Common surgeries increase the risk of chronic opioid use in opioid-naive adults, especially those using antidepressants or benzodiazepines before their operations, and those with substance abuse histories, according to an insurance claims analysis from Stanford (Calif.) University.

The researchers reviewed opioid prescribing in the first postop year – excluding the first 90 days – for 641,941 patients and compared that information with opioid prescribing for 18,011,137 adult patients who did not have surgery. None of the subjects had filled an opioid prescription in the previous year (JAMA Intern Med. 2016 Jul 11. doi: 10.1001/jamainternmed.2016.3298).

Chronic opioid use, defined as filling at least 120 days of opioid prescriptions within the first year of surgery, ranged up to 1.41% for total knee replacement, versus 0.136% in the nonsurgical controls. After adjustment for potential confounders, knee replacement increased the risk fivefold; open cholecystectomy almost fourfold; total hip replacement and simple mastectomy almost threefold; and laparoscopic cholecystectomy and open appendectomy almost twofold. Cesarean delivery increased the risk of chronic use by 28%.

With the exception of knee and hip replacements, “these procedures are not indicated to relieve pain and are not thought to place patients at risk for long-term pain ... Our results suggest that primary care clinicians and surgeons should monitor opioid use closely in the postsurgical period,” wrote Eric C. Sun, MD, PhD, of the department of anesthesiology, perioperative and pain medicine at Stanford (Calif.) University, and his colleagues.

Preoperative antidepressants and benzodiazepines carried about the same risk of chronic use as alcohol abuse (odds ratio 1.83; P less than .001), while drug abuse history increased the risk even more (OR 3.15; P less than .001). Male sex, age over 50 years, and history of depression were also associated with chronic use on multivariate analysis. Meanwhile, transurethral prostatectomy, laparoscopic appendectomy, functional endoscopic sinus surgery, and cataract surgery did not increase chronic use risk.

“Surgical patients, particularly those at higher risk for chronic opioid use, may benefit from techniques to reduce the risk such as multimodal analgesia and regional anesthesia, particularly in light of literature suggesting that these interventions may improve other perioperative outcomes ... Patients may also benefit from other preoperative and postoperative interventions, such as evidence-based psychobehavioral pain management skills,” the investigators said.

It wasn’t clear until now that even opioid-naive patients are at risk for opioid problems after surgery. Stanford’s investigation is not the first to link surgery and opioid abuse, but previous studies tended to focus on patients with preexisting use and more painful operations.

The study included prescriptions for oral and patch fentanyl, hydrocodone, oral hydromorphone, methadone, morphine, oxymorphone, and oxycodone. Hydrocodone cough remedies and acetaminophen/codeine analgesics were excluded.

Nonsurgical patients tended to be younger than their surgical peers (mean 42 vs. 44 years) and more likely to be male (49% vs. 26%).

The authors had no disclosures. The work was funded in part by the Foundation for Anesthesia Education and Research and the Anesthesia Quality Institute. Claims data came from MarketScan (Truven Health Analytics).

[email protected]

Common surgeries increase the risk of chronic opioid use in opioid-naive adults, especially those using antidepressants or benzodiazepines before their operations, and those with substance abuse histories, according to an insurance claims analysis from Stanford (Calif.) University.

The researchers reviewed opioid prescribing in the first postop year – excluding the first 90 days – for 641,941 patients and compared that information with opioid prescribing for 18,011,137 adult patients who did not have surgery. None of the subjects had filled an opioid prescription in the previous year (JAMA Intern Med. 2016 Jul 11. doi: 10.1001/jamainternmed.2016.3298).

Chronic opioid use, defined as filling at least 120 days of opioid prescriptions within the first year of surgery, ranged up to 1.41% for total knee replacement, versus 0.136% in the nonsurgical controls. After adjustment for potential confounders, knee replacement increased the risk fivefold; open cholecystectomy almost fourfold; total hip replacement and simple mastectomy almost threefold; and laparoscopic cholecystectomy and open appendectomy almost twofold. Cesarean delivery increased the risk of chronic use by 28%.

With the exception of knee and hip replacements, “these procedures are not indicated to relieve pain and are not thought to place patients at risk for long-term pain ... Our results suggest that primary care clinicians and surgeons should monitor opioid use closely in the postsurgical period,” wrote Eric C. Sun, MD, PhD, of the department of anesthesiology, perioperative and pain medicine at Stanford (Calif.) University, and his colleagues.

Preoperative antidepressants and benzodiazepines carried about the same risk of chronic use as alcohol abuse (odds ratio 1.83; P less than .001), while drug abuse history increased the risk even more (OR 3.15; P less than .001). Male sex, age over 50 years, and history of depression were also associated with chronic use on multivariate analysis. Meanwhile, transurethral prostatectomy, laparoscopic appendectomy, functional endoscopic sinus surgery, and cataract surgery did not increase chronic use risk.

“Surgical patients, particularly those at higher risk for chronic opioid use, may benefit from techniques to reduce the risk such as multimodal analgesia and regional anesthesia, particularly in light of literature suggesting that these interventions may improve other perioperative outcomes ... Patients may also benefit from other preoperative and postoperative interventions, such as evidence-based psychobehavioral pain management skills,” the investigators said.

It wasn’t clear until now that even opioid-naive patients are at risk for opioid problems after surgery. Stanford’s investigation is not the first to link surgery and opioid abuse, but previous studies tended to focus on patients with preexisting use and more painful operations.

The study included prescriptions for oral and patch fentanyl, hydrocodone, oral hydromorphone, methadone, morphine, oxymorphone, and oxycodone. Hydrocodone cough remedies and acetaminophen/codeine analgesics were excluded.

Nonsurgical patients tended to be younger than their surgical peers (mean 42 vs. 44 years) and more likely to be male (49% vs. 26%).

The authors had no disclosures. The work was funded in part by the Foundation for Anesthesia Education and Research and the Anesthesia Quality Institute. Claims data came from MarketScan (Truven Health Analytics).

[email protected]

Common surgeries increase the risk of chronic opioid use in opioid-naive adults, especially those using antidepressants or benzodiazepines before their operations, and those with substance abuse histories, according to an insurance claims analysis from Stanford (Calif.) University.

The researchers reviewed opioid prescribing in the first postop year – excluding the first 90 days – for 641,941 patients and compared that information with opioid prescribing for 18,011,137 adult patients who did not have surgery. None of the subjects had filled an opioid prescription in the previous year (JAMA Intern Med. 2016 Jul 11. doi: 10.1001/jamainternmed.2016.3298).

Chronic opioid use, defined as filling at least 120 days of opioid prescriptions within the first year of surgery, ranged up to 1.41% for total knee replacement, versus 0.136% in the nonsurgical controls. After adjustment for potential confounders, knee replacement increased the risk fivefold; open cholecystectomy almost fourfold; total hip replacement and simple mastectomy almost threefold; and laparoscopic cholecystectomy and open appendectomy almost twofold. Cesarean delivery increased the risk of chronic use by 28%.

With the exception of knee and hip replacements, “these procedures are not indicated to relieve pain and are not thought to place patients at risk for long-term pain ... Our results suggest that primary care clinicians and surgeons should monitor opioid use closely in the postsurgical period,” wrote Eric C. Sun, MD, PhD, of the department of anesthesiology, perioperative and pain medicine at Stanford (Calif.) University, and his colleagues.

Preoperative antidepressants and benzodiazepines carried about the same risk of chronic use as alcohol abuse (odds ratio 1.83; P less than .001), while drug abuse history increased the risk even more (OR 3.15; P less than .001). Male sex, age over 50 years, and history of depression were also associated with chronic use on multivariate analysis. Meanwhile, transurethral prostatectomy, laparoscopic appendectomy, functional endoscopic sinus surgery, and cataract surgery did not increase chronic use risk.

“Surgical patients, particularly those at higher risk for chronic opioid use, may benefit from techniques to reduce the risk such as multimodal analgesia and regional anesthesia, particularly in light of literature suggesting that these interventions may improve other perioperative outcomes ... Patients may also benefit from other preoperative and postoperative interventions, such as evidence-based psychobehavioral pain management skills,” the investigators said.

It wasn’t clear until now that even opioid-naive patients are at risk for opioid problems after surgery. Stanford’s investigation is not the first to link surgery and opioid abuse, but previous studies tended to focus on patients with preexisting use and more painful operations.

The study included prescriptions for oral and patch fentanyl, hydrocodone, oral hydromorphone, methadone, morphine, oxymorphone, and oxycodone. Hydrocodone cough remedies and acetaminophen/codeine analgesics were excluded.

Nonsurgical patients tended to be younger than their surgical peers (mean 42 vs. 44 years) and more likely to be male (49% vs. 26%).

The authors had no disclosures. The work was funded in part by the Foundation for Anesthesia Education and Research and the Anesthesia Quality Institute. Claims data came from MarketScan (Truven Health Analytics).

[email protected]

During surgery, the ObGyn discovered that pelvic adhesions had distorted the patient’s anatomy; he converted to laparotomy, which left a larger scar. Two days after surgery, the patient was found to have a bowel injury and underwent additional surgery that included placement of surgical mesh, leaving an enlarged scar.

PATIENT'S CLAIM: The ObGyn was negligent in injuring the patient’s bowel during hysterectomy and not detecting the injury intraoperatively. Her scars were larger because of the additional repair operation.

PHYSICIAN'S DEFENSE: Bowel injury is a known complication of the procedure. Many bowel injuries are not detected intraoperatively. The ObGyn made every effort to prevent and check for injury during the procedure.

VERDICT: An Illinois defense verdict was returned.

Uterus and bowel injured during D&C: $1.5M verdict
A 56-year-old woman underwent hysteroscopy and dilation and curettage (D&C). During the procedure, the gynecologist recognized that he had perforated the uterus and injured the bowel and called in a general surgeon to resect 5 cm of the bowel and repair the uterus.

PATIENT'S CLAIM:The patient has a large abdominal scar and a chronically distended abdomen. She experienced a year of daily pain and suffering. The D&C was unnecessary and improperly performed: the standard of care is for the gynecologist to operate in a gentle manner; that did not occur.

PHYSICIAN'S DEFENSE:The D&C was medically necessary. The gynecologist exercised the proper standard of care.

VERDICT:A $1.5 million New Jersey verdict was returned. The jury found the D&C necessary, but determined that the gynecologist deviated from the accepted standard of care in his performance of the procedure.

