Association between mucosectomy and endoscopic outcomes in patients with ileal pouch-anal anastomosis.

Background: In patients with inflammatory bowel disease (IBD) for whom medical therapy is unsuccessful or who develop colitis-associated neoplasia, restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is often indicated. One consideration for surgeons performing this procedure is whether to create this anastomosis using a stapled technique without mucosectomy or using a hand-sewn technique with mucosectomy. This study tested the association between IPAA anastomosis technique and cuffitis and/or pouchitis, assessed endoscopically. Methods: This was a retrospective cohort study. We included consecutive adult patients with IBD who had undergone IPAA and had received index pouchoscopies at Columbia University Irving Medical Center between 2020 and 2022. Patients were then followed up from this index pouchoscopy for ≤12 months to a subsequent pouchoscopy. The primary exposure was mucosectomy vs non-mucosectomy and the primary outcome was cuffitis and/or pouchitis, defined as a Pouch Disease Activity Index endoscopy subscore of ≥1. Results: There were 76 patients who met study criteria including 49 (64%) who had undergone mucosectomy and 27 (36%) who had not. Rates of cuffitis and/or pouchitis were 49% among those with mucosectomy vs 41% among those without mucosectomy (P = 0.49). Time-to-event analysis affirmed these findings (log-rank P = 0.77). Stricture formation was more likely among patients with mucosectomy compared with those without mucosectomy (45% vs 19%, P = 0.02). Conclusions: There was no association between anastomosis technique and cuffitis and/or pouchitis among patients with IBD. These results may support the selection of stapled anastomosis over hand-sewn anastomosis with mucosectomy.

Gut colonization with multidrug resistant organisms in the intensive care unit: a systematic review and meta-analysis.

BACKGROUND: Gut colonization with multidrug-resistant organisms (MDRO) frequently precedes infection among patients in the intensive care unit (ICU), although the dynamics of colonization are not completely understood. We performed a systematic review and meta-analysis of ICU studies which described the cumulative incidence and rates of MDRO gut acquisition. METHODS: We systematically searched PubMed, Embase, and Web of Science for studies published from 2010 to 2023 reporting on gut acquisition of MDRO in the ICU. MDRO were defined as multidrug resistant non-Pseudomonas Gram-negative bacteria (NP-GN), Pseudomonas spp., and vancomycin-resistant Enterococcus (VRE). We included observational studies which obtained perianal or rectal swabs at ICU admission (within 48 h) and at one or more subsequent timepoints. Our primary outcome was the incidence rate of gut acquisition of MDRO, defined as any MDRO newly detected after ICU admission (i.e., not present at baseline) for all patient-time at risk. The study was registered with PROSPERO, CRD42023481569. RESULTS: Of 482 studies initially identified, 14 studies with 37,305 patients met criteria for inclusion. The pooled incidence of gut acquisition of MDRO during ICU hospitalization was 5% (range: 1-43%) with a pooled incidence rate of 12.2 (95% CI 8.1-18.6) per 1000 patient-days. Median time to acquisition ranged from 4 to 26 days after ICU admission. Results were similar for NP-GN and Pseudomonas spp., with insufficient data to assess VRE. Among six studies which provided sufficient data to perform curve fitting, there was a quasi-linear increase in gut MDRO colonization of 1.41% per day which was stable through 30 days of ICU hospitalization (R2 = 0.50, p < 0.01). CONCLUSIONS: Acquisition of gut MDRO was common in the ICU and increases with days spent in ICU through 30 days of follow-up. These data may guide future interventions seeking to prevent gut acquisition of MDRO in the ICU.

Esophagogastroduodenoscopy findings that do no not explain dysphagia are associated with underutilization of high-resolution manometry.

