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Importance: Aspirin may reduce severity of metabolic dysfunction–associated steatotic liver disease (MASLD) and lower the incidence of end-stage liver disease and hepatocellular carcinoma, in patients with MASLD. However, the effect of aspirin on MASLD is unknown. Objective: To test whether low-dose aspirin reduces liver fat content, compared with placebo, in adults with MASLD. Design, Setting, and Participants: This 6-month, phase 2, randomized, double-blind, placebo-controlled clinical trial was conducted at a single hospital in Boston, Massachusetts. Participants were aged 18 to 70 years with established MASLD without cirrhosis. Enrollment occurred between August 20, 2019, and July 19, 2022, with final follow-up on February 23, 2023. Interventions: Participants were randomized (1:1) to receive either once-daily aspirin, 81 mg (n = 40) or identical placebo pills (n = 40) for 6 months. Main Outcomes and Measures: The primary end point was mean absolute change in hepatic fat content, measured by proton magnetic resonance spectroscopy (MRS) at 6-month follow-up. The 4 key secondary outcomes included mean percentage change in hepatic fat content by MRS, the proportion achieving at least 30% reduction in hepatic fat, and the mean absolute and relative reductions in hepatic fat content, measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF). Analyses adjusted for the baseline value of the corresponding outcome. Minimal clinically important differences for study outcomes were not prespecified. Results: Among 80 randomized participants (mean age, 48 years; 44 [55%] women; mean hepatic fat content, 35% [indicating moderate steatosis]), 71 (89%) completed 6-month follow-up. The mean absolute change in hepatic fat content by MRS was −6.6% with aspirin vs 3.6% with placebo (difference, −10.2% [95% CI, −27.7% to −2.6%]; P =.009). Compared with placebo, aspirin treatment significantly reduced relative hepatic fat content (−8.8 vs 30.0 percentage points; mean difference, −38.8 percentage points [95% CI, −66.7 to −10.8]; P =.007), increased the proportion of patients with 30% or greater relative reduction in hepatic fat (42.5% vs 12.5%; mean difference, 30.0% [95% CI, 11.6% to 48.4%]; P =.006), reduced absolute hepatic fat content by MRI-PDFF (−2.7% vs 0.9%; mean difference, −3.7% [95% CI, −6.1% to −1.2%]; P =.004]), and reduced relative hepatic fat content by MRI-PDFF (−11.7 vs 15.7 percentage points; mean difference, −27.3 percentage points [95% CI, −45.2 to −9.4]; P =.003). Thirteen participants (32.5%) in each group experienced an adverse event, most commonly upper respiratory tract infections (10.0% in each group) or arthralgias (5.0% for aspirin vs 7.5% for placebo). One participant randomized to aspirin (2.5%) experienced drug-related heartburn. Conclusions and Relevance: In this preliminary randomized clinical trial of patients with MASLD, 6 months of daily low-dose aspirin significantly reduced hepatic fat quantity compared with placebo. Further study in a larger sample size is necessary to confirm these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT04031729 Key Points: Question: In patients with metabolic dysfunction–associated steatotic liver disease (MASLD), does 81 mg of aspirin daily reduce the quantity of hepatic fat at 6-month follow-up compared with placebo? Findings: In this phase 2 randomized clinical trial of 80 individuals with MASLD, daily aspirin reduced the quantity of hepatic fat at 6-month follow-up compared with placebo (mean difference, −10.2%). Meaning: In a preliminary randomized clinical trial of adults with MASLD, 6 months of daily low-dose aspirin significantly reduced liver fat content compared with placebo, but findings are preliminary and require confirmation in a larger population. This randomized clinical trial compares use of low-dose aspirin vs placebo in reducing hepatic fat among adult patients with metabolic dysfunction–associated steatotic liver disease (MASLD) without cirrhosis. [ABSTRACT FROM AUTHOR]

