UNASSIGNED: Acute kidney injury (AKI) in cancer patients receiving immune checkpoint inhibitors (ICIs) may recognize multiple causes. Here, we reviewed cases of biopsy-proven acute tubulointerstitial nephritis (ATIN) to describe the clinical characteristics and outcomes of this condition.
UNASSIGNED: We conducted a pooled analysis of clinical cases of ICI-related biopsy-proven ATIN up to 1 May 2022. We collected data on clinical characteristics, AKI, biopsy findings, laboratory examinations, and renal outcomes.
UNASSIGNED: Eighty-five patients (61.4 ± 19 years, 56 male) were evaluated. Melanoma was the most prevalent diagnosis (51%), followed by non-small cell lung cancer (30%). ICI treatment consisted of PD-1, PDL-1 (nivolumab, pembrolizumab, atezolizumab), and CTLA-4 inhibitors (i) (ipilimumab) or combination PD-1i+CTLA4i. Renal toxicity developed after a median of four cycles of therapy. Fifty-one patients (65.5%) developed the most severe form of AKI- stage 3, including five patients requiring dialysis. All the 19 patients treated with dual ICI blockade developed AKI-stage 3, compared with 29 patients out of the 60 receiving a single agent (p<0.001). Most events were managed with corticosteroids associated with ICI withdrawal. In 15 patients ICI was restarted, but in six (40%) AKI recurred. Overall, 32 patients (40%) presented a complete renal recovery, which chance was inversely associated with dual ICI blockade (OR 0.15, 95CI 0.03-0.7, p=0.01).
UNASSIGNED: ICI-related ATIN may develop late after the therapy initiation, presenting as severe AKI, particularly in patients with dual ICI blockade. Although this complication may be partially reversible, concerns remain about the renal function sequelae and the possibility of restarting ICI treatment.

Heat exposures occur in many occupations. Heat has been linked to key carcinogenic processes, however, evidence for associations with cancer risk is sparse. We examined potential associations between occupational heat exposure and prostate cancer risk in a multi-country study.
We analysed a large, pooled dataset of 3142 histologically confirmed prostate cancer cases and 3512 frequency-matched controls from three countries: Canada, France, and Spain. Three exposure indices: ever exposure, lifetime cumulative exposure and duration of exposure, were developed using the Finnish Job-Exposure Matrix, FINJEM, applied to the lifetime occupational history of participants. We estimated odds ratios (ORs) and 95% confidence intervals (CIs), using conditional logistic regression models stratified by 5-year age groups and study, adjusting for potential confounders. Potential interactions with exposure to other occupational agents were also explored.
Overall, we found no association for ever occupational heat exposure (OR 0.97; 95% CI 0.87, 1.09), nor in the highest categories of lifetime cumulative exposure (OR 1.04; 95% CI 0.89, 1.23) or duration (OR 1.03; 95% CI 0.88, 1.22). When using only the Spanish case-control study and a Spanish Job Exposure Matrix (JEM), some weakly elevated ORs were observed.
Findings from this study provide no clear evidence for an association between occupational heat exposure and prostate cancer risk.

While being in a committed relationship is associated with a better prostate cancer prognosis, little is known about how marital status relates to its incidence. Social support provided by marriage/relationship could promote a healthy lifestyle and an increased healthcare seeking behavior. We investigated the association between marital status and prostate cancer risk using data from the PRACTICAL Consortium. Pooled analyses were conducted combining 12 case-control studies based on histologically-confirmed incident prostate cancers and controls with information on marital status prior to diagnosis/interview. Marital status was categorized as married/partner, separated/divorced, single, or widowed. Tumours with Gleason scores ≥ 8 defined high-grade cancers, and low-grade otherwise. NCI-SEER\'s summary stages (local, regional, distant) indicated the extent of the cancer. Logistic regression was used to derive odds ratios (ORs) and 95% confidence intervals (CI) for the association between marital status and prostate cancer risk, adjusting for potential confounders. Overall, 14,760 cases and 12,019 controls contributed to analyses. Compared to men who were married/with a partner, widowed men had an OR of 1.19 (95% CI 1.03-1.35) of prostate cancer, with little difference between low- and high-grade tumours. Risk estimates among widowers were 1.14 (95% CI 0.97-1.34) for local, 1.53 (95% CI 1.22-1.92) for regional, and 1.56 (95% CI 1.05-2.32) for distant stage tumours. Single men had elevated risks of high-grade cancers. Our findings highlight elevated risks of incident prostate cancer among widowers, more often characterized by tumours that had spread beyond the prostate at the time of diagnosis. Social support interventions and closer medical follow-up in this sub-population are warranted.

