The utility of a CT grading scale in deciding on surgical intervention for patients with suspected small bowel obstruction.

Background: A grading system was developed for computerized tomography (CT) scans evaluating patients with suspected small bowel obstruction (SBO). We hypothesized that patients with a higher grade of suspected SBO on CT scan would be more likely to require surgical intervention. Methods: Retrospective chart review of patients who presented to the Emergency Room (ER) who had a CT of the abdomen and pelvis for suspected SBO. Patients were divided into 5 groups: Grade 1 (SBO unlikely), Grade 2 (probable partial or early SBO), Grade 3 (probable high grade SBO), Grade 4 (SBO with changes concerning for ischemia) and Not Graded. Results: The CT scans of 655 patients were graded. Of the 22 patients with a grade 1 SBO, only 1 went for surgery (4.5 %). For grade 2 patients, 23 out of 299 had an operation (7.7 %), for grade 3 it was 84 out of 299 (28.1 %) and for grade 4 SBO, 25 out of 35 patients (71.4 %) had surgery. The p value is <0.00001. The three most common intraoperative findings were SBO obstruction from adhesions alone (48 % of cases), followed by incarcerated hernias (12 %) and ischemic bowel (9 %). Only 8 cases out of 133 operations (6 % of total) had no findings at time of surgery other than dilated bowel. Conclusions: The CT grading scale for SBO developed at our institution shows excellent correlation between grade and going for surgery, with few negative results, and can be a useful tool among other factors for general surgeons when deciding whether or not to operate on a patient with suspected SBO.

Protocol for three-dimensional whole-mount imaging of the vascular network in the intestinal muscle.

Three-dimensional (3D) imaging of vascular networks is essential for the investigation of vascular patterning and organization. Here, we present a step-by-step protocol for the 3D visualization of the vasculature within whole-mount preparations of the mouse intestinal muscularis propria layer. We then detail the quantitative analysis of the resulting images for parameters such as vessel density, vessel diameter, the number of endothelial cells, and proliferation. The protocol can be easily extended to study cell-cell interactions such as neuro-vascular or immune-vascular interactions. For complete details on the use and execution of this protocol, please refer to Schrenk et al.1.

Microbial community organization designates distinct pulmonary exacerbation types and predicts treatment outcome in cystic fibrosis.

Polymicrobial infection of the airways is a hallmark of obstructive lung diseases such as cystic fibrosis (CF), non-CF bronchiectasis, and chronic obstructive pulmonary disease. Pulmonary exacerbations (PEx) in these conditions are associated with accelerated lung function decline and higher mortality rates. Understanding PEx ecology is challenged by high inter-patient variability in airway microbial community profiles. We analyze bacterial communities in 880 CF sputum samples collected during an observational prospective cohort study and develop microbiome descriptors to model community reorganization prior to and during 18 PEx. We identify two microbial dysbiosis regimes with opposing ecology and dynamics. Pathogen-governed PEx show hierarchical community reorganization and reduced diversity, whereas anaerobic bloom PEx display stochasticity and increased diversity. A simulation of antimicrobial treatment predicts better efficacy for hierarchically organized communities. This link between PEx, microbiome organization, and treatment success advances the development of personalized clinical management in CF and, potentially, other obstructive lung diseases.

Rationale and design for a pragmatic randomized trial to assess gene-based prescribing for SSRIs in the treatment of depression.

Specific selective serotonin reuptake inhibitors (SSRIs) metabolism is strongly influenced by two pharmacogenes, CYP2D6 and CYP2C19. However, the effectiveness of prospectively using pharmacogenetic variants to select or dose SSRIs for depression is uncertain in routine clinical practice. The objective of this prospective, multicenter, pragmatic randomized controlled trial is to determine the effectiveness of genotype-guided selection and dosing of antidepressants on control of depression in participants who are 8 years or older with ≥3 months of depressive symptoms who require new or revised therapy. Those randomized to the intervention arm undergo pharmacogenetic testing at baseline and receive a pharmacy consult and/or automated clinical decision support intervention based on an actionable phenotype, while those randomized to the control arm have pharmacogenetic testing at the end of 6-months. In both groups, depression and drug tolerability outcomes are assessed at baseline, 1 month, 3 months (primary), and 6 months. The primary end point is defined by change in Patient-Reported Outcomes Measurement Information System (PROMIS) Depression score assessed at 3 months versus baseline. Secondary end points include change inpatient health questionnaire (PHQ-8) measure of depression severity, remission rates defined by PROMIS score < 16, medication adherence, and medication side effects. The primary analysis will compare the PROMIS score difference between trial arms among those with an actionable CYP2D6 or CYP2C19 genetic result or a CYP2D6 drug-drug interaction. The trial has completed accrual of 1461 participants, of which 562 were found to have an actionable phenotype to date, and follow-up will be complete in April of 2024.

