Background Obesity and abdominal obesity are independently associated with morbidity and mortality. Physical activity attenuates these risks. We examined trends in obesity, abdominal obesity, physical activity, and caloric intake in U.S. adults from 1988 to 2010. Methods Univariate and multivariate analyses were performed using National Health and Nutrition Examination Survey (NHANES) data. Results Average body-mass index (BMI) increased by 0.37% (95% CI, 0.30-0.44%) per year in both women and men. Average waist circumference increased by 0.37% (95% CI, 0.30-0.43%) and 0.27% (95% CI, 0.22-0.32%) per year in women and men, respectively. The prevalence of obesity and abdominal obesity increased substantially, as did the prevalence of abdominal obesity among overweight adults. Younger women experienced the greatest increases. The proportion of adults who reported no leisure-time physical activity increased from 19.1% (95% CI, 17.3-21.0%) to 51.7% (95% CI, 48.9-54.5%) in women, and from 11.4% (95% CI, 10.0-12.8%) to 43.5% (95% CI, 40.7-46.3%) in men. Average daily caloric intake did not change significantly. BMI and waist circumference trends were associated with physical activity level, but not caloric intake. The associated changes in adjusted BMIs were 8.3% (95% CI, 6.9-9.6%) higher among women and 1.7% (95% CI, 0.68-2.8%) higher among men with no leisure-time physical activity compared to those with an ideal level of leisure-time physical activity. Conclusions Our analyses highlight important dimensions of the public health problem of obesity, including trends in younger women and in abdominal obesity, and lend support to the emphasis placed on physical activity by the Institute of Medicine.

No abstract

There are more than 70 distinct sarcomas, and this diversity complicates the development of precision-based therapeutics for these cancers. Prospective comprehensive genomic profiling could overcome this challenge by providing insight into sarcomas’ molecular drivers. Through targeted panel sequencing of 7494 sarcomas representing 44 histologies, we identify highly recurrent and type-specific alterations that aid in diagnosis and treatment decisions. Sequencing could lead to refinement or reassignment of 10.5% of diagnoses. Nearly one-third of patients (31.7%) harbor potentially actionable alterations, including a significant proportion (2.6%) with kinase gene rearrangements; 3.9% have a tumor mutational burden ≥10 mut/Mb. We describe low frequencies of microsatellite instability (<0.3%) and a high degree of genome-wide loss of heterozygosity (15%) across sarcomas, which are not readily explained by homologous recombination deficiency (observed in 2.5% of cases). In a clinically annotated subset of 118 patients, we validate actionable genetic events as therapeutic targets. Collectively, our findings reveal the genetic landscape of human sarcomas, which may inform future development of therapeutics and improve clinical outcomes for patients with these rare cancers.

GI illnesses account for substantial clinical and economic burdens on US emergency medical services.

OBJECTIVES Heritable and environmental factors may contribute to differences in colorectal cancer (CRC) incidence across populations. We capitalized on the resources of the California Cancer Registry (CCR) and California’s diverse Asian population to perform a cohort study exploring the relationships between CRC incidence, nativity, and neighborhood-level factors across Asian subgroups. METHODS We identified CRC cases in the CCR from 1990 to 2004 and calculated age-adjusted CRC incidence rates for non-Hispanic Whites and US-born vs. foreign-born Asian ethnic subgroups, stratified by neighborhood socioeconomic status (SES) and “ethnic enclave.” Trends were studied with joinpoint analysis. RESULTS CRC incidence was lowest among foreign-born South Asians (22.0/100,000; 95% confidence interval (CI): 19.7–24.5/100,000) and highest among foreign-born Japanese (74.6/100,000; 95% CI: 70.1–79.2/100,000). Women in all Asian subgroups except Japanese, and men in all Asian subgroups except Japanese and US-born Chinese, had lower CRC incidence than non-Hispanic Whites. Among Chinese men and Filipino women and men, CRC incidence was lower among foreign-born than US-born persons; the opposite was observed for Japanese women and men. Among non-Hispanic Whites, but not most Asian subgroups, CRC incidence decreased over time. CRC incidence was inversely associated with neighborhood SES among non-Hispanic Whites, and level of ethnic enclave among Asians. CONCLUSIONS CRC incidence rates differ substantially across Asian subgroups in California. The significant associations between CRC incidence and nativity and residence in an ethnic enclave suggest a substantial effect of acquired environmental factors. The absence of declines in CRC incidence rates among most Asians during our study period may point to disparities in screening compared with Whites.

