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1. Incidence of sexually transmitted infections and association with behavioural factors: Time‐to‐event analysis of a large pre‐exposure prophylaxis ( PrEP ) cohort

   https://doi.org/10.1111/hiv.13543  

   Hovaguimian, Frédérique ; Kouyos, Roger D. ; Kusejko, Katharina ; Schmidt, Axel J. ; Tarr, Philip E. ; Bernasconi, Enos ; Braun, Dominique L. ; Calmy, Alexandra ; Notter, Julia ; Stoeckle, Marcel ; et al ( September 2023 , HIV Medicine)

   Our objective was to obtain long‐term data on the incidence of sexually transmitted infections (STIs) and their association with behavioural factors after widespread pre‐exposure prophylaxis (PrEP) implementation.

   This was a time‐to‐event analysis of a national PrEP cohort in Switzerland (SwissPrEPared study). Participants were people without HIV interested in taking PrEP with at least two STI screening visits. Primary outcomes were incidence rate of gonorrhoea, chlamydia, and syphilis. The association between behavioural factors and STI diagnosis was expressed using hazard ratios. We adjusted for testing frequency and calendar year.

   This analysis included 3907 participants enrolled between April 2019 and April 2022, yielding 3815.7 person‐years of follow‐up for gonorrhoea (15 134 screenings), 3802.5 for chlamydia (15 141 screenings), and 3858.6 for syphilis (15 001 screenings). The median age was 39 years (interquartile range [IQR] 32–47), 93.8% (n = 3664) identified as men who have sex with men (MSM). The incidence was 22.8 (95% confidence interval [CI] 21.3–24.4) per 100 person‐years for gonorrhoea, 26.3 (95% CI 24.7–28.0) for chlamydia, and 4.4 (95% CI 3.8–5.1) for syphilis. Yearly incidence rates decreased between 2019 (all bacterial STIs: 81.6; 95% CI 59.1–109.9) and 2022 (all bacterial STIs: 49.8; 95% CI 44.6–55.3). Participants reporting chemsex substance use were at higher risk of incident STIs, as were those reporting multiple sexual partners. Younger age was associated with a higher risk of gonorrhoea and chlamydia.

   Incidence rates of bacterial STIs decreased over time. Young MSM, those with multiple partners, and those using chemsex substances were at increased risk of STIs.

    

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2. Factors Associated With Nonadherence to Lung Cancer Screening Across Multiple Screening Time Points

   https://doi.org/10.1001/jamanetworkopen.2023.15250  

   Lin, Yannan ; Liang, Li-Jung ; Ding, Ruiwen ; Prosper, Ashley Elizabeth ; Aberle, Denise R. ; Hsu, William ( May 2023 , JAMA Network Open)

   Screening with low-dose computed tomography (CT) has been shown to reduce mortality from lung cancer in randomized clinical trials in which the rate of adherence to follow-up recommendations was over 90%; however, adherence to Lung Computed Tomography Screening Reporting & Data System (Lung-RADS) recommendations has been low in practice. Identifying patients who are at risk of being nonadherent to screening recommendations may enable personalized outreach to improve overall screening adherence.

   To identify factors associated with patient nonadherence to Lung-RADS recommendations across multiple screening time points.

   This cohort study was conducted at a single US academic medical center across 10 geographically distributed sites where lung cancer screening is offered. The study enrolled individuals who underwent low-dose CT screening for lung cancer between July 31, 2013, and November 30, 2021.

   Low-dose CT screening for lung cancer.

   The main outcome was nonadherence to follow-up recommendations for lung cancer screening, defined as failing to complete a recommended or more invasive follow-up examination (ie, diagnostic dose CT, positron emission tomography–CT, or tissue sampling vs low-dose CT) within 15 months (Lung-RADS score, 1 or 2), 9 months (Lung-RADS score, 3), 5 months (Lung-RADS score, 4A), or 3 months (Lung-RADS score, 4B/X). Multivariable logistic regression was used to identify factors associated with patient nonadherence to baseline Lung-RADS recommendations. A generalized estimating equations model was used to assess whether the pattern of longitudinal Lung-RADS scores was associated with patient nonadherence over time.

