Testosterone Therapy Associated with Adverse Outcomes After Coronary Angiography

By Amy Orciari Herman

Testosterone supplementation is associated with a significantly increased risk for cardiovascular events among older male angiography patients, according to a retrospective study in JAMA.

Researchers examined outcomes among some 8700 veterans who'd undergone coronary angiography and had total testosterone levels below 300 ng/mL. Some 14% began testosterone therapy (usually patch or injection) at a median 1.5 years after angiography.

At 3 years, the primary outcome — a composite of all-cause mortality, MI, and ischemic stroke — had occurred in 26% of the testosterone group and 20% of the untreated group. After adjustment for coronary artery disease and other confounders, the relative risk for the primary outcome was 30% higher with testosterone therapy.

Harlan Krumholz, a cardiologist with NEJM Journal Watch, commented: "Amid the onslaught of ads promoting testosterone, this study provides cautionary information — and reminds us that chasing surrogate outcomes, like testosterone levels, may actually cause harm. We need outcomes studies to understand better the safety of these products."

Management of Children with Marfan Syndrome Mary Wu Chang, MD Reviewing Tinkle BT et al., Pediatrics 2013 Oct 132:e1059 Guidance on diagnosis, referral, and patient advising of these children.

Marfan syndrome, a multisystem connective tissue disorder affecting the ocular, musculoskeletal, and cardiovascular systems, occurs in 1 in 5000 individuals. Transmission is autosomal dominant, but one quarter of cases result from new mutations. Most cases are caused by defects in FBN1, the gene that encodes for fibrillin. The phenotypical spectrum is wide, and features can present at any age. These authors offer guidance on recognizing and managing Marfan syndrome in children. Diagnosis is clinically based utilizing well-defined (revised Ghent) criteria. Aortic root aneurysm and ectopia lentis (dislocated lens) are considered the cardinal features. In the absence of family history, the presence of these two features is sufficient for the unequivocal diagnosis of Marfan syndrome. Genetic testing is reserved for patients in whom there is strong clinical suspicion but full criteria are missing. Because some features are age-dependent, children and adolescents may be categorized as “potential Marfan syndrome” and evaluated periodically in lieu of genetic testing. Excessive linear growth of the long bones is characteristic. Patients are taller than expected given familial height (mean final height: males, 75 inches; females, 69 inches). Growth of tubular bones is accelerated, leading to disproportionate features, including arachnodactyly (long, slender fingers) and pectus excavatum/carinatum (sunken or protruding chest). Scoliosis occurs in over half of patients. Facial features can be variable, subtle, and evolve over time. Ocular manifestations include ectopia lentis, retinal detachment, glaucoma, and cataracts. Cardiovascular complications — aortic dilation/rupture, aortic valve insufficiency, and pulmonary artery enlargement — are the major source of morbidity and mortality and require lifelong monitoring. Aortic dilation is progressive; it is usually discernible before age 18 but can occur at any age. Mitral valve prolapse with congestive heart failure is the leading cause of cardiovascular morbidity and mortality in young children. Stretch marks and inguinal hernias are common, despite the slender habitus. Recurrent hernias or hernias at surgical repair sites are a hallmark of Marfan syndrome and other connective tissue disorders. Contact and competitive sports, activity requiring “burst” movement (e.g., sprinting), and intense static exertion (e.g., weight-lifting) should be avoided due to high cardiovascular risk. High-impact sports (e.g., boxing) carry a high risk for ocular trauma. Intelligence is normal, and life expectancy can approach normal range.

Management of Children with Marfan Syndrome Mary Wu Chang, MD Reviewing Tinkle BT et al., Pediatrics 2013 Oct 132:e1059 Guidance on diagnosis, referral, and patient advising of these children.

Marfan syndrome, a multisystem connective tissue disorder affecting the ocular, musculoskeletal, and cardiovascular systems, occurs in 1 in 5000 individuals. Transmission is autosomal dominant, but one quarter of cases result from new mutations. Most cases are caused by defects in FBN1, the gene that encodes for fibrillin. The phenotypical spectrum is wide, and features can present at any age. These authors offer guidance on recognizing and managing Marfan syndrome in children. Diagnosis is clinically based utilizing well-defined (revised Ghent) criteria. Aortic root aneurysm and ectopia lentis (dislocated lens) are considered the cardinal features. In the absence of family history, the presence of these two features is sufficient for the unequivocal diagnosis of Marfan syndrome. Genetic testing is reserved for patients in whom there is strong clinical suspicion but full criteria are missing. Because some features are age-dependent, children and adolescents may be categorized as “potential Marfan syndrome” and evaluated periodically in lieu of genetic testing. Excessive linear growth of the long bones is characteristic. Patients are taller than expected given familial height (mean final height: males, 75 inches; females, 69 inches). Growth of tubular bones is accelerated, leading to disproportionate features, including arachnodactyly (long, slender fingers) and pectus excavatum/carinatum (sunken or protruding chest). Scoliosis occurs in over half of patients. Facial features can be variable, subtle, and evolve over time. Ocular manifestations include ectopia lentis, retinal detachment, glaucoma, and cataracts. Cardiovascular complications — aortic dilation/rupture, aortic valve insufficiency, and pulmonary artery enlargement — are the major source of morbidity and mortality and require lifelong monitoring. Aortic dilation is progressive; it is usually discernible before age 18 but can occur at any age. Mitral valve prolapse with congestive heart failure is the leading cause of cardiovascular morbidity and mortality in young children. Stretch marks and inguinal hernias are common, despite the slender habitus. Recurrent hernias or hernias at surgical repair sites are a hallmark of Marfan syndrome and other connective tissue disorders. Contact and competitive sports, activity requiring “burst” movement (e.g., sprinting), and intense static exertion (e.g., weight-lifting) should be avoided due to high cardiovascular risk. High-impact sports (e.g., boxing) carry a high risk for ocular trauma. Intelligence is normal, and life expectancy can approach normal range.