In patients with dysphagia that is not explained by upper endoscopy, high-resolution esophageal manometry (HRM) is the next logical step in diagnostic testing. This study investigated predictors of failure to refer for HRM after an upper endoscopy that was performed for but did not explain dysphagia. This was a retrospective cohort study of patients >18 years of age who underwent esophagogastroduodenoscopy (EGD) for dysphagia from 2015 to 2021. Patients with EGD findings that explained dysphagia (e.g. esophageal mass, eosinophilic esophagitis, Schatzki ring, etc.) were excluded from the main analyses. The primary outcome was failure to refer for HRM within 1 year of the index non-diagnostic EGD. We also investigated delayed referral for HRM, defined as HRM performed after the median. Multivariable logistic regression modeling was used to identify risk factors that independently predicted failure to refer for HRM, conditioned on the providing endoscopist. Among 2132 patients who underwent EGD for dysphagia, 1240 (58.2%) did not have findings to explain dysphagia on the index EGD. Of these 1240 patients, 148 (11.9%) underwent HRM within 1 year of index EGD. Endoscopic findings (e.g. hiatal hernia, tortuous esophagus, Barrett's esophagus, surgically altered anatomy not involving the gastroesophageal junction, and esophageal varices) perceived to explain dysphagia were independently associated with failure to refer for HRM (adjusted odds ratio 0.45, 95% confidence interval 0.25-0.80). Of the 148 patients who underwent HRM within 1 year of index EGD, 29.7% were diagnosed with a disorder of esophagogastric junction outflow, 17.6% with a disorder of peristalsis, and 2.0% with both disorders of esophagogastric outflow and peristalsis. The diagnosis made by HRM was similar among those who had incidental EGD findings that were non-diagnostic for dysphagia compared with those who had completely normal EGD findings. Demographic factors including race/ethnicity, insurance type, and income were not associated with failure to refer for HRM or delayed HRM. Patients with dysphagia and endoscopic findings unrelated to dysphagia have a similar prevalence of esophageal motility disorders to those with normal endoscopic examinations, yet these patients are less likely to undergo HRM. Provider education is indicated to increase HRM referral in these patients.

Timing and clinical risk factors for early acquisition of gut pathogen colonization with multidrug resistant organisms in the intensive care unit.

BACKGROUND: Microbiome restitution therapies are being developed to prevent gut pathogen colonization among patients in the intensive care unit (ICU) and in other select populations. If preventive therapies are to be effective, they must be administered prior to pathogen acquisition. The timing and risk factors for early acquisition of gut pathogen colonization (within 72 h) are currently unknown and could be helpful to guide ICU trial design. METHODS: This was a prospective cohort study. Patients in the ICU had deep rectal swabs performed within 4 h of ICU admission and exactly 72 h later. Early gut pathogen colonization was classified as the new presence (based on culture of rectal swabs) of one or more of the following organisms of interest: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant (VRE), and Gram-negative bacteria that showed multidrug resistance (MDR) or third generation Cephalosporin resistance (Ceph-R). Clinical risk factors for early acquisition of gut pathogen colonization were captured using the Acute Physiology and Chronic Health Evaluation IV (APACHE IV) scoring system. FINDINGS: Among 131 patients who were swabbed at ICU admission and 72 h later, the rates of gut pathogen colonization at ICU admission were 11.4%, 10.6%, 38.6%, and 8.3% for MRSA, VRE, MDR and Ceph-R Gram-negatives respectively. Among the patients who were negative for a given pathogen at ICU admission, the rates of early acquisition of gut pathogen colonization were 7.8% for MRSA (95% CI 3.6 to 14.2%), 7.7% for VRE (95% CI 3.6 to 14.1%), 11.3% for MDR Gram-negatives (95% CI 4.4 to 18.8%), and 4.2% for Ceph-R Gram-negatives (95% CI 1.4 to 9.5%). There were no clinical risk factors which independently predicted early acquisition of gut pathogen colonization. INTERPRETATION: Early gut pathogen colonization was common in the ICU, but our single-center study could not identify any clinical risk factors which were significantly associated with acquisition of gut pathogens.

Visceral Adiposity Independently Predicts Time to Flare in Inflammatory Bowel Disease but Body Mass Index Does Not.