Bowel perforation during myomectomy: $200,000 verdictA 44-year-old woman underwent hysteroscopic myomectomy. During the procedure the ObGyn realized that he had perforated the uterus. He switched to a laparoscopic procedure, found a 3-cm uterine tear, and converted to laparotomy to repair the injury. The postsurgical pathology report revealed multiple colon fragments.

Three days after surgery, the patient became ill and was found to have a bowel injury. She underwent bowel resection with colostomy and, a year later, colostomy reversal. She sustained abdominal scarring.

PATIENT'S CLAIM: The ObGyn was negligent in performing the myomectomy. He should have identified the bowel injury intraoperatively. When the pathology report indicated multiple colon fragments, he should have investigated rather than wait for the patient to develop symptoms.

PHYSICIAN'S DEFENSE: Uterine and colon injuries are known complications of the procedure and can occur within the standard of care. The ObGyn intraoperatively inspected the organs adjacent to the uterus but there was no evident injury. The patient’s postsurgical treatment was proper.

VERDICT: A $200,000 Illinois verdict was returned.

Injured ureter allegedly not treatedA 42-year-old woman underwent hysterectomy on December 6. Postoperatively, she reported increasing dysuria with pain and fever. On December 13, a computed tomography (CT) scan suggested a partial ureter obstruction. Despite test results, the gynecologist elected to continue to monitor the patient. The patient’s symptoms continued to worsen and, on December 27, she underwent a second CT scan that identified an obstructed ureter. The gynecologist referred the patient to a urologist, who determined that the patient had sustained a significant ureter injury that required placement of a nephrostomy tube.

PATIENT'S CLAIM: The gynecologist failed to identify the injury during surgery. The gynecologist was negligent in not consulting a urologist after results of the first CT scan.

PHYSICIAN'S DEFENSE: Uterine injury is a known complication of the procedure. The gynecologist inspected adjacent organs during surgery but did not find an injury. Postoperative treatment was appropriate.

VERDICT: The case was presented before a medical review board that concluded that there was no error after the first injury, there was no duty to trace the ureter, and a urology consult was not required after the first CT scan. A Louisiana defense verdict was returned.

During surgery, the ObGyn discovered that pelvic adhesions had distorted the patient’s anatomy; he converted to laparotomy, which left a larger scar. Two days after surgery, the patient was found to have a bowel injury and underwent additional surgery that included placement of surgical mesh, leaving an enlarged scar.

PATIENT'S CLAIM: The ObGyn was negligent in injuring the patient’s bowel during hysterectomy and not detecting the injury intraoperatively. Her scars were larger because of the additional repair operation.

PHYSICIAN'S DEFENSE: Bowel injury is a known complication of the procedure. Many bowel injuries are not detected intraoperatively. The ObGyn made every effort to prevent and check for injury during the procedure.

VERDICT: An Illinois defense verdict was returned.

Uterus and bowel injured during D&C: $1.5M verdict
A 56-year-old woman underwent hysteroscopy and dilation and curettage (D&C). During the procedure, the gynecologist recognized that he had perforated the uterus and injured the bowel and called in a general surgeon to resect 5 cm of the bowel and repair the uterus.

PATIENT'S CLAIM:The patient has a large abdominal scar and a chronically distended abdomen. She experienced a year of daily pain and suffering. The D&C was unnecessary and improperly performed: the standard of care is for the gynecologist to operate in a gentle manner; that did not occur.

PHYSICIAN'S DEFENSE:The D&C was medically necessary. The gynecologist exercised the proper standard of care.

VERDICT:A $1.5 million New Jersey verdict was returned. The jury found the D&C necessary, but determined that the gynecologist deviated from the accepted standard of care in his performance of the procedure.

Bowel perforation during myomectomy: $200,000 verdictA 44-year-old woman underwent hysteroscopic myomectomy. During the procedure the ObGyn realized that he had perforated the uterus. He switched to a laparoscopic procedure, found a 3-cm uterine tear, and converted to laparotomy to repair the injury. The postsurgical pathology report revealed multiple colon fragments.

Three days after surgery, the patient became ill and was found to have a bowel injury. She underwent bowel resection with colostomy and, a year later, colostomy reversal. She sustained abdominal scarring.

PATIENT'S CLAIM: The ObGyn was negligent in performing the myomectomy. He should have identified the bowel injury intraoperatively. When the pathology report indicated multiple colon fragments, he should have investigated rather than wait for the patient to develop symptoms.

PHYSICIAN'S DEFENSE: Uterine and colon injuries are known complications of the procedure and can occur within the standard of care. The ObGyn intraoperatively inspected the organs adjacent to the uterus but there was no evident injury. The patient’s postsurgical treatment was proper.

VERDICT: A $200,000 Illinois verdict was returned.

Injured ureter allegedly not treatedA 42-year-old woman underwent hysterectomy on December 6. Postoperatively, she reported increasing dysuria with pain and fever. On December 13, a computed tomography (CT) scan suggested a partial ureter obstruction. Despite test results, the gynecologist elected to continue to monitor the patient. The patient’s symptoms continued to worsen and, on December 27, she underwent a second CT scan that identified an obstructed ureter. The gynecologist referred the patient to a urologist, who determined that the patient had sustained a significant ureter injury that required placement of a nephrostomy tube.

PATIENT'S CLAIM: The gynecologist failed to identify the injury during surgery. The gynecologist was negligent in not consulting a urologist after results of the first CT scan.

PHYSICIAN'S DEFENSE: Uterine injury is a known complication of the procedure. The gynecologist inspected adjacent organs during surgery but did not find an injury. Postoperative treatment was appropriate.

VERDICT: The case was presented before a medical review board that concluded that there was no error after the first injury, there was no duty to trace the ureter, and a urology consult was not required after the first CT scan. A Louisiana defense verdict was returned.

During surgery, the ObGyn discovered that pelvic adhesions had distorted the patient’s anatomy; he converted to laparotomy, which left a larger scar. Two days after surgery, the patient was found to have a bowel injury and underwent additional surgery that included placement of surgical mesh, leaving an enlarged scar.

PATIENT'S CLAIM: The ObGyn was negligent in injuring the patient’s bowel during hysterectomy and not detecting the injury intraoperatively. Her scars were larger because of the additional repair operation.

PHYSICIAN'S DEFENSE: Bowel injury is a known complication of the procedure. Many bowel injuries are not detected intraoperatively. The ObGyn made every effort to prevent and check for injury during the procedure.

VERDICT: An Illinois defense verdict was returned.

Uterus and bowel injured during D&C: $1.5M verdict
A 56-year-old woman underwent hysteroscopy and dilation and curettage (D&C). During the procedure, the gynecologist recognized that he had perforated the uterus and injured the bowel and called in a general surgeon to resect 5 cm of the bowel and repair the uterus.

PATIENT'S CLAIM:The patient has a large abdominal scar and a chronically distended abdomen. She experienced a year of daily pain and suffering. The D&C was unnecessary and improperly performed: the standard of care is for the gynecologist to operate in a gentle manner; that did not occur.

PHYSICIAN'S DEFENSE:The D&C was medically necessary. The gynecologist exercised the proper standard of care.

VERDICT:A $1.5 million New Jersey verdict was returned. The jury found the D&C necessary, but determined that the gynecologist deviated from the accepted standard of care in his performance of the procedure.

Bowel perforation during myomectomy: $200,000 verdictA 44-year-old woman underwent hysteroscopic myomectomy. During the procedure the ObGyn realized that he had perforated the uterus. He switched to a laparoscopic procedure, found a 3-cm uterine tear, and converted to laparotomy to repair the injury. The postsurgical pathology report revealed multiple colon fragments.

Three days after surgery, the patient became ill and was found to have a bowel injury. She underwent bowel resection with colostomy and, a year later, colostomy reversal. She sustained abdominal scarring.

PATIENT'S CLAIM: The ObGyn was negligent in performing the myomectomy. He should have identified the bowel injury intraoperatively. When the pathology report indicated multiple colon fragments, he should have investigated rather than wait for the patient to develop symptoms.

PHYSICIAN'S DEFENSE: Uterine and colon injuries are known complications of the procedure and can occur within the standard of care. The ObGyn intraoperatively inspected the organs adjacent to the uterus but there was no evident injury. The patient’s postsurgical treatment was proper.

VERDICT: A $200,000 Illinois verdict was returned.

Injured ureter allegedly not treatedA 42-year-old woman underwent hysterectomy on December 6. Postoperatively, she reported increasing dysuria with pain and fever. On December 13, a computed tomography (CT) scan suggested a partial ureter obstruction. Despite test results, the gynecologist elected to continue to monitor the patient. The patient’s symptoms continued to worsen and, on December 27, she underwent a second CT scan that identified an obstructed ureter. The gynecologist referred the patient to a urologist, who determined that the patient had sustained a significant ureter injury that required placement of a nephrostomy tube.

PATIENT'S CLAIM: The gynecologist failed to identify the injury during surgery. The gynecologist was negligent in not consulting a urologist after results of the first CT scan.

PHYSICIAN'S DEFENSE: Uterine injury is a known complication of the procedure. The gynecologist inspected adjacent organs during surgery but did not find an injury. Postoperative treatment was appropriate.

VERDICT: The case was presented before a medical review board that concluded that there was no error after the first injury, there was no duty to trace the ureter, and a urology consult was not required after the first CT scan. A Louisiana defense verdict was returned.

PARENT'S CLAIM: The pregnancy was at high risk because of the mother’s hypertension. The ObGyns misread the FHR at triage and discontinued FHR monitoring too early. If continuous FHR monitoring had occurred, fetal distress would have been detected earlier, resulting in a better outcome for the baby.

PHYSICIAN'S DEFENSE: There were no signs of fetal distress when the FHR monitoring was discontinued. Placental abruption is an acute event that cannot be predicted.

VERDICT: A Missouri defense verdict was returned.

Should the ObGyn have come to the hospital earlier?At 39 weeks’ gestation, a mother presented to the hospital for induction of labor. A FHR monitor was immediately placed. That evening, the ObGyn, who was not at the hospital, was notified that the mother had an elevated temperature and that the fetus was experiencing tachycardia. The ObGyn prescribed antibiotics, and the fever subsided. After an hour, the patient was fully dilated and started to push under the nurse’s supervision. Twenty minutes later, the ObGyn was notified that the fetus was experiencing variable decelerations. The ObGyn arrived in 30 minutes and ordered cesarean delivery. The baby was born 24 minutes later.