"Understanding why she had to leave me": The roles of religion and spirituality in narratives of parents grieving the loss of a child to cancer.

Religion and spirituality often influence how people experience illness, death, and grief. The roles of religion and spirituality for parents who have lost a child to cancer remain underexplored. This study aimed to describe how cancer-bereaved parents talk about religion and spirituality when reflecting on their experiences. Participants whose children died of cancer one to six years prior to participation completed a one-on-one semi-structured interview. Interview transcripts underwent qualitative analysis. Content pertaining to religion and/or spirituality underwent subsequent in-depth analysis to identify themes. Of 30 interviews analyzed, 28 contained religion/spirituality content. Four themes arose: (1) life after death, (2) divine control, (3) evolution of faith after loss, and (4) religious and spiritual interactions within the medical community. The absence of supports for religious and spiritual needs represents a gap in bereavement care. Future work should clarify needs and explore potential interventions.

Itaconic acid inhibits nontuberculous mycobacterial growth in pH dependent manner while 4-octyl-itaconic acid enhances THP-1 clearance of nontuberculous mycobacteria in vitro.

Increasingly prevalent, nontuberculous mycobacteria (NTM) infections affect approximately 20% of people with cystic fibrosis (CF). Previous studies of CF sputum identified lower levels of the host metabolite itaconate in those infected with NTM. Itaconate can inhibit the growth of M. tuberculosis (MTB) in vitro via the inhibition of the glyoxylate cycle enzyme (ICL), but its impact on NTM is unclear. To test itaconic acid's (IA) effect on NTM growth, laboratory and CF clinical strains of Mycobacterium abscessus and Mycobacterium avium were cultured in 7H9 minimal media supplemented with 1-10 mM of IA and short-chain fatty acids (SCFA). M. avium and M. abscessus grew when supplemented with SCFAs, whereas the addition of IA (≥ 10 mM) completely inhibited NTM growth. NTM supplemented with acetate or propionate and 5 mM IA displayed slower growth than NTM cultured with SCFA and ≤ 1 mM of IA. However, IA's inhibition of NTM was pH dependent; as similar and higher quantities (100 mM) of pH adjusted IA (pH 7) did not inhibit growth in vitro, while in an acidic minimal media (pH 6.1), 1 to 5 mM of non-pH adjusted IA inhibited growth. None of the examined isolates displayed the ability to utilize IA as a carbon source, and IA added to M. abscessus isocitrate lyase (ICL) decreased enzymatic activity. Lastly, the addition of cell-permeable 4-octyl itaconate (4-OI) to THP-1 cells enhanced NTM clearance, demonstrating a potential role for IA/itaconate in host defense against NTM infections.

Factors Determining Black Carbon Exposures among Pregnant Women Enrolled in the HAPIN Trial.

Residential biomass burning is an important source of black carbon (BC) exposure among rural communities in low- and middle-income countries. We collected 7165 personal BC samples and individual/household level information from 3103 pregnant women enrolled in the Household Air Pollution Intervention Network trial. Women in the intervention arm received free liquefied petroleum gas stoves and fuel throughout pregnancy; women in the control arm continued the use of biomass stoves. Median (IQR) postintervention BC exposures were 9.6 µg/m3 (5.2-14.0) for controls and 2.8 µg/m3 (1.6-4.8) for the intervention group. Using mixed models, we characterized predictors of BC exposure and assessed how exposure contrasts differed between arms by select predictors. Primary stove type was the strongest predictor (R2 = 0.42); the models including kerosene use, kitchen location, education, occupation, or stove use hours also provided additional explanatory power from the base model adjusted only for the study site. Our full, trial-wide, model explained 48% of the variation in BC exposures. We found evidence that the BC exposure contrast between arms differed by study site, adherence to the assigned study stove, and whether the participant cooked. Our findings highlight factors that may be addressed before and during studies to implement more impactful cookstove intervention trials.

A Web-Based Intervention for Insufficiently Active College Students: Feasibility and Preliminary Efficacy.

