Rising Incidence of Non-Cardia Gastric Cancer among Young Women in the United States, 2000-2018: A Time-Trend Analysis Using the USCS Database.

INTRODUCTION: Although the global incidence of non-cardia gastric cancer (NCGC) is decreasing, there are limited data on sex-specific incidence in the United States. This study aimed to investigate time trends of NCGC from the SEER database to externally validate findings in a SEER-independent national database, and to further assess trends among subpopulations. METHODS: Age-adjusted incidence rates of NCGC were obtained from the SEER database from 2000 to 2018. We used joinpoint models to calculate average annual percentage change (AAPC) to determine sex-specific trends among older (≥55 years) and younger adults (15-54 years). Using the same methodology, findings were then externally validated using SEER-independent data from the National Program of Cancer Registries (NPCR). Stratified analyses by race, histopathology, and staging at diagnosis were also conducted in younger adults. RESULTS: Overall, there were 169,828 diagnoses of NCGC from both independent databases during the period 2000-2018. In SEER, among those <55 years, incidence increased at a higher rate in women (AAPC = 3.22%, p < 0.01) than men (AAPC = 1.51%, p = 0.03), with non-parallel trends (p = 0.02), while a decreasing trend was seen in both men (AAPC = -2.16%, p < 0.01) and women (AAPC = -1.37%, p < 0.01) of the ≥55 years group. Validation analysis of the SEER-independent NPCR database from 2001 to 2018 showed similar findings. Further stratified analyses showed that incidence is disproportionately increasing in young non-Hispanic White women [AAPC = 2.28%, p < 0.01] while remaining stable in their counterpart men [AAPC = 0.58%, p = 0.24] with non-parallel trends (p = 0.04). This pattern was not observed in other race groups. CONCLUSION: NCGC incidence has been increasing at a greater rate in younger women compared to counterpart men. This disproportionate increase was mainly seen in young non-Hispanic White women. Future studies should investigate the etiologies of these trends.

Association Between Metabolic Syndrome Inflammatory Biomarkers and COVID-19 Severity.

Context: Metabolic syndrome (MetS) is associated with increased risk of severe COVID-19. MetS inflammatory biomarkers share similarities with those of COVID-19, yet this association is poorly explored. Objective: Biomarkers of COVID-19 patients with and without MetS, the combination of diabetes, hypertension, obesity, and/or dyslipidemia, were analyzed to identify biological predictors of COVID-19 severity. Methods: In this prospective observational study, at a large academic emergency department in Boston, Massachusetts, clinical and proteomics data were analyzed from March 24 to April 30, 2020. Patients age ≥18 with a clinical concern for COVID-19 upon arrival and acute respiratory distress were included. The main outcome was severe COVID-19 as defined using World Health Organization COVID-19 outcomes scores ≤4, which describes patients who died, required invasive mechanical ventilation, or required supplemental oxygen. Results: Among 155 COVID-19 patients, 90 (58.1%) met the definition of MetS and 65 (41.9%) were identified as Control. The MetS cohort was more likely to have severe COVID-19 compared with the Control cohort (OR 2.67 [CI 1.09-6.55]). Biomarkers, including CXCL10 (OR 1.94 [CI 1.38-2.73]), CXCL9 (OR 1.79 [CI 1.09-2.93]), HGF (OR 3.30 [CI 1.65-6.58]), and IL6 (OR 2.09 [CI 1.49-2.94]) were associated with severe COVID-19. However, when stratified by MetS, only CXCL10 (OR 2.39 [CI 1.38-4.14]) and IL6 (OR 3.14 [CI 1.53-6.45]) were significantly associated with severe COVID-19. Conclusions: MetS-associated severe COVID-19 is characterized by an immune signature of elevated levels of CXCL10 and IL6. Clinical trials targeting CXCL10 or IL6 antagonism in this population may be warranted.

Increasing Pancreatic Cancer Incidence in Young Women in the United States: A Population-Based Time-Trend Analysis, 2001-2018.

