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BackgroundIFNL4 genetic variants that are strongly associated with clearance of hepatitis C virus have been linked to risk of certain opportunistic infections (OIs) and cancers, including Kaposi sarcoma, cytomegalovirus infection, and herpes simplex virus infection. As the interferon (IFN) λ family plays a role in response to viral, bacterial, and fungal infections, IFNL4 genotype might affect risk for a wide range of OIs/cancers.MethodsWe examined associations between genotype for the functional IFNL4 rs368234815 polymorphism and incidence of 16 OIs/cancers among 2310 men with human immunodeficiency virus (2038 white; 272 black) enrolled in the Multicenter AIDS Cohort Study during 1984-1990. Our primary analyses used Cox proportional hazards models adjusted for self-reported racial ancestry to estimate hazard ratios with 95% confidence intervals, comparing participants with the genotypes that generate IFN-λ4 and those with the genotype that abrogates IFN-λ4. We censored follow-up at the introduction of highly effective antiretroviral therapies.ResultsWe found no statistically significant association between IFNL4 genotype and the incidence of Kaposi sarcoma (hazard ratio, 0.92 [95% confidence interval, .76-1.11]), cytomegalovirus infection (0.94 [.71-1.24]), herpes simplex virus infection (1.37 [.68-2.93]), or any other OI/cancer. We observed consistent results using additive genetic models and after controlling for CD4 cell count through time-dependent adjustment or restriction to participants with a low CD4 cell count.ConclusionsThe absence of associations between IFNL4 genotype and these OIs/cancers provides evidence that this gene does not affect the risk of disease from opportunistic pathogens.

Background & aimsGallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear.MethodsWe pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study.ResultsDuring 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR ≥5 vs. 0 births 1.72; 95% CI 1.25-2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06-1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04-1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09-1.31) and EHBDC (HR 1.11; 95% CI 1.01-1.22) in Asian women only.ConclusionWe observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography.Lay summaryOur findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic bile duct cancer and extrahepatic bile duct cancer. We did not see this same association in women from Western countries. Age at menopause was not associated with the risk of any biliary tract cancers.

Background Males have 2–3-fold greater risk of cancer than females at most shared anatomic sites, possibly reflecting enhanced immune surveillance against cancer in females. We examined whether these sex differences remained among immunocompromised adults. Methods Using the Transplant Cancer Match (TCM) study, we estimated the male-to-female incidence rate ratio in TCM (M:F IRRTransplant) for 15 cancer sites diagnosed between 1995 and 2017 using Poisson regression. Male to female IRRs in the general population (M:F IRRGP) were calculated using expected cancer counts from the Surveillance, Epidemiology, and End Results Program, standardized to the transplant population on age, race and ethnicity, and diagnosis year. Male to female IRRs were compared using a chi-square test. Results Among 343 802 solid organ transplants, 211 206 (61.4%) were among men and 132 596 (38.6%) among women. An excess cancer incidence in males was seen in transplant recipients, but the sex difference was attenuated for cancers of the lip (M:F IRRTransplant: 1.81 vs M:F IRRGP: 3.96; P  <  .0001), stomach (1.51 vs 2.09; P  =  .002), colorectum (0.98 vs 1.43; P  <  .0001), liver (2.39 vs 3.44; P  =  .002), kidney (1.67 vs 2.24; P  <  .0001), bladder (2.02 vs 4.19; P  <  .0001), Kaposi sarcoma (1.79 vs 3.26; P  =  .0009), and non-Hodgkin lymphoma (1.34 vs 1.64; P  <  .0001). The M:F IRRTransplant was not statistically different from the M:F IRRGP for other cancer sites. Conclusions Although male solid organ transplant recipients have higher cancer incidence than female recipients, the attenuation in the male to female ratio for many cancers studied relative to the general population might suggest the importance of immunosurveillance, with some loss of advantage in female recipients due to immunosuppression after transplantation. [ABSTRACT FROM AUTHOR]

Hallux sesamoid injuries are well described and can be debilitating and chronically disabling. The role of orthobiologics such as platelet-rich plasma (PRP) in sesamoid injuries has not been reported. This study describes three cases of recalcitrant hallux sesamoid injuries in teenage athletes who returned to impact activities, pain free, following one treatment of PRP. This is a case-series study describing three teenage athletes presenting to a tertiary level pediatric sports medicine practice with chronic hallux sesamoid injuries. The three patients (two female, one male) described in this case series were 13-, 16-, and 17-year-old athletes. Their primary sports were ballet, basketball, and Irish step dance, respectively. All three athletes received PRP: two received unilateral treatment (one tibial sesamoid, one fibular sesamoid) and one received treatment to bilateral tibial sesamoids. The average duration of symptoms prior to PRP was 52.5 weeks (14–128 weeks). The average time out of their primary sport was 48.7 weeks (20–78 weeks). Three of the 4 sesamoids treated with PRP were tibial sesamoids. Each site of injury was treated with one treatment of leukocyte-rich PRP. All three athletes were cleared to return to impact activities such as running and jumping at 6–9 weeks following PRP, specifically 9 weeks after the final PRP injection for the patient who underwent bilateral treatments. In the three cases provided of sesamoid injuries treated with PRP, the time to return to impact activities was less than reported for athletes not treated with PRP. Acknowledging that other management factors likely contributed to return to impact activities, this case series sets the groundwork for future research investigating the role of PRP with needle fenestration in the treatment of sesamoid injuries. [ABSTRACT FROM AUTHOR]