BACKGROUND: One third of college students do not achieve aerobic activity levels recommended for physical and mental health. The web-based "I Can Be Active!" intervention was designed to help college students increase their physical activity. The intervention was grounded in the Multi-Process Action Control (M-PAC) framework which emphasizes translating intention into sustainable action. OBJECTIVE: The primary purpose was to evaluate the feasibility of the intervention with insufficiently active young adult college students. The secondary purposes were to describe the preliminary effects of the intervention on: (1) the M-PAC constructs and (2) physical activity. METHODS: Twenty-one college students, ages 18 to 24, were enrolled in the pre-post quasi-experimental study to test the 8-week intervention during Spring 2021. Data were collected via self-report questionnaires, web-analytics, and interviews. Feasibility outcomes included recruitment, retention, acceptability, practicality, and implementation. Preliminary efficacy outcomes were self-report M-PAC constructs and physical activity. Data analyses included descriptive statistics, t tests, Wilcoxon signed rank tests, Hedge's g, and thematic analysis. RESULTS: Recruitment and retention rates were 70% and 71%, respectively. Participants reacted positively to the program, content, and features, except the manual entry step tracker and private social media group. Positive trends and significant increases were found in the regulatory and reflexive M-PAC constructs (self-regulation, habit, and identity) and physical activity. CONCLUSIONS: Findings support the feasibility and preliminary effects of the intervention for insufficiently active college students and highlight implications for intervention refinement. Future research will test intervention effectiveness using a randomized controlled trial with a larger diverse sample of college students.

Critical left main coronary artery stenosis presenting as cardiac arrest in coarctation of the aorta patient.

Congenital coronary artery stenosis coexisting with aortic coarctation in nonsyndromic patients has not previously been reported. This report describes a nonsyndromic aortic coarctation patient who experienced intraoperative cardiac arrest due to a previously undiagnosed critical left main coronary artery stenosis. The patient was successfully resuscitated, underwent patch coronary ostioplasty, and was discharged home. He remains well for four months following repair.

Gun violence revictimization in New York State: What increases the risk of being shot again?

BACKGROUND: While gun injuries are more likely to occur in in urban settings and affect people of color, factors associated with gun violence revictimization-suffering multiple incidents of gun violence-are unknown. We examined victim demographics and environmental factors associated with gun violence revictimization in New York state (NYS). METHODS: The 2005-2020 NYS hospital discharge database was queried for patients aged 12-65 years with firearm-related hospital encounters. Patient and environmental variables were extracted. Patient home zip code was used to determine the Social Deprivation Index (SDI) for each patient's area of residence. We conducted bivariate and multivariate analyses among patients who suffered a single incident of gun violence or gun violence revictimization. RESULTS: We identified 38,974 gun violence victims among whom 2,243 (5.8%) suffered revictimization. The proportion of revictimization rose from 4% in 2008 to 8% in 2020 (p < 0.01). The median [IQR] time from first to second incident among those who suffered revictimization was 359 [81-1,167] days. Revictimization was more common among Blacks (75.0% vs 65.1%, p < 0.01), patients with Medicaid (54.9% vs 43.2%, p < 0.01), and in areas of higher deprivation (84.8 percentile vs 82.1 percentile, p < 0.01). CONCLUSIONS: Gun violence revictimization is on the rise. People of color and those residing in areas with high social deprivation are more likely to be re-injured. Our findings emphasize the importance of community-level over individual-level interventions for prevention of gun violence revictimization. LEVEL OF EVIDENCE: Epidemiological, Level III.

Clinical factors associated with patterns of endocrine therapy adherence in premenopausal breast cancer patients.

INTRODUCTION: Patients with hormone receptor positive breast cancer are recommended at least five years of adjuvant endocrine therapy, but adherence to this treatment is often suboptimal. We investigated longitudinal trends in adjuvant endocrine therapy (AET) adherence among premenopausal breast cancer patients and identified clinical characteristics, including baseline comorbidities and non-cancer chronic medication use, associated with AET adherence. METHODS: We included stage I-III premenopausal breast cancer patients diagnosed during 2002-2011 and registered in the Danish Breast Cancer Group clinical database who initiated AET. We used group-based trajectory modeling to describe AET adherence patterns. We also linked patients to Danish population-based registries and fit multinomial logistic models to compute odds ratios (ORs) and 95% confidence intervals (95% CIs) associating clinical characteristics with AET adherence patterns. RESULTS: We identified three adherence patterns among 4,353 women-high adherers (57%), slow decliners (36%), and rapid decliners (6.9%). Women with stage I disease (vs. stage II; OR: 1.9, 95% CI 1.5, 2.5), without chemotherapy (vs. chemotherapy; OR: 4.3, 95% CI 3.0, 6.1), with prevalent comorbid disease (Charlson Comorbidity Index score ≥ 1 vs. 0; OR: 1.6, 95% CI 1.1, 2.3), and with a history of chronic non-cancer medication use (vs. none; OR: 1.3, 95% CI 1.0, 1.8) were more likely to be rapid decliners compared with high adherers. CONCLUSIONS: Women with stage I cancer, no chemotherapy, higher comorbidity burden, and history of chronic non-cancer medication use were less likely to adhere to AET. Taking steps to promote adherence in these groups of women may reduce their risk of recurrence.