BACKGROUND & AIMS Screening decreases colorectal cancer (CRC) incidence and mortality. Colonoscopy has become the most common CRC screening test in the United States, but the degree to which it protects against CRC of the proximal colon is unclear. We examined US trends in rates of resection for proximal vs distal CRC, which reflect CRC incidence, in the context of national CRC screening data, before and since Medicare’s 2001 decision to pay for screening colonoscopy. METHODS We used the Nationwide Inpatient Sample, the largest US all-payer inpatient database, to estimate age-adjusted rates of resection for distal and proximal CRC, from 1993 to 2009, in adults. Temporal trends were analyzed using Joinpoint regression analysis. RESULTS The rate of resection for distal CRC decreased from 38.7 per 100,000 persons (95% confidence interval [CI], 35.4 – 42.0) to 23.2 per 100,000 persons (95% CI, 20.9 –25.5) from 1993 to 2009, with annual decreases of 1.2% (95% CI, 0.1%–2.3%) from 1993 to 1999, followed by larger annual decreases of 3.8% (95% CI, 3.3%– 4.3%) from 1999 to 2009 (P < .001). In contrast, the rate of resection for proximal CRC decreased from 30.0 per 100,000 persons (95% CI, 27.4 –32.5) to 22.7 per 100,000 persons (95% CI, 20.6 –24.7) from 1993 to 2009, but significant annual decreases of 3.1% (95% CI, 2.3%– 4.0%) occurred only after 2002 (P < .001). Rates of resection for CRC decreased for adults ages 50 years and older, but increased for younger adults. CONCLUSIONS These findings support the hypothesis that population-level decreases in rates of resection for distal CRC are associated with screening, in general, and that implementation of screening colonoscopy, specifically, might be an important factor that contributes to population-level decreases in rates of resection for proximal CRC.

Black people have a higher incidence of colorectal cancer and worse survival rates when compared with white people. Comprehensive genomic profiling was performed in 46,140 colorectal adenocarcinoma cases. Ancestry-informative markers identified 5,301 patients of African descent (AFR) and 33,770 patients of European descent (EUR). AFR were younger, had fewer microsatellite instability–high (MSI-H) tumors, and had significantly more frequent alterations in KRAS, APC, and PIK3CA. AFR had increased frequency of KRAS mutations, specifically KRASG12D and KRASG13. There were no differences in rates of actionable kinase driver alterations (HER2, MET, NTRK, ALK, ROS1, and RET). In patients with young-onset colorectal cancer (&lt;50 years), AFR and EUR had a similar frequency of MSI-H and tumor mutational burden–high (TMB-H) tumors, and strikingly different trends in APC mutations by age, as well as differences in MAPK pathway alterations. These findings inform treatment decisions, impact prognosis, and underscore the need for model systems representative of the diverse U.S. population. Significance: KRAS (particularly KRASG12D/G13), APC, and PIK3CA were more frequently altered in AFR who had a lower frequency of MSI-H tumors. There were no differences in actionable kinase driver alterations. In young-onset colorectal cancer, both ancestries had a similar frequency of MSI-H/TMB-H tumors, but strikingly different trends in APC.

ImportanceThe KEYNOTE-177 trial demonstrated that patients with metastatic colorectal cancer (MCRC) with high microsatellite instability (MSI-H) and/or mismatch repair deficiency (DMMR) have better outcomes when receiving first-line immune checkpoint inhibitors (ICIs) compared with chemotherapy. Data on performance of ICIs in patients with MCRC in standard practice settings remain limited, and direct MMR vs MSI outcome association comparisons are lacking.ObjectiveTo validate MSI (determined by next-generation sequencing [NGS]) as a biomarker of ICI effectiveness among patients with MCRC in standard practice settings and examine the association of MSI assessed by NGS, DMMR by immunohistochemistry, and tumor mutational burden (cutoff, 10 mutations/megabase) with ICI outcomes.Design, Setting, and ParticipantsThis comparative effectiveness research study of outcomes in prospectively defined biomarker subgroups used data from a deidentified clinicogenomic database and included patients who received Foundation Medicine testing (FoundationOne or FoundationOne CDx) during routine clinical care at approximately 280 US academic or community-based cancer clinics between March 2014 and December 2021. The population included 1 cohort of patients with MSI-H MCRC who received first-line ICIs or chemotherapy and a second cohort who received ICIs in any line of therapy (LOT) for biomarker examination.ExposuresICI therapy or chemotherapy assigned at physician discretion without randomization.Main Outcomes and MeasuresThe main outcomes were time to next treatment (TTNT), progression-free survival (PFS), and overall survival (OS). Hazard ratios were adjusted for known prognostic imbalances. Comparisons of explanatory power used the likelihood ratio test.ResultsA total of 138 patients (median age, 67.0 years [IQR, 56.2-74.0 years]; 73 [52.9%] female) with MSI-H MCRC received first-line ICIs or chemotherapy. A total of 182 patients (median age, 64.5 years [IQR, 55.2-72.0]; 98 [53.8%] female) received ICIs in any LOT. Patients receiving first-line ICIs vs chemotherapy had longer TTNT (median, not reached [NR] vs 7.23 months [IQR, 6.21-9.72 months]; adjusted hazard ratio [AHR], 0.17; 95% CI, 0.08-0.35; P &amp;lt; .001), PFS (median, 24.87 months [IQR, 19.10 months to NR] vs 5.65 months [IQR, 4.70-8.34 months]; AHR, 0.31; 95% CI, 0.18-0.52; P &amp;lt; .001), and OS (median, NR vs 24.1 months [IQR, 13.90 months to NR]; HR, 0.45; 95% CI, 0.23-0.88; P = .02). MSI added to DMMR better anticipated TTNT and PFS in patients receiving ICIs than DMMR alone. The same was not observed when DMMR evaluation was added to MSI.Conclusions and RelevanceIn this comparative effectiveness research study, MSI assessed by NGS robustly identified patients with favorable outcomes on first-line ICIs vs chemotherapy and appeared to better anticipate ICI outcomes compared with DMMR.