so months old, she said.

The trial was powered to detect differences in SPT, not actual egg allergies, which were diagnosed in 13 children (11%) in the rice group and eight (7%) in the egg group; the difference was not statistically significant. “Not all kids who are sensitized will be allergic,” she noted.

The study groups were well matched; there were about equal numbers of boys and girls in each, and, in both groups, about 15% of children were exposed to second hand smoke at home and almost all were breastfed.

The work was funded by the Australian government, among others. The investigators have no disclosures.

[email protected]

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Key clinical point: If at-risk infants have negative skin prick tests (SPTs) at 4 months, tell their moms to introduce egg into their weaning diets.

Major finding: At 12 months, SPTs were positive (3 mm or more) for whole egg in 25 of 122 children (20%) in the rice group, but only 13 of 122 (11%) in the egg group (odds ratio, 0.46; 95% confidence interval, 0.22-0.95; P = .03).

Data source: Randomized clinical trial or 244 infants at risk for egg allergy.

Disclosures: The work was funded by the Australian government, among others. The investigators have no disclosures.

Sports Medicine Fellowship: What Should I Be Looking For?

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Sports Medicine Fellowship: What Should I Be Looking For?

The Orthopaedic Sports Medicine Fellowship Match was first established in 2008 as a joint-sponsored venture between the American Orthopaedic Society for Sports Medicine and the Arthroscopy Association of North America to pair applicants with participating training programs.1 Operated under the San Francisco Match,2 the current fellowship match process was adopted to systematically coordinate training appointments and eliminate the role of “exploding offers,” which are pressured early decisions predicated on immediate acceptance. Other advantages of this system include its operation through a central application service to avoid redundancy of submitted paperwork, as well as to create greater awareness and to publicize training options and standardization of the match timeline.1

In its current state, the orthopedic sports medicine match represents 96 programs with 230 positions, accounting for approximately 97% of training programs and fellowship positions.1 While unaccredited options remain available through the Match, many programs have migrated towards American Council for Graduate Medical Education (ACGME) accreditation because of an increased focus on objective learning metrics during fellowship and the requirement for Subspecialty Certification in Orthopaedic Sports Medicine through the American Board of Orthopaedic Surgery.3 However, other programs have also eschewed the increasing constraints and administrative resources associated with ACGME accreditation, particularly among fellowships based at community-based hospitals or private practices that lack formal affiliation with academic institutions or residency training programs.

Along with a greater understanding of the historical background of the match process, fellowship applicants must also appreciate the relative merits of fellowship training. More than 90% of orthopedic surgery residents now pursue further subspecialty fellowship training, with some individuals opting for 2 additional fellowship opportunities.4 As a so-called “nontraditional applicant,” I represent a different demographic, returning to fellowship after years of clinical practice while serving in the military. Individual preferences notwithstanding, I wanted to take the opportunity to emphasize some important considerations in deliberating between different fellowship programs.

  • Geography. Your eventual desired practice location may play a role in determining fellowship location or, at least, region of the country. Additionally, this can be an important factor in family happiness. In competitive markets, such as the Northeast or the West Coast, you may make inroads and establish professional connections that result in potential job opportunities. Conversely, other programs may adopt anticompetitive measures to limit local practice options.
  • Training setting. Despite the trending consolidation of fellowship training programs in affiliated university and hospital-based teaching systems, many community-based programs and private-practice models thrive, providing an alternative to traditional academic training centers. The latter may provide more in-depth exposure to practice management, billing/coding, and ancillary services. The former typically offer a more structured, academically oriented environment with formal teaching conferences and a broader department hierarchy.
  • Program size. Some applicants may prefer a larger, more diverse array of teaching staff or fellows, while others gravitate toward fewer, more personal mentoring relationships that allow more intimate familiarity with practice habits or surgical techniques.
  • Associated training programs. Affiliations with a residency or physician-extender training program can offer benefits and drawbacks, including offloading clerical work, shared hands-on experience in the clinic and operating room, and midlevel supervisory responsibilities. This can offer useful opportunities to formulate an individual teaching style and valuable mentoring relationships. However, it can also impose greater time requirements or detract from one-on-one teaching with staff.
  • Reputation. Applicants may attach distinction to a well-established regional or national reputation associated with a given training program. Often, certain programs may carry prestige as a result of their academic name, hospital affiliation, or accomplishments. This can offer certain marketing advantages for patient recruitment. However, less renowned programs may provide better training opportunities and confer higher esteem among your professional colleagues. Program reputation can change dramatically with time, so this should be balanced with other potential strengths and overall training experience.
  • Practice “niches”/areas of interest. With increasing adoption of arthroscopic techniques among practicing surgeons and a relative excess of sports medicine–trained orthopedists, it is paramount to develop a novel skill set during fellowship to differentiate you from other graduates. I sought a sports medicine fellowship that would offer me a broad-based exposure to arthroscopic and open knee and shoulder reconstruction, chondral restoration techniques, hip arthroscopy and preservation, and shoulder arthroplasty. Opportunities in elbow reconstruction, foot and ankle arthroscopy, and pediatric sports medicine may also be valuable as a distinguishing factor in searching for jobs after training.
  • Marketability. Closely intertwined with reputation and scope of practice, an institution’s marketability is another intangible attribute to consider. Professional or collegiate team coverage offers significant market value for patient advertising, and it is frequently publicized by orthopedic practices and hospital systems. Additionally, the importance of ACGME accreditation should also be considered.
  • Nonmedical training. This is increasingly important in subsequent subspecialty training. Further education on the business aspects of orthopedic surgery should be emphasized. Additionally, dedicated curricula on professional or leadership development are important for career progression.
  • Mentorship. Throughout the interview process, one of my foremost priorities was a strong and enduring pattern of mentorship. Fellowship offers the opportunity to establish 1 or multiple mentors in your subspecialty. These individuals will be instrumental in the development of your early professional career and your approach to clinical practice. From discussions about complicated patients to advice on contract negotiations, your ideal mentor should champion your early successes and work generously on your behalf, even long after fellowship has ended. 

  • Research opportunities. Given my academic career goals, I actively pursued a program with rich clinical and laboratory resources, and an established infrastructure for accomplishing high-quality, relevant research. Interested individuals should gauge the availability of research support staff, biomechanical or bench-level laboratory collaboration, grant or institutional research funding, cadaveric specimens, or clinical outcomes data for research conducted by fellows. However, not all fellowship applicants have a vested interest in research during fellowship, so I would encourage inquiries regarding core research requirements and expectations.
  • Clinical exposure. This encompasses several different and equally important variables, including diversity of clinical or surgical caseloads, case complexity, operative exposure, athletic team coverage, and office or clinical experience. Interestingly, this latter aspect of training is often neglected but cannot be overemphasized. Outpatient clinical evaluation is key to honing important physical examination techniques and critically evaluating patients’ outcomes postoperatively.
  • Surgical autonomy. Hands-on operative experience and surgical autonomy vary widely among fellowship programs. Most fellowships advocate for a graduated level of surgical responsibility dependent on individual abilities and staff comfort, while others offer greater potential for independence. Conversely, some programs espouse more of an “observership” model, and arthroscopic simulators and/or cadaveric skills laboratories are designed to complement operative experience. While most fellowship applicants desire maximal case participation, we must also recognize the value in watching talented surgeons performing technically demanding procedures.
  • Family. You cannot put a premium on your personal contentment and family’s well-being. Proximity to a support network can be important with the work demands and time constraints of fellowship.
 

 

Despite financial obligations and significant time commitments, the fellowship match process offers an incredible range of programs and practice environments. Inevitably, no program can completely fulfill all your criteria, but you should be able to tailor your learning style, professional ambitions, and personal preferences with an excellent training program. For many, fellowship represents the last, and perhaps most integral, stage of formal surgical training. Considering all factors of your chosen fellowship program will ensure a rich and fulfilling educational experience.

References

1.    Sports medicine/arthroscopy fellowship match. American Orthopaedic Society for Sports Medicine website. https://www.sportsmed.org/AOSSMIMIS/Members/Members/Education/Sports_Medicine_Arthroscopy_Fellowship_Match.aspx. Accessed December 21, 2015.

2.    Orthopaedic sports medicine fellowship. SF Match website. https://www.sfmatch.org/SpecialtyInsideAll.aspx?id=11&typ=1&name=Orthopaedic%20Sports%20Medicine. Accessed December 21, 2015.

3.    Orthopaedic sports medicine. American Board of Orthopaedic Surgery website. https://www.abos.org/certification/sports-subspecialty.aspx. Accessed December 21, 2015.

4.    Hariri S, York SC, O’Connor MI, Parsley BS, McCarthy JC. Career plans of current orthopaedic residents with a focus on sex-based and generational differences. J Bone Joint Surg Am. 2011;93(5):e16.

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The Orthopaedic Sports Medicine Fellowship Match was first established in 2008 as a joint-sponsored venture between the American Orthopaedic Society for Sports Medicine and the Arthroscopy Association of North America to pair applicants with participating training programs.1 Operated under the San Francisco Match,2 the current fellowship match process was adopted to systematically coordinate training appointments and eliminate the role of “exploding offers,” which are pressured early decisions predicated on immediate acceptance. Other advantages of this system include its operation through a central application service to avoid redundancy of submitted paperwork, as well as to create greater awareness and to publicize training options and standardization of the match timeline.1

In its current state, the orthopedic sports medicine match represents 96 programs with 230 positions, accounting for approximately 97% of training programs and fellowship positions.1 While unaccredited options remain available through the Match, many programs have migrated towards American Council for Graduate Medical Education (ACGME) accreditation because of an increased focus on objective learning metrics during fellowship and the requirement for Subspecialty Certification in Orthopaedic Sports Medicine through the American Board of Orthopaedic Surgery.3 However, other programs have also eschewed the increasing constraints and administrative resources associated with ACGME accreditation, particularly among fellowships based at community-based hospitals or private practices that lack formal affiliation with academic institutions or residency training programs.

Along with a greater understanding of the historical background of the match process, fellowship applicants must also appreciate the relative merits of fellowship training. More than 90% of orthopedic surgery residents now pursue further subspecialty fellowship training, with some individuals opting for 2 additional fellowship opportunities.4 As a so-called “nontraditional applicant,” I represent a different demographic, returning to fellowship after years of clinical practice while serving in the military. Individual preferences notwithstanding, I wanted to take the opportunity to emphasize some important considerations in deliberating between different fellowship programs.