Ten hours after birth, the baby began to have seizures. He was transferred to another hospital and remained in the neonatal intensive care unit for 15 days. The child received a diagnosis of cerebral palsy.

PARENT'S CLAIM: The ObGyn was negligent in not coming to the hospital when the mother was feverish and the baby tachycardic. The baby experienced an acute hypoxic ischemic injury; an earlier cesarean delivery would have avoided brain injury.

PHYSICIAN'S DEFENSE: There was no breach in the standard of care. The infant did not meet all the criteria for an acute hypoxic ischemic injury. Based on a computed tomography scan taken after seizures began, the infant’s brain injury most likely occurred hours before birth.

VERDICT: A Virginia defense verdict was returned.

These cases were selected by the editors of 
OBG Management from "Medical Malpractice Verdicts, Settlements, & Experts," with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts 
and awards.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

PARENT'S CLAIM: The pregnancy was at high risk because of the mother’s hypertension. The ObGyns misread the FHR at triage and discontinued FHR monitoring too early. If continuous FHR monitoring had occurred, fetal distress would have been detected earlier, resulting in a better outcome for the baby.

PHYSICIAN'S DEFENSE: There were no signs of fetal distress when the FHR monitoring was discontinued. Placental abruption is an acute event that cannot be predicted.

VERDICT: A Missouri defense verdict was returned.

Should the ObGyn have come to the hospital earlier?At 39 weeks’ gestation, a mother presented to the hospital for induction of labor. A FHR monitor was immediately placed. That evening, the ObGyn, who was not at the hospital, was notified that the mother had an elevated temperature and that the fetus was experiencing tachycardia. The ObGyn prescribed antibiotics, and the fever subsided. After an hour, the patient was fully dilated and started to push under the nurse’s supervision. Twenty minutes later, the ObGyn was notified that the fetus was experiencing variable decelerations. The ObGyn arrived in 30 minutes and ordered cesarean delivery. The baby was born 24 minutes later.

Ten hours after birth, the baby began to have seizures. He was transferred to another hospital and remained in the neonatal intensive care unit for 15 days. The child received a diagnosis of cerebral palsy.

PARENT'S CLAIM: The ObGyn was negligent in not coming to the hospital when the mother was feverish and the baby tachycardic. The baby experienced an acute hypoxic ischemic injury; an earlier cesarean delivery would have avoided brain injury.

PHYSICIAN'S DEFENSE: There was no breach in the standard of care. The infant did not meet all the criteria for an acute hypoxic ischemic injury. Based on a computed tomography scan taken after seizures began, the infant’s brain injury most likely occurred hours before birth.

VERDICT: A Virginia defense verdict was returned.

These cases were selected by the editors of 
OBG Management from "Medical Malpractice Verdicts, Settlements, & Experts," with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts 
and awards.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

PARENT'S CLAIM: The pregnancy was at high risk because of the mother’s hypertension. The ObGyns misread the FHR at triage and discontinued FHR monitoring too early. If continuous FHR monitoring had occurred, fetal distress would have been detected earlier, resulting in a better outcome for the baby.

PHYSICIAN'S DEFENSE: There were no signs of fetal distress when the FHR monitoring was discontinued. Placental abruption is an acute event that cannot be predicted.

VERDICT: A Missouri defense verdict was returned.

Should the ObGyn have come to the hospital earlier?At 39 weeks’ gestation, a mother presented to the hospital for induction of labor. A FHR monitor was immediately placed. That evening, the ObGyn, who was not at the hospital, was notified that the mother had an elevated temperature and that the fetus was experiencing tachycardia. The ObGyn prescribed antibiotics, and the fever subsided. After an hour, the patient was fully dilated and started to push under the nurse’s supervision. Twenty minutes later, the ObGyn was notified that the fetus was experiencing variable decelerations. The ObGyn arrived in 30 minutes and ordered cesarean delivery. The baby was born 24 minutes later.

Ten hours after birth, the baby began to have seizures. He was transferred to another hospital and remained in the neonatal intensive care unit for 15 days. The child received a diagnosis of cerebral palsy.

PARENT'S CLAIM: The ObGyn was negligent in not coming to the hospital when the mother was feverish and the baby tachycardic. The baby experienced an acute hypoxic ischemic injury; an earlier cesarean delivery would have avoided brain injury.

PHYSICIAN'S DEFENSE: There was no breach in the standard of care. The infant did not meet all the criteria for an acute hypoxic ischemic injury. Based on a computed tomography scan taken after seizures began, the infant’s brain injury most likely occurred hours before birth.

VERDICT: A Virginia defense verdict was returned.

These cases were selected by the editors of 
OBG Management from "Medical Malpractice Verdicts, Settlements, & Experts," with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts 
and awards.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

HELSINKI, FINLAND – A brief period of immobilization after intrauterine insemination did not improve pregnancy rates and was actually associated with a slight reduction in the pregnancy rate in a large single-center, randomized controlled trial.

The findings conflict with those of some prior smaller studies and contradict a widely held belief in the benefit of immobilization, which is usually carried out while the patient is in a supine position with the knees raised, Joukje van Rijswijk, MD, reported at the annual meeting of the European Society of Human Reproduction and Embryology.

In 479 patients with idiopathic or mild male subfertility and an indication for IUI who were randomized to 15 minutes of immobilization following IUI (950 cycles) or immediate mobilization (984 cycles), the cumulative ongoing pregnancy rate per couple was 32.2% and 40.3% in the groups, respectively (odds ratio, 0.70). The difference between the groups was not statistically significant, said Dr. van Rijswijk of VU University Medical Center, Amsterdam, The Netherlands.

Randomization in the study was stratified for the diagnosis of idiopathic or mild male subfertility. After adjustment for duration of subfertility, the difference between the group still did not reach statistical significance (odds ratio, 0.72), Dr. van Rijswijk said.

IUI is an established treatment for idiopathic and mild male subfertility, and while several factors are associated with pregnancy outcomes, the role of direct mobilization has remained controversial. Two recent studies showed a beneficial effect but were of questionable quality. For example, one of the studies found that 10 and 15 minutes of immobilization, vs. 5 minutes, had a beneficial effect on pregnancy rates, but the results were based on just one treatment cycle and “not on the more real-world context of multiple cycles,” according to an ESHRE press release.

The responsible mechanism for the benefit of immobilization remains unclear, Dr. van Rijswijk said, explaining that it is known from other studies that sperm cells can reach the fallopian tube 5 minutes after intravaginal insemination and can survive for several days in the womb.

“Why should bed rest affect that? There’s no biological explanation for a positive effect of immobilization,” she said.

“In our opinion, immobilization after IUI has no positive effect on pregnancy rates, and there is no reason why patients should stay immobilized after treatment,” she concluded, adding that the findings are “sufficiently strong to render the recommendation for bed rest obsolete.”

As for whether immobilization is also unwarranted for natural conception, Dr. van Rijswijk said the two insemination techniques are too different, thus the findings are not generalizable.

She reported having no relevant financial disclosures. The trial was funded by the VU University Medical Center.

[email protected]

HELSINKI, FINLAND – A brief period of immobilization after intrauterine insemination did not improve pregnancy rates and was actually associated with a slight reduction in the pregnancy rate in a large single-center, randomized controlled trial.

The findings conflict with those of some prior smaller studies and contradict a widely held belief in the benefit of immobilization, which is usually carried out while the patient is in a supine position with the knees raised, Joukje van Rijswijk, MD, reported at the annual meeting of the European Society of Human Reproduction and Embryology.

In 479 patients with idiopathic or mild male subfertility and an indication for IUI who were randomized to 15 minutes of immobilization following IUI (950 cycles) or immediate mobilization (984 cycles), the cumulative ongoing pregnancy rate per couple was 32.2% and 40.3% in the groups, respectively (odds ratio, 0.70). The difference between the groups was not statistically significant, said Dr. van Rijswijk of VU University Medical Center, Amsterdam, The Netherlands.

Randomization in the study was stratified for the diagnosis of idiopathic or mild male subfertility. After adjustment for duration of subfertility, the difference between the group still did not reach statistical significance (odds ratio, 0.72), Dr. van Rijswijk said.

IUI is an established treatment for idiopathic and mild male subfertility, and while several factors are associated with pregnancy outcomes, the role of direct mobilization has remained controversial. Two recent studies showed a beneficial effect but were of questionable quality. For example, one of the studies found that 10 and 15 minutes of immobilization, vs. 5 minutes, had a beneficial effect on pregnancy rates, but the results were based on just one treatment cycle and “not on the more real-world context of multiple cycles,” according to an ESHRE press release.

The responsible mechanism for the benefit of immobilization remains unclear, Dr. van Rijswijk said, explaining that it is known from other studies that sperm cells can reach the fallopian tube 5 minutes after intravaginal insemination and can survive for several days in the womb.

“Why should bed rest affect that? There’s no biological explanation for a positive effect of immobilization,” she said.

“In our opinion, immobilization after IUI has no positive effect on pregnancy rates, and there is no reason why patients should stay immobilized after treatment,” she concluded, adding that the findings are “sufficiently strong to render the recommendation for bed rest obsolete.”

As for whether immobilization is also unwarranted for natural conception, Dr. van Rijswijk said the two insemination techniques are too different, thus the findings are not generalizable.

She reported having no relevant financial disclosures. The trial was funded by the VU University Medical Center.

[email protected]

HELSINKI, FINLAND – A brief period of immobilization after intrauterine insemination did not improve pregnancy rates and was actually associated with a slight reduction in the pregnancy rate in a large single-center, randomized controlled trial.

The findings conflict with those of some prior smaller studies and contradict a widely held belief in the benefit of immobilization, which is usually carried out while the patient is in a supine position with the knees raised, Joukje van Rijswijk, MD, reported at the annual meeting of the European Society of Human Reproduction and Embryology.

In 479 patients with idiopathic or mild male subfertility and an indication for IUI who were randomized to 15 minutes of immobilization following IUI (950 cycles) or immediate mobilization (984 cycles), the cumulative ongoing pregnancy rate per couple was 32.2% and 40.3% in the groups, respectively (odds ratio, 0.70). The difference between the groups was not statistically significant, said Dr. van Rijswijk of VU University Medical Center, Amsterdam, The Netherlands.

