Background Accumulating evidence indicates important gender differences in substance use disorders. Little is known, however, about gender differences and opioid use disorders. Objectives To compare demographic characteristics, substance use severity, and other associated areas of functioning (as measured by the Addiction Severity Index–Lite; ASI) among opioid-dependent men and women participating in a multisite effectiveness trial. Methods Participants were 892 adults screened for the National Institute on Drug Abuse’s (NIDA) Clinical Trials Network (CTN) investigation of the effectiveness of two buprenorphine tapering schedules. Results The majority of men and women tested positive for oxycodone (68% and 65%, respectively) and morphine (89% each). More women than men tested positive for amphetamines (4% vs. 1%, p<0.01), methamphetamine (11% vs. 4%, p<0.01) and phencyclidine (8% vs. 4%, p=0.02). More men than women tested positive for methadone (11% vs. 6%, p=0.05) and marijuana (22% vs. 15%, p=0.03). Craving for opioids was significantly higher among women (p<0.01). Men evidenced higher alcohol (p<0.01) and legal (p=0.04) ASI composite scores, whereas women had higher drug (p<0.01), employment (p<0.01), family (p<0.01), medical (p<0.01), and psychiatric (p<0.01) ASI composite scores. Women endorsed significantly more current and past medical problems. Conclusions Important gender differences in the clinical profiles of opioid-dependent individuals were observed with regard to substance use severity, craving, medical conditions, and impairment in associated areas of functioning. The findings enhance understanding of the characteristics of treatment-seeking men and women with opioid dependence, and may be useful in improving identification, prevention, and treatment efforts for this challenging and growing population.

Cancer-associated thrombocytosis and high concentrations of circulating transforming growth factor–β1 (TGF-β1) are frequently observed in patients with progressive cancers. Using genetic and pharmacological approaches, we show a direct link between thrombin catalytic activity and release of mature TGF-β1 from platelets. We found that thrombin cleaves glycoprotein A repetitions predominant (GARP), a cell surface docking receptor for latent TGF-β1 (LTGF-β1) on platelets, resulting in liberation of active TGF-β1 from the GARP–LTGF-β1 complex. Furthermore, systemic inhibition of thrombin obliterates TGF-β1 maturation in platelet releasate and rewires the tumor microenvironment toward favorable antitumor immunity, which translates into efficient cancer control either alone or in combination with programmed cell death 1–based immune checkpoint blockade therapy. Last, we demonstrate that soluble GARP and GARP–LTGF-β1 complex are present in the circulation of patients with cancer. Together, our data reveal a mechanism of cancer immune evasion that involves thrombin-mediated GARP cleavage and the subsequent TGF-β1 release from platelets. We propose that blockade of GARP cleavage is a valuable therapeutic strategy to overcome cancer’s resistance to immunotherapy.

Limited evidence supports use of oral antibiotics for Enterobacteriaceae-associated bacteremic urinary tract infection. This retrospective cohort study found no statistically significant difference in the composite outcome of treatment failure in patients who received exclusively intravenous versus intravenous/oral antibiotics for the treatment of bacteremic urinary tract infections.

While the incidence of pediatric kidney stones appears to be increasing, little is known about the demographic, clinical, laboratory, imaging, and management variables in this patient population. We sought to describe various characteristics of our stone-forming pediatric population. To that end, we retrospectively reviewed the charts of pediatric patients with nephrolithiasis confirmed by imaging. Data were collected on multiple variables from each patient and analyzed for trends. For body mass index (BMI) controls, data from the general pediatrics population similar to our nephrolithiasis population were used. Data on 155 pediatric nephrolithiasis patients were analyzed. Of the 54 calculi available for analysis, 98% were calcium-based. Low urine volume, elevated supersaturation of calcium phosphate, elevated supersaturation of calcium oxalate, and hypercalciuria were the most commonly identified abnormalities on analysis of 24-hour urine collections. Our stone-forming population did not have a higher BMI than our general pediatrics population, making it unlikely that obesity is a risk factor for nephrolithiasis in children. More girls presented with their first stone during adolescence, suggesting a role for reproductive hormones contributing to stone risk, while boys tended to present more commonly at a younger age, though this did not reach statistical significance. These intriguing findings warrant further investigation.