BACKGROUND: Obesity is associated with progression of inflammatory bowel disease (IBD). Visceral adiposity may be a more meaningful measure of obesity compared with traditional measures such as body mass index (BMI). This study compared visceral adiposity vs BMI as predictors of time to IBD flare among patients with Crohn's disease and ulcerative colitis. METHODS: This was a retrospective cohort study. IBD patients were included if they had a colonoscopy and computed tomography (CT) scan within a 30-day window of an IBD flare. They were followed for 6 months or until their next flare. The primary exposure was the ratio of visceral adipose tissue to subcutaneous adipose tissue (VAT:SAT) obtained from CT imaging. BMI was calculated at the time of index CT scan. RESULTS: A total of 100 Crohn's disease and 100 ulcerative colitis patients were included. The median age was 43 (interquartile range, 31-58) years, 39% had disease duration of 10 years or more, and 14% had severe disease activity on endoscopic examination. Overall, 23% of the cohort flared with median time to flare 90 (interquartile range, 67-117) days. Higher VAT:SAT was associated with shorter time to IBD flare (hazard ratio of 4.8 for VAT:SAT ≥1.0 vs VAT:SAT ratio <1.0), whereas higher BMI was not associated with shorter time to flare (hazard ratio of 0.73 for BMI ≥25 kg/m2 vs BMI <25 kg/m2). The relationship between increased VAT:SAT and shorter time to flare appeared stronger for Crohn's than for ulcerative colitis. CONCLUSIONS: Visceral adiposity was associated with decreased time to IBD flare, but BMI was not. Future studies could test whether interventions that decrease visceral adiposity will improve IBD disease activity.

An increased ratio of visceral to subcutaneous adipose tissue was associated with a shorter time to flare in patients with both Crohn's and ulcerative colitis. Conversely, increased body mass index was not associated with a shorter time to flare in inflammatory bowel disease patients.

Proton pump Inhibitors and Risk of Enteric Infection in Inflammatory Bowel Disease: A Self-controlled Case Series.

BACKGROUND: We tested whether proton pump inhibitors (PPIs) are associated with enteric infections among those with inflammatory bowel disease (IBD), after adequately accounting for baseline differences between PPI users and nonusers. METHODS: This was a self-controlled case series, with each patient serving as their own control. Ambulatory patients with IBD were included if they were tested for enteric infection by multiplex polymerase chain reaction testing panel (GIPCR) and/or Clostridoides difficile toxin PCR from 2015 to 2019 and received PPIs for some but not all of this period. Rates of enteric infections were compared between the PPI-exposed period vs pre- and post-PPI periods identical in duration to the exposed period. Conditional Poisson regression was used to adjust for time-varying factors. RESULTS: Two hundred twenty-one IBD patients were included (49% ulcerative colitis, 46% Crohn's disease, and 5% indeterminate colitis). The median PPI duration was 7 months (interquartile range 4 to 11 months). A total of 25 (11%) patients had a positive GIPCR or C. difficile test in the PPI period, 9 (4%) in the pre-PPI period, and 8 (4%) in the post-PPI period. Observed incidence rates for enteric infections were 2.5, 7.4, and 2.2 per 100 person years for the pre-PPI, PPI, and post-PPI periods, respectively (adjusted incidence rate ratios, 2.8; 95% confidence interval [CI] 1.3-6.0) for PPI vs pre-PPI and 2.9 (95% CI, 1.3-6.4) for PPI vs post-PPI). The adjusted absolute excess risk associated with PPIs was 4.9 infections per 100 person years. CONCLUSIONS: Proton pump inhibitors were associated with a 3-fold increased risk for enteric infection among those with IBD but had a modest absolute risk.

We tested whether proton pump inhibitors (PPIs) are associated with enteric infections among those with inflammatory bowel disease (IBD) by using a case-controlled series method, which allows for controlling of residual confounding. We studied ambulatory IBD patients who were tested for enteric infection from 2015 to 2019 and received PPIs for some of this period. Rates of enteric infections were compared between the PPI exposed period vs pre- and post-PPI periods identical in duration to the exposed period. We found that PPIs were associated with a 3-fold increased risk for enteric infection among those with IBD but had a modest absolute risk.

Impact of a Purified Microbiome Therapeutic on Abundance of Antimicrobial Resistance Genes in Patients With Recurrent Clostridioides difficile Infection.