While childbearing protects against risk of epithelial ovarian cancer (EOC), few studies have explored the impact on maternal EOC risk of sex of offspring, which may affect the maternal environment during pregnancy. We performed a pooled analysis among parous participants from 12 case-controls studies comprising 6872 EOC patients and 9101 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable logistic regression for case-control associations and polytomous logistic regression for histotype-specific associations, all adjusted for potential confounders. In general, no associations were found between offspring sex and EOC risk. However, compared to bearing only female offspring, bearing one or more male offspring was associated with increased risk of mucinous EOC (OR = 1.45; 95% CI = 1.01-2.07), which appeared to be limited to women reporting menarche before age 13 compared to later menarche (OR = 1.71 vs 0.99; P-interaction = 0.02). Bearing increasing numbers of male offspring was associated with greater risks of mucinous tumors (OR = 1.31, 1.84, 2.31, for 1, 2 and 3 or more male offspring, respectively; trend-p = 0.005). Stratifying by hormonally-associated conditions suggested that compared to bearing all female offspring, bearing a male offspring was associated with lower risk of endometrioid cancer among women with a history of adult acne, hirsutism, or polycystic ovary syndrome (OR = 0.49, 95% CI = 0.28-0.83) but with higher risk among women without any of those conditions (OR = 1.64 95% CI = 1.14-2.34; P-interaction = 0.003). Offspring sex influences the childbearing-EOC risk relationship for specific histotypes and conditions. These findings support the differing etiologic origins of EOC histotypes and highlight the importance of EOC histotype-specific epidemiologic studies. These findings also suggest the need to better understand how pregnancy affects EOC risk.

Night shift work has been suspected to increase breast cancer risk but epidemiological studies have been inconsistent due to heterogeneous assessment of exposure to night work. To overcome this limitation, we pooled data of five population-based case-control studies from Australia, Canada, France, Germany, and Spain into a single harmonized dataset using a common definition of night work including 6093 breast cancer cases and 6933 population controls. The odds ratio for breast cancer in women who ever worked at night for at least 3 h between midnight and 5 a.m. as compared to never night workers was 1.12 (95% CI 1.00-1.25). Among pre-menopausal women, this odds ratio was 1.26 [1.06-1.51], increasing to 1.36 [1.07-1.74] for night shifts ≥ 10 h, 1.80 [1.20-2.71] for work ≥ 3 nights/week, and 2.55 [1.03-6.30] for both duration of night work ≥ 10 years and exposure intensity ≥ 3 nights/week. Breast cancer risk in pre-menopausal women was higher in current or recent night workers (OR = 1.41 [1.06-1.88]) than in those who had stopped night work more than 2 years ago. Breast cancer in post-menopausal women was not associated with night work whatever the exposure metric. The increase in risk was restricted to ER+ tumors, particularly those who were both ER+ and HER2+ . These results support the hypothesis that night shift work increases the risk of breast cancer in pre-menopausal women, particularly those with high intensity and long duration of exposure. Risk difference between pre- and post-menopausal women deserves further scrutiny.

Cases of lymphohematopoietic cancer from three petroleum industry cohorts, matched to controls from the respective cohort, were pooled into single study. Average benzene exposure was quantitatively estimated in ppm for each job based on measured data from the relevant country, adjusted for the specific time period, site and job exposure characteristics and the certainty of the exposure estimate scored. The probability of dermal exposure and of peak exposure was also assessed. Before risk was examined, an exposure estimate comparison and rationalisation exercise was performed across the studies to ensure accuracy and consistency of approach. This article evaluates the final exposure estimates and their use in the risk assessments. Overall benzene exposure estimates were low: 90% of participants accumulated less than 20 ppm-years. Mean cumulative exposure was estimated as 5.15 ppm-years, mean duration was 22 years, and mean exposure intensity was 0.2 ppm. 46% of participants were allocated a peak exposure (>3 ppm at least weekly). 40% of participants had a high probability of dermal exposure (based on the relative probability of at least weekly exposure). There were differences in mean intensity of exposure, probability of peak, and/or dermal exposure associated with job category, job site, and decade of exposure. Terminal Operators handling benzene-containing products were the most highly exposed group, followed by Tanker Drivers carrying gasoline. Exposures were higher around 1940-1950 and lower in more recent decades. Overall confidence in the exposure estimates was highest for recently held jobs and for white-collar jobs. We used sensitivity analyses, which included and excluded case-sets on the basis of exposure certainty scores, to inform the risk assessment. The above analyses demonstrated that the different patterns of exposure across the three studies are largely attributable to differences in jobs, site types, and time frames rather than study. This provides reassurance that the previous rationalisation of exposures achieved inter-study consistency and that the data could be confidently pooled.

