Identification of environmental factors that promote intestinal inflammation.

Genome-wide association studies have identified risk loci linked to inflammatory bowel disease (IBD)1-a complex chronic inflammatory disorder of the gastrointestinal tract. The increasing prevalence of IBD in industrialized countries and the augmented disease risk observed in migrants who move into areas of higher disease prevalence suggest that environmental factors are also important determinants of IBD susceptibility and severity2. However, the identification of environmental factors relevant to IBD and the mechanisms by which they influence disease has been hampered by the lack of platforms for their systematic investigation. Here we describe an integrated systems approach, combining publicly available databases, zebrafish chemical screens, machine learning and mouse preclinical models to identify environmental factors that control intestinal inflammation. This approach established that the herbicide propyzamide increases inflammation in the small and large intestine. Moreover, we show that an AHR-NF-κB-C/EBPß signalling axis operates in T cells and dendritic cells to promote intestinal inflammation, and is targeted by propyzamide. In conclusion, we developed a pipeline for the identification of environmental factors and mechanisms of pathogenesis in IBD and, potentially, other inflammatory diseases.

Psychological Distress is Prevalent and Interdependent Among Patients with Decompensated Cirrhosis and Their Caregivers.

OBJECTIVES: Little is known about the interdependence of psychological distress among patients with decompensated cirrhosis (DC) and their caregivers. METHODS: In this cross-sectional study we examined the interdependence of psychological distress (Hospital Anxiety and Depression Scale) among 127 patient-caregiver dyads using Actor-Partner Interdependence Modeling. RESULTS: Among dyads, 26% had both partners reporting clinically significant anxiety and 18% reporting clinically significant depression. Caregiver anxiety significantly predicted patient depression (ß=0.20, p=0.02). CONCLUSIONS: Psychological distress was prevalent and interdependent among dyads. These results underscore the need to develop interventions to reduce psychological distress in both patients with DC and their caregivers.

Financial burden following adult liver transplantation is common and associated with adverse recipient outcomes.

The financial impact of liver transplantation has been underexplored. We aimed to identify associations between high financial burden (≥10% annual income spent on out-of-pocket medical costs) and work productivity, financial distress (coping behaviors in response to the financial burden), and financial toxicity (health-related quality of life, HRQOL) among adult recipients of liver transplant. Between June 2021 and May 2022, we surveyed 207 adult recipients of liver transplant across 5 US transplant centers. Financial burden and distress were measured by 25 items adapted from national surveys of cancer survivors. Participants also completed the Work Productivity and Activity Impairment and EQ-5D-5L HRQOL questionnaires. In total, 23% of recipients reported high financial burden which was significantly associated with higher daily activity impairment (32.9% vs. 23.3%, p =0.048). In adjusted analyses, the high financial burden was significantly and independently associated with delayed or foregone medical care (adjusted odds ratio, 3.95; 95% CI, 1.85-8.42) and being unable to afford basic necessities (adjusted odds ratio, 5.12; 95% CI: 1.61-16.37). Recipients experiencing high financial burden had significantly lower self-reported HRQOL as measured by the EQ-5D-5L compared to recipients with low financial burden (67.8 vs. 76.1, p =0.008) and an age-matched and sex-matched US general population (67.8 vs. 79.1, p <0.001). In this multicenter cohort study, nearly 1 in 4 adult recipients of liver transplant experienced a high financial burden, which was significantly associated with delayed or foregone medical care and lower self-reported HRQOL. These findings underscore the need to evaluate and address the financial burden in this population before and after transplantation.

Hospital-Level Care at Home for Patients with Cirrhosis.