  • Geography. Your eventual desired practice location may play a role in determining fellowship location or, at least, region of the country. Additionally, this can be an important factor in family happiness. In competitive markets, such as the Northeast or the West Coast, you may make inroads and establish professional connections that result in potential job opportunities. Conversely, other programs may adopt anticompetitive measures to limit local practice options.
  • Training setting. Despite the trending consolidation of fellowship training programs in affiliated university and hospital-based teaching systems, many community-based programs and private-practice models thrive, providing an alternative to traditional academic training centers. The latter may provide more in-depth exposure to practice management, billing/coding, and ancillary services. The former typically offer a more structured, academically oriented environment with formal teaching conferences and a broader department hierarchy.
  • Program size. Some applicants may prefer a larger, more diverse array of teaching staff or fellows, while others gravitate toward fewer, more personal mentoring relationships that allow more intimate familiarity with practice habits or surgical techniques.
  • Associated training programs. Affiliations with a residency or physician-extender training program can offer benefits and drawbacks, including offloading clerical work, shared hands-on experience in the clinic and operating room, and midlevel supervisory responsibilities. This can offer useful opportunities to formulate an individual teaching style and valuable mentoring relationships. However, it can also impose greater time requirements or detract from one-on-one teaching with staff.
  • Reputation. Applicants may attach distinction to a well-established regional or national reputation associated with a given training program. Often, certain programs may carry prestige as a result of their academic name, hospital affiliation, or accomplishments. This can offer certain marketing advantages for patient recruitment. However, less renowned programs may provide better training opportunities and confer higher esteem among your professional colleagues. Program reputation can change dramatically with time, so this should be balanced with other potential strengths and overall training experience.
  • Practice “niches”/areas of interest. With increasing adoption of arthroscopic techniques among practicing surgeons and a relative excess of sports medicine–trained orthopedists, it is paramount to develop a novel skill set during fellowship to differentiate you from other graduates. I sought a sports medicine fellowship that would offer me a broad-based exposure to arthroscopic and open knee and shoulder reconstruction, chondral restoration techniques, hip arthroscopy and preservation, and shoulder arthroplasty. Opportunities in elbow reconstruction, foot and ankle arthroscopy, and pediatric sports medicine may also be valuable as a distinguishing factor in searching for jobs after training.
  • Marketability. Closely intertwined with reputation and scope of practice, an institution’s marketability is another intangible attribute to consider. Professional or collegiate team coverage offers significant market value for patient advertising, and it is frequently publicized by orthopedic practices and hospital systems. Additionally, the importance of ACGME accreditation should also be considered.
  • Nonmedical training. This is increasingly important in subsequent subspecialty training. Further education on the business aspects of orthopedic surgery should be emphasized. Additionally, dedicated curricula on professional or leadership development are important for career progression.
  • Mentorship. Throughout the interview process, one of my foremost priorities was a strong and enduring pattern of mentorship. Fellowship offers the opportunity to establish 1 or multiple mentors in your subspecialty. These individuals will be instrumental in the development of your early professional career and your approach to clinical practice. From discussions about complicated patients to advice on contract negotiations, your ideal mentor should champion your early successes and work generously on your behalf, even long after fellowship has ended. 

  • Research opportunities. Given my academic career goals, I actively pursued a program with rich clinical and laboratory resources, and an established infrastructure for accomplishing high-quality, relevant research. Interested individuals should gauge the availability of research support staff, biomechanical or bench-level laboratory collaboration, grant or institutional research funding, cadaveric specimens, or clinical outcomes data for research conducted by fellows. However, not all fellowship applicants have a vested interest in research during fellowship, so I would encourage inquiries regarding core research requirements and expectations.
  • Clinical exposure. This encompasses several different and equally important variables, including diversity of clinical or surgical caseloads, case complexity, operative exposure, athletic team coverage, and office or clinical experience. Interestingly, this latter aspect of training is often neglected but cannot be overemphasized. Outpatient clinical evaluation is key to honing important physical examination techniques and critically evaluating patients’ outcomes postoperatively.
  • Surgical autonomy. Hands-on operative experience and surgical autonomy vary widely among fellowship programs. Most fellowships advocate for a graduated level of surgical responsibility dependent on individual abilities and staff comfort, while others offer greater potential for independence. Conversely, some programs espouse more of an “observership” model, and arthroscopic simulators and/or cadaveric skills laboratories are designed to complement operative experience. While most fellowship applicants desire maximal case participation, we must also recognize the value in watching talented surgeons performing technically demanding procedures.
  • Family. You cannot put a premium on your personal contentment and family’s well-being. Proximity to a support network can be important with the work demands and time constraints of fellowship.
 

 

Despite financial obligations and significant time commitments, the fellowship match process offers an incredible range of programs and practice environments. Inevitably, no program can completely fulfill all your criteria, but you should be able to tailor your learning style, professional ambitions, and personal preferences with an excellent training program. For many, fellowship represents the last, and perhaps most integral, stage of formal surgical training. Considering all factors of your chosen fellowship program will ensure a rich and fulfilling educational experience.

The Orthopaedic Sports Medicine Fellowship Match was first established in 2008 as a joint-sponsored venture between the American Orthopaedic Society for Sports Medicine and the Arthroscopy Association of North America to pair applicants with participating training programs.1 Operated under the San Francisco Match,2 the current fellowship match process was adopted to systematically coordinate training appointments and eliminate the role of “exploding offers,” which are pressured early decisions predicated on immediate acceptance. Other advantages of this system include its operation through a central application service to avoid redundancy of submitted paperwork, as well as to create greater awareness and to publicize training options and standardization of the match timeline.1

In its current state, the orthopedic sports medicine match represents 96 programs with 230 positions, accounting for approximately 97% of training programs and fellowship positions.1 While unaccredited options remain available through the Match, many programs have migrated towards American Council for Graduate Medical Education (ACGME) accreditation because of an increased focus on objective learning metrics during fellowship and the requirement for Subspecialty Certification in Orthopaedic Sports Medicine through the American Board of Orthopaedic Surgery.3 However, other programs have also eschewed the increasing constraints and administrative resources associated with ACGME accreditation, particularly among fellowships based at community-based hospitals or private practices that lack formal affiliation with academic institutions or residency training programs.

Along with a greater understanding of the historical background of the match process, fellowship applicants must also appreciate the relative merits of fellowship training. More than 90% of orthopedic surgery residents now pursue further subspecialty fellowship training, with some individuals opting for 2 additional fellowship opportunities.4 As a so-called “nontraditional applicant,” I represent a different demographic, returning to fellowship after years of clinical practice while serving in the military. Individual preferences notwithstanding, I wanted to take the opportunity to emphasize some important considerations in deliberating between different fellowship programs.

  • Geography. Your eventual desired practice location may play a role in determining fellowship location or, at least, region of the country. Additionally, this can be an important factor in family happiness. In competitive markets, such as the Northeast or the West Coast, you may make inroads and establish professional connections that result in potential job opportunities. Conversely, other programs may adopt anticompetitive measures to limit local practice options.
  • Training setting. Despite the trending consolidation of fellowship training programs in affiliated university and hospital-based teaching systems, many community-based programs and private-practice models thrive, providing an alternative to traditional academic training centers. The latter may provide more in-depth exposure to practice management, billing/coding, and ancillary services. The former typically offer a more structured, academically oriented environment with formal teaching conferences and a broader department hierarchy.
  • Program size. Some applicants may prefer a larger, more diverse array of teaching staff or fellows, while others gravitate toward fewer, more personal mentoring relationships that allow more intimate familiarity with practice habits or surgical techniques.
  • Associated training programs. Affiliations with a residency or physician-extender training program can offer benefits and drawbacks, including offloading clerical work, shared hands-on experience in the clinic and operating room, and midlevel supervisory responsibilities. This can offer useful opportunities to formulate an individual teaching style and valuable mentoring relationships. However, it can also impose greater time requirements or detract from one-on-one teaching with staff.
  • Reputation. Applicants may attach distinction to a well-established regional or national reputation associated with a given training program. Often, certain programs may carry prestige as a result of their academic name, hospital affiliation, or accomplishments. This can offer certain marketing advantages for patient recruitment. However, less renowned programs may provide better training opportunities and confer higher esteem among your professional colleagues. Program reputation can change dramatically with time, so this should be balanced with other potential strengths and overall training experience.
  • Practice “niches”/areas of interest. With increasing adoption of arthroscopic techniques among practicing surgeons and a relative excess of sports medicine–trained orthopedists, it is paramount to develop a novel skill set during fellowship to differentiate you from other graduates. I sought a sports medicine fellowship that would offer me a broad-based exposure to arthroscopic and open knee and shoulder reconstruction, chondral restoration techniques, hip arthroscopy and preservation, and shoulder arthroplasty. Opportunities in elbow reconstruction, foot and ankle arthroscopy, and pediatric sports medicine may also be valuable as a distinguishing factor in searching for jobs after training.
  • Marketability. Closely intertwined with reputation and scope of practice, an institution’s marketability is another intangible attribute to consider. Professional or collegiate team coverage offers significant market value for patient advertising, and it is frequently publicized by orthopedic practices and hospital systems. Additionally, the importance of ACGME accreditation should also be considered.
  • Nonmedical training. This is increasingly important in subsequent subspecialty training. Further education on the business aspects of orthopedic surgery should be emphasized. Additionally, dedicated curricula on professional or leadership development are important for career progression.
  • Mentorship. Throughout the interview process, one of my foremost priorities was a strong and enduring pattern of mentorship. Fellowship offers the opportunity to establish 1 or multiple mentors in your subspecialty. These individuals will be instrumental in the development of your early professional career and your approach to clinical practice. From discussions about complicated patients to advice on contract negotiations, your ideal mentor should champion your early successes and work generously on your behalf, even long after fellowship has ended. 

  • Research opportunities. Given my academic career goals, I actively pursued a program with rich clinical and laboratory resources, and an established infrastructure for accomplishing high-quality, relevant research. Interested individuals should gauge the availability of research support staff, biomechanical or bench-level laboratory collaboration, grant or institutional research funding, cadaveric specimens, or clinical outcomes data for research conducted by fellows. However, not all fellowship applicants have a vested interest in research during fellowship, so I would encourage inquiries regarding core research requirements and expectations.
  • Clinical exposure. This encompasses several different and equally important variables, including diversity of clinical or surgical caseloads, case complexity, operative exposure, athletic team coverage, and office or clinical experience. Interestingly, this latter aspect of training is often neglected but cannot be overemphasized. Outpatient clinical evaluation is key to honing important physical examination techniques and critically evaluating patients’ outcomes postoperatively.
  • Surgical autonomy. Hands-on operative experience and surgical autonomy vary widely among fellowship programs. Most fellowships advocate for a graduated level of surgical responsibility dependent on individual abilities and staff comfort, while others offer greater potential for independence. Conversely, some programs espouse more of an “observership” model, and arthroscopic simulators and/or cadaveric skills laboratories are designed to complement operative experience. While most fellowship applicants desire maximal case participation, we must also recognize the value in watching talented surgeons performing technically demanding procedures.
  • Family. You cannot put a premium on your personal contentment and family’s well-being. Proximity to a support network can be important with the work demands and time constraints of fellowship.
 