BACKGROUND & AIMS: Previous studies have shown an increasing incidence of pancreatic cancer (PC), especially in younger women; however, this has not been externally validated. In addition, there are limited data about contributing factors to this trend. We report age and sex-specific time-trend analysis of PC age-adjusted incidence rates (aIRs) using the National Program of Cancer Registries database without Surveillance Epidemiology and End Results data. METHODS: PC aIR, mortality rates, annual percentage change, and average annual percentage change (AAPC) were calculated and assessed for parallelism and identicalness. Age-specific analyses were conducted in older (≥55 years) and younger (<55 years) adults. PC incidence based on demographics, tumor characteristics, and mortality were evaluated in younger adults. RESULTS: A total of 454,611 patients were diagnosed with PC between 2001 and 2018 with significantly increasing aIR in women (AAPC = 1.27%) and men (AAPC = 1.14%) without a difference (P = .37). Similar results were seen in older adults. However, in younger adults (53,051 cases; 42.9% women), women experienced a greater increase in aIR than men (AAPCs = 2.36%, P < .001 vs 0.62%, P = 0.62) with nonparallel trends (P < .001) and AAPC difference of 1.74% (P < .001). This AAPC difference appears to be due to rising aIR in Blacks (2.23%; P < .001), adenocarcinoma histopathologic subtype (0.89%; P = .003), and location in the head-of-pancreas (1.64%; P < .001). PC mortality was found to be unchanged in women but decreasing in counterpart men (AAPC difference = 0.54%; P = .001). CONCLUSION: Using nationwide data, covering ≈64.5% of the U.S. population, we externally validate a rapidly increasing aIR of PC in younger women. There was a big separation of the incidence trend between women and men aged 15-34 years between 2001 and 2018 (>200% difference), and it did not show slowing down.

Pancreatic Cancer Incidence Trends by Race, Ethnicity, Age and Sex in the United States: A Population-Based Study, 2000-2018.

BACKGROUND AND AIMS: Pancreatic cancer (PC) incidence is increasing at a greater rate in young women compared to young men. We performed a race- and ethnicity-specific evaluation of incidence trends in subgroups stratified by age and sex to investigate the association of race and ethnicity with these trends. METHODS: Age-adjusted PC incidence rates (IR) from the years 2000 to 2018 were obtained from the SEER 21 database. Non-Hispanic White (White), Non-Hispanic Black (Black) and Hispanic patients were included. Age categories included older (ages ≥ 55) and younger (ages < 55) adults. Time-trends were described as annual percentage change (APC) and average APC (AAPC). RESULTS: Younger White [AAPC difference = 0.73, p = 0.01)], Black [AAPC difference = 1.96, p = 0.01)] and Hispanic [AAPC difference = 1.55, p = 0.011)] women experienced a greater rate of increase in IR compared to their counterpart men. Younger Hispanic women experienced a greater rate of increase in IR compared to younger Black women [AAPC difference = -1.28, p = 0.028)] and younger White women [AAPC difference = -1.35, p = 0.011)]. CONCLUSION: Younger women of all races and ethnicities experienced a greater rate of increase in PC IR compared to their counterpart men; however, younger Hispanic and Black women experienced a disproportionately greater increase. Hispanic women experienced a greater rate of increase in IR compared to younger Black and White women.

Safety and Tolerability of High-Resolution Esophageal Manometry in Children and Adults.

INTRODUCTION: While high-resolution manometry (HRM) is widely accepted as a safe procedure, no study has assessed the safety profile of HRM in clinical practice. This study aimed to determine the safety and tolerability of HRM and to investigate potential determinants of intolerability. METHODS: We obtained HRM procedure reports, demographics, and clinical data (2005-2022) at a tertiary center using electronic chart review. Our primary outcome was HRM tolerability. Multivariable regression was performed to identify associations between the outcome and covariates including age, sex, race, and comorbidities. RESULTS: A total of 5,107 patients (60.3% female) were included. Of them, 5,050 patients (98.9%) tolerated HRM well and 57 patients (1.1%) did not. Age had a statistically significant effect on tolerance: those younger than 18 years had more than a 5-fold increase in not tolerating HRM compared with those aged 18-79 years (5.77% vs 0.99%; odds ratio [OR] = 5.44, 95% confidence interval [CI] 1.60-18.45; P = 0.007), and those aged 80 years or older were also more likely to terminate HRM (2.43% vs 0.99%; OR = 2.56, 95% CI 1.13-5.76; P = 0.024). While prior foregut surgery had a significant effect on tolerance (OR = 8.06, 95% CI 2.29-28.39; P = 0.001), other factors of race, sex, body mass index, and psychological or cognitive disorders had no significant impact. No serious complications were identified. DISCUSSION: HRM is safe and well-tolerated with approximately 1 in every 100 patients being unable to tolerate HRM. Intolerance was more commonly seen in children and seniors due to minor symptoms of discomfort without serious complications. These data points are crucial to counsel patients in whom HRM is being considered.

Abdominal Bloating in the United States: Results of a Survey of 88,795 Americans Examining Prevalence and Healthcare Seeking.