Randomization in the study was stratified for the diagnosis of idiopathic or mild male subfertility. After adjustment for duration of subfertility, the difference between the group still did not reach statistical significance (odds ratio, 0.72), Dr. van Rijswijk said.

IUI is an established treatment for idiopathic and mild male subfertility, and while several factors are associated with pregnancy outcomes, the role of direct mobilization has remained controversial. Two recent studies showed a beneficial effect but were of questionable quality. For example, one of the studies found that 10 and 15 minutes of immobilization, vs. 5 minutes, had a beneficial effect on pregnancy rates, but the results were based on just one treatment cycle and “not on the more real-world context of multiple cycles,” according to an ESHRE press release.

The responsible mechanism for the benefit of immobilization remains unclear, Dr. van Rijswijk said, explaining that it is known from other studies that sperm cells can reach the fallopian tube 5 minutes after intravaginal insemination and can survive for several days in the womb.

“Why should bed rest affect that? There’s no biological explanation for a positive effect of immobilization,” she said.

“In our opinion, immobilization after IUI has no positive effect on pregnancy rates, and there is no reason why patients should stay immobilized after treatment,” she concluded, adding that the findings are “sufficiently strong to render the recommendation for bed rest obsolete.”

As for whether immobilization is also unwarranted for natural conception, Dr. van Rijswijk said the two insemination techniques are too different, thus the findings are not generalizable.

She reported having no relevant financial disclosures. The trial was funded by the VU University Medical Center.

[email protected]

Local tender erythema is a typical manifestation of cellulitis, which is commonly seen by dermatologists; however, cutaneous manifestations of other diseases may bear resemblance to the more banal cellulitis. We present the case of a patient with tuberculous cellulitis, a rare variant of cutaneous tuberculosis.

Case Report

An 89-year-old man presented to a local primary care physician with a fever (temperature, 38°C). Infectious disease was suspected. Antibiotic therapy with oral cefaclor and intravenous cefotiam hydrochloride was started, but the patient’s fever did not subside. Six days after initiation of treatment, he was referred to our dermatology department for evaluation of a painful erythematous rash on the left thigh that had suddenly appeared. The patient had a history of pulmonary tuberculosis 71 years prior. He also underwent surgical treatment of pancreatic cancer 14 years prior. Additionally, he had chronic kidney disease (CKD) and polymyalgia rheumatica, which was currently being treated with oral prednisolone 5 mg once daily.

Physical examination revealed a hot and tender erythematous plaque on the left thigh (Figure 1). The edge of the lesion was not well defined and there was no regional lymphadenopathy.

A complete blood cell count revealed anemia (white blood cell count, 8070/μL [reference range, 4000–9,000/μL]; neutrophils, 77.1% [reference range, 44%–74%]; lymphocytes, 13.8% [reference range, 20%–50%]; hemoglobin, 9.3 g/dL [reference range, 13.0–17.0 g/dL]; and platelet count, 329×10³/μL [reference range, 150–400×10³/μL]). The C-reactive protein level was 7.3 mg/dL (reference range, 0.08–0.3 mg/dL). The creatinine level was 2.93 mg/dL (reference range, 0.6–1.2 mg/dL). There were no signs of liver dysfunction.

A blood culture was negative. A purified protein derivative (tuberculin) skin test was negative (6×7 mm [reference range, ≤9 mm). A chest computed tomography (CT) scan showed small centrilobular nodules that had not changed in number or size since evaluation 3 months prior.

The antibiotics were changed to meropenem hydrate 0.5 g and clindamycin 300 mg twice daily for presumed bacterial cellulitis, then meropenem hydrate 1 g and clindamycin 600 mg daily, but there was still no improvement after about 1 week. Therefore, a skin biopsy was performed on the left thigh. The specimen showed epithelioid cell granulomas throughout the dermis and subcutis (Figure 2). Ziehl-Neelsen stain revealed numerous acid-fast bacilli (Figure 3). Polymerase chain reaction was positive for Mycobacterium tuberculosis in the skin biopsy specimen and gastric fluid. Additionally, M tuberculosis was isolated from the skin biopsy specimen, gastric fluid, and sputum culture. After the series of treatments described above, a remarkable increase in nodule size and number was observed in a follow-up chest CT scan compared with the prior examination. These pulmonary lesions showed bronchogenic spread.

A diagnosis of tuberculous cellulitis with pulmonary tuberculosis was made. Treatment with isoniazid 200 mg once daily, rifampin 300 mg once daily, and ethambutol 500 mg once every other day was started; the dosages were reduced from the standard dose due to the patient’s CKD.¹ Four days after initiation of these medications, the patient was transferred to a hospital specifically for the treatment of tuberculosis. Approximately 8 months after treatment with isoniazid, rifampin, and ethambutol, M tuberculosis could not be detected in the sputum and a chest CT revealed that the pulmonary lesions were remarkably improved. However, polymerase chain reaction of the skin biopsy specimen was still positive for M tuberculosis. It was determined that debridement of the skin lesion was needed, but the patient died from complications of deteriorating CKD 10 months after the initiation of the antituberculosis medications.

Comment

Cellulitis is a suppurative inflammation involving the subcutis.² Local tender erythema, malaise, chills, and fever may be present at the onset. Cellulitis is commonly seen by dermatologists, and it is well known that other infectious diseases such as necrotizing fasciitis, cutaneous and subcutaneous mycoses,³ and nontuberculous mycobacterial infections⁴ sometimes present as cellulitislike skin lesions. Moreover, noninfectious diseases, such as Wells syndrome, thrombophlebitis, reactive angioendotheliomatosis,⁵ cutaneous metastasis of a primary malignancy,⁶ subcutaneous panniculitislike T-cell lymphoma,⁷ Langerhans cell histiocytosis,⁸ Sweet syndrome,⁹ adult-onset Still disease,¹⁰ and fixed drug eruption caused by acetaminophen¹¹ should be excluded. These differential diagnoses and diagnostic clues of cellulitislike erythema are summarized in Table 1.^3-16

Cutaneous tuberculosis presenting as cellulitis, so-called tuberculous cellulitis, also is characterized as a clinical mimicker of cellulitis. On the other hand, histologically, it has features of cutaneous tuberculosis (eg, necrotic granuloma).^12,14,15 Tuberculous cellulitis is rare and therefore may often be misdiagnosed even in highly endemic areas. We summarized the clinical information of 5 well-documented cases of tuberculous cellulitis along with the current case in Table 2.^12-16 All of these cases had an associated disease and involved patients who were currently taking oral corticosteroids. If a patient undergoing immunosuppressive therapy develops cellulitislike erythema, tuberculous cellulitis should be considered in the differential diagnosis.

Cutaneous tuberculosis generally is classified into 4 types according to the mechanism of disease acquisition: (1) inoculation from an exogenous source, (2) endogenous cutaneous spread contiguously or by autoinoculation, (3) hematogenous spread to the skin, and (4) tuberculids. In our case, it was suspected that the cellulitislike erythema may have been caused by hematogenous spread from pulmonary tuberculosis. Considering that negative reactions to purified protein derivative (tuberculin) skin tests often are observed in cases of miliary tuberculosis (widespread dissemination of M tuberculosis to 2 or more organs via hematogenous spread), we suspected that our patient could proceed to miliary tuberculosis; in fact, a case was reported in which miliary tuberculosis emerged approximately 3 weeks after the onset of erythema,¹³ as observed in the present case. Therefore, erythema in the setting of tuberculosis may be a predictor of miliary tuberculosis. The types of cutaneous lesions caused by tuberculosis infection also are dependent on multiple host factors.² Cutaneous tuberculosis with an atypical clinical appearance has become more common because of the increasing number of immunocompromised patients.¹⁷

In addition, most cases of cutaneous tuberculosis are not associated with pain. Generally, tuberculous cellulitis also causes nontender erythematous plaques or nodules.² However, in some cases of tuberculous cellulitis, including our case, tender skin lesions have been reported.^12-14 Therefore, this symptom is not a sensitive factor for differential diagnosis.

We suggest that tuberculous cellulitis should always be included in the differential diagnosis of a cellulitislike rash with or without pain if the skin lesion is not improved despite antibiotic therapy.

Local tender erythema is a typical manifestation of cellulitis, which is commonly seen by dermatologists; however, cutaneous manifestations of other diseases may bear resemblance to the more banal cellulitis. We present the case of a patient with tuberculous cellulitis, a rare variant of cutaneous tuberculosis.

Case Report

An 89-year-old man presented to a local primary care physician with a fever (temperature, 38°C). Infectious disease was suspected. Antibiotic therapy with oral cefaclor and intravenous cefotiam hydrochloride was started, but the patient’s fever did not subside. Six days after initiation of treatment, he was referred to our dermatology department for evaluation of a painful erythematous rash on the left thigh that had suddenly appeared. The patient had a history of pulmonary tuberculosis 71 years prior. He also underwent surgical treatment of pancreatic cancer 14 years prior. Additionally, he had chronic kidney disease (CKD) and polymyalgia rheumatica, which was currently being treated with oral prednisolone 5 mg once daily.

Physical examination revealed a hot and tender erythematous plaque on the left thigh (Figure 1). The edge of the lesion was not well defined and there was no regional lymphadenopathy.

A complete blood cell count revealed anemia (white blood cell count, 8070/μL [reference range, 4000–9,000/μL]; neutrophils, 77.1% [reference range, 44%–74%]; lymphocytes, 13.8% [reference range, 20%–50%]; hemoglobin, 9.3 g/dL [reference range, 13.0–17.0 g/dL]; and platelet count, 329×10³/μL [reference range, 150–400×10³/μL]). The C-reactive protein level was 7.3 mg/dL (reference range, 0.08–0.3 mg/dL). The creatinine level was 2.93 mg/dL (reference range, 0.6–1.2 mg/dL). There were no signs of liver dysfunction.

A blood culture was negative. A purified protein derivative (tuberculin) skin test was negative (6×7 mm [reference range, ≤9 mm). A chest computed tomography (CT) scan showed small centrilobular nodules that had not changed in number or size since evaluation 3 months prior.