BACKGROUND: Patients with cirrhosis have a 30-day readmission rate of over 30%. Novel care delivery models are needed to reduce healthcare costs and utilization associated with cirrhosis care. One such model is Home Hospital (HH), which provides inpatient-level care at home. Limited evidence currently exists supporting HH for cirrhosis patients. AIMS: The aims of this study were to characterize patients with cirrhosis who received hospital-level care at home in a two-site clinical trial and to describe the care they received. Secondary aims included describing their outcomes, including adverse events, readmissions and mortality. METHODS: We identified all patients with cirrhosis who enrolled in HH as part of a two-site clinical trial between 2017 and 2022. HH services include daily clinician visits, intravenous and oral medications, continuous vital sign monitoring, and telehealth specialist consultation. We collected sociodemographic data and analyzed HH stays, including interventions, outcomes, adverse events, and follow-up. RESULTS: 22 patients with cirrhosis (45% Hispanic; 50% limited English proficiency, median MELD-Na 12) enrolled in HH during the study period. Interventions included lab chemistries (82%), intravenous medications (77%), specialist consultation (23%), and advanced diagnostics/procedures (23%). The median length of stay was 7 days (IQR 4-12); 186 bed-days were saved. Two patients (9%) experienced adverse events (AKI). No patients required escalation of care; 9% were readmitted within 30 days. CONCLUSIONS: In this two-site study, HH was feasible for patients with cirrhosis, holding promise as a hepatology delivery model. Future randomized trials are needed to further evaluate the efficacy of HH for patients with cirrhosis.

Prognosis of Transplant-Ineligible Patients with Cirrhosis and Acute Kidney Injury Who Initiate Renal Replacement Therapy.

BACKGROUND: Data to guide dialysis decision-making for transplant-ineligible patients with cirrhosis are lacking. AIMS: We aimed to describe the processes, predictors, and outcomes of renal replacement therapy (RRT) initiation for transplant-ineligible patients with cirrhosis at a single liver transplantation center. METHODS: We conducted a mixed-methods study of a retrospective cohort of 372 transplant-ineligible inpatients with cirrhosis with acute kidney injury (AKI) due to hepatorenal syndrome (HRS-AKI) or acute tubular necrosis (ATN) between 2008 and 2015. We performed survival analyses to evaluate 6-month survival and renal recovery and examined end-of-life care outcomes. We used a consensus-driven medical record review to characterize processes leading to RRT initiation. RESULTS: We identified 266 (71.5%) patients who received RRT and 106 (28.5%) who did not receive RRT (non-RRT). Median survival was 12.5 days (RRT) vs. 2.0 days (non-RRT) (HR 0.36, 95%CI 0.28-0.46); 6-month survival was 15% (RRT) vs. 0% (non-RRT). RRT patients were more likely to die in the intensive care unit (88% vs. 32%, p < 0.001). HRS-AKI patients were more likely to be RRT dependent at 6 months than ATN patients (86% vs. 27%, p = 0.007). The most common reasons for RRT initiation were unclear etiology of AKI on presentation (32%) and belief of likely reversibility of ATN (82%). CONCLUSION: Most transplant-ineligible patients who were initiated on RRT experienced very short-term mortality and received intensive end-of-life care. However, approximately 1 in 6 were alive at 6 months. Our findings underscore the critical need for structured clinical processes to support high-quality serious illness communication and RRT decision-making for this population.

Health care-related transportation insecurity is associated with adverse health outcomes among adults with chronic liver disease.