 

Despite financial obligations and significant time commitments, the fellowship match process offers an incredible range of programs and practice environments. Inevitably, no program can completely fulfill all your criteria, but you should be able to tailor your learning style, professional ambitions, and personal preferences with an excellent training program. For many, fellowship represents the last, and perhaps most integral, stage of formal surgical training. Considering all factors of your chosen fellowship program will ensure a rich and fulfilling educational experience.

References

1.    Sports medicine/arthroscopy fellowship match. American Orthopaedic Society for Sports Medicine website. https://www.sportsmed.org/AOSSMIMIS/Members/Members/Education/Sports_Medicine_Arthroscopy_Fellowship_Match.aspx. Accessed December 21, 2015.

2.    Orthopaedic sports medicine fellowship. SF Match website. https://www.sfmatch.org/SpecialtyInsideAll.aspx?id=11&typ=1&name=Orthopaedic%20Sports%20Medicine. Accessed December 21, 2015.

3.    Orthopaedic sports medicine. American Board of Orthopaedic Surgery website. https://www.abos.org/certification/sports-subspecialty.aspx. Accessed December 21, 2015.

4.    Hariri S, York SC, O’Connor MI, Parsley BS, McCarthy JC. Career plans of current orthopaedic residents with a focus on sex-based and generational differences. J Bone Joint Surg Am. 2011;93(5):e16.

References

1.    Sports medicine/arthroscopy fellowship match. American Orthopaedic Society for Sports Medicine website. https://www.sportsmed.org/AOSSMIMIS/Members/Members/Education/Sports_Medicine_Arthroscopy_Fellowship_Match.aspx. Accessed December 21, 2015.

2.    Orthopaedic sports medicine fellowship. SF Match website. https://www.sfmatch.org/SpecialtyInsideAll.aspx?id=11&typ=1&name=Orthopaedic%20Sports%20Medicine. Accessed December 21, 2015.

3.    Orthopaedic sports medicine. American Board of Orthopaedic Surgery website. https://www.abos.org/certification/sports-subspecialty.aspx. Accessed December 21, 2015.

4.    Hariri S, York SC, O’Connor MI, Parsley BS, McCarthy JC. Career plans of current orthopaedic residents with a focus on sex-based and generational differences. J Bone Joint Surg Am. 2011;93(5):e16.

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Celebrate Match Day, Future of Hospital Medicine Program

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SHM’s Future of Hospital Medicine program is designed to help medical students and residents learn more about a career in hospital medicine and demonstrate how SHM will support future hospitalists throughout their careers. Get ready to celebrate one of the most exciting days in the medical education community with SHM: Match Day.

This year’s Match Day takes place on Friday, March 18.

Do you remember when you opened your letter? Do you know someone who is matching this year? Share your stories with SHM on Twitter @SHMLive and use the official Match Day 2016 hashtag, #Match2016, and #FutureofHospitalMedicine, plus encourage your students to do so as well. Follow along with the excitement and join in the conversation throughout the day.

It’s hard to believe, but Match Day 2017 is closer than you think. Fourth-year medical students can visit www.futureofhospitalmedicine.org for all of the resources needed to be successful, including:

  • Residency match application checklist
  • Application tool kit
  • An overview of matching for fellowship applicants
  • National Residency Matching Program FAQs
  • Information on how to register to match
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SHM’s Future of Hospital Medicine program is designed to help medical students and residents learn more about a career in hospital medicine and demonstrate how SHM will support future hospitalists throughout their careers. Get ready to celebrate one of the most exciting days in the medical education community with SHM: Match Day.

This year’s Match Day takes place on Friday, March 18.

Do you remember when you opened your letter? Do you know someone who is matching this year? Share your stories with SHM on Twitter @SHMLive and use the official Match Day 2016 hashtag, #Match2016, and #FutureofHospitalMedicine, plus encourage your students to do so as well. Follow along with the excitement and join in the conversation throughout the day.

It’s hard to believe, but Match Day 2017 is closer than you think. Fourth-year medical students can visit www.futureofhospitalmedicine.org for all of the resources needed to be successful, including:

  • Residency match application checklist
  • Application tool kit
  • An overview of matching for fellowship applicants
  • National Residency Matching Program FAQs
  • Information on how to register to match

SHM’s Future of Hospital Medicine program is designed to help medical students and residents learn more about a career in hospital medicine and demonstrate how SHM will support future hospitalists throughout their careers. Get ready to celebrate one of the most exciting days in the medical education community with SHM: Match Day.

This year’s Match Day takes place on Friday, March 18.

Do you remember when you opened your letter? Do you know someone who is matching this year? Share your stories with SHM on Twitter @SHMLive and use the official Match Day 2016 hashtag, #Match2016, and #FutureofHospitalMedicine, plus encourage your students to do so as well. Follow along with the excitement and join in the conversation throughout the day.

It’s hard to believe, but Match Day 2017 is closer than you think. Fourth-year medical students can visit www.futureofhospitalmedicine.org for all of the resources needed to be successful, including:

  • Residency match application checklist
  • Application tool kit
  • An overview of matching for fellowship applicants
  • National Residency Matching Program FAQs
  • Information on how to register to match
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Q&A: Identifying gaps in the treatment of endometriosis

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Despite the high prevalence of endometriosis – a condition that is estimated to affect about 10% of women of reproductive age – available treatments are inadequate for some women with chronic pain, and diagnosis is often delayed.

Stacey A. Missmer, Sc.D., the scientific director of the Boston Center for Endometriosis, is looking to advance understanding of the condition through the Women’s Health Study: From Adolescence to Adulthood. In an interview, Dr. Missmer, who is also the director of epidemiologic research in reproductive medicine at Brigham and Women’s Hospital in Boston, shared the progress of the study and her assessment of the treatment landscape.

Question: How would you rate the currently available treatments – both in terms of medications and surgery – in relieving the symptoms of endometriosis?

Stacey A. Missmer, Sc.D.

Dr. Missmer: The currently available treatments work well for some women and girls with pelvic pain, but it gets more difficult once that pain becomes chronic. If women have geographic and financial access to assisted reproductive treatment, then this works well for most women with endometriosis who also have subfertility. The great dilemma is that for pelvic pain, new nonhormonal/nonsurgical treatments have been slow to come for those who do not find relief with current treatments. These girls and young women are impacted just when they most need to be afforded a high quality of life that allows them to pursue all of their goals and dreams unimpeded by the symptoms associated with endometriosis.

Question: How does the Women’s Health Study: From Adolescence to Adulthood help advance treatment options?

Dr. Missmer: I am very proud of the Women’s Health Study: From Adolescence to Adulthood (A2A). Most studies of endometriosis have focused on women in their 30s and 40s, particularly those who present with infertility as their main health concern. However, we know that for women with endometriosis, the majority experience pain as their presenting symptom, and most report that endometriotic pain began during their teens and 20s. Uniquely, the A2A is a cohort of girl as young as 7 and young women, as well as those up to age 50. It is also uniquely a longitudinal cohort. By enrolling these girls and women now and following them into the future, we will be able to identify what characteristics in adolescence and young adulthood predicted who responds well to current treatments both in the short term and long into their reproductive and productive years.

We’ll also be able to discover the characteristics of those who did not respond as well, and we expect that this will drive us toward identifying unique groups of patients – and consequent biologic markers and patterns that are the basis for developing new treatments and prognostic tools for endometriosis.

Since November 2012, we have enrolled nearly 1,000 participants. Our initial enrollees are now completing their third year of lifestyle and symptom questionnaires, clinical details, and providing biologic samples. Their contributions are invaluable and are designed to be consistent with the harmonized data collection tools that we developed in collaboration with our national and international colleagues through the World Endometriosis Research Foundation (WERF). These Endometriosis Phenome and Biobanking Harmonisation Project (EPHect) tools are publicly available and will allow us to combine data from our cohort with participants at other sites to begin to detect geographic and patient-specific treatment response differences across the globe.

Question: What other studies are you closely watching?

Dr. Missmer: I am thrilled about the opportunities that the WERF EPHect tools offer us and our respected colleagues across the globe. I’m quite excited to see what new collaborations are formed and what creative hypotheses are tested. We’re in the midst of a renaissance in endometriosis understanding. Despite its prevalence and potentially debilitating impact on girls and women, endometriosis research is dramatically underfunded. This impacts discovery itself, but it also diminishes the ability for young enthusiastic brilliant scientists to be drawn to and remain dedicated to our field.

Question: How far are we from a noninvasive test that physicians could use to diagnose endometriosis and monitor its progression?

Dr. Missmer: How far in terms of a time line is difficult to determine. Again, I stress that I believe wholeheartedly that we are in the midst of a renaissance for endometriosis. We now have the tools to advance multidisciplinary scientific discovery with the ability to conduct studies with large numbers of diverse girls and women and to rigorously detect changes in their symptoms across the life course. I have no doubt that this will lead to advancement of precision medicine that allows endometriosis-focused scientists to develop noninvasive diagnostics and novel treatments. The key is that everyone in the field of endometriosis work together with this goal in mind.

 

 

[email protected]

On Twitter @maryellenny

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Despite the high prevalence of endometriosis – a condition that is estimated to affect about 10% of women of reproductive age – available treatments are inadequate for some women with chronic pain, and diagnosis is often delayed.

Stacey A. Missmer, Sc.D., the scientific director of the Boston Center for Endometriosis, is looking to advance understanding of the condition through the Women’s Health Study: From Adolescence to Adulthood. In an interview, Dr. Missmer, who is also the director of epidemiologic research in reproductive medicine at Brigham and Women’s Hospital in Boston, shared the progress of the study and her assessment of the treatment landscape.

Question: How would you rate the currently available treatments – both in terms of medications and surgery – in relieving the symptoms of endometriosis?

Stacey A. Missmer, Sc.D.

Dr. Missmer: The currently available treatments work well for some women and girls with pelvic pain, but it gets more difficult once that pain becomes chronic. If women have geographic and financial access to assisted reproductive treatment, then this works well for most women with endometriosis who also have subfertility. The great dilemma is that for pelvic pain, new nonhormonal/nonsurgical treatments have been slow to come for those who do not find relief with current treatments. These girls and young women are impacted just when they most need to be afforded a high quality of life that allows them to pursue all of their goals and dreams unimpeded by the symptoms associated with endometriosis.

Question: How does the Women’s Health Study: From Adolescence to Adulthood help advance treatment options?