OBJECTIVE: Socioeconomic status (SES) is a known predictor of survival for several cancers and it has been suggested that SES differences affecting tumour stage at diagnosis may be the most important explanatory factor for this. However, only a limited number of studies have investigated SES differences in tumour stage at diagnosis of ovarian cancer. In a pooled analysis, we investigated whether SES as represented by level of education is predictive for advanced tumour stage at diagnosis of ovarian cancer, overall and by histotype. The effect of cigarette smoking and body mass index (BMI) on the association was also evaluated.
METHODS: From 18 case-control studies, we obtained information on 10,601 women diagnosed with epithelial ovarian cancer. Study specific odds ratios (ORs) with corresponding 95% confidence intervals (CI) were obtained from logistic regression models and combined into a pooled odds ratio (pOR) using a random effects model.
RESULTS: Overall, women who completed ≤high school had an increased risk of advanced tumour stage at diagnosis compared with women who completed >high school (pOR 1.15; 95% CI 1.03-1.28). The risk estimates for the different histotypes of ovarian cancer resembled that observed for ovarian cancers combined but did not reach statistical significance. Our results were unchanged when we included BMI and cigarette smoking.
CONCLUSIONS: Lower level of education was associated with an increased risk of advanced tumour stage at diagnosis of ovarian cancer. The observed socioeconomic difference in stage at diagnosis of ovarian cancer calls for further studies on how to reduce this diagnostic delay.

BACKGROUND: The potential role of vitamin D in the aetiology of pancreatic cancer is unclear, with recent studies suggesting both positive and negative associations.
METHODS: We used data from nine case-control studies from the International Pancreatic Cancer Case-Control Consortium (PanC4) to examine associations between pancreatic cancer risk and dietary vitamin D intake. Study-specific odds ratios (ORs) were estimated using multivariable logistic regression, and ORs were then pooled using a random-effects model. From a subset of four studies, we also calculated pooled estimates of association for supplementary and total vitamin D intake.
RESULTS: Risk of pancreatic cancer increased with dietary intake of vitamin D [per 100 international units (IU)/day: OR = 1.13, 95% confidence interval (CI) 1.07-1.19, P = 7.4 × 10(-6), P-heterogeneity = 0.52; ≥230 versus <110 IU/day: OR = 1.31, 95% CI 1.10-1.55, P = 2.4 × 10(-3), P-heterogeneity = 0.81], with the association possibly stronger in people with low retinol/vitamin A intake.
CONCLUSIONS: Increased risk of pancreatic cancer was observed with higher levels of dietary vitamin D intake. Additional studies are required to determine whether or not our finding has a causal basis.

Using data from rotavirus vaccine effectiveness (VE) studies, we assessed whether rotavirus season modifies rotavirus VE in infants. In the first year of life, adjusted VE was 72% for children born during rotavirus season and 84% for children born in other months (P = .01). Seasonal factors may interfere with vaccine performance.

BACKGROUND: Type 2 diabetes mellitus has been associated with an excess risk of pancreatic cancer, but the magnitude of the risk and the time-risk relationship are unclear, and there is limited information on the role of antidiabetic medications.
METHODS: We analyzed individual-level data from 15 case-control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates.
RESULTS: Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes 2 or more years before cancer diagnosis (or interview, for controls), corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72-2.09). Consistent risk estimates were observed across strata of selected covariates, including body mass index and tobacco smoking. Pancreatic cancer risk decreased with duration of diabetes, but a significant excess risk was still evident 20 or more years after diabetes diagnosis (OR 1.30, 95% CI 1.03-1.63). Among diabetics, long duration of oral antidiabetic use was associated with a decreased pancreatic cancer risk (OR 0.31, 95% CI 0.14-0.69, for ≥15 years). Conversely, insulin use was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI 3.75-8.35, for <5 years), but not for longer duration of use (OR 0.95, 95% CI 0.53-1.70, for ≥15 years).
CONCLUSIONS: This study provides the most definitive quantification to date of an excess risk of pancreatic cancer among diabetics. It also shows that a 30% excess risk persists for more than two decades after diabetes diagnosis, thus supporting a causal role of diabetes in pancreatic cancer. Oral antidiabetics may decrease the risk of pancreatic cancer, whereas insulin showed an inconsistent duration-risk relationship.