   Among 1979 included patients, 1111 (56.1%) were aged 65 years or older at baseline screening (mean [SD] age, 65.3 [6.6] years), and 1176 (59.4%) were male. The odds of being nonadherent were lower among patients with a baseline Lung-RADS score of 1 or 2 vs 3 (adjusted odds ratio [AOR], 0.35; 95% CI, 0.25-0.50), 4A (AOR, 0.21; 95% CI, 0.13-0.33), or 4B/X, (AOR, 0.10; 95% CI, 0.05-0.19); with a postgraduate vs college degree (AOR, 0.70; 95% CI, 0.53-0.92); with a family history of lung cancer vs no family history (AOR, 0.74; 95% CI, 0.59-0.93); with a high age-adjusted Charlson Comorbidity Index score (≥4) vs a low score (0 or 1) (AOR, 0.67; 95% CI, 0.46-0.98); in the high vs low income category (AOR, 0.79; 95% CI, 0.65-0.98); and referred by physicians from pulmonary or thoracic-related departments vs another department (AOR, 0.56; 95% CI, 0.44-0.73). Among 830 eligible patients who had completed at least 2 screening examinations, the adjusted odds of being nonadherent to Lung-RADS recommendations at the following screening were increased in patients with consecutive Lung-RADS scores of 1 to 2 (AOR, 1.38; 95% CI, 1.12-1.69).

   In this retrospective cohort study, patients with consecutive negative lung cancer screening results were more likely to be nonadherent with follow-up recommendations. These individuals are potential candidates for tailored outreach to improve adherence to recommended annual lung cancer screening.

    

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3. Identification of prognostic factors in childhood T‐cell acute lymphoblastic leukemia: Results from DFCI ALL Consortium Protocols 05‐001 and 11‐001

   https://doi.org/10.1002/pbc.28719  

   Burns, Melissa A. ; Place, Andrew E. ; Stevenson, Kristen E. ; Gutiérrez, Alejandro ; Forrest, Suzanne ; Pikman, Yana ; Vrooman, Lynda M. ; Harris, Marian H. ; Weinberg, Olga K. ; Hunt, Sarah K. ; et al ( October 2020 , Pediatric Blood & Cancer)

   While outcomes for pediatric T‐cell acute lymphoblastic leukemia (T‐ALL) are favorable, there are few widely accepted prognostic factors, limiting the ability to risk stratify therapy.

   Dana‐Farber Cancer Institute (DFCI) Protocols 05‐001 and 11‐001 enrolled pediatric patients with newly diagnosed B‐ or T‐ALL from 2005 to 2011 and from 2012 to 2015, respectively. Protocol therapy was nearly identical for patients with T‐ALL (N = 123), who were all initially assigned to the high‐risk arm. End‐induction minimal residual disease (MRD) was assessed by reverse transcription polymerase chain reaction (RT‐PCR) or next‐generation sequencing (NGS), but was not used to modify postinduction therapy. Early T‐cell precursor (ETP) status was determined by flow cytometry. Cases with sufficient diagnostic DNA were retrospectively evaluated by targeted NGS of known genetic drivers of T‐ALL, including Notch, PI3K, and Ras pathway genes.

   The 5‐year event‐free survival (EFS) and overall survival (OS) for patients with T‐ALL was 81% (95% CI, 73‐87%) and 90% (95% CI, 83‐94%), respectively. ETP phenotype was associated with failure to achieve complete remission, but not with inferior OS. Low end‐induction MRD (<10⁻⁴) was associated with superior disease‐free survival (DFS). Pathogenic mutations of the PI3K pathway were mutually exclusive of ETP phenotype and were associated with inferior 5‐year DFS and OS.

   Together, our findings demonstrate that ETP phenotype, end‐induction MRD, and PI3K pathway mutation status are prognostically relevant in pediatric T‐ALL and should be considered for risk classification in future trials. DFCI Protocols 05‐001 and 11‐001 are registered atwww.clinicaltrials.govas NCT00165087 and NCT01574274, respectively.

    

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4. Copper deficiency is an independent risk factor for mortality in patients with advanced liver disease

   https://doi.org/10.1097/HC9.0000000000000076  

   Yu, Lei ; Yousuf, Sarim ; Yousuf, Shahrukh ; Yeh, Jeffrey ; Biggins, Scott W. ; Morishima, Chihiro ; Shyu, Irene ; O’Shea-Stone, Galen ; Eilers, Brian ; Waldum, Annie ; et al ( March 2023 , Hepatology Communications)

   Copper is an essential trace metal serving as a cofactor in innate immunity, metabolism, and iron transport. We hypothesize that copper deficiency may influence survival in patients with cirrhosis through these pathways.