Key Points: Question: Among people with weight loss within the past 2 years, is the rate of cancer diagnosis significantly increased during the subsequent 12 months compared with those without recent weight loss? Findings: Among 157 474 health professionals followed up for a mean of 28 years, recent weight loss of greater than 10.0% of body weight was associated with an increased rate of cancer during the next 12 months vs those without recent weight loss (1362 cancer cases/100 000 person-years vs 869 cancer cases/100 000 person-years, respectively; between-group difference, 493 cases/100 000 person-years). Meaning: Recent weight loss was associated with a significantly higher rate of cancer during the next 12 months compared with those without recent weight loss. Importance: Weight loss is common in primary care. Among individuals with recent weight loss, the rates of cancer during the subsequent 12 months are unclear compared with those without recent weight loss. Objective: To determine the rates of subsequent cancer diagnoses over 12 months among health professionals with weight loss during the prior 2 years compared with those without recent weight loss. Design, Setting, and Participants: Prospective cohort analysis of females aged 40 years or older from the Nurses' Health Study who were followed up from June 1978 until June 30, 2016, and males aged 40 years or older from the Health Professionals Follow-Up Study who were followed up from January 1988 until January 31, 2016. Exposure: Recent weight change was calculated from the participant weights that were reported biennially. The intentionality of weight loss was categorized as high if both physical activity and diet quality increased, medium if only 1 increased, and low if neither increased. Main Outcome and Measures: Rates of cancer diagnosis during the 12 months after weight loss. Results: Among 157 474 participants (median age, 62 years [IQR, 54-70 years]; 111 912 were female [71.1%]; there were 2631 participants [1.7%] who self-identified as Asian, Native American, or Native Hawaiian; 2678 Black participants [1.7%]; and 149 903 White participants [95.2%]) and during 1.64 million person-years of follow-up, 15 809 incident cancer cases were identified (incident rate, 964 cases/100 000 person-years). During the 12 months after reported weight change, there were 1362 cancer cases/100 000 person-years among all participants with recent weight loss of greater than 10.0% of body weight compared with 869 cancer cases/100 000 person-years among those without recent weight loss (between-group difference, 493 cases/100 000 person-years [95% CI, 391-594 cases/100 000 person-years]; P <.001). Among participants categorized with low intentionality for weight loss, there were 2687 cancer cases/100 000 person-years for those with weight loss of greater than 10.0% of body weight compared with 1220 cancer cases/100 000 person-years for those without recent weight loss (between-group difference, 1467 cases/100 000 person-years [95% CI, 799-2135 cases/100 000 person-years]; P <.001). Cancer of the upper gastrointestinal tract (cancer of the esophagus, stomach, liver, biliary tract, or pancreas) was particularly common among participants with recent weight loss; there were 173 cancer cases/100 000 person-years for those with weight loss of greater than 10.0% of body weight compared with 36 cancer cases/100 000 person-years for those without recent weight loss (between-group difference, 137 cases/100 000 person-years [95% CI, 101-172 cases/100 000 person-years]; P <.001). Conclusions and Relevance: Health professionals with weight loss within the prior 2 years had a significantly higher risk of cancer during the subsequent 12 months compared with those without recent weight loss. Cancer of the upper gastrointestinal tract was particularly common among participants with recent weight loss compared with those without recent weight loss. This study compares the rates of subsequent cancer diagnoses over 12 months among health professionals in the Nurses' Health Study and the Health Professionals Follow-Up Study with weight loss during the prior 2 years compared with those without recent weight loss. [ABSTRACT FROM AUTHOR]

A study was conducted to evaluate the efficacy of aspirin on the rate of survival among individuals diagnosed with colorectal cancer. Results indicated that regular use of aspirin was effective in lowering the risk of colorectal cancer as well as overall rate of mortality.

A study is conducted to examine the influence of aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) in prevention of colorectal cancer. Results reveal that regular, long-term aspirin use reduces risk of colorectal cancer and non-aspirin NSAIDs appear to have a similar effect.

Importance: It is important to document patterns of prescription drug use to inform both clinical practice and research.Objective: To evaluate trends in prescription drug use among adults living in the United States.Design, Setting, and Participants: Temporal trends in prescription drug use were evaluated using nationally representative data from the National Health and Nutrition Examination Survey (NHANES). Participants included 37,959 noninstitutionalized US adults, aged 20 years and older. Seven NHANES cycles were included (1999-2000 to 2011-2012), and the sample size per cycle ranged from 4861 to 6212.Exposures: Calendar year, as represented by continuous NHANES cycle.Main Outcomes and Measures: Within each NHANES cycle, use of prescription drugs in the prior 30 days was assessed overall and by drug class. Temporal trends across cycles were evaluated. Analyses were weighted to represent the US adult population.Results: Results indicate an increase in overall use of prescription drugs among US adults between 1999-2000 and 2011-2012 with an estimated 51% of US adults reporting use of any prescription drugs in 1999-2000 and an estimated 59% reporting use of any prescription drugs in 2011-2012 (difference, 8% [95% CI, 3.8%-12%]; P for trend <.001). The prevalence of polypharmacy (use of ≥5 prescription drugs) increased from an estimated 8.2% in 1999-2000 to 15% in 2011-2012 (difference, 6.6% [95% CI, 4.4%-8.2%]; P for trend <.001). These trends remained statistically significant with age adjustment. Among the 18 drug classes used by more than 2.5% of the population at any point over the study period, the prevalence of use increased in 11 drug classes including antihyperlipidemic agents, antidepressants, prescription proton-pump inhibitors, and muscle relaxants.Conclusions and Relevance: In this nationally representative survey, significant increases in overall prescription drug use and polypharmacy were observed. These increases persisted after accounting for changes in the age distribution of the population. The prevalence of prescription drug use increased in the majority of, but not all, drug classes. [ABSTRACT FROM AUTHOR]