Sofosbuvir and Ledipasvir Phase II, and When Small Studies Make a Big Impact Dr. Paul Sax highlights a phase II study that yielded “pretty spectacular results” for treating hepatitis C in his HIV and ID Observations blog.

According to the results of a recent study, an interferon-free regimen — a fixed-dose combination of sofosbuvir and ledipasvir — has the potential to cure most patients with genotype-1 HCV infection. Although we should avoid overstating the importance of this particular treatment approach, says Dr. Paul Sax in HIV and ID Observations, there is reason to be “ecstatic” about these findings.

Dolutegravir Regimen Superior to Standard Combination ART for HIV

By Kelly Young

An HIV treatment regimen of dolutegravir plus abacavir-lamivudine is superior to a currently recommended combination pill, according to a phase III trial published in the New England Journal of Medicine.

In the manufacturer-conducted SINGLE study, roughly 850 treatment-naive patients were randomized to dolutegravir (an integrase inhibitor) plus abacavir-lamivudine or to efavirenz-tenofovir disoproxil fumarate-emtricitabine (EFV/TDF/FTC). After 48 weeks of treatment, the dolutegravir group had a higher percentage of patients with HIV-1 RNA levels under 50 copies per milliliter (88% vs. 81%). The number of adverse events was lower in the dolutegravir group.

In his blog HIV and ID Observations, Paul Sax writes: "Up until the SINGLE study, one could argue that EFV-based treatments — especially TDF/FTC/EFV — represented the gold standard against which all other regimens must compete. Has that now changed? I think it has."

Dolutegravir Regimen Superior to Standard Combination ART for HIV

By Kelly Young

An HIV treatment regimen of dolutegravir plus abacavir-lamivudine is superior to a currently recommended combination pill, according to a phase III trial published in the New England Journal of Medicine.

In the manufacturer-conducted SINGLE study, roughly 850 treatment-naive patients were randomized to dolutegravir (an integrase inhibitor) plus abacavir-lamivudine or to efavirenz-tenofovir disoproxil fumarate-emtricitabine (EFV/TDF/FTC). After 48 weeks of treatment, the dolutegravir group had a higher percentage of patients with HIV-1 RNA levels under 50 copies per milliliter (88% vs. 81%). The number of adverse events was lower in the dolutegravir group.

In his blog HIV and ID Observations, Paul Sax writes: "Up until the SINGLE study, one could argue that EFV-based treatments — especially TDF/FTC/EFV — represented the gold standard against which all other regimens must compete. Has that now changed? I think it has."

Large Study Shows No Increase in Overall Cancer Risk in Children Born After Assisted Reproductive Technology Robert W. Rebar, MD Reviewing Williams CL et al., N Engl J Med 2013 Nov 7; 369:1819 Risk for certain rare neoplasms may be modestly increased, but this must be confirmed in future studies.

Children born after assisted reproductive technology (ART) are at slightly increased risk for prematurity, low birth weight, and congenital malformations, but information about long-term risks for rare but serious diseases is sparse. In a population-based study, investigators linked data on all children born after ART in Britain from 1992 through 2008 with national registry data on childhood tumors to determine incidence of cancer before age 15 in these children compared with those in the general population during the same period. The cohort consisted of 106,000 children born after nondonor ART (mean follow-up, 6.6 years). A total of 108 cancers were identified in this group compared with 109.7 expected cancers (standardized incidence ratio [SIR], 0.98; 95% confidence interval, 0.81–1.19). Risks for leukemia, neuroblastoma, retinoblastoma, central nervous system tumors, renal tumors, and germ cell tumors were not increased. Excess risks for hepatoblastoma (SIR, 3.64; 95% CI, 1.34–7.93) and rhabdomyosarcoma (SIR, 2.62; 95% CI 1.26–4.82) were observed, and were not associated with imprinting disorders. Hepatoblastoma was associated with low birth weight.

Large Study Shows No Increase in Overall Cancer Risk in Children Born After Assisted Reproductive Technology Robert W. Rebar, MD Reviewing Williams CL et al., N Engl J Med 2013 Nov 7; 369:1819 Risk for certain rare neoplasms may be modestly increased, but this must be confirmed in future studies.

Children born after assisted reproductive technology (ART) are at slightly increased risk for prematurity, low birth weight, and congenital malformations, but information about long-term risks for rare but serious diseases is sparse. In a population-based study, investigators linked data on all children born after ART in Britain from 1992 through 2008 with national registry data on childhood tumors to determine incidence of cancer before age 15 in these children compared with those in the general population during the same period. The cohort consisted of 106,000 children born after nondonor ART (mean follow-up, 6.6 years). A total of 108 cancers were identified in this group compared with 109.7 expected cancers (standardized incidence ratio [SIR], 0.98; 95% confidence interval, 0.81–1.19). Risks for leukemia, neuroblastoma, retinoblastoma, central nervous system tumors, renal tumors, and germ cell tumors were not increased. Excess risks for hepatoblastoma (SIR, 3.64; 95% CI, 1.34–7.93) and rhabdomyosarcoma (SIR, 2.62; 95% CI 1.26–4.82) were observed, and were not associated with imprinting disorders. Hepatoblastoma was associated with low birth weight.