BACKGROUND & AIMS: Although abdominal bloating is a common symptom, comparatively little is known about its prevalence in the community. This study aimed to examine the prevalence of bloating and assess related health care seeking using survey data from a nationally representative sample of nearly 89,000 Americans. METHODS: Participants completed the National Gastrointestinal (GI) Survey II to measure the presence and severity of GI symptoms including bloating. We assessed the prevalence of bloating in the past 7 days, as well as severity and health care seeking for bloating. Multivariable regression was performed to identify associations between the outcomes and covariates. RESULTS: Of 88,795 survey completers, 12,324 (13.9%) reported bloating in the past 7 days. Women and those with comorbidities (eg, irritable bowel syndrome, chronic constipation, ulcerative colitis) and concomitant GI symptoms (eg, abdominal pain, excess gas) had higher odds for bloating (all P < .001). These factors were also associated with more severe bloating (all P < .001). Among those who reported recent bloating, 58.5% never sought care for bloating-29% of whom were self-managing symptoms or were uncomfortable discussing symptoms with their providers. CONCLUSIONS: Bloating is common in the community because nearly 1 in 7 Americans have experienced this symptom in the past week. Women and those with certain comorbidities and concomitant GI symptoms are more likely to experience bloating and have more severe symptoms. Nearly one third of sufferers who have not sought care are managing symptoms on their own or are uncomfortable discussing it with their providers, emphasizing that efforts should be made to proactively inquire about bloating.

Measuring and Improving Quality of Colonoscopy for Colorectal Cancer Screening.

Colorectal cancer (CRC) is largely preventable, yet it remains a major public health issue as it is the third most common and deadly malignancy in the United States. While there are many ways to screen for CRC, colonoscopy remains the gold standard as it is the only test that is both cancer-detecting and cancer-preventing through removal of precancerous polyps. Through identifying and removing neoplastic lesions, colonoscopy reduces CRC incidence by 31%-91% and CRC mortality by 65%-88%. However, colonoscopy is not an infallible test-there is a chance for missed lesions during the exam and there is substantial variation in outcomes among endoscopists. To enhance the quality of colonoscopic exams, and ultimately to improve CRC outcomes, quality indicators have been developed for measuring endoscopists' performance. In this review, we describe the colonoscopic quality indicators and benchmarks recommended by the American Society for Gastrointestinal Endoscopy/American College of Gastroenterology Task Force on Quality in Endoscopy for screening colonoscopies in average-risk individuals. Measuring and monitoring endoscopists' performance on these measures are critical first steps in striving toward conducting high quality exams. We also review the evidence for interventions that aim to improve critical measures including adenoma detection rate, withdrawal time, cecal intubation, and bowel preparation quality. Finally, we provide a preview of the forthcoming Advancing Care for Appropriate Colon Health Merit-Based Incentive Payment System Value Pathway by the Centers for Medicare & Medicaid Services and its potential impact on clinical practice.

Singapore First Aid Guidelines 2021.

The Singapore Resuscitation and First Aid Council is updating the guidelines for first aid based on the latest evidence-based review from the International First Aid Taskforce Consensus on Science with Treatment Recommendations published in 2020. This is part of the regular updating of standards of care and training for first aid. This article presents some of the updated evidence-based approaches to first aid treatments in common emergencies such as asthma, chronic bronchitis, anaphylaxis, shock, unresponsiveness, seizure, heat disorders, ingested poisons, bleeding, head and spinal injury, bites and dental injuries. These updated treatments will be incorporated into the Standard and Child First Aid course syllabus in Singapore.

Racial Disparities in Malignant Primary Brain Tumor Survival in Texas From 1995 to 2013.

BACKGROUND: Differences among the top five races in Texas will be explored to determine if racial, geographic, and healthcare disparities exist in patients undergoing treatment for a primary malignant brain tumor. METHODS: Data were obtained from the Texas Cancer Registry from 1995 to 2013. SAS 9.3 (SAS Institute, Inc., Cary, NC) and SEER*Stat 8.3.2 (National Cancer Institute, Bethesda, MD) software were used to analyze death from malignant brain tumors and cause-specific survival. Survival rates were compared using Kaplan-Meier curves and Log-Rank tests. Hazard ratios were estimated using the Cox proportional hazards regression model. RESULTS: Median survival was highest among Asians at 92 months (95% CI: 72, 142) and least among Whites at 20 months (95% CI: 19, 21). Patients living in the Upper Gulf Coast region of Texas had the longest survival time at 31 months (95% CI 29-35%), while those patients in the Texas Panhandle had the shortest survival time at 18 months (95% CI 14-23%). Patients with a poverty index of 0-5% had the highest median survival time of 32 months (95% CI 29-35%), as compared to patients with a poverty index of 10-20% who had a median survival of 22 months (95% CI 21-24%). CONCLUSIONS: Ethnic minorities and higher socioeconomic class demonstrated survival advantage. White males had the worst survival of those with primary malignant brain tumors. Other significant factors affecting a patient's survival rate included geographic location, poverty index, sex, and age, thus suggesting a potential genetic and environmental influence.