   We performed a retrospective cohort study involving 183 consecutive patients with cirrhosis or portal hypertension. Copper from blood and liver tissues was measured using inductively coupled plasma mass spectrometry. Polar metabolites were measured using nuclear magnetic resonance spectroscopy. Copper deficiency was defined by serum or plasma copper below 80 µg/dL for women or 70 µg/dL for men.

   The prevalence of copper deficiency was 17% (N=31). Copper deficiency was associated with younger age, race, zinc and selenium deficiency, and higher infection rates (42% vs. 20%,p=0.01). Serum copper correlated positively with albumin, ceruloplasmin, hepatic copper, and negatively with IL-1β. Levels of polar metabolites involved in amino acids catabolism, mitochondrial transport of fatty acids, and gut microbial metabolism differed significantly according to copper deficiency status. During a median follow-up of 396 days, mortality was 22.6% in patients with copper deficiency compared with 10.5% in patients without. Liver transplantation rates were similar (32% vs. 30%). Cause-specific competing risk analysis showed that copper deficiency was associated with a significantly higher risk of death before transplantation after adjusting for age, sex, MELD-Na, and Karnofsky score (HR: 3.40, 95% CI, 1.18–9.82,p=0.023).

   In advanced cirrhosis, copper deficiency is relatively common and is associated with an increased infection risk, a distinctive metabolic profile, and an increased risk of death before transplantation.

    

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5. Climate change, extreme events, and increased risk of salmonellosis: foodborne diseases active surveillance network (FoodNet), 2004-2014

   https://doi.org/10.1186/s12940-021-00787-y  

   Morgado, Michele E. ; Jiang, Chengsheng ; Zambrana, Jordan ; Upperman, Crystal Romeo ; Mitchell, Clifford ; Boyle, Michelle ; Sapkota, Amy R. ; Sapkota, Amir ( September 2021 , Environmental Health)

   Infections with nontyphoidalSalmonellacause an estimated 19,336 hospitalizations each year in the United States. Sources of infection can vary by state and include animal and plant-based foods, as well as environmental reservoirs. Several studies have recognized the importance of increased ambient temperature and precipitation in the spread and persistence ofSalmonellain soil and food. However, the impact of extreme weather events onSalmonellainfection rates among the most prevalent serovars, has not been fully evaluated across distinct U.S. regions.

   To address this knowledge gap, we obtainedSalmonellacase data forS.Enteriditis,S.Typhimurium,S.Newport, andS.Javiana (2004-2014; n = 32,951) from the Foodborne Diseases Active Surveillance Network (FoodNet), and weather data from the National Climatic Data Center (1960-2014). Extreme heat and precipitation events for the study period (2004-2014) were identified using location and calendar day specific 95^thpercentile thresholds derived using a 30-year baseline (1960-1989). Negative binomial generalized estimating equations were used to evaluate the association between exposure to extreme events and salmonellosis rates.

   We observed that extreme heat exposure was associated with increased rates of infection withS.Newport in Maryland (Incidence Rate Ratio (IRR): 1.07, 95% Confidence Interval (CI): 1.01, 1.14), and Tennessee (IRR: 1.06, 95% CI: 1.04, 1.09), both FoodNet sites with high densities of animal feeding operations (e.g., broiler chickens and cattle). Extreme precipitation events were also associated with increased rates ofS.Javiana infections, by 22% in Connecticut (IRR: 1.22, 95% CI: 1.10, 1.35) and by 5% in Georgia (IRR: 1.05, 95% CI: 1.01, 1.08), respectively. In addition, there was an 11% (IRR: 1.11, 95% CI: 1.04-1.18) increased rate ofS. Newport infections in Maryland associated with extreme precipitation events.

   Overall, our study suggests a stronger association between extreme precipitation events, compared to extreme heat, and salmonellosis across multiple U.S. regions. In addition, the rates of infection withSalmonellaserovars that persist in environmental or plant-based reservoirs, such asS.Javiana andS.Newport, appear to be of particular significance regarding increased heat and rainfall events.

    

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