BACKGROUND: Health care-related transportation insecurity (delayed or forgone medical care due to transportation barriers) is being increasingly recognized as a social risk factor affecting health outcomes. We estimated the national burden and adverse outcomes of health care-related transportation insecurity among US adults with chronic liver disease (CLD). METHODS: Using the U.S. National Health Interview Survey from 2014 to 2018, we identified adults with self-reported CLD. We used complex weighted survey analysis to obtain national estimates of health care-related transportation insecurity. We examined the associations between health care-related transportation insecurity and health care-related financial insecurity, food insecurity, self-reported health status, work productivity, health care use, and mortality. RESULTS: Of the 3643 (representing 5.2 million) US adults with CLD, 267 [representing 307,628 (6%; 95% CI: 5%-7%)] reported health care-related transportation insecurity. Adults with CLD experiencing health care-related transportation insecurity had 3.5 times higher odds of cost-related medication nonadherence [aOR, 3.5; (2.4-5.0)], 3.5 times higher odds of food insecurity [aOR, 3.5; (2.4-5.3)], 2.5 times higher odds of worsening self-reported health status over the past year [aOR, 2.5; (1.7-3.7)], 3.1 times higher odds of being unable to work due to poor health over the past year [aOR, 3.1; (2.0-4.9)], and 1.7 times higher odds of being in a higher-risk category group for number of hospitalizations annually [aOR, 1.7; (1.2-2.5)]. Health care-related transportation insecurity was independently associated with mortality after controlling for age, income, insurance status, comorbidity burden, financial insecurity, and food insecurity [aHR, 1.7; (1.4-2.0)]. CONCLUSIONS: Health care-related transportation insecurity is a critical social risk factor that is associated with health care-related financial insecurity, food insecurity, poorer self-reported health status and work productivity, and increased health care use and mortality among US adults with CLD. Efforts to screen for and reduce health care-related transportation insecurity are warranted.

The Edmonton Symptom Assessment System is a valid, reliable, and responsive tool to assess symptom burden in decompensated cirrhosis.

BACKGROUND: While there is a growing need for interventions addressing symptom burden in patients with decompensated cirrhosis (DC), the lack of validated symptom assessment tools is a critical barrier. We investigated the psychometric properties of the revised Edmonton Symptom Assessment System (ESAS-r) in a longitudinal cohort of patients with DC. METHODS: Adult outpatients with DC were prospectively recruited from a liver transplant center and completed ESAS-r at baseline and week 12. We examined reliability, floor/ceiling effects, structural validity, and known-groups validity. We examined the convergent and predictive validity of ESAS-r with health-related quality of life using the Short Form Liver Disease Quality of Life (SF-LDQOL) and responsiveness to changes in anxiety and depression using the Hospital Anxiety and Depression Scale and Patient Health Questionnaire-9 from baseline to week 12. RESULTS: From August 2018 to September 2022, 218 patients (9% Child-Pugh A, 59% Child-Pugh B, and 32% Child-Pugh C) were prospectively recruited and completed the ESAS-r, SF-LDQOL, Patient Health Questionnaire-9, and Hospital Anxiety and Depression Scale at baseline and week 12 (n = 135). ESAS-r had strong reliability (Cronbach's alpha 0.86), structural validity (comparative fit index 0.95), known-groups validity (Child-Pugh A: 25.1 vs. B: 37.5 vs. C: 41.4, p = 0.006), and convergent validity (r = -0.67 with SF-LDQOL). Floor effects were 9% and ceiling effects were 0.5%. Changes in ESAS-r scores from baseline to week 12 significantly predicted changes in SF-LDQOL (ß = -0.36, p < 0.001), accounting for 30% of the variation. ESAS-r was strongly responsive to clinically meaningful changes in SF-LDQOL, Patient Health Questionnaire-9, and Hospital Anxiety and Depression Scale. CONCLUSIONS: ESAS-r is a reliable, valid, and responsive tool for assessing symptom burden in patients with DC and can predict changes in health-related quality of life. Future directions include its implementation as a key outcome measure in cirrhosis care and clinical trials.

Severe Necrotizing Pancreatitis in a Pediatric Patient with COVID-19: A Case Report.

We describe a 15-year-old female diagnosed with necrotizing pancreatitis in the setting of coronavirus disease 2019 with severe complications including splenic vein and portal vein thromboses, pleural effusion requiring chest tube, acute hypoxic respiratory failure requiring noninvasive positive-pressure ventilation, and new-onset insulin-dependent diabetes mellitus, requiring over a month-long hospitalization. Following discharge, the patient experienced a prolonged loss of appetite, nausea, and extreme weight loss., During her prolonged hospitalization, she was diagnosed with necrotizing pancreatitis with walled-off collection which was ultimately treated with transgastric endoscopic ultrasound-guided drainage, multiple endoscopic necrosectomies, lumen-apposing metal stents, and double-pigtail plastic stent. Nine months after her initial presentation, patient's clinical symptoms improved, and her weight stabilized. This case highlights the importance of recognizing acute and necrotizing pancreatitis and its morbidities as complications associated with coronavirus disease 2019.