The article presents a study related to identification of neuroanatomical characteristics on preoperative imaging that differentiates responders from nonresponders to dorsal anterior cingulotomy. Topics discussed include identification of features of anterior cingulate cortex structure, obsessive compulsive disorder (OCD) due to intrusive thoughts and repetitive intentional behaviors and preoperative structural variations in patients' response to cingulotomy.

Importance Aspirin use reduces the risk of colorectal carcinoma. Experimental evidence implicates a role of RAF kinases in up-regulation of prostaglandin-endoperoxide synthase 2 (PTGS2, cyclooxygenase 2), suggesting that BRAF-mutant colonic cells might be less sensitive to the antitumor effects of aspirin than BRAF-wild-type neoplastic cells. Objective To examine whether the association of aspirin intake with colorectal cancer risk differs according to status of tumor BRAF oncogene mutation. Design and Setting We collected biennial questionnaire data on aspirin use and followed up participants in the Nurses' Health Study (from 1980) and the Health Professionals Follow-up Study (from 1986) until July 1, 2006, for cancer incidence and until January 1, 2012, for cancer mortality. Duplication-method Cox proportional cause-specific hazards regression for competing risks data was used to compute hazard ratios (HRs) for colorectal carcinoma incidence according to BRAF mutation status. Main Outcomes and Measures Incidence of colorectal cancer cases according to tumor BRAF mutation status. Results Among 127 865 individuals, with 3 165 985 person-years of follow-up, we identified 1226 incident rectal and colon cancers with available molecular data. Compared with nonuse, regular aspirin use was associated with lower BRAF-wild-type cancer risk (multivariable HR, 0.73; 95% CI, 0.64 to 0.83; age-adjusted incidence rate difference [RD], -9.7; 95% CI, -12.6 to -6.7 per 100000 person-years). This association was observed irrespective of status of tumor PTGS2 expression or PIK3CA or KRAS mutation. In contrast, regular aspirin use was not associated with a lower risk of BRAF-mutated cancer (multivariable HR, 1.03; 95% CI, 0.76 to 1.38; age-adjusted, incidence RD,0.7; 95% CI, -0.3 to 1.7 per 100000 person-years: P for heterogeneity=.037, between BRAF-wild-type vs BRAF-mutated cancer risks). Compared with no aspirin use, aspirin use of more than 14 tablets per week was associated with a lower risk of BRAF-wild-type cancer (multivariable HR, 0.43; 95% CI, 0.25 to 0.75; age-adjusted incidence RD,-19.8; 95% CI, -26.3 to -13.3 per 100000 person-years). The relationship between the number of aspirin tablets per week and colorectal cancer risk differed significantly by BRAF mutation status (P for heterogeneity = .005). Conclusions and Relevance Regular aspirin use was associated with lower risk of BRAF-wild-type colorectal cancer but not with BRAF-mutated cancer risk. These findings suggest that BRAF-mutant colon tumor cells may be less sensitive to the effect of aspirin. Given the modest absolute risk difference, further investigations are necessary to determine clinical implications of our findings. [ABSTRACT FROM AUTHOR]

Objective: Toidentify factors that influence the total and negative lymph node counts in colorectal cancer resection specimens independent of pathologists and surgeons. Design: We used multivariate negative binomial regression. Covariates included age, sex, body mass index, family history of colorectal carcinoma, year of diagnosis, hospital setting, tumor location, resected colorectal length (specimen length), tumor size, circumferential growth, TNM stage, lymphocytic reactions and other pathological features, and tumor molecular features (microsatellite instability, CpG island methylator phenotype, long interspersed nucleotide element 1 [LINE-1] methylation, and BRAF, KRAS, and PIK3CA mutations). Setting: Two US nationwide prospective cohort studies. Patients: Patients with rectal and colon cancer (N=918). Main Outcome Measures: The negative and total node counts (continuous). Results: Specimen length, tumor size, ascending colon location, T3N0M0 stage, and year of diagnosis were positively associated with the negative node count (all P⩽.002). Mutation of KRAS might also be positively associated with the negative node count (P=.03; borderline significance considering multiple hypothesis testing). Among node-negative (stages I and II) cases, specimen length, tumor size, and ascending colon location remained significantly associated with the node count (all P⩽.002), and PIK3CA and KRAS mutations might also be positively associated (P=.03 and P=.049, respectively, with borderline significance). Conclusions: This molecular pathological epidemiology study shows that specimen length, tumor size, tumor location, TNM stage, and year of diagnosis are operator- independent predictors of the lymph node count. These crucial variables should be examined in any future evaluation of the adequacy of lymph node harvest and nodal staging when devising individualized treatment plans for patients with colorectal cancer. [ABSTRACT FROM AUTHOR]