Dr. Missmer: I am very proud of the Women’s Health Study: From Adolescence to Adulthood (A2A). Most studies of endometriosis have focused on women in their 30s and 40s, particularly those who present with infertility as their main health concern. However, we know that for women with endometriosis, the majority experience pain as their presenting symptom, and most report that endometriotic pain began during their teens and 20s. Uniquely, the A2A is a cohort of girl as young as 7 and young women, as well as those up to age 50. It is also uniquely a longitudinal cohort. By enrolling these girls and women now and following them into the future, we will be able to identify what characteristics in adolescence and young adulthood predicted who responds well to current treatments both in the short term and long into their reproductive and productive years.

We’ll also be able to discover the characteristics of those who did not respond as well, and we expect that this will drive us toward identifying unique groups of patients – and consequent biologic markers and patterns that are the basis for developing new treatments and prognostic tools for endometriosis.

Since November 2012, we have enrolled nearly 1,000 participants. Our initial enrollees are now completing their third year of lifestyle and symptom questionnaires, clinical details, and providing biologic samples. Their contributions are invaluable and are designed to be consistent with the harmonized data collection tools that we developed in collaboration with our national and international colleagues through the World Endometriosis Research Foundation (WERF). These Endometriosis Phenome and Biobanking Harmonisation Project (EPHect) tools are publicly available and will allow us to combine data from our cohort with participants at other sites to begin to detect geographic and patient-specific treatment response differences across the globe.

Question: What other studies are you closely watching?

Dr. Missmer: I am thrilled about the opportunities that the WERF EPHect tools offer us and our respected colleagues across the globe. I’m quite excited to see what new collaborations are formed and what creative hypotheses are tested. We’re in the midst of a renaissance in endometriosis understanding. Despite its prevalence and potentially debilitating impact on girls and women, endometriosis research is dramatically underfunded. This impacts discovery itself, but it also diminishes the ability for young enthusiastic brilliant scientists to be drawn to and remain dedicated to our field.

Question: How far are we from a noninvasive test that physicians could use to diagnose endometriosis and monitor its progression?

Dr. Missmer: How far in terms of a time line is difficult to determine. Again, I stress that I believe wholeheartedly that we are in the midst of a renaissance for endometriosis. We now have the tools to advance multidisciplinary scientific discovery with the ability to conduct studies with large numbers of diverse girls and women and to rigorously detect changes in their symptoms across the life course. I have no doubt that this will lead to advancement of precision medicine that allows endometriosis-focused scientists to develop noninvasive diagnostics and novel treatments. The key is that everyone in the field of endometriosis work together with this goal in mind.

 

 

[email protected]

On Twitter @maryellenny

Despite the high prevalence of endometriosis – a condition that is estimated to affect about 10% of women of reproductive age – available treatments are inadequate for some women with chronic pain, and diagnosis is often delayed.

Stacey A. Missmer, Sc.D., the scientific director of the Boston Center for Endometriosis, is looking to advance understanding of the condition through the Women’s Health Study: From Adolescence to Adulthood. In an interview, Dr. Missmer, who is also the director of epidemiologic research in reproductive medicine at Brigham and Women’s Hospital in Boston, shared the progress of the study and her assessment of the treatment landscape.

Question: How would you rate the currently available treatments – both in terms of medications and surgery – in relieving the symptoms of endometriosis?

Stacey A. Missmer, Sc.D.

Dr. Missmer: The currently available treatments work well for some women and girls with pelvic pain, but it gets more difficult once that pain becomes chronic. If women have geographic and financial access to assisted reproductive treatment, then this works well for most women with endometriosis who also have subfertility. The great dilemma is that for pelvic pain, new nonhormonal/nonsurgical treatments have been slow to come for those who do not find relief with current treatments. These girls and young women are impacted just when they most need to be afforded a high quality of life that allows them to pursue all of their goals and dreams unimpeded by the symptoms associated with endometriosis.

Question: How does the Women’s Health Study: From Adolescence to Adulthood help advance treatment options?

Dr. Missmer: I am very proud of the Women’s Health Study: From Adolescence to Adulthood (A2A). Most studies of endometriosis have focused on women in their 30s and 40s, particularly those who present with infertility as their main health concern. However, we know that for women with endometriosis, the majority experience pain as their presenting symptom, and most report that endometriotic pain began during their teens and 20s. Uniquely, the A2A is a cohort of girl as young as 7 and young women, as well as those up to age 50. It is also uniquely a longitudinal cohort. By enrolling these girls and women now and following them into the future, we will be able to identify what characteristics in adolescence and young adulthood predicted who responds well to current treatments both in the short term and long into their reproductive and productive years.

We’ll also be able to discover the characteristics of those who did not respond as well, and we expect that this will drive us toward identifying unique groups of patients – and consequent biologic markers and patterns that are the basis for developing new treatments and prognostic tools for endometriosis.

Since November 2012, we have enrolled nearly 1,000 participants. Our initial enrollees are now completing their third year of lifestyle and symptom questionnaires, clinical details, and providing biologic samples. Their contributions are invaluable and are designed to be consistent with the harmonized data collection tools that we developed in collaboration with our national and international colleagues through the World Endometriosis Research Foundation (WERF). These Endometriosis Phenome and Biobanking Harmonisation Project (EPHect) tools are publicly available and will allow us to combine data from our cohort with participants at other sites to begin to detect geographic and patient-specific treatment response differences across the globe.

Question: What other studies are you closely watching?

Dr. Missmer: I am thrilled about the opportunities that the WERF EPHect tools offer us and our respected colleagues across the globe. I’m quite excited to see what new collaborations are formed and what creative hypotheses are tested. We’re in the midst of a renaissance in endometriosis understanding. Despite its prevalence and potentially debilitating impact on girls and women, endometriosis research is dramatically underfunded. This impacts discovery itself, but it also diminishes the ability for young enthusiastic brilliant scientists to be drawn to and remain dedicated to our field.

Question: How far are we from a noninvasive test that physicians could use to diagnose endometriosis and monitor its progression?

Dr. Missmer: How far in terms of a time line is difficult to determine. Again, I stress that I believe wholeheartedly that we are in the midst of a renaissance for endometriosis. We now have the tools to advance multidisciplinary scientific discovery with the ability to conduct studies with large numbers of diverse girls and women and to rigorously detect changes in their symptoms across the life course. I have no doubt that this will lead to advancement of precision medicine that allows endometriosis-focused scientists to develop noninvasive diagnostics and novel treatments. The key is that everyone in the field of endometriosis work together with this goal in mind.

 

 

[email protected]

On Twitter @maryellenny

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Itraconazole targets basal cell carcinoma

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WAIKOLOA, HAWAII – The familiar oral triazole antifungal agent itraconazole (Sporanox) is under active investigation for an unexpected use: as adjunctive therapy in patients with locally advanced or metastatic basal cell carcinoma.

“The promise of this drug is that the use of itraconazole with vismodegib or sonidegib may actually enhance the effectiveness of those drugs and also reduce the frequency of grade 2 toxicities by perhaps allowing a lower dose of vismodegib or sonidegib,” Dr. David L. Swanson said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Dr. David L. Swanson

“Be looking for this drug that we use to treat toenail fungus as a potential drug for locally advanced or metastatic basal cell carcinoma,” advised Dr. Swanson, a dermatologist at the Mayo Clinic in Scottsdale, Ariz.

Vismodegib (Erivedge) has been a game changer for patients with inoperable locally advanced or metastatic breast cancer. “The response to this drug was amazing,” Dr. Swanson said of the landmark study which led to its approval in 2012 (N Engl J Med. 2012; 366[23]:2171-9).

Sonidegib (Odomzo), which like vismodegib inhibits the essential Hedgehog signaling pathway component known as Smoothened, was approved by the Food and Drug Administration in 2015 as the second oral drug in this novel class.

While the clinical benefits of these two drugs in patients with the most horrific basal cell carcinomas are extremely impressive, vismodegib and sonidegib have two major drawbacks: The tumors eventually develop resistance and commence growing again, and onerous grade 2 side effects requiring dose reduction are extremely common. The most frequent of these limiting side effects are a disturbed sense of taste, muscle spasms, alopecia, and weight loss.

The hope is that itraconazole may be of help with both issues, according to Dr. Swanson. It turns out that the antifungal agent is also an inhibitor of the Hedgehog pathway, and via a different mechanism than that of vismodegib and sonidegib.

He pointed to an international open-label exploratory phase II study led by Dr. Jean Y. Tang of Stanford (Calif.) University. The investigators treated 19 patients with a total of 90 basal cell carcinomas with oral itraconazole at 200 mg twice a day for 1 month or 100 mg twice a day for an average of 2.3 months.

The treatment reduced Hedgehog signaling pathway activity by 65%, Ki67 tumor cell proliferation by 45%, and tumor area by 24% (J Clin Oncol. 2014 Mar 10;32[8]:745-51).

These results aren’t as dramatic as what’s achieved using vismodegib or sonidegib. As stand-alone therapy, itraconazole doesn’t compare with those agents. However, the hope is that when itraconazole is prescribed in conjunction with vismodegib or sonidegib it will permit the latter drugs to be used at lower doses with no drop-off in efficacy, which would mean less grade 2 toxicity. Moreover, since itraconazole inhibits Hedgehog signaling through a mechanism that is different from that of the more potent agents, combination therapy might delay onset of tumor resistance, Dr. Swanson explained.

He reported having no financial conflicts of interest regarding his presentation.

SDEF and this news organization are owned by the same parent company.

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WAIKOLOA, HAWAII – The familiar oral triazole antifungal agent itraconazole (Sporanox) is under active investigation for an unexpected use: as adjunctive therapy in patients with locally advanced or metastatic basal cell carcinoma.

“The promise of this drug is that the use of itraconazole with vismodegib or sonidegib may actually enhance the effectiveness of those drugs and also reduce the frequency of grade 2 toxicities by perhaps allowing a lower dose of vismodegib or sonidegib,” Dr. David L. Swanson said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Dr. David L. Swanson

“Be looking for this drug that we use to treat toenail fungus as a potential drug for locally advanced or metastatic basal cell carcinoma,” advised Dr. Swanson, a dermatologist at the Mayo Clinic in Scottsdale, Ariz.

Vismodegib (Erivedge) has been a game changer for patients with inoperable locally advanced or metastatic breast cancer. “The response to this drug was amazing,” Dr. Swanson said of the landmark study which led to its approval in 2012 (N Engl J Med. 2012; 366[23]:2171-9).

Sonidegib (Odomzo), which like vismodegib inhibits the essential Hedgehog signaling pathway component known as Smoothened, was approved by the Food and Drug Administration in 2015 as the second oral drug in this novel class.