The antibiotics were changed to meropenem hydrate 0.5 g and clindamycin 300 mg twice daily for presumed bacterial cellulitis, then meropenem hydrate 1 g and clindamycin 600 mg daily, but there was still no improvement after about 1 week. Therefore, a skin biopsy was performed on the left thigh. The specimen showed epithelioid cell granulomas throughout the dermis and subcutis (Figure 2). Ziehl-Neelsen stain revealed numerous acid-fast bacilli (Figure 3). Polymerase chain reaction was positive for Mycobacterium tuberculosis in the skin biopsy specimen and gastric fluid. Additionally, M tuberculosis was isolated from the skin biopsy specimen, gastric fluid, and sputum culture. After the series of treatments described above, a remarkable increase in nodule size and number was observed in a follow-up chest CT scan compared with the prior examination. These pulmonary lesions showed bronchogenic spread.

A diagnosis of tuberculous cellulitis with pulmonary tuberculosis was made. Treatment with isoniazid 200 mg once daily, rifampin 300 mg once daily, and ethambutol 500 mg once every other day was started; the dosages were reduced from the standard dose due to the patient’s CKD.¹ Four days after initiation of these medications, the patient was transferred to a hospital specifically for the treatment of tuberculosis. Approximately 8 months after treatment with isoniazid, rifampin, and ethambutol, M tuberculosis could not be detected in the sputum and a chest CT revealed that the pulmonary lesions were remarkably improved. However, polymerase chain reaction of the skin biopsy specimen was still positive for M tuberculosis. It was determined that debridement of the skin lesion was needed, but the patient died from complications of deteriorating CKD 10 months after the initiation of the antituberculosis medications.

Comment

Cellulitis is a suppurative inflammation involving the subcutis.² Local tender erythema, malaise, chills, and fever may be present at the onset. Cellulitis is commonly seen by dermatologists, and it is well known that other infectious diseases such as necrotizing fasciitis, cutaneous and subcutaneous mycoses,³ and nontuberculous mycobacterial infections⁴ sometimes present as cellulitislike skin lesions. Moreover, noninfectious diseases, such as Wells syndrome, thrombophlebitis, reactive angioendotheliomatosis,⁵ cutaneous metastasis of a primary malignancy,⁶ subcutaneous panniculitislike T-cell lymphoma,⁷ Langerhans cell histiocytosis,⁸ Sweet syndrome,⁹ adult-onset Still disease,¹⁰ and fixed drug eruption caused by acetaminophen¹¹ should be excluded. These differential diagnoses and diagnostic clues of cellulitislike erythema are summarized in Table 1.^3-16

Cutaneous tuberculosis presenting as cellulitis, so-called tuberculous cellulitis, also is characterized as a clinical mimicker of cellulitis. On the other hand, histologically, it has features of cutaneous tuberculosis (eg, necrotic granuloma).^12,14,15 Tuberculous cellulitis is rare and therefore may often be misdiagnosed even in highly endemic areas. We summarized the clinical information of 5 well-documented cases of tuberculous cellulitis along with the current case in Table 2.^12-16 All of these cases had an associated disease and involved patients who were currently taking oral corticosteroids. If a patient undergoing immunosuppressive therapy develops cellulitislike erythema, tuberculous cellulitis should be considered in the differential diagnosis.

Cutaneous tuberculosis generally is classified into 4 types according to the mechanism of disease acquisition: (1) inoculation from an exogenous source, (2) endogenous cutaneous spread contiguously or by autoinoculation, (3) hematogenous spread to the skin, and (4) tuberculids. In our case, it was suspected that the cellulitislike erythema may have been caused by hematogenous spread from pulmonary tuberculosis. Considering that negative reactions to purified protein derivative (tuberculin) skin tests often are observed in cases of miliary tuberculosis (widespread dissemination of M tuberculosis to 2 or more organs via hematogenous spread), we suspected that our patient could proceed to miliary tuberculosis; in fact, a case was reported in which miliary tuberculosis emerged approximately 3 weeks after the onset of erythema,¹³ as observed in the present case. Therefore, erythema in the setting of tuberculosis may be a predictor of miliary tuberculosis. The types of cutaneous lesions caused by tuberculosis infection also are dependent on multiple host factors.² Cutaneous tuberculosis with an atypical clinical appearance has become more common because of the increasing number of immunocompromised patients.¹⁷

In addition, most cases of cutaneous tuberculosis are not associated with pain. Generally, tuberculous cellulitis also causes nontender erythematous plaques or nodules.² However, in some cases of tuberculous cellulitis, including our case, tender skin lesions have been reported.^12-14 Therefore, this symptom is not a sensitive factor for differential diagnosis.

We suggest that tuberculous cellulitis should always be included in the differential diagnosis of a cellulitislike rash with or without pain if the skin lesion is not improved despite antibiotic therapy.

Local tender erythema is a typical manifestation of cellulitis, which is commonly seen by dermatologists; however, cutaneous manifestations of other diseases may bear resemblance to the more banal cellulitis. We present the case of a patient with tuberculous cellulitis, a rare variant of cutaneous tuberculosis.

Case Report

An 89-year-old man presented to a local primary care physician with a fever (temperature, 38°C). Infectious disease was suspected. Antibiotic therapy with oral cefaclor and intravenous cefotiam hydrochloride was started, but the patient’s fever did not subside. Six days after initiation of treatment, he was referred to our dermatology department for evaluation of a painful erythematous rash on the left thigh that had suddenly appeared. The patient had a history of pulmonary tuberculosis 71 years prior. He also underwent surgical treatment of pancreatic cancer 14 years prior. Additionally, he had chronic kidney disease (CKD) and polymyalgia rheumatica, which was currently being treated with oral prednisolone 5 mg once daily.

Physical examination revealed a hot and tender erythematous plaque on the left thigh (Figure 1). The edge of the lesion was not well defined and there was no regional lymphadenopathy.

A complete blood cell count revealed anemia (white blood cell count, 8070/μL [reference range, 4000–9,000/μL]; neutrophils, 77.1% [reference range, 44%–74%]; lymphocytes, 13.8% [reference range, 20%–50%]; hemoglobin, 9.3 g/dL [reference range, 13.0–17.0 g/dL]; and platelet count, 329×10³/μL [reference range, 150–400×10³/μL]). The C-reactive protein level was 7.3 mg/dL (reference range, 0.08–0.3 mg/dL). The creatinine level was 2.93 mg/dL (reference range, 0.6–1.2 mg/dL). There were no signs of liver dysfunction.

A blood culture was negative. A purified protein derivative (tuberculin) skin test was negative (6×7 mm [reference range, ≤9 mm). A chest computed tomography (CT) scan showed small centrilobular nodules that had not changed in number or size since evaluation 3 months prior.

The antibiotics were changed to meropenem hydrate 0.5 g and clindamycin 300 mg twice daily for presumed bacterial cellulitis, then meropenem hydrate 1 g and clindamycin 600 mg daily, but there was still no improvement after about 1 week. Therefore, a skin biopsy was performed on the left thigh. The specimen showed epithelioid cell granulomas throughout the dermis and subcutis (Figure 2). Ziehl-Neelsen stain revealed numerous acid-fast bacilli (Figure 3). Polymerase chain reaction was positive for Mycobacterium tuberculosis in the skin biopsy specimen and gastric fluid. Additionally, M tuberculosis was isolated from the skin biopsy specimen, gastric fluid, and sputum culture. After the series of treatments described above, a remarkable increase in nodule size and number was observed in a follow-up chest CT scan compared with the prior examination. These pulmonary lesions showed bronchogenic spread.

A diagnosis of tuberculous cellulitis with pulmonary tuberculosis was made. Treatment with isoniazid 200 mg once daily, rifampin 300 mg once daily, and ethambutol 500 mg once every other day was started; the dosages were reduced from the standard dose due to the patient’s CKD.¹ Four days after initiation of these medications, the patient was transferred to a hospital specifically for the treatment of tuberculosis. Approximately 8 months after treatment with isoniazid, rifampin, and ethambutol, M tuberculosis could not be detected in the sputum and a chest CT revealed that the pulmonary lesions were remarkably improved. However, polymerase chain reaction of the skin biopsy specimen was still positive for M tuberculosis. It was determined that debridement of the skin lesion was needed, but the patient died from complications of deteriorating CKD 10 months after the initiation of the antituberculosis medications.

Comment

Cellulitis is a suppurative inflammation involving the subcutis.² Local tender erythema, malaise, chills, and fever may be present at the onset. Cellulitis is commonly seen by dermatologists, and it is well known that other infectious diseases such as necrotizing fasciitis, cutaneous and subcutaneous mycoses,³ and nontuberculous mycobacterial infections⁴ sometimes present as cellulitislike skin lesions. Moreover, noninfectious diseases, such as Wells syndrome, thrombophlebitis, reactive angioendotheliomatosis,⁵ cutaneous metastasis of a primary malignancy,⁶ subcutaneous panniculitislike T-cell lymphoma,⁷ Langerhans cell histiocytosis,⁸ Sweet syndrome,⁹ adult-onset Still disease,¹⁰ and fixed drug eruption caused by acetaminophen¹¹ should be excluded. These differential diagnoses and diagnostic clues of cellulitislike erythema are summarized in Table 1.^3-16

Cutaneous tuberculosis presenting as cellulitis, so-called tuberculous cellulitis, also is characterized as a clinical mimicker of cellulitis. On the other hand, histologically, it has features of cutaneous tuberculosis (eg, necrotic granuloma).^12,14,15 Tuberculous cellulitis is rare and therefore may often be misdiagnosed even in highly endemic areas. We summarized the clinical information of 5 well-documented cases of tuberculous cellulitis along with the current case in Table 2.^12-16 All of these cases had an associated disease and involved patients who were currently taking oral corticosteroids. If a patient undergoing immunosuppressive therapy develops cellulitislike erythema, tuberculous cellulitis should be considered in the differential diagnosis.