BACKGROUND: The gastrointestinal microbiota is an important line of defense against colonization with antimicrobial resistant (AR) bacteria. In this post hoc analysis of the phase 3 ECOSPOR III trial, we assessed impact of a microbiota-based oral therapeutic (fecal microbiota spores, live; VOWST Oral Spores [VOS], formerly SER-109]; Seres Therapeutics) compared with placebo, on AR gene (ARG) abundance in patients with recurrent Clostridioides difficile infection (rCDI). METHODS: Adults with rCDI were randomized to receive VOS or placebo orally for 3 days following standard-of-care antibiotics. ARG and taxonomic profiles were generated using whole metagenomic sequencing of stool at baseline and weeks 1, 2, 8, and 24 posttreatment. RESULTS: Baseline (n = 151) and serial posttreatment stool samples collected through 24 weeks (total N = 472) from 182 patients (59.9% female; mean age: 65.5 years) in ECOSPOR III as well as 68 stool samples obtained at a single time point from a healthy cohort were analyzed. Baseline ARG abundance was similar between arms and significantly elevated versus the healthy cohort. By week 1, there was a greater decline in ARG abundance in VOS versus placebo (P = .003) in association with marked decline of Proteobacteria and repletion of spore-forming Firmicutes, as compared with baseline. We observed abundance of Proteobacteria and non-spore-forming Firmicutes were associated with ARG abundance, while spore-forming Firmicutes abundance was negatively associated. CONCLUSIONS: This proof-of-concept analysis suggests that microbiome remodeling with Firmicutes spores may be a potential novel approach to reduce ARG colonization in the gastrointestinal tract.

The Salivary Microbiome and Predicted Metabolite Production Are Associated with Barrett's Esophagus and High-Grade Dysplasia or Adenocarcinoma.

BACKGROUND: Esophageal adenocarcinoma (EAC) is rising in incidence, and established risk factors do not explain this trend. Esophageal microbiome alterations have been associated with Barrett's esophagus (BE) and dysplasia and EAC. The oral microbiome is tightly linked to the esophageal microbiome; this study aimed to identify salivary microbiome-related factors associated with BE, dysplasia, and EAC. METHODS: Clinical data and oral health history were collected from patients with and without BE. The salivary microbiome was characterized, assessing differential relative abundance of taxa by 16S rRNA gene sequencing and associations between microbiome composition and clinical features. Microbiome metabolic modeling was used to predict metabolite production. RESULTS: A total of 244 patients (125 non-BE and 119 BE) were analyzed. Patients with high-grade dysplasia (HGD)/EAC had a significantly higher prevalence of tooth loss (P = 0.001). There were significant shifts with increased dysbiosis associated with HGD/EAC, independent of tooth loss, with the largest shifts within the genus Streptococcus. Modeling predicted significant shifts in the microbiome metabolic capacities, including increases in L-lactic acid and decreases in butyric acid and L-tryptophan production in HGD/EAC. CONCLUSIONS: Marked dysbiosis in the salivary microbiome is associated with HGD and EAC, with notable increases within the genus Streptococcus and accompanying changes in predicted metabolite production. Further work is warranted to identify the biological significance of these alterations and to validate metabolic shifts. IMPACT: There is an association between oral dysbiosis and HGD/EAC. Further work is needed to establish the diagnostic, predictive, and causal potential of this relationship.

Assessment of refeeding syndrome definitions and 30-day mortality in critically ill adults: A comparison study.