Genomic Analysis and Surveillance of Respiratory Syncytial Virus (RSV) Using Wastewater-Based Epidemiology (WBE).

Respiratory syncytial virus (RSV) causes severe infections in infants, immunocompromised or elderly individuals resulting in annual epidemics of respiratory disease. Currently, limited clinical surveillance and the lack of predictable seasonal dynamics limits the public health response. Wastewater-based epidemiology (WBE) has recently been used globally as a key metric in determining prevalence of SARS-CoV-2 in the community but its application to other respiratory viruses is limited. In this study, we present an integrated genomic WBE approach, applying RT-qPCR and partial G-gene sequencing to track RSV levels and variants in the community. We report increasing detection of RSV in wastewater concomitant with increasing numbers of positive clinical cases. Analysis of wastewater-derived RSV sequences permitted identification of distinct circulating lineages within and between seasons. Altogether, our genomic WBE platform has the potential to complement ongoing global surveillance and aid the management of RSV by informing the timely deployment of pharmaceutical and non-pharmaceutical interventions.

Transplanting human infant gut microbiome species into Galleria mellonella.

OBJECTIVE: Study of the human infant gut microbiome requires the use of surrogate mammalian species such as mice. We sought to investigate the usefulness of the greater wax moth larva, Galleria mellonella, as an alternative. RESULTS: We have analysed the native gut microbiome of Galleria and developed methods for clearing the native microbiome and introducing species from human infant faecal samples. We find that some species, e.g. enterococci, are more successful at recolonisation, but that others, e.g. Bifidobacterium, are less so. The work paves the way for using Galleria rather than mice in this and similar work.

Unveiling the pathogenic mechanisms of Clostridium perfringens toxins and virulence factors.

Clostridium perfringens causes multiple diseases in humans and animals. Its pathogenic effect is supported by a broad and heterogeneous arsenal of toxins and other virulence factors associated with a specific host tropism. Molecular approaches have indicated that most C. perfringens toxins produce membrane pores, leading to osmotic cell disruption and apoptosis. However, identifying mechanisms involved in cell tropism and selective toxicity effects should be studied more. The differential presence and polymorphisms of toxin-encoding genes and genes encoding other virulence factors suggest that molecular mechanisms might exist associated with host preference, receptor binding, and impact on the host; however, this information has not been reviewed in detail. Therefore, this review aims to clarify the current state of knowledge on the structural features and mechanisms of action of the major toxins and virulence factors of C. perfringens and discuss the impact of genetic diversity of toxinotypes in tropism for several hosts.

Survival outcomes in pediatric patients with metastatic Ewing sarcoma who achieve a rapid complete response of pulmonary metastases.

PURPOSE: Our objectives were to compare overall survival (OS) and pulmonary relapse between patients with metastatic Ewing sarcoma (EWS) at diagnosis who achieve rapid complete response (RCR) and those with residual pulmonary nodules after induction chemotherapy (non-RCR). PATIENTS AND METHODS: This retrospective cohort study included children under 20 years with metastatic EWS treated from 2007 to 2020 at 19 institutions in the Pediatric Surgical Oncology Research Collaborative. Chi-square tests were conducted for differences among groups. Kaplan-Meier curves were generated for OS and pulmonary relapse. RESULTS: Among 148 patients with metastatic EWS at diagnosis, 61 (41.2%) achieved RCR. Five-year OS was 71.2% for patients who achieved RCR, and 50.2% for those without RCR (p = .04), and in multivariable regression among patients with isolated pulmonary metastases, RCR (hazards ratio [HR] 0.42; 95% confidence interval [CI]: 0.17-0.99) and whole lung irradiation (WLI) (HR 0.35; 95% CI: 0.16-0.77) were associated with improved survival. Pulmonary relapse occurred in 57 (37%) patients, including 18 (29%) in the RCR and 36 (41%) in the non-RCR groups (p = .14). Five-year pulmonary relapse rates did not significantly differ based on RCR (33.0%) versus non-RCR (47.0%, p = .13), or WLI (38.8%) versus no WLI (46.0%, p = .32). DISCUSSION: Patients with EWS who had isolated pulmonary metastases at diagnosis had improved OS if they achieved RCR and received WLI, despite having no significant differences in rates of pulmonary relapse.