Context: Alterations of the WNT signaling pathway and cadherin-associated protein β 1 (CTNNB1 or β-catenin) have been implicated in colorectal carcinogenesis and metabolic diseases.Objective: To test the hypothesis that CTNNB1 activation in colorectal cancer modifies prognostic associations of body mass index (BMI) and level of postdiagnosis physical activity.Design, Setting, and Patients: Two US prospective cohort studies (Nurses' Health Study and the Health Professionals Follow-up Study) were used to evaluate CTNNB1 localization by immunohistochemistry in 955 patients with stage I, II, III, or IV colon and rectal cancer from 1980 through 2004. A Cox proportional hazards model was used to compute the hazard ratio (HR) for mortality, adjusting for clinical and tumor features, including microsatellite instability, CpG island methylator phenotype, level of long interspersed nucleotide element 1 methylation, mutations in KRAS, BRAF, or PIK3CA, and tumor protein p53.Main Outcome Measures: Colorectal cancer-specific mortality and overall mortality through June 30, 2009.Results: In obese patients (BMI ≥30), positive status for nuclear CTNNB1 was associated with significantly better colorectal cancer-specific survival (adjusted HR, 0.24 [95% confidence interval {CI}, 0.12-0.49], P <.001 for interaction; 5-year survival: 0.85 for patients with positive nuclear CTNNB1 status vs 0.78 for those with negative status) and overall survival (adjusted HR, 0.56 [95% CI, 0.35-0.90], P = .03 for interaction; 5-year survival: 0.77 for patients with positive nuclear CTNNB1 status vs 0.74 for those with negative status), while CTNNB1 status was not associated with prognosis among nonobese patients (BMI <30). Among patients with negative status for nuclear CTNNB1 and cancer in stages I, II, or III, postdiagnosis physical activity was associated with better colorectal cancer-specific survival (adjusted HR, 0.33 [95% CI, 0.13-0.81], P = .05 for interaction; 5-year survival: 0.97 for ≥18 vs 0.89 for <18 metabolic equivalent task hours/week), while postdiagnosis physical activity was not associated with colorectal cancer-specific survival among patients with positive status for nuclear CTNNB1 (adjusted HR, 1.07 [95% CI, 0.50-2.30]).Conclusions: Among obese patients only, activation of CTNNB1 was associated with better colorectal cancer-specific survival and overall survival. Postdiagnosis physical activity was associated with better colorectal cancer-specific survival only among patients with negative status for nuclear CTNNB1. These molecular pathological epidemiology findings suggest that the effects of alterations in the WNT-CTNNB1 pathway on outcome are modified by BMI and physical activity. [ABSTRACT FROM AUTHOR]

The article focuses on a study on the association of wingless type (WNT)-cadherin-associated protein β1 (CTNNB1 or βcatenin) activation in colorectal cancer with changes in the prognostic associations of body mass index (BMI) and level of postdiagnosis physical activity. The study has involved data from the Nurses' Health Study and the Health Professionals Follow-up Study in which cohort participants received follow-up questionnaires on dietary and lifestyle factors and new cancer diagnosis. Results of the study are given, one is the association between the positive status for nuclear CTNNB1 and better cancer-specific and overall mortality in obese patients. It concludes that tumor cell behavior is influenced by CTNNB1 changes and energy balance status.

Background: The monoclonal antibody natalizumab is a novel therapeutic option in the treatment of relapsing forms of multiple sclerosis. In general, therapy with natalizumab is well tolerated. Allergic reactions and acute infusion reactions typically occur during or shortly after infusion, with a peak at the second infusion. Delayed infusion reactions resembling serum sickness-type reactions (type III reaction) are commonly reported in other monoclonal antibody therapies (eg, infliximab and rituximab), but are not described yet for natalizumab. Results: Delayed infusion reactions occurred in 4 of 40 relapse-remitting multiple sclerosis patients treated with natalizumab. Conclusions: Clinicians need to consider the occurrence of infusion reactions, with especially delayed reactions occurring more frequently than previously assumed. Our cases illustrate that some of these infusion reactions may be treated effectively with steroids and reduction of the infusion rate. In cases of antibodymediated reactions, treatment should be stopped immediately. [ABSTRACT FROM AUTHOR]