While the clinical benefits of these two drugs in patients with the most horrific basal cell carcinomas are extremely impressive, vismodegib and sonidegib have two major drawbacks: The tumors eventually develop resistance and commence growing again, and onerous grade 2 side effects requiring dose reduction are extremely common. The most frequent of these limiting side effects are a disturbed sense of taste, muscle spasms, alopecia, and weight loss.

The hope is that itraconazole may be of help with both issues, according to Dr. Swanson. It turns out that the antifungal agent is also an inhibitor of the Hedgehog pathway, and via a different mechanism than that of vismodegib and sonidegib.

He pointed to an international open-label exploratory phase II study led by Dr. Jean Y. Tang of Stanford (Calif.) University. The investigators treated 19 patients with a total of 90 basal cell carcinomas with oral itraconazole at 200 mg twice a day for 1 month or 100 mg twice a day for an average of 2.3 months.

The treatment reduced Hedgehog signaling pathway activity by 65%, Ki67 tumor cell proliferation by 45%, and tumor area by 24% (J Clin Oncol. 2014 Mar 10;32[8]:745-51).

These results aren’t as dramatic as what’s achieved using vismodegib or sonidegib. As stand-alone therapy, itraconazole doesn’t compare with those agents. However, the hope is that when itraconazole is prescribed in conjunction with vismodegib or sonidegib it will permit the latter drugs to be used at lower doses with no drop-off in efficacy, which would mean less grade 2 toxicity. Moreover, since itraconazole inhibits Hedgehog signaling through a mechanism that is different from that of the more potent agents, combination therapy might delay onset of tumor resistance, Dr. Swanson explained.

He reported having no financial conflicts of interest regarding his presentation.

SDEF and this news organization are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – The familiar oral triazole antifungal agent itraconazole (Sporanox) is under active investigation for an unexpected use: as adjunctive therapy in patients with locally advanced or metastatic basal cell carcinoma.

“The promise of this drug is that the use of itraconazole with vismodegib or sonidegib may actually enhance the effectiveness of those drugs and also reduce the frequency of grade 2 toxicities by perhaps allowing a lower dose of vismodegib or sonidegib,” Dr. David L. Swanson said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Dr. David L. Swanson

“Be looking for this drug that we use to treat toenail fungus as a potential drug for locally advanced or metastatic basal cell carcinoma,” advised Dr. Swanson, a dermatologist at the Mayo Clinic in Scottsdale, Ariz.

Vismodegib (Erivedge) has been a game changer for patients with inoperable locally advanced or metastatic breast cancer. “The response to this drug was amazing,” Dr. Swanson said of the landmark study which led to its approval in 2012 (N Engl J Med. 2012; 366[23]:2171-9).

Sonidegib (Odomzo), which like vismodegib inhibits the essential Hedgehog signaling pathway component known as Smoothened, was approved by the Food and Drug Administration in 2015 as the second oral drug in this novel class.

While the clinical benefits of these two drugs in patients with the most horrific basal cell carcinomas are extremely impressive, vismodegib and sonidegib have two major drawbacks: The tumors eventually develop resistance and commence growing again, and onerous grade 2 side effects requiring dose reduction are extremely common. The most frequent of these limiting side effects are a disturbed sense of taste, muscle spasms, alopecia, and weight loss.

The hope is that itraconazole may be of help with both issues, according to Dr. Swanson. It turns out that the antifungal agent is also an inhibitor of the Hedgehog pathway, and via a different mechanism than that of vismodegib and sonidegib.

He pointed to an international open-label exploratory phase II study led by Dr. Jean Y. Tang of Stanford (Calif.) University. The investigators treated 19 patients with a total of 90 basal cell carcinomas with oral itraconazole at 200 mg twice a day for 1 month or 100 mg twice a day for an average of 2.3 months.

The treatment reduced Hedgehog signaling pathway activity by 65%, Ki67 tumor cell proliferation by 45%, and tumor area by 24% (J Clin Oncol. 2014 Mar 10;32[8]:745-51).

These results aren’t as dramatic as what’s achieved using vismodegib or sonidegib. As stand-alone therapy, itraconazole doesn’t compare with those agents. However, the hope is that when itraconazole is prescribed in conjunction with vismodegib or sonidegib it will permit the latter drugs to be used at lower doses with no drop-off in efficacy, which would mean less grade 2 toxicity. Moreover, since itraconazole inhibits Hedgehog signaling through a mechanism that is different from that of the more potent agents, combination therapy might delay onset of tumor resistance, Dr. Swanson explained.

He reported having no financial conflicts of interest regarding his presentation.

SDEF and this news organization are owned by the same parent company.

[email protected]

References

References

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EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR

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Inside the Article

A New Approach to “Birthmarks”

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A New Approach to “Birthmarks”

A 4-month-old boy is brought in by his mother for evaluation of a “birthmark” that has become more prominent with time. The child complains a bit when the lesion is touched.

His mother gives a history of a normal full-term pregnancy, with an uneventful delivery. Other than the skin lesion, there have been no other known problems with the child’s health.

EXAMINATION
The lesion in question is a 2-cm bright red nodule in the middle of the child’s forehead. There is a faint blue halo around it, but no other abnormalities are seen in the area or elsewhere on the child’s body. The patient otherwise appears well developed and well nourished; he is quite alert and reactive to verbal stimuli.

 

What is the diagnosis?

 

 

 

 

 

DISCUSSION
Most first-year medical students could tell you this was a case of an infantile hemangioma—but within the past five years, the categorization and treatment of hemangiomas have changed rapidly.

Hemangiomas are benign and usually self-involuting vascular tumors; they are distinct from the family of permanent congenital vascular lesions, such as port wine stains. About 80% occur on the face or neck, and they more commonly occur in female patients. Those that occur near the skin’s surface tend to be bright red, while those of deeper origin are more bluish. Hemangiomas can also occur in extracutaneous areas (eg, the liver); these are usually detected via imaging.

Most infantile hemangiomas appear in the first few weeks of life but begin to involute shortly after they reach maximal size (usually by age 12 months). Involution is complete by age 5 in about 50% of cases and by age 7 in 70% of them. The remainder usually resolve by age 12.

Until recently, the parents of an affected child would be told that the lesions were benign and would likely disappear on their own by the time the child was ages 7 to 10—all true enough. These lesions were treated only when they were large or symptomatic, or if their location blocked or otherwise interfered with the function of the eyes, ears, mouth, anus, or vagina. Unfortunately, this approach ignored the psychosocial aspects of having a prominent and fire-engine red lesion, which often becomes the object of unwanted attention, and even ridicule, at a crucial developmental age.

In the past, the main treatment options were destructive in nature (laser, excision) and often caused as many problems as they solved. Pharmacologic treatment with oral prednisone, and later with interferon, was also tried with mixed success.

In 2008, in a serendipitous observation, a French team came up with a groundbreaking approach: giving systemic propranolol multiple times over a 12 to 18–month period. This method proved to be both safe and effective when used in the right setting by specialists (pediatric dermatologists and/or pediatricians) experienced in this modality. It was found that the lesions responded best if treated before age 6 months.

This has worked so well and so safely that it has quickly become routine. But it will take time before it is sufficiently well known to become the actual standard of care for these common lesions.

TAKE-HOME LEARNING POINTS
• Infantile hemangiomas (IH) usually resolve (involute) by age 12 at the latest.

• IH, by definition, is different from permanent congenital vascular malformations, such as port wine stains.

• About 80% of IHs occur on the head and neck; they are often the object of unwanted attention or even ridicule.

• A new treatment approach, systemic propranolol, is now being used routinely and successfully. It works best when the patient is 6 months old or younger.

• Ideally, this new treatment approach should be overseen by the relevant specialist, be it in a pediatric or dermatologic setting. 

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Joe R. Monroe, MPAS, PA

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Joe R. Monroe, MPAS, PA

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Joe R. Monroe, MPAS, PA

A 4-month-old boy is brought in by his mother for evaluation of a “birthmark” that has become more prominent with time. The child complains a bit when the lesion is touched.

His mother gives a history of a normal full-term pregnancy, with an uneventful delivery. Other than the skin lesion, there have been no other known problems with the child’s health.

EXAMINATION
The lesion in question is a 2-cm bright red nodule in the middle of the child’s forehead. There is a faint blue halo around it, but no other abnormalities are seen in the area or elsewhere on the child’s body. The patient otherwise appears well developed and well nourished; he is quite alert and reactive to verbal stimuli.

 

What is the diagnosis?

 

 

 

 

 

DISCUSSION
Most first-year medical students could tell you this was a case of an infantile hemangioma—but within the past five years, the categorization and treatment of hemangiomas have changed rapidly.

Hemangiomas are benign and usually self-involuting vascular tumors; they are distinct from the family of permanent congenital vascular lesions, such as port wine stains. About 80% occur on the face or neck, and they more commonly occur in female patients. Those that occur near the skin’s surface tend to be bright red, while those of deeper origin are more bluish. Hemangiomas can also occur in extracutaneous areas (eg, the liver); these are usually detected via imaging.

Most infantile hemangiomas appear in the first few weeks of life but begin to involute shortly after they reach maximal size (usually by age 12 months). Involution is complete by age 5 in about 50% of cases and by age 7 in 70% of them. The remainder usually resolve by age 12.

Until recently, the parents of an affected child would be told that the lesions were benign and would likely disappear on their own by the time the child was ages 7 to 10—all true enough. These lesions were treated only when they were large or symptomatic, or if their location blocked or otherwise interfered with the function of the eyes, ears, mouth, anus, or vagina. Unfortunately, this approach ignored the psychosocial aspects of having a prominent and fire-engine red lesion, which often becomes the object of unwanted attention, and even ridicule, at a crucial developmental age.

In the past, the main treatment options were destructive in nature (laser, excision) and often caused as many problems as they solved. Pharmacologic treatment with oral prednisone, and later with interferon, was also tried with mixed success.

In 2008, in a serendipitous observation, a French team came up with a groundbreaking approach: giving systemic propranolol multiple times over a 12 to 18–month period. This method proved to be both safe and effective when used in the right setting by specialists (pediatric dermatologists and/or pediatricians) experienced in this modality. It was found that the lesions responded best if treated before age 6 months.

This has worked so well and so safely that it has quickly become routine. But it will take time before it is sufficiently well known to become the actual standard of care for these common lesions.

TAKE-HOME LEARNING POINTS
• Infantile hemangiomas (IH) usually resolve (involute) by age 12 at the latest.

• IH, by definition, is different from permanent congenital vascular malformations, such as port wine stains.

• About 80% of IHs occur on the head and neck; they are often the object of unwanted attention or even ridicule.