Cutaneous tuberculosis generally is classified into 4 types according to the mechanism of disease acquisition: (1) inoculation from an exogenous source, (2) endogenous cutaneous spread contiguously or by autoinoculation, (3) hematogenous spread to the skin, and (4) tuberculids. In our case, it was suspected that the cellulitislike erythema may have been caused by hematogenous spread from pulmonary tuberculosis. Considering that negative reactions to purified protein derivative (tuberculin) skin tests often are observed in cases of miliary tuberculosis (widespread dissemination of M tuberculosis to 2 or more organs via hematogenous spread), we suspected that our patient could proceed to miliary tuberculosis; in fact, a case was reported in which miliary tuberculosis emerged approximately 3 weeks after the onset of erythema,¹³ as observed in the present case. Therefore, erythema in the setting of tuberculosis may be a predictor of miliary tuberculosis. The types of cutaneous lesions caused by tuberculosis infection also are dependent on multiple host factors.² Cutaneous tuberculosis with an atypical clinical appearance has become more common because of the increasing number of immunocompromised patients.¹⁷

In addition, most cases of cutaneous tuberculosis are not associated with pain. Generally, tuberculous cellulitis also causes nontender erythematous plaques or nodules.² However, in some cases of tuberculous cellulitis, including our case, tender skin lesions have been reported.^12-14 Therefore, this symptom is not a sensitive factor for differential diagnosis.

We suggest that tuberculous cellulitis should always be included in the differential diagnosis of a cellulitislike rash with or without pain if the skin lesion is not improved despite antibiotic therapy.

SCOTTSDALE, ARIZ. – Although cost-effective, a mobile phone appointment reminder service only minimally increased attendance rates at dermatology outpatient clinics, according to a large longitudinal study.

“There was a small, statistically significant increase in attendance at the adult dermatology clinic, but there was very little effect at satellite and specialty dermatology clinics,” said Dr. Noori Kim of Johns Hopkins University in Baltimore.

Baseline attendance rates were high, exceeding 80%, so perhaps mobile phone appointment reminders have little effect in that setting, she said. In addition, most reminders were by phone call, not text, which could have limited their efficacy if patients did not answer the phone or listen to their voicemail, Dr. Kim added during an oral presentation at the annual meeting of the Society for Investigative Dermatology.

©Hocus Focus Studio/iStockphoto.com

When patients miss medical appointments, it’s usually because they forget them. In this study, the first to assess mobile phone appointment reminders in dermatology, the investigators compared daily attendance at Johns Hopkins outpatient dermatology clinics before and after implementing an automated mobile phone appointment reminder system. The baseline time period without the service spanned four months in 2014, while the comparison period with the system covered the same four-month period a year later.

Patients kept 90% of 11,455 dermatology appointments scheduled during the pre-service period. A year later, the attendance rate was nearly identical, at 89%. Likewise, there were no statistically significant changes in attendance at Johns Hopkins specialty, satellite, pediatric dermatology, and pediatric laser clinics.

In contrast, attendance at the adult dermatology clinic rose by about three percentage points after the service was implemented, from 81% (2,530 visits attended of 3,141 scheduled) to 84% (2,965 visits attended of 3,533 scheduled), and the difference was statistically significant.

“About 88% of reminders were answered across sites, with little variance. The cost was about $5,500 for a 17-month period,” Dr. Kim said. She noted that 71% of patients opted into the service at the adult clinic with the increased attendance rate, compared with about 30% of patients at the other clinics that showed no statistically significant increase in attendance rates.

The “strong continuity already present between patients and providers” and high baseline attendance rates might have limited any effects of mobile phone messaging at these other clinics, she said. Attendance rates also did not change significantly at three Johns Hopkins dermatology clinics that never implemented mobile phone reminders, she noted.

Dr. Kim reported no funding sources and had no disclosures.

SCOTTSDALE, ARIZ. – Although cost-effective, a mobile phone appointment reminder service only minimally increased attendance rates at dermatology outpatient clinics, according to a large longitudinal study.

“There was a small, statistically significant increase in attendance at the adult dermatology clinic, but there was very little effect at satellite and specialty dermatology clinics,” said Dr. Noori Kim of Johns Hopkins University in Baltimore.

Baseline attendance rates were high, exceeding 80%, so perhaps mobile phone appointment reminders have little effect in that setting, she said. In addition, most reminders were by phone call, not text, which could have limited their efficacy if patients did not answer the phone or listen to their voicemail, Dr. Kim added during an oral presentation at the annual meeting of the Society for Investigative Dermatology.

©Hocus Focus Studio/iStockphoto.com

When patients miss medical appointments, it’s usually because they forget them. In this study, the first to assess mobile phone appointment reminders in dermatology, the investigators compared daily attendance at Johns Hopkins outpatient dermatology clinics before and after implementing an automated mobile phone appointment reminder system. The baseline time period without the service spanned four months in 2014, while the comparison period with the system covered the same four-month period a year later.

Patients kept 90% of 11,455 dermatology appointments scheduled during the pre-service period. A year later, the attendance rate was nearly identical, at 89%. Likewise, there were no statistically significant changes in attendance at Johns Hopkins specialty, satellite, pediatric dermatology, and pediatric laser clinics.

In contrast, attendance at the adult dermatology clinic rose by about three percentage points after the service was implemented, from 81% (2,530 visits attended of 3,141 scheduled) to 84% (2,965 visits attended of 3,533 scheduled), and the difference was statistically significant.

“About 88% of reminders were answered across sites, with little variance. The cost was about $5,500 for a 17-month period,” Dr. Kim said. She noted that 71% of patients opted into the service at the adult clinic with the increased attendance rate, compared with about 30% of patients at the other clinics that showed no statistically significant increase in attendance rates.

The “strong continuity already present between patients and providers” and high baseline attendance rates might have limited any effects of mobile phone messaging at these other clinics, she said. Attendance rates also did not change significantly at three Johns Hopkins dermatology clinics that never implemented mobile phone reminders, she noted.

Dr. Kim reported no funding sources and had no disclosures.

SCOTTSDALE, ARIZ. – Although cost-effective, a mobile phone appointment reminder service only minimally increased attendance rates at dermatology outpatient clinics, according to a large longitudinal study.

“There was a small, statistically significant increase in attendance at the adult dermatology clinic, but there was very little effect at satellite and specialty dermatology clinics,” said Dr. Noori Kim of Johns Hopkins University in Baltimore.

Baseline attendance rates were high, exceeding 80%, so perhaps mobile phone appointment reminders have little effect in that setting, she said. In addition, most reminders were by phone call, not text, which could have limited their efficacy if patients did not answer the phone or listen to their voicemail, Dr. Kim added during an oral presentation at the annual meeting of the Society for Investigative Dermatology.

©Hocus Focus Studio/iStockphoto.com

When patients miss medical appointments, it’s usually because they forget them. In this study, the first to assess mobile phone appointment reminders in dermatology, the investigators compared daily attendance at Johns Hopkins outpatient dermatology clinics before and after implementing an automated mobile phone appointment reminder system. The baseline time period without the service spanned four months in 2014, while the comparison period with the system covered the same four-month period a year later.

Patients kept 90% of 11,455 dermatology appointments scheduled during the pre-service period. A year later, the attendance rate was nearly identical, at 89%. Likewise, there were no statistically significant changes in attendance at Johns Hopkins specialty, satellite, pediatric dermatology, and pediatric laser clinics.

In contrast, attendance at the adult dermatology clinic rose by about three percentage points after the service was implemented, from 81% (2,530 visits attended of 3,141 scheduled) to 84% (2,965 visits attended of 3,533 scheduled), and the difference was statistically significant.

“About 88% of reminders were answered across sites, with little variance. The cost was about $5,500 for a 17-month period,” Dr. Kim said. She noted that 71% of patients opted into the service at the adult clinic with the increased attendance rate, compared with about 30% of patients at the other clinics that showed no statistically significant increase in attendance rates.

The “strong continuity already present between patients and providers” and high baseline attendance rates might have limited any effects of mobile phone messaging at these other clinics, she said. Attendance rates also did not change significantly at three Johns Hopkins dermatology clinics that never implemented mobile phone reminders, she noted.

Dr. Kim reported no funding sources and had no disclosures.

The cost of end-of-life care for Americans on traditional Medicare is higher for those in their early 70s than for beneficiaries in their 80s or 90s, according to the Kaiser Family Foundation.

In 2014, the per-capita cost of care peaked at $43,353 for those who died at age 73, compared with $36,841 who died at age 80 and $27,779 for 90-year-old decedents, Kaiser found in its analysis of claims data from the Centers for Medicare & Medicaid Services Chronic Conditions Data Warehouse.

“This is a pattern we weren’t really expecting to see,” Juliette Cubanski, associate director of the program on Medicare policy for Kaiser, said in an article on the findings distributed by Kaiser Health News. “It kind of goes against the notion that doctors are throwing everything including the kitchen sink at people at the end of life regardless of how old they are,” she added.

The trend was quite different, and much less costly, for those who lived through the entire year. Their per-capita cost of care started at $5,271 for 66-year-olds and peaked at $14,620 for those aged 97. Medicare per capita spending for all decedents was nearly four times higher, at $34,529, than the $9,121 spent for each beneficiary who survived the year, the Kaiser report showed.

The largest share of that difference came from inpatient hospital care, which was 51% of decedents’ per-capita cost but only 27% for survivors. The cost for each group: $17,574 for decedents and $2,497 for survivors, according to Kaiser, which pointed out that its analysis covered only traditional Medicare beneficiaries during the calendar year in which they died and did not include spending in the full 12 months before their deaths.

The gap between decedents and survivors has narrowed in recent years. The growth rate from 2000 – when spending was $19,130 – to 2014 was 4.3% a year for decedents, while spending for survivors rose 5.5% annually from its $4,322 starting level at the turn of the century, the report noted.

[email protected]

The cost of end-of-life care for Americans on traditional Medicare is higher for those in their early 70s than for beneficiaries in their 80s or 90s, according to the Kaiser Family Foundation.

In 2014, the per-capita cost of care peaked at $43,353 for those who died at age 73, compared with $36,841 who died at age 80 and $27,779 for 90-year-old decedents, Kaiser found in its analysis of claims data from the Centers for Medicare & Medicaid Services Chronic Conditions Data Warehouse.

“This is a pattern we weren’t really expecting to see,” Juliette Cubanski, associate director of the program on Medicare policy for Kaiser, said in an article on the findings distributed by Kaiser Health News. “It kind of goes against the notion that doctors are throwing everything including the kitchen sink at people at the end of life regardless of how old they are,” she added.

The trend was quite different, and much less costly, for those who lived through the entire year. Their per-capita cost of care started at $5,271 for 66-year-olds and peaked at $14,620 for those aged 97. Medicare per capita spending for all decedents was nearly four times higher, at $34,529, than the $9,121 spent for each beneficiary who survived the year, the Kaiser report showed.