Virus Emissions from Toilet Flushing: Comparing Urine-Diverting to Mix Flush Toilets.

High levels of viruses can be found in human excrement from infected individuals, a fraction of which can be emitted from toilet flushing. Unlike the common mix flush toilet (MFT), the urine-diverting toilet (UDT) separates urine from the toilet water. Specific focus on urine-associated viruses is needed because the UDT can emit different levels of urine-associated and fecal-borne viruses and urine has different properties compared to feces that can affect emission levels (e.g., protein content). In this work, we quantified emission levels of surrogate bacteriophages for urine-associated and fecal-borne viruses, MS2 and T3, from flushing a UDT and an MFT, with and without protein in the water. Emission levels of viruses in the water of the UDT were lower than that of the MFT by up to 1.2-log10 and 1.3-log10 for T3 and MS2, respectively. If urine is completely diverted in the UDT, virus emissions can be reduced by up to 4-log10. Based on these results and typical levels in urine and feces, we estimate that up to 107 and 108 gene copies of human viruses per flush can be released from the UDT and MFT, respectively. Lower emissions observed with the UDT suggest reduced exposure to viruses from flushing the UDT.

Validation of N95 Filtering Facepiece Respirator Decontamination Methods Available at a Large University Hospital.

BACKGROUND: Due to unprecedented shortages in N95 filtering facepiece respirators, healthcare systems have explored N95 reprocessing. No single, full-scale reprocessing publication has reported an evaluation including multiple viruses, bacteria, and fungi along with respirator filtration and fit. METHODS: We explored reprocessing methods using new 3M 1860 N95 respirators, including moist (50%-75% relative humidity [RH]) heat (80-82°C for 30 minutes), ethylene oxide (EtO), pulsed xenon UV-C (UV-PX), hydrogen peroxide gas plasma (HPGP), and hydrogen peroxide vapor (HPV). Respirator samples were analyzed using 4 viruses (MS2, phi6, influenza A virus [IAV], murine hepatitis virus [MHV)]), 3 bacteria (Escherichia coli, Staphylococcus aureus, Geobacillus stearothermophilus spores, and vegetative bacteria), and Aspergillus niger. Different application media were tested. Decontaminated respirators were evaluated for filtration integrity and fit. RESULTS: Heat with moderate RH most effectively inactivated virus, resulting in reductions of >6.6-log10 MS2, >6.7-log10 Phi6, >2.7-log10 MHV, and >3.9-log10 IAV and prokaryotes, except for G stearothermohphilus. Hydrogen peroxide vapor was moderately effective at inactivating tested viruses, resulting in 1.5- to >4-log10 observable inactivation. Staphylococcus aureus inactivation by HPV was limited. Filtration efficiency and proper fit were maintained after 5 cycles of heat with moderate RH and HPV. Although it was effective at decontamination, HPGP resulted in decreased filtration efficiency, and EtO treatment raised toxicity concerns. Observed virus inactivation varied depending upon the application media used. CONCLUSIONS: Both moist heat and HPV are scalable N95 reprocessing options because they achieve high levels of biological indicator inactivation while maintaining respirator fit and integrity.

Humidity and Deposition Solution Play a Critical Role in Virus Inactivation by Heat Treatment of N95 Respirators.