Cognition and Amyloid-ß in Older Veterans: Characterization and Longitudinal Outcomes of Data-Derived Phenotypes.

Background: Within older Veterans, multiple factors may contribute to cognitive difficulties. Beyond Alzheimer's disease (AD), psychiatric (e.g., PTSD) and health comorbidities (e.g., TBI) may also impact cognition. Objective: This study aimed to derive subgroups based on objective cognition, subjective cognitive decline (SCD), and amyloid burden, and then compare subgroups on clinical characteristics, biomarkers, and longitudinal change in functioning and global cognition. Methods: Cluster analysis of neuropsychological measures, SCD, and amyloid PET was conducted on 228 predominately male Vietnam-Era Veterans from the Department of Defense-Alzheimer's Disease Neuroimaging Initiative. Cluster-derived subgroups were compared on baseline characteristics as well as 1-year changes in everyday functioning and global cognition. Results: The cluster analysis identified 3 groups. Group 1 (n = 128) had average-to-above average cognition with low amyloid burden. Group 2 (n = 72) had the lowest memory and language, highest SCD, and average amyloid burden; they also had the most severe PTSD, pain, and worst sleep quality. Group 3 (n = 28) had the lowest attention/executive functioning, slightly low memory and language, elevated amyloid and the worst AD biomarkers, and the fastest rate of everyday functioning and cognitive decline. CONCLUSIONS: Psychiatric and health factors likely contributed to Group 2's low memory and language performance. Group 3 was most consistent with biological AD, yet attention/executive function was the lowest score. The complexity of older Veterans' co-morbid conditions may interact with AD pathology to show attention/executive dysfunction (rather than memory) as a prominent early symptom. These results could have important implications for the implementation of AD-modifying drugs in older Veterans.

Evacuation and Health Care Outcomes Among Assisted Living Residents After Hurricane Irma.

Importance: Evacuation has been found to be associated with adverse outcomes among nursing home residents during hurricanes, but the outcomes for assisted living (AL) residents remain unknown. Objective: To examine the association between evacuation and health care outcomes (ie, emergency department visits, hospitalizations, mortality, and nursing home visits) among Florida AL residents exposed to Hurricane Irma. Design, Setting, and Participants: Retrospective cohort study using 2017 Medicare claims data. Participants were a cohort of Florida AL residents who were aged 65 years or older, enrolled in Medicare fee-for-service, and resided in 9-digit zip codes corresponding to US assisted living communities with 25 or more beds on September 10, 2017, the day of Hurricane Irma's landfall. Propensity score matching was used to match evacuated residents to those that sheltered-in-place based on resident and AL characteristics. Data were analyzed from September 2022 to February 2024. Exposure: Whether the AL community evacuated or sheltered-in-place before Hurricane Irma made landfall. Main Outcomes and Measures: Thirty- and 90-day emergency department visits, hospitalizations, mortality, and nursing home admissions. Results: The study cohort included 25 130 Florida AL residents (mean [SD] age 81 [9] years); 3402 (13.5%) evacuated and 21 728 (86.5%) did not evacuate. The evacuated group had 2223 women (65.3%), and the group that sheltered-in-place had 14 556 women (67.0%). In the evacuated group, 42 residents (1.2%) were Black, 93 (2.7%) were Hispanic, and 3225 (94.8%) were White. In the group that sheltered in place, 490 residents (2.3%) were Black, 707 (3.3%) were Hispanic, and 20 212 (93.0%) were White. After 1:4 propensity score matching, when compared with sheltering-in-place, evacuation was associated with a 16% greater odds of emergency department visits (adjusted odds ratio [AOR], 1.16; 95% CI, 1.01-1.33; P = .04) and 51% greater odds of nursing home visits (AOR, 1.51; 95% CI, 1.14-2.00; P = .01) within 30 days of Hurricane Irma's landfall. Hospitalization and mortality did not vary significantly by evacuation status within 30 or 90 days after the landfall date. Conclusions and Relevance: In this cohort study of Florida AL residents, there was an increased risk of nursing home and emergency department visits within 30 days of Hurricane Irma's landfall among residents from communities that evacuated before the storm when compared with residents from communities that sheltered-in-place. The stress and disruption caused by evacuation may yield poorer immediate health outcomes after a major storm for AL residents. Therefore, the potential benefits and harms of evacuating vs sheltering-in-place must be carefully considered when developing emergency planning and response.