The largest share of that difference came from inpatient hospital care, which was 51% of decedents’ per-capita cost but only 27% for survivors. The cost for each group: $17,574 for decedents and $2,497 for survivors, according to Kaiser, which pointed out that its analysis covered only traditional Medicare beneficiaries during the calendar year in which they died and did not include spending in the full 12 months before their deaths.

The gap between decedents and survivors has narrowed in recent years. The growth rate from 2000 – when spending was $19,130 – to 2014 was 4.3% a year for decedents, while spending for survivors rose 5.5% annually from its $4,322 starting level at the turn of the century, the report noted.

[email protected]

The cost of end-of-life care for Americans on traditional Medicare is higher for those in their early 70s than for beneficiaries in their 80s or 90s, according to the Kaiser Family Foundation.

In 2014, the per-capita cost of care peaked at $43,353 for those who died at age 73, compared with $36,841 who died at age 80 and $27,779 for 90-year-old decedents, Kaiser found in its analysis of claims data from the Centers for Medicare & Medicaid Services Chronic Conditions Data Warehouse.

“This is a pattern we weren’t really expecting to see,” Juliette Cubanski, associate director of the program on Medicare policy for Kaiser, said in an article on the findings distributed by Kaiser Health News. “It kind of goes against the notion that doctors are throwing everything including the kitchen sink at people at the end of life regardless of how old they are,” she added.

The trend was quite different, and much less costly, for those who lived through the entire year. Their per-capita cost of care started at $5,271 for 66-year-olds and peaked at $14,620 for those aged 97. Medicare per capita spending for all decedents was nearly four times higher, at $34,529, than the $9,121 spent for each beneficiary who survived the year, the Kaiser report showed.

The largest share of that difference came from inpatient hospital care, which was 51% of decedents’ per-capita cost but only 27% for survivors. The cost for each group: $17,574 for decedents and $2,497 for survivors, according to Kaiser, which pointed out that its analysis covered only traditional Medicare beneficiaries during the calendar year in which they died and did not include spending in the full 12 months before their deaths.

The gap between decedents and survivors has narrowed in recent years. The growth rate from 2000 – when spending was $19,130 – to 2014 was 4.3% a year for decedents, while spending for survivors rose 5.5% annually from its $4,322 starting level at the turn of the century, the report noted.

[email protected]

The Walter Reed Army Institute of Research (WRAIR) is teaming up with the vaccine division of Sanofi Pasteur to co-develop a Zika virus vaccine. The vaccine is one of 2 vaccines that showed promise in a test on mice; the other is being developed by Dan Barouch and colleagues of Beth Israel Deaconess Medical Center in Boston.

Data concerning the 2 vaccines effectiveness in laboratory testing were published in the June 28 issue of Nature. “These data demonstrate that protection against the Zika virus challenge can be achieved by single-shot subunit and inactivated virus vaccines in mice and that Env-specific antibody titers represent key immunologic correlates of protection,” Larocca and colleagues reported. “Our findings suggest that the development of a ZIKV vaccine for humans will likely be readily achievable.”

The WRAIR researchers developed the vaccine in close collaboration with the NIH’s National Institute of Allergy and Infectious Diseases (NIAID). The vaccine was created from a purified, inactivated Zika virus.

“[It] has been proven to be safe, effective and able to meet regulatory requirements of the U.S. Food and Drug Administration,” Army COL Stephen J. Thomas, MD, an infectious diseases physician, vaccinologist, and the WRAIR Zika program lead told DoD News. 

According to the agreement between Sanofi Pasteur and WRAIR, the organizations will share data related to the development of immunologic assays designed to measure neutralizing antibody responses following natural infection and immunization with the vaccine candidate, biologic samples generated during the performance of nonhuman primate studies, and biologic samples generated during the performance of human safety and immunogenicity studies.

In addition, the company will provide production of clinical material in compliance with current GMP (good manufacturing processes) to support phase II testing. “We’re looking at this from both a short- and long-term perspective, collaborating to get into the clinic quicker to provide a vaccine in response to the current emergency,” said John Shiver, PhD, senior vice president of R&D at Sanofi Pasteur.

David Loew, head of Sanofi Pasteur, commented,“In addition to exploring our own vaccine technology...we are looking at other pathways to get a Zika vaccine into the clinic as soon as possible”." Loew added, “This exciting collaboration with the WRAIR creates the opportunity to rapidly move forward.”

According to the NIH, later this year NIAID and WRAIR expect to start 2 clinical trials of inactivated viral vaccines, including the one described in the Nature study. The trials, each involving dozens of volunteers, will test whether the vaccines are safe and elicit an immune response in people.

The Walter Reed Army Institute of Research (WRAIR) is teaming up with the vaccine division of Sanofi Pasteur to co-develop a Zika virus vaccine. The vaccine is one of 2 vaccines that showed promise in a test on mice; the other is being developed by Dan Barouch and colleagues of Beth Israel Deaconess Medical Center in Boston.

Data concerning the 2 vaccines effectiveness in laboratory testing were published in the June 28 issue of Nature. “These data demonstrate that protection against the Zika virus challenge can be achieved by single-shot subunit and inactivated virus vaccines in mice and that Env-specific antibody titers represent key immunologic correlates of protection,” Larocca and colleagues reported. “Our findings suggest that the development of a ZIKV vaccine for humans will likely be readily achievable.”

The WRAIR researchers developed the vaccine in close collaboration with the NIH’s National Institute of Allergy and Infectious Diseases (NIAID). The vaccine was created from a purified, inactivated Zika virus.

“[It] has been proven to be safe, effective and able to meet regulatory requirements of the U.S. Food and Drug Administration,” Army COL Stephen J. Thomas, MD, an infectious diseases physician, vaccinologist, and the WRAIR Zika program lead told DoD News. 

According to the agreement between Sanofi Pasteur and WRAIR, the organizations will share data related to the development of immunologic assays designed to measure neutralizing antibody responses following natural infection and immunization with the vaccine candidate, biologic samples generated during the performance of nonhuman primate studies, and biologic samples generated during the performance of human safety and immunogenicity studies.

In addition, the company will provide production of clinical material in compliance with current GMP (good manufacturing processes) to support phase II testing. “We’re looking at this from both a short- and long-term perspective, collaborating to get into the clinic quicker to provide a vaccine in response to the current emergency,” said John Shiver, PhD, senior vice president of R&D at Sanofi Pasteur.

David Loew, head of Sanofi Pasteur, commented,“In addition to exploring our own vaccine technology...we are looking at other pathways to get a Zika vaccine into the clinic as soon as possible”." Loew added, “This exciting collaboration with the WRAIR creates the opportunity to rapidly move forward.”

According to the NIH, later this year NIAID and WRAIR expect to start 2 clinical trials of inactivated viral vaccines, including the one described in the Nature study. The trials, each involving dozens of volunteers, will test whether the vaccines are safe and elicit an immune response in people.

The Walter Reed Army Institute of Research (WRAIR) is teaming up with the vaccine division of Sanofi Pasteur to co-develop a Zika virus vaccine. The vaccine is one of 2 vaccines that showed promise in a test on mice; the other is being developed by Dan Barouch and colleagues of Beth Israel Deaconess Medical Center in Boston.

Data concerning the 2 vaccines effectiveness in laboratory testing were published in the June 28 issue of Nature. “These data demonstrate that protection against the Zika virus challenge can be achieved by single-shot subunit and inactivated virus vaccines in mice and that Env-specific antibody titers represent key immunologic correlates of protection,” Larocca and colleagues reported. “Our findings suggest that the development of a ZIKV vaccine for humans will likely be readily achievable.”

The WRAIR researchers developed the vaccine in close collaboration with the NIH’s National Institute of Allergy and Infectious Diseases (NIAID). The vaccine was created from a purified, inactivated Zika virus.

“[It] has been proven to be safe, effective and able to meet regulatory requirements of the U.S. Food and Drug Administration,” Army COL Stephen J. Thomas, MD, an infectious diseases physician, vaccinologist, and the WRAIR Zika program lead told DoD News. 

According to the agreement between Sanofi Pasteur and WRAIR, the organizations will share data related to the development of immunologic assays designed to measure neutralizing antibody responses following natural infection and immunization with the vaccine candidate, biologic samples generated during the performance of nonhuman primate studies, and biologic samples generated during the performance of human safety and immunogenicity studies.

In addition, the company will provide production of clinical material in compliance with current GMP (good manufacturing processes) to support phase II testing. “We’re looking at this from both a short- and long-term perspective, collaborating to get into the clinic quicker to provide a vaccine in response to the current emergency,” said John Shiver, PhD, senior vice president of R&D at Sanofi Pasteur.

David Loew, head of Sanofi Pasteur, commented,“In addition to exploring our own vaccine technology...we are looking at other pathways to get a Zika vaccine into the clinic as soon as possible”." Loew added, “This exciting collaboration with the WRAIR creates the opportunity to rapidly move forward.”

According to the NIH, later this year NIAID and WRAIR expect to start 2 clinical trials of inactivated viral vaccines, including the one described in the Nature study. The trials, each involving dozens of volunteers, will test whether the vaccines are safe and elicit an immune response in people.

Drug release in a cancer cell

Image courtesy of PNAS

A class of newly discovered compounds can kill multidrug-resistant lymphoma cells by blocking the cells’ defenses against drugs, according to a study published in Bioorganic & Medicinal Chemistry Letters.

Researchers found this class of molecules—called selenocompounds—could kill multidrug-resistant murine T-lymphoma cells.

In fact, 4 of the compounds triggered apoptotic events in more than 80% of the cells.

“Our research reports a new way to fight multidrug resistance in cancer,” said study author Enrique Domínguez-Álvarez, PhD, of the University of Navarra in Pamplona, Spain.

“We are realistic, and we know that much more research needs to be done, but we are excited about these promising results that open new and unexplored possibilities.”

In previous studies, Dr Domínguez-Álvarez and his colleagues discovered 57 new molecules— selenocompounds—that prevented the growth of, and even killed, cancer cells.

While reading up on similar compounds, the researchers found that some could enhance the potency of chemotherapy drugs, so they decided to investigate.

When faced with aggressive treatment, cancer cells can sometimes develop a defense mechanism called an efflux pump—a protein in the cell membrane that can push the drug back out of the cancer cell to protect it. One such protein is called ABCB1.