Supply shortages of N95 respirators during the coronavirus disease 2019 (COVID-19) pandemic have motivated institutions to develop feasible and effective N95 respirator reuse strategies. In particular, heat decontamination is a treatment method that scales well and can be implemented in settings with variable or limited resources. Prior studies using multiple inactivation methods, however, have often focused on a single virus under narrowly defined conditions, making it difficult to develop guiding principles for inactivating emerging or difficult-to-culture viruses. We systematically explored how temperature, humidity, and virus deposition solutions impact the inactivation of viruses deposited and dried on N95 respirator coupons. We exposed four virus surrogates across a range of structures and phylogenies, including two bacteriophages (MS2 and phi6), a mouse coronavirus (murine hepatitis virus [MHV]), and a recombinant human influenza A virus subtype H3N2 (IAV), to heat treatment for 30 min in multiple deposition solutions across several temperatures and relative humidities (RHs). We observed that elevated RH was essential for effective heat inactivation of all four viruses tested. For heat treatments between 72°C and 82°C, RHs greater than 50% resulted in a >6-log10 inactivation of bacteriophages, and RHs greater than 25% resulted in a >3.5-log10 inactivation of MHV and IAV. Furthermore, deposition of viruses in host cell culture media greatly enhanced virus inactivation by heat and humidity compared to other deposition solutions, such as phosphate-buffered saline, phosphate-buffered saline with bovine serum albumin, and human saliva. Past and future heat treatment methods must therefore explicitly account for deposition solutions as a factor that will strongly influence observed virus inactivation rates. Overall, our data set can inform the design and validation of effective heat-based decontamination strategies for N95 respirators and other porous surfaces, especially for emerging viruses that may be of immediate and future public health concern.IMPORTANCE Shortages of personal protective equipment, including N95 respirators, during the coronavirus (CoV) disease 2019 (COVID-19) pandemic have highlighted the need to develop effective decontamination strategies for their reuse. This is particularly important in health care settings for reducing exposure to respiratory viruses, like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. Although several treatment methods are available, a widely accessible strategy will be necessary to combat shortages on a global scale. We demonstrate that the combination of heat and humidity inactivates a range of RNA viruses, including both viral pathogens and common viral pathogen surrogates, after deposition on N95 respirators and achieves the necessary virus inactivation detailed by the U.S. Food and Drug Administration guidelines to validate N95 respirator decontamination technologies. We further demonstrate that depositing viruses onto surfaces when suspended in culture media can greatly enhance observed inactivation, adding caution to how heat and humidity treatment methods are validated.

Deactivation of E. coli in water using Fe3+-saturated montmorillonite impregnated filter paper.

In areas with high exposure to pathogen contaminated water and lack the economic means for water treatment, low cost and convenient point-of-use drinking water disinfection materials/devices are essential. Using a simple craft paper making method, Fe3+-saturated montmorillonite impregnated filter paper was constructed to filter live Escherichia coli (E. coli)-spiked water. The Scanning Electron Microscopic images of the E. coli cells in contact with the Fe3+-saturated montmorillonite impregnated filter paper showed: 1) Fe3+-saturated montmorillonite particles were uniformly coated on the cellulose paper fiber, creating large mineral surface for cell contact; and 2) E. coli cell membrane was dehydrated and damaged, resulting cell deactivation upon contacting with the Fe3+-saturated montmorillonite particles impregnated in the paper. The E. coli cells passing through the Fe3+-saturated montmorillonite impregnated filter paper were not viable as further confirmed by the microfluidic dielectrophoresis analysis. They remained non-viable at room temperature even after 5 days, as shown by the results from both the Colony Counting test and the Colilert test. More than 99.5% deactivation efficiency was achieved when the ratio of the volume of the E. coli contaminated water to the mass of Fe3+-saturated montmorillonite was maintained at <1:1.5 (mL/mg). The Fe3+-saturated montmorillonite impregnated filter paper maintained ~74% E. coli deactivation efficiency even after the 8th consecutive use. About 0.52 mg Fe3+, which is bioavailable, could be leached into the water for every 2 L E coli-contaminated water that is treated with the filter paper. The treated water could therefore provide iron supplement to a person at a level within the range of the FDA recommended human daily intake of iron. The results from this study has clearly demonstrated promising potential of using the Fe3+-saturated montmorillonite impregnated filter paper for low cost (~$0.07/L treated water for this study) and convenient point-of-use drinking water disinfection.