A preliminary study for the assessment of PD-L1 and PD-L2 on circulating tumor cells by microfluidic-based chipcytometry.

AIM: Expression of PD-L1 in the tumor is associated with more favorable responses to anti-PD-1 therapy in multiple cancers. However, obtaining tumor biopsies for PD-L1 interrogation is an invasive procedure and challenging to assess repeatedly as the disease progresses. MATERIALS & METHODS: Here we assess an alternative, minimally invasive approach to analyze blood samples for circulating tumor cells (CTCs) that have broken away from the tumor and entered the periphery. Our approach uses sized-based microfluidic CTC enrichment and subsequent characterization with microfluidic-based cytometry (chipcytometry). CONCLUSION: We demonstrate tumor-cell detection and characterization for PD-L1, and other markers, in both spiked and patient samples. This preliminary communication is the first report using chipcytometry for the characterization of CTCs.

Approaches to Predicting Outcomes in Patients with Acute Kidney Injury.

Despite recognition that Acute Kidney Injury (AKI) leads to substantial increases in morbidity, mortality, and length of stay, accurate prognostication of these clinical events remains difficult. It remains unclear which approaches to variable selection and model building are most robust. We used data from a randomized trial of AKI alerting to develop time-updated prognostic models using stepwise regression compared to more advanced variable selection techniques. We randomly split data into training and validation cohorts. Outcomes of interest were death within 7 days, dialysis within 7 days, and length of stay. Data elements eligible for model-building included lab values, medications and dosages, procedures, and demographics. We assessed model discrimination using the area under the receiver operator characteristic curve and r-squared values. 2241 individuals were available for analysis. Both modeling techniques created viable models with very good discrimination ability, with AUCs exceeding 0.85 for dialysis and 0.8 for death prediction. Model performance was similar across model building strategies, though the strategy employing more advanced variable selection was more parsimonious. Very good to excellent prediction of outcome events is feasible in patients with AKI. More advanced techniques may lead to more parsimonious models, which may facilitate adoption in other settings.

Provider acceptance of an automated electronic alert for acute kidney injury.

BACKGROUND: Clinical decision support systems, including electronic alerts, ideally provide immediate and relevant patient-specific information to improve clinical decision-making. Despite the growing capabilities of such alerts in conjunction with an expanding electronic medical record, there is a paucity of information regarding their perceived usefulness. We surveyed healthcare providers' opinions concerning the practicality and efficacy of a specific text-based automated electronic alert for acute kidney injury (AKI) in a single hospital during a randomized trial of AKI alerts. METHODS: Providers who had received at least one electronic AKI alert in the previous 6 months, as part of a separate randomized controlled trial (clinicaltrials.gov #01862419), were asked to complete a survey concerning their opinions about this specific AKI alert system. Individual approval of the alert system was defined by a provider's desire to continue receiving the alert after termination of the trial. RESULTS: A total of 98 individuals completed the survey, including 62 physicians, 27 pharmacists and 7 non-physician providers. Sixty-nine percent of responders approved the alert, with no significant difference among the various professions (P = 0.28). Alert approval was strongly correlated with the belief that the alerts improved patient care (P < 0.0001), and negatively correlated with the belief that alerts did not provide novel information (P = 0.0001). With each additional 30 days of trial duration, odds of approval decreased by 20% (3-35%) (P = 0.02). CONCLUSIONS: The alert system was generally well received, although approval waned with time. Approval was correlated with the belief that this type of alert improved patient care. These findings suggest that perceived efficacy is critical to the success of future alert trials.

Intermedilysin release by Streptococcus intermedius: effects of various antibacterial drugs at sub-MIC levels.

Intermedilysin is a cytolytic toxin produced by Streptococcus intermedius, a pathogen of humans. In vitro studies showed that exposure of S. intermedius to sub-minimum inhibitory concentration (MIC) levels (1/2 MIC) of protein-inhibiting antibiotics and nucleic acid-inhibiting antibiotics decreased intermedilysin release by S. intermedius. The most potent antibiotic was clindamycin. On the other hand, exposure to cell wall-inhibiting antibiotics generally showed insignificant changes in intermedilysin release at sub-MIC concentrations. Investigations into possible mechanisms underlying this sub-MIC effect with clindamycin showed that there was selective decrease in biosynthesis and release of toxin after exposure to 1/2 MIC condition. However, no significant differences in the mRNA levels of the intermedilysin gene were observed.