• A new treatment approach, systemic propranolol, is now being used routinely and successfully. It works best when the patient is 6 months old or younger.

• Ideally, this new treatment approach should be overseen by the relevant specialist, be it in a pediatric or dermatologic setting. 

A 4-month-old boy is brought in by his mother for evaluation of a “birthmark” that has become more prominent with time. The child complains a bit when the lesion is touched.

His mother gives a history of a normal full-term pregnancy, with an uneventful delivery. Other than the skin lesion, there have been no other known problems with the child’s health.

EXAMINATION
The lesion in question is a 2-cm bright red nodule in the middle of the child’s forehead. There is a faint blue halo around it, but no other abnormalities are seen in the area or elsewhere on the child’s body. The patient otherwise appears well developed and well nourished; he is quite alert and reactive to verbal stimuli.

 

What is the diagnosis?

 

 

 

 

 

DISCUSSION
Most first-year medical students could tell you this was a case of an infantile hemangioma—but within the past five years, the categorization and treatment of hemangiomas have changed rapidly.

Hemangiomas are benign and usually self-involuting vascular tumors; they are distinct from the family of permanent congenital vascular lesions, such as port wine stains. About 80% occur on the face or neck, and they more commonly occur in female patients. Those that occur near the skin’s surface tend to be bright red, while those of deeper origin are more bluish. Hemangiomas can also occur in extracutaneous areas (eg, the liver); these are usually detected via imaging.

Most infantile hemangiomas appear in the first few weeks of life but begin to involute shortly after they reach maximal size (usually by age 12 months). Involution is complete by age 5 in about 50% of cases and by age 7 in 70% of them. The remainder usually resolve by age 12.

Until recently, the parents of an affected child would be told that the lesions were benign and would likely disappear on their own by the time the child was ages 7 to 10—all true enough. These lesions were treated only when they were large or symptomatic, or if their location blocked or otherwise interfered with the function of the eyes, ears, mouth, anus, or vagina. Unfortunately, this approach ignored the psychosocial aspects of having a prominent and fire-engine red lesion, which often becomes the object of unwanted attention, and even ridicule, at a crucial developmental age.

In the past, the main treatment options were destructive in nature (laser, excision) and often caused as many problems as they solved. Pharmacologic treatment with oral prednisone, and later with interferon, was also tried with mixed success.

In 2008, in a serendipitous observation, a French team came up with a groundbreaking approach: giving systemic propranolol multiple times over a 12 to 18–month period. This method proved to be both safe and effective when used in the right setting by specialists (pediatric dermatologists and/or pediatricians) experienced in this modality. It was found that the lesions responded best if treated before age 6 months.

This has worked so well and so safely that it has quickly become routine. But it will take time before it is sufficiently well known to become the actual standard of care for these common lesions.

TAKE-HOME LEARNING POINTS
• Infantile hemangiomas (IH) usually resolve (involute) by age 12 at the latest.

• IH, by definition, is different from permanent congenital vascular malformations, such as port wine stains.

• About 80% of IHs occur on the head and neck; they are often the object of unwanted attention or even ridicule.

• A new treatment approach, systemic propranolol, is now being used routinely and successfully. It works best when the patient is 6 months old or younger.

• Ideally, this new treatment approach should be overseen by the relevant specialist, be it in a pediatric or dermatologic setting. 

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Revisiting the ‘Key Principles and Characteristics of an Effective Hospital Medicine Group'

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It has been two years since the “Key Characteristics” was published in the Journal of Hospital Medicine.1 The SHM board of directors envisions the Key Characteristics as a tool to improve the performance of hospital medicine groups (HMGs) and “raise the bar” for the specialty.

At SHM’s annual meeting (www.hospitalmedicine2016.org) next month in San Diego, the Key Characteristics will provide the framework for the Practice Management Pre-Course (Sunday, March 6). The pre-course faculty, of which I am a member, will address all 10 principles of the Key Characteristics (see Table 1), including case studies and practical ideas for performance improvement. As a preview, I will cover Principle 6 and provide a few practical tips that you can implement in your practice.

For a more comprehensive discussion of all the Key Characteristics and how to use them, visit the SHM website (visit www.hospitalmedicine.org, then click on the “Practice Management” icon at the top of the landing page).

Characteristic 6.1

The HMG has systems in place to ensure effective and reliable communication with the patient’s primary care physician and/or other provider(s) involved in the patient’s care in the non-acute-care setting.

Practical tip: Your practice probably has administrative procedures in place to notify PCPs that their patient has been admitted to the hospital, using the electronic health record or secure email, if available, or messaging by fax/phone. But are you receiving vital information from the PCP’s office or from the nursing facility? Establish a protocol for obtaining key history, medication, and diagnostic testing information from these sources. One approach is to request this information when notifying the PCP of the patient’s admission.

Practical tip: Use the “grocery store test” to determine when to contact the PCP during the hospital stay. For example, if the PCP were to run into a family member of the patient in the grocery store, would the PCP want to have learned of a change in the patient’s condition in advance of the family member encounter?

Practical tip: Because reaching skilling nursing facility (SNF) physicians/providers (SNFists) can be challenging, hold an annual social event so that they can meet the hospitalists in your practice face-to-face. At the event, exchange cellphone or beeper numbers with the SNFists, and establish an explicit understanding of how handoffs will occur, especially for high-risk patients.

Characteristic 6.2

The HMG contributes in meaningful ways to the hospital’s efforts to improve care transitions.

Because of readmissions penalties, every hospital in the country is concerned with care transitions and avoiding readmissions. But HMGs want to know which interventions reliably decrease readmissions. The Commonwealth Fund recently released the results of a study of 428 hospitals that participated in national efforts to reduce readmissions, including the State Action on Avoidable Rehospitalizations (STAAR) and Hospital to Home (H2H) initiatives. The study’s primary conclusions were as follows:

  • The only strategy consistently associated with reduced risk-standardized readmissions was discharging patients with their appointments already made.2 No other single strategy was reliably associated with a reduction.
  • Hospitals that implemented three or more readmission reduction strategies showed a significant decrease in risk-standardized readmissions versus those implementing fewer than three.

Practical tip: Ensure patients leave the hospital with a PCP follow-up appointment made and in hand.

Practical tip: Work with your hospital on at least three definitive strategies to reduce readmissions.

Implement to Improve Your HMG

The basic and updated 2015 versions of the “Key Principles and Characteristics of an Effective Hospital Medicine Group” can be downloaded from the SHM website (visit www.hospitalmedicine.org, then click on the “Practice Management” icon at the top of the landing page). The updated 2015 version provides definitions and requirements and suggested approaches to demonstrating the characteristic that enables the HMG to conduct a comprehensive self-assessment.

 

 

In addition, there is a new tool intended for use by hospitalist practice administrators that cross-references the Key Characteristics with another tool, The Core Competencies for a Hospitalist Practice Administrator. TH


Dr. Whitcomb is Chief Medical Officer of Remedy Partners. He is co-founder and past president of SHM. Email him at [email protected].

References

  1. Cawley P, Deitelzweig S, Flores L, et al. The key principles and characteristics of an effective hospital medicine group: an assessment guide for hospitals and hospitalists. J Hosp Med. 2014;9(2):123-128.
  2. Bradley EH, Brewster A, Curry L. National campaigns to reduce readmissions: what have we learned? The Commonwealth Fund website. Available at: commonwealthfund.org/publications/blog/2015/oct/national-campaigns-to-reduce-readmissions. Accessed December 28, 2015.

Table 1. The Key Principles and Characteristics of an Effective Hospital Medicine Group (HMG)1

The HMG:

  1. Has effective leadership.
  2. Has engaged hospitalists.
  3. Has adequate resources.
  4. Has an effective planning and management infrastructure.
  5. Is aligned with the hospital and/or health system.
  6. Supports care coordination across care settings.
  7. Plays a leadership role in addressing key clinical issues in the hospital and/or health system: teaching, quality, safety, efficiency, and the patient/family experience.
  8. Takes a thoughtful and rational approach to its scope of clinical activities.
  9. Has implemented a practice model that is patient- and family-centered, is team-based, and emphasizes effective communication and care coordination.
  10. Recruits and retains qualified clinicians.

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It has been two years since the “Key Characteristics” was published in the Journal of Hospital Medicine.1 The SHM board of directors envisions the Key Characteristics as a tool to improve the performance of hospital medicine groups (HMGs) and “raise the bar” for the specialty.

At SHM’s annual meeting (www.hospitalmedicine2016.org) next month in San Diego, the Key Characteristics will provide the framework for the Practice Management Pre-Course (Sunday, March 6). The pre-course faculty, of which I am a member, will address all 10 principles of the Key Characteristics (see Table 1), including case studies and practical ideas for performance improvement. As a preview, I will cover Principle 6 and provide a few practical tips that you can implement in your practice.

For a more comprehensive discussion of all the Key Characteristics and how to use them, visit the SHM website (visit www.hospitalmedicine.org, then click on the “Practice Management” icon at the top of the landing page).

Characteristic 6.1

The HMG has systems in place to ensure effective and reliable communication with the patient’s primary care physician and/or other provider(s) involved in the patient’s care in the non-acute-care setting.

Practical tip: Your practice probably has administrative procedures in place to notify PCPs that their patient has been admitted to the hospital, using the electronic health record or secure email, if available, or messaging by fax/phone. But are you receiving vital information from the PCP’s office or from the nursing facility? Establish a protocol for obtaining key history, medication, and diagnostic testing information from these sources. One approach is to request this information when notifying the PCP of the patient’s admission.

Practical tip: Use the “grocery store test” to determine when to contact the PCP during the hospital stay. For example, if the PCP were to run into a family member of the patient in the grocery store, would the PCP want to have learned of a change in the patient’s condition in advance of the family member encounter?

Practical tip: Because reaching skilling nursing facility (SNF) physicians/providers (SNFists) can be challenging, hold an annual social event so that they can meet the hospitalists in your practice face-to-face. At the event, exchange cellphone or beeper numbers with the SNFists, and establish an explicit understanding of how handoffs will occur, especially for high-risk patients.

Characteristic 6.2

The HMG contributes in meaningful ways to the hospital’s efforts to improve care transitions.

Because of readmissions penalties, every hospital in the country is concerned with care transitions and avoiding readmissions. But HMGs want to know which interventions reliably decrease readmissions. The Commonwealth Fund recently released the results of a study of 428 hospitals that participated in national efforts to reduce readmissions, including the State Action on Avoidable Rehospitalizations (STAAR) and Hospital to Home (H2H) initiatives. The study’s primary conclusions were as follows:

  • The only strategy consistently associated with reduced risk-standardized readmissions was discharging patients with their appointments already made.2 No other single strategy was reliably associated with a reduction.
  • Hospitals that implemented three or more readmission reduction strategies showed a significant decrease in risk-standardized readmissions versus those implementing fewer than three.