Dr Domínguez-Álvarez and his colleagues tested the selenocompounds to see if they stopped this mechanism from working and found that the compounds do block the ABCB1 pump, effectively shutting down the defense mechanism.

In fact, 4 of the compounds were stronger inhibitors of the ABCB1 pump than the reference inhibitor the team tested, verapamil (1.7–3.6-fold stronger).

These 4 compounds were also significantly more cytotoxic than verapamil or thioridazine. The compounds triggered apoptotic events in more than 80% of the examined multidrug-resistant mouse T-lymphoma cells.

Dr Domínguez-Álvarez and his colleagues said the next step for this research will be to synthesize similar compounds to determine the most promising derivatives.

Dependent on funding, the team will consider further steps as well, such as testing the compounds in vivo.

Drug release in a cancer cell

Image courtesy of PNAS

A class of newly discovered compounds can kill multidrug-resistant lymphoma cells by blocking the cells’ defenses against drugs, according to a study published in Bioorganic & Medicinal Chemistry Letters.

Researchers found this class of molecules—called selenocompounds—could kill multidrug-resistant murine T-lymphoma cells.

In fact, 4 of the compounds triggered apoptotic events in more than 80% of the cells.

“Our research reports a new way to fight multidrug resistance in cancer,” said study author Enrique Domínguez-Álvarez, PhD, of the University of Navarra in Pamplona, Spain.

“We are realistic, and we know that much more research needs to be done, but we are excited about these promising results that open new and unexplored possibilities.”

In previous studies, Dr Domínguez-Álvarez and his colleagues discovered 57 new molecules— selenocompounds—that prevented the growth of, and even killed, cancer cells.

While reading up on similar compounds, the researchers found that some could enhance the potency of chemotherapy drugs, so they decided to investigate.

When faced with aggressive treatment, cancer cells can sometimes develop a defense mechanism called an efflux pump—a protein in the cell membrane that can push the drug back out of the cancer cell to protect it. One such protein is called ABCB1.

Dr Domínguez-Álvarez and his colleagues tested the selenocompounds to see if they stopped this mechanism from working and found that the compounds do block the ABCB1 pump, effectively shutting down the defense mechanism.

In fact, 4 of the compounds were stronger inhibitors of the ABCB1 pump than the reference inhibitor the team tested, verapamil (1.7–3.6-fold stronger).

These 4 compounds were also significantly more cytotoxic than verapamil or thioridazine. The compounds triggered apoptotic events in more than 80% of the examined multidrug-resistant mouse T-lymphoma cells.

Dr Domínguez-Álvarez and his colleagues said the next step for this research will be to synthesize similar compounds to determine the most promising derivatives.

Dependent on funding, the team will consider further steps as well, such as testing the compounds in vivo.

Drug release in a cancer cell

Image courtesy of PNAS

A class of newly discovered compounds can kill multidrug-resistant lymphoma cells by blocking the cells’ defenses against drugs, according to a study published in Bioorganic & Medicinal Chemistry Letters.

Researchers found this class of molecules—called selenocompounds—could kill multidrug-resistant murine T-lymphoma cells.

In fact, 4 of the compounds triggered apoptotic events in more than 80% of the cells.

“Our research reports a new way to fight multidrug resistance in cancer,” said study author Enrique Domínguez-Álvarez, PhD, of the University of Navarra in Pamplona, Spain.

“We are realistic, and we know that much more research needs to be done, but we are excited about these promising results that open new and unexplored possibilities.”

In previous studies, Dr Domínguez-Álvarez and his colleagues discovered 57 new molecules— selenocompounds—that prevented the growth of, and even killed, cancer cells.

While reading up on similar compounds, the researchers found that some could enhance the potency of chemotherapy drugs, so they decided to investigate.

When faced with aggressive treatment, cancer cells can sometimes develop a defense mechanism called an efflux pump—a protein in the cell membrane that can push the drug back out of the cancer cell to protect it. One such protein is called ABCB1.

Dr Domínguez-Álvarez and his colleagues tested the selenocompounds to see if they stopped this mechanism from working and found that the compounds do block the ABCB1 pump, effectively shutting down the defense mechanism.

In fact, 4 of the compounds were stronger inhibitors of the ABCB1 pump than the reference inhibitor the team tested, verapamil (1.7–3.6-fold stronger).

These 4 compounds were also significantly more cytotoxic than verapamil or thioridazine. The compounds triggered apoptotic events in more than 80% of the examined multidrug-resistant mouse T-lymphoma cells.

Dr Domínguez-Álvarez and his colleagues said the next step for this research will be to synthesize similar compounds to determine the most promising derivatives.

Dependent on funding, the team will consider further steps as well, such as testing the compounds in vivo.

Scanning electron

micrograph of a T cell

Image from NIAID

The “asymmetric division” of T cells could provide new ways to enhance cancer immunotherapy, according to researchers.

When a T cell divides, the activity of the enzyme mTORC1, which controls protein production, splits unevenly between the progeny.

Results of a new study suggest this uneven division reprograms the daughter cells so that one goes on to become an effector T cell and the other becomes a memory T cell.

This study was published in Nature Immunology.

“One of the critical steps needed to improve cancer immunotherapy, in general, is finding out ways to make antitumor T cells persist or hang around in the body longer,” said study author Jonathan Powell, MD, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

With that in mind, Dr Powell and his colleagues analyzed murine T cells. They found that when a “mother” T cell that is naïve to immune threats encounters such a threat and divides, one of its daughter cells inherits far more mTORC1 activity than the other daughter cell.

The researchers activated mouse T cells using a virus. Once the T cells divided, the team used antibodies to detect mTORC1 activity in each of the daughter cells.

Then, the researchers sorted the daughter cells and examined their function by injecting them into mice given two identical infections and tracking the cells’ activity.

The team found the difference in mTORC1 activity levels between the daughter cells varied depending on the population of cells studied.

And the lopsided distribution of mTORC1 activity appeared to reprogram the use of energy and other metabolic activities of each daughter cell.

The cells with high levels of mTORC1 activity were found to be potently activated, killer/effector T cells, while the cells with low mTORC1 levels behaved like memory T cells, persisting for long periods of time and rapidly activating upon reinfection.

The researchers said this finding could be used to improve immunotherapy, but another aspect of this discovery is the prospect that asymmetric partitioning of mTORC1 might be widespread across cells in many biological systems.

Dr Powell said it’s possible the mechanism may help explain how stem cells develop into more specialized cells in the bone marrow, for instance, or how cells differentiate to become hair, skin, or brain cells in a growing embryo.

“We think there will be implications for biology well beyond the immune system,” he concluded.

Scanning electron

micrograph of a T cell

Image from NIAID

The “asymmetric division” of T cells could provide new ways to enhance cancer immunotherapy, according to researchers.

When a T cell divides, the activity of the enzyme mTORC1, which controls protein production, splits unevenly between the progeny.

Results of a new study suggest this uneven division reprograms the daughter cells so that one goes on to become an effector T cell and the other becomes a memory T cell.

This study was published in Nature Immunology.

“One of the critical steps needed to improve cancer immunotherapy, in general, is finding out ways to make antitumor T cells persist or hang around in the body longer,” said study author Jonathan Powell, MD, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

With that in mind, Dr Powell and his colleagues analyzed murine T cells. They found that when a “mother” T cell that is naïve to immune threats encounters such a threat and divides, one of its daughter cells inherits far more mTORC1 activity than the other daughter cell.

The researchers activated mouse T cells using a virus. Once the T cells divided, the team used antibodies to detect mTORC1 activity in each of the daughter cells.

Then, the researchers sorted the daughter cells and examined their function by injecting them into mice given two identical infections and tracking the cells’ activity.

The team found the difference in mTORC1 activity levels between the daughter cells varied depending on the population of cells studied.

And the lopsided distribution of mTORC1 activity appeared to reprogram the use of energy and other metabolic activities of each daughter cell.

The cells with high levels of mTORC1 activity were found to be potently activated, killer/effector T cells, while the cells with low mTORC1 levels behaved like memory T cells, persisting for long periods of time and rapidly activating upon reinfection.

The researchers said this finding could be used to improve immunotherapy, but another aspect of this discovery is the prospect that asymmetric partitioning of mTORC1 might be widespread across cells in many biological systems.

Dr Powell said it’s possible the mechanism may help explain how stem cells develop into more specialized cells in the bone marrow, for instance, or how cells differentiate to become hair, skin, or brain cells in a growing embryo.

“We think there will be implications for biology well beyond the immune system,” he concluded.

Scanning electron

micrograph of a T cell

Image from NIAID

The “asymmetric division” of T cells could provide new ways to enhance cancer immunotherapy, according to researchers.

When a T cell divides, the activity of the enzyme mTORC1, which controls protein production, splits unevenly between the progeny.

Results of a new study suggest this uneven division reprograms the daughter cells so that one goes on to become an effector T cell and the other becomes a memory T cell.

This study was published in Nature Immunology.

“One of the critical steps needed to improve cancer immunotherapy, in general, is finding out ways to make antitumor T cells persist or hang around in the body longer,” said study author Jonathan Powell, MD, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

With that in mind, Dr Powell and his colleagues analyzed murine T cells. They found that when a “mother” T cell that is naïve to immune threats encounters such a threat and divides, one of its daughter cells inherits far more mTORC1 activity than the other daughter cell.

The researchers activated mouse T cells using a virus. Once the T cells divided, the team used antibodies to detect mTORC1 activity in each of the daughter cells.

Then, the researchers sorted the daughter cells and examined their function by injecting them into mice given two identical infections and tracking the cells’ activity.

The team found the difference in mTORC1 activity levels between the daughter cells varied depending on the population of cells studied.

And the lopsided distribution of mTORC1 activity appeared to reprogram the use of energy and other metabolic activities of each daughter cell.

The cells with high levels of mTORC1 activity were found to be potently activated, killer/effector T cells, while the cells with low mTORC1 levels behaved like memory T cells, persisting for long periods of time and rapidly activating upon reinfection.

The researchers said this finding could be used to improve immunotherapy, but another aspect of this discovery is the prospect that asymmetric partitioning of mTORC1 might be widespread across cells in many biological systems.

Dr Powell said it’s possible the mechanism may help explain how stem cells develop into more specialized cells in the bone marrow, for instance, or how cells differentiate to become hair, skin, or brain cells in a growing embryo.

“We think there will be implications for biology well beyond the immune system,” he concluded.