BACKGROUND: Patients in the intensive care unit (ICU) are at high risk for refeeding syndrome (RFS), yet there is uncertainty regarding how RFS should be operationalized in the ICU. We evaluated different definitions for RFS and tested how they associated with patient-centered outcomes in the ICU. METHODS: This was a retrospective comparison study. Patients age ≥18 years were eligible if they were newly initiated on enteral feeding while hospitalized in the ICU. Eight definitions for RFS were operationalized, including that from the American Society for Parenteral and Enteral Nutrition (ASPEN), all based on electrolyte levels from immediately before until up to 5 days after the initiation of enteral nutrition. Patients were followed for death or for ICU-free days, a measure of healthcare utilization. RESULTS: In all, 2123 patients were identified, including 406 (19.1%) who died within 30 days of ICU admission and 1717 (80.9%) who did not. Prevalence of RFS varied from 1.5% to 88% (ASPEN definition) depending on the RFS definition used. The excess risk for death associated with RFS varied from 33% to 92% across definitions. The development of RFS based on the ASPEN definition was associated with a greater decrease in ICU-free days compared with other definitions, but the relationship was not statistically significant. CONCLUSION: Eight definitions for RFS were evaluated, none of which showed strong associations with death or ICU-free days. It may be challenging to achieve a standardized definition for RFS that is based on electrolyte values and predicts mortality or ICU-free days.

The Salivary Microbiome and Predicted Metabolite Production are Associated with Progression from Barrett's Esophagus to Esophageal Adenocarcinoma.

Esophageal adenocarcinoma (EAC) is rising in incidence and associated with poor survival, and established risk factors do not explain this trend. Microbiome alterations have been associated with progression from the precursor Barrett's esophagus (BE) to EAC, yet the oral microbiome, tightly linked to the esophageal microbiome and easier to sample, has not been extensively studied in this context. We aimed to assess the relationship between the salivary microbiome and neoplastic progression in BE to identify microbiome-related factors that may drive EAC development. We collected clinical data and oral health and hygiene history and characterized the salivary microbiome from 250 patients with and without BE, including 78 with advanced neoplasia (high grade dysplasia or early adenocarcinoma). We assessed differential relative abundance of taxa by 16S rRNA gene sequencing and associations between microbiome composition and clinical features and used microbiome metabolic modeling to predict metabolite production. We found significant shifts and increased dysbiosis associated with progression to advanced neoplasia, with these associations occurring independent of tooth loss, and the largest shifts were with the genus Streptococcus. Microbiome metabolic models predicted significant shifts in the metabolic capacities of the salivary microbiome in patients with advanced neoplasia, including increases in L-lactic acid and decreases in butyric acid and L-tryptophan production. Our results suggest both a mechanistic and predictive role for the oral microbiome in esophageal adenocarcinoma. Further work is warranted to identify the biological significance of these alterations, to validate metabolic shifts, and to determine whether they represent viable therapeutic targets for prevention of progression in BE.

Obesity among those newly diagnosed with Crohn's disease and ulcerative colitis compared with the general population.

Objective: Obesity is a potentially modifiable risk factor for inflammatory bowel disease (IBD). We aimed to evaluate the body mass index (BMI) of those diagnosed with IBD early versus late in life in the context of age-adjusted background population. Design/method: Patients with a new diagnosis of IBD from 2000 to 2021 were included. Early-onset IBD was classified as age <18 and late-onset IBD classified as age ≥65. Obesity was classified as BMI ≥30 kg/m2. Population data were obtained from community surveys. Results: Included were 1573 patients (56.0%) with Crohn's disease (CD) and 1234 (44.0%) with ulcerative colitis (UC). Overall, the median BMI at IBD diagnosis was 20 kg/m2 (IQR 18-24) among those diagnosed at age <18 vs 26.9 kg/m2 (IQR 23.1-30.0) among those diagnosed at age ≥65 (rank-sum p<0.01). In all age groups, BMI was stable during the 1-year preceding IBD diagnosis. At age <18, 11.5% of the background population was obese compared with 3.8% of those with newly diagnosed CD (p<0.01) and 4.8% of those with newly diagnosed UC (p=0.05). At age ≥65, 23.6% of the population was obese compared with 24.3% of those with newly diagnosed CD (p=0.78) and 29.5% of those with newly diagnosed UC (p=0.01). Conclusion: Patients with IBD diagnosed at age <18 were less likely to be obese compared with the age-adjusted background population whereas those diagnosed at age ≥65 were more likely to be obese. Future prospective studies should investigate obesity as a modifiable risk factor for late-life IBD.

Trends in use of proton pump inhibitors among adults in the United States from 1999 to 2018.

PURPOSE: Proton pump inhibitors (PPIs) are among the most commonly