Practical tip: Ensure patients leave the hospital with a PCP follow-up appointment made and in hand.

Practical tip: Work with your hospital on at least three definitive strategies to reduce readmissions.

Implement to Improve Your HMG

The basic and updated 2015 versions of the “Key Principles and Characteristics of an Effective Hospital Medicine Group” can be downloaded from the SHM website (visit www.hospitalmedicine.org, then click on the “Practice Management” icon at the top of the landing page). The updated 2015 version provides definitions and requirements and suggested approaches to demonstrating the characteristic that enables the HMG to conduct a comprehensive self-assessment.

 

 

In addition, there is a new tool intended for use by hospitalist practice administrators that cross-references the Key Characteristics with another tool, The Core Competencies for a Hospitalist Practice Administrator. TH


Dr. Whitcomb is Chief Medical Officer of Remedy Partners. He is co-founder and past president of SHM. Email him at [email protected].

References

  1. Cawley P, Deitelzweig S, Flores L, et al. The key principles and characteristics of an effective hospital medicine group: an assessment guide for hospitals and hospitalists. J Hosp Med. 2014;9(2):123-128.
  2. Bradley EH, Brewster A, Curry L. National campaigns to reduce readmissions: what have we learned? The Commonwealth Fund website. Available at: commonwealthfund.org/publications/blog/2015/oct/national-campaigns-to-reduce-readmissions. Accessed December 28, 2015.

Table 1. The Key Principles and Characteristics of an Effective Hospital Medicine Group (HMG)1

The HMG:

  1. Has effective leadership.
  2. Has engaged hospitalists.
  3. Has adequate resources.
  4. Has an effective planning and management infrastructure.
  5. Is aligned with the hospital and/or health system.
  6. Supports care coordination across care settings.
  7. Plays a leadership role in addressing key clinical issues in the hospital and/or health system: teaching, quality, safety, efficiency, and the patient/family experience.
  8. Takes a thoughtful and rational approach to its scope of clinical activities.
  9. Has implemented a practice model that is patient- and family-centered, is team-based, and emphasizes effective communication and care coordination.
  10. Recruits and retains qualified clinicians.

It has been two years since the “Key Characteristics” was published in the Journal of Hospital Medicine.1 The SHM board of directors envisions the Key Characteristics as a tool to improve the performance of hospital medicine groups (HMGs) and “raise the bar” for the specialty.

At SHM’s annual meeting (www.hospitalmedicine2016.org) next month in San Diego, the Key Characteristics will provide the framework for the Practice Management Pre-Course (Sunday, March 6). The pre-course faculty, of which I am a member, will address all 10 principles of the Key Characteristics (see Table 1), including case studies and practical ideas for performance improvement. As a preview, I will cover Principle 6 and provide a few practical tips that you can implement in your practice.

For a more comprehensive discussion of all the Key Characteristics and how to use them, visit the SHM website (visit www.hospitalmedicine.org, then click on the “Practice Management” icon at the top of the landing page).

Characteristic 6.1

The HMG has systems in place to ensure effective and reliable communication with the patient’s primary care physician and/or other provider(s) involved in the patient’s care in the non-acute-care setting.

Practical tip: Your practice probably has administrative procedures in place to notify PCPs that their patient has been admitted to the hospital, using the electronic health record or secure email, if available, or messaging by fax/phone. But are you receiving vital information from the PCP’s office or from the nursing facility? Establish a protocol for obtaining key history, medication, and diagnostic testing information from these sources. One approach is to request this information when notifying the PCP of the patient’s admission.

Practical tip: Use the “grocery store test” to determine when to contact the PCP during the hospital stay. For example, if the PCP were to run into a family member of the patient in the grocery store, would the PCP want to have learned of a change in the patient’s condition in advance of the family member encounter?

Practical tip: Because reaching skilling nursing facility (SNF) physicians/providers (SNFists) can be challenging, hold an annual social event so that they can meet the hospitalists in your practice face-to-face. At the event, exchange cellphone or beeper numbers with the SNFists, and establish an explicit understanding of how handoffs will occur, especially for high-risk patients.

Characteristic 6.2

The HMG contributes in meaningful ways to the hospital’s efforts to improve care transitions.

Because of readmissions penalties, every hospital in the country is concerned with care transitions and avoiding readmissions. But HMGs want to know which interventions reliably decrease readmissions. The Commonwealth Fund recently released the results of a study of 428 hospitals that participated in national efforts to reduce readmissions, including the State Action on Avoidable Rehospitalizations (STAAR) and Hospital to Home (H2H) initiatives. The study’s primary conclusions were as follows:

  • The only strategy consistently associated with reduced risk-standardized readmissions was discharging patients with their appointments already made.2 No other single strategy was reliably associated with a reduction.
  • Hospitals that implemented three or more readmission reduction strategies showed a significant decrease in risk-standardized readmissions versus those implementing fewer than three.

Practical tip: Ensure patients leave the hospital with a PCP follow-up appointment made and in hand.

Practical tip: Work with your hospital on at least three definitive strategies to reduce readmissions.

Implement to Improve Your HMG

The basic and updated 2015 versions of the “Key Principles and Characteristics of an Effective Hospital Medicine Group” can be downloaded from the SHM website (visit www.hospitalmedicine.org, then click on the “Practice Management” icon at the top of the landing page). The updated 2015 version provides definitions and requirements and suggested approaches to demonstrating the characteristic that enables the HMG to conduct a comprehensive self-assessment.

 

 

In addition, there is a new tool intended for use by hospitalist practice administrators that cross-references the Key Characteristics with another tool, The Core Competencies for a Hospitalist Practice Administrator. TH


Dr. Whitcomb is Chief Medical Officer of Remedy Partners. He is co-founder and past president of SHM. Email him at [email protected].

References

  1. Cawley P, Deitelzweig S, Flores L, et al. The key principles and characteristics of an effective hospital medicine group: an assessment guide for hospitals and hospitalists. J Hosp Med. 2014;9(2):123-128.
  2. Bradley EH, Brewster A, Curry L. National campaigns to reduce readmissions: what have we learned? The Commonwealth Fund website. Available at: commonwealthfund.org/publications/blog/2015/oct/national-campaigns-to-reduce-readmissions. Accessed December 28, 2015.

Table 1. The Key Principles and Characteristics of an Effective Hospital Medicine Group (HMG)1

The HMG:

  1. Has effective leadership.
  2. Has engaged hospitalists.
  3. Has adequate resources.
  4. Has an effective planning and management infrastructure.
  5. Is aligned with the hospital and/or health system.
  6. Supports care coordination across care settings.
  7. Plays a leadership role in addressing key clinical issues in the hospital and/or health system: teaching, quality, safety, efficiency, and the patient/family experience.
  8. Takes a thoughtful and rational approach to its scope of clinical activities.
  9. Has implemented a practice model that is patient- and family-centered, is team-based, and emphasizes effective communication and care coordination.
  10. Recruits and retains qualified clinicians.

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Regimen can reduce risk of malaria during pregnancy

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Thu, 03/10/2016 - 06:00
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Regimen can reduce risk of malaria during pregnancy

Pregnant woman

Photo by Nina Matthews

A 2-drug prophylactic regimen can reduce the risk of Plasmodium falciparum malaria during pregnancy, according to a study published in NEJM.

Monthly treatment with the regimen, dihydroartemisinin-piperaquine (DP), reduced the rate of symptomatic malaria, placental malaria, and parasitemia, when compared to less frequent dosing with DP or treatment with sulfadoxine-pyrimethamine (SP), the current standard prophylactic regimen.

Researchers therefore believe DP may be a feasible alternative to SP, which has become less effective over time.

“The malaria parasite’s resistance to SP is widespread, especially in sub-Saharan Africa,” said study author Abel Kakuru, MD, of the Infectious Diseases Research Collaboration in Kampala, Uganda.

“But we are still using the same drugs because we have no better alternatives.”

In an attempt to identify a better alternative, Dr Kakuru and his colleagues studied 300 pregnant women from Tororo, Uganda, from June 2014 through October 2014. All of the subjects were age 16 or older and anywhere from 12 to 20 weeks pregnant.

The women were randomized to receive 1 of 3 regimens for malaria prophylaxis:

  • DP once a month
  • DP at 20, 28, and 30 weeks of pregnancy
  • SP at 20, 28, and 30 weeks of pregnancy.

Participants had monthly checkups at the study clinic, where they received regular blood tests for malaria. The researchers also assessed malaria infection in the placenta.

Placental malaria was confirmed in 50% of women in the SP group, 34% in the 3-dose-DP group (P=0.03), and 27% in the monthly DP group (P=0.001).

Forty-one percent of the women on SP had malaria parasites in their blood, compared to 17% in the 3-dose DP group (P<0.001), and 5% in the monthly DP group (P<0.001).

None of the women on monthly DP had symptomatic malaria during pregnancy. But there were 41 episodes of malaria during pregnancy in the SP group and 12 episodes in the 3-dose DP group.

The researchers also evaluated the women and infants in the study for a composite adverse birth outcome of spontaneous abortion, stillbirth, low birth weight, preterm delivery, or birth defects.

The risk of any adverse birth outcome was 9% in the monthly DP group, 21% in the 3-dose DP group (P=0.02), and 19% in the SP group (P=0.05).

The researchers concluded that monthly dosing of DP provided the best protection against malaria and called for additional studies to determine if the regimen would provide an effective alternative treatment in other parts of Uganda and elsewhere in Africa.

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Pregnant woman

Photo by Nina Matthews

A 2-drug prophylactic regimen can reduce the risk of Plasmodium falciparum malaria during pregnancy, according to a study published in NEJM.

Monthly treatment with the regimen, dihydroartemisinin-piperaquine (DP), reduced the rate of symptomatic malaria, placental malaria, and parasitemia, when compared to less frequent dosing with DP or treatment with sulfadoxine-pyrimethamine (SP), the current standard prophylactic regimen.

Researchers therefore believe DP may be a feasible alternative to SP, which has become less effective over time.

“The malaria parasite’s resistance to SP is widespread, especially in sub-Saharan Africa,” said study author Abel Kakuru, MD, of the Infectious Diseases Research Collaboration in Kampala, Uganda.

“But we are still using the same drugs because we have no better alternatives.”

In an attempt to identify a better alternative, Dr Kakuru and his colleagues studied 300 pregnant women from Tororo, Uganda, from June 2014 through October 2014. All of the subjects were age 16 or older and anywhere from 12 to 20 weeks pregnant.

The women were randomized to receive 1 of 3 regimens for malaria prophylaxis:

  • DP once a month
  • DP at 20, 28, and 30 weeks of pregnancy
  • SP at 20, 28, and 30 weeks of pregnancy.

Participants had monthly checkups at the study clinic, where they received regular blood tests for malaria. The researchers also assessed malaria infection in the placenta.

Placental malaria was confirmed in 50% of women in the SP group, 34% in the 3-dose-DP group (P=0.03), and 27% in the monthly DP group (P=0.001).

Forty-one percent of the women on SP had malaria parasites in their blood, compared to 17% in the 3-dose DP group (P<0.001), and 5% in the monthly DP group (P<0.001).

None of the women on monthly DP had symptomatic malaria during pregnancy. But there were 41 episodes of malaria during pregnancy in the SP group and 12 episodes in the 3-dose DP group.

The researchers also evaluated the women and infants in the study for a composite adverse birth outcome of spontaneous abortion, stillbirth, low birth weight, preterm delivery, or birth defects.

The risk of any adverse birth outcome was 9% in the monthly DP group, 21% in the 3-dose DP group (P=0.02), and 19% in the SP group (P=0.05).

The researchers concluded that monthly dosing of DP provided the best protection against malaria and called for additional studies to determine if the regimen would provide an effective alternative treatment in other parts of Uganda and elsewhere in Africa.

Pregnant woman

Photo by Nina Matthews

A 2-drug prophylactic regimen can reduce the risk of Plasmodium falciparum malaria during pregnancy, according to a study published in NEJM.

Monthly treatment with the regimen, dihydroartemisinin-piperaquine (DP), reduced the rate of symptomatic malaria, placental malaria, and parasitemia, when compared to less frequent dosing with DP or treatment with sulfadoxine-pyrimethamine (SP), the current standard prophylactic regimen.

Researchers therefore believe DP may be a feasible alternative to SP, which has become less effective over time.

“The malaria parasite’s resistance to SP is widespread, especially in sub-Saharan Africa,” said study author Abel Kakuru, MD, of the Infectious Diseases Research Collaboration in Kampala, Uganda.

“But we are still using the same drugs because we have no better alternatives.”

In an attempt to identify a better alternative, Dr Kakuru and his colleagues studied 300 pregnant women from Tororo, Uganda, from June 2014 through October 2014. All of the subjects were age 16 or older and anywhere from 12 to 20 weeks pregnant.

The women were randomized to receive 1 of 3 regimens for malaria prophylaxis:

  • DP once a month
  • DP at 20, 28, and 30 weeks of pregnancy
  • SP at 20, 28, and 30 weeks of pregnancy.

Participants had monthly checkups at the study clinic, where they received regular blood tests for malaria. The researchers also assessed malaria infection in the placenta.

Placental malaria was confirmed in 50% of women in the SP group, 34% in the 3-dose-DP group (P=0.03), and 27% in the monthly DP group (P=0.001).

Forty-one percent of the women on SP had malaria parasites in their blood, compared to 17% in the 3-dose DP group (P<0.001), and 5% in the monthly DP group (P<0.001).

None of the women on monthly DP had symptomatic malaria during pregnancy. But there were 41 episodes of malaria during pregnancy in the SP group and 12 episodes in the 3-dose DP group.

The researchers also evaluated the women and infants in the study for a composite adverse birth outcome of spontaneous abortion, stillbirth, low birth weight, preterm delivery, or birth defects.

The risk of any adverse birth outcome was 9% in the monthly DP group, 21% in the 3-dose DP group (P=0.02), and 19% in the SP group (P=0.05).

The researchers concluded that monthly dosing of DP provided the best protection against malaria and called for additional studies to determine if the regimen would provide an effective alternative treatment in other parts of Uganda and elsewhere in Africa.

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Germline mutations linked to hematologic malignancies

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Three generations of a family

 

A new study suggests mutations in the gene DDX41 occur in families where hematologic malignancies are common.

 

Previous research showed that both germline and acquired DDX41 mutations occur in families with multiple cases of late-onset myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

 

The new study, published in Blood, has linked germline mutations in DDX41 to chronic myeloid leukemia and lymphomas as well.

 

“This is the first gene identified in families with lymphoma and represents a major breakthrough for the field,” said study author Hamish Scott, PhD, of the University of Adelaide in South Australia.

 

“Researchers are recognizing now that genetic predisposition to blood cancer is more common than previously thought, and our study shows the importance of taking a thorough family history at diagnosis.”

 

To conduct this study, Dr Scott and his colleagues screened 2 cohorts of families with a range of hematologic disorders (malignant and non-malignant). One cohort included 240 individuals from 93 families in Australia. The other included 246 individuals from 198 families in the US.

 

In all, 9 of the families (3%) had germline DDX41 mutations.

 

Three families carried the recurrent p.D140Gfs*2 mutation, which was linked to AML.

 

One family carried a germline mutation—p.R525H, c.1574G.A—that was previously described only as a somatic mutation at the time of progression to MDS or AML. In the current study, the mutation was again linked to MDS and AML.

 

Five families carried novel DDX41 mutations.

 

One of these mutations was a germline substitution—c.435-2_435-1delAGinsCA—that was linked to MDS in 1 family.

 

Two families had a missense start-loss substitution—c.3G.A, p.M1I—that was linked to MDS, AML, chronic myeloid leukemia, and non-Hodgkin lymphoma.

 

One family had a DDX41 missense variant—c.490C.T, p.R164W. This was linked to Hodgkin and non-Hodgkin lymphoma (including 3 cases of follicular lymphoma). There was a possible link to multiple myeloma as well, but the diagnosis could not be confirmed.

 

And 1 family had a missense mutation in the helicase domain—p.G530D—that was linked to AML.

 

“DDX41 is a new type of cancer predisposition gene, and we are still investigating its function,” Dr Scott noted.

 

“But it appears to have dual roles in regulating the correct expression of genes in the cell and also enabling the immune system to respond to threats such as bacteria and viruses, as well as the development of cancer cells. Immunotherapy is a promising approach for cancer treatment, and our research to understand the function of DDX41 will help design better therapies.”

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Topics

 

 

 

Three generations of a family

 

A new study suggests mutations in the gene DDX41 occur in families where hematologic malignancies are common.

 

Previous research showed that both germline and acquired DDX41 mutations occur in families with multiple cases of late-onset myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

 

The new study, published in Blood, has linked germline mutations in DDX41 to chronic myeloid leukemia and lymphomas as well.

 

“This is the first gene identified in families with lymphoma and represents a major breakthrough for the field,” said study author Hamish Scott, PhD, of the University of Adelaide in South Australia.

 

“Researchers are recognizing now that genetic predisposition to blood cancer is more common than previously thought, and our study shows the importance of taking a thorough family history at diagnosis.”

 

To conduct this study, Dr Scott and his colleagues screened 2 cohorts of families with a range of hematologic disorders (malignant and non-malignant). One cohort included 240 individuals from 93 families in Australia. The other included 246 individuals from 198 families in the US.

 

In all, 9 of the families (3%) had germline DDX41 mutations.

 

Three families carried the recurrent p.D140Gfs*2 mutation, which was linked to AML.

 

One family carried a germline mutation—p.R525H, c.1574G.A—that was previously described only as a somatic mutation at the time of progression to MDS or AML. In the current study, the mutation was again linked to MDS and AML.

 

Five families carried novel DDX41 mutations.

 

One of these mutations was a germline substitution—c.435-2_435-1delAGinsCA—that was linked to MDS in 1 family.

 

Two families had a missense start-loss substitution—c.3G.A, p.M1I—that was linked to MDS, AML, chronic myeloid leukemia, and non-Hodgkin lymphoma.

 

One family had a DDX41 missense variant—c.490C.T, p.R164W. This was linked to Hodgkin and non-Hodgkin lymphoma (including 3 cases of follicular lymphoma). There was a possible link to multiple myeloma as well, but the diagnosis could not be confirmed.

 

And 1 family had a missense mutation in the helicase domain—p.G530D—that was linked to AML.

 

“DDX41 is a new type of cancer predisposition gene, and we are still investigating its function,” Dr Scott noted.

 

“But it appears to have dual roles in regulating the correct expression of genes in the cell and also enabling the immune system to respond to threats such as bacteria and viruses, as well as the development of cancer cells. Immunotherapy is a promising approach for cancer treatment, and our research to understand the function of DDX41 will help design better therapies.”

 

 

 

Three generations of a family

 

A new study suggests mutations in the gene DDX41 occur in families where hematologic malignancies are common.

 

Previous research showed that both germline and acquired DDX41 mutations occur in families with multiple cases of late-onset myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

 

The new study, published in Blood, has linked germline mutations in DDX41 to chronic myeloid leukemia and lymphomas as well.

 

“This is the first gene identified in families with lymphoma and represents a major breakthrough for the field,” said study author Hamish Scott, PhD, of the University of Adelaide in South Australia.

 

“Researchers are recognizing now that genetic predisposition to blood cancer is more common than previously thought, and our study shows the importance of taking a thorough family history at diagnosis.”

 

To conduct this study, Dr Scott and his colleagues screened 2 cohorts of families with a range of hematologic disorders (malignant and non-malignant). One cohort included 240 individuals from 93 families in Australia. The other included 246 individuals from 198 families in the US.

 

In all, 9 of the families (3%) had germline DDX41 mutations.

 

Three families carried the recurrent p.D140Gfs*2 mutation, which was linked to AML.

 

One family carried a germline mutation—p.R525H, c.1574G.A—that was previously described only as a somatic mutation at the time of progression to MDS or AML. In the current study, the mutation was again linked to MDS and AML.

 

Five families carried novel DDX41 mutations.

 

One of these mutations was a germline substitution—c.435-2_435-1delAGinsCA—that was linked to MDS in 1 family.

 

Two families had a missense start-loss substitution—c.3G.A, p.M1I—that was linked to MDS, AML, chronic myeloid leukemia, and non-Hodgkin lymphoma.

 

One family had a DDX41 missense variant—c.490C.T, p.R164W. This was linked to Hodgkin and non-Hodgkin lymphoma (including 3 cases of follicular lymphoma). There was a possible link to multiple myeloma as well, but the diagnosis could not be confirmed.

 

And 1 family had a missense mutation in the helicase domain—p.G530D—that was linked to AML.

 

“DDX41 is a new type of cancer predisposition gene, and we are still investigating its function,” Dr Scott noted.

 

“But it appears to have dual roles in regulating the correct expression of genes in the cell and also enabling the immune system to respond to threats such as bacteria and viruses, as well as the development of cancer cells. Immunotherapy is a promising approach for cancer treatment, and our research to understand the function of DDX41 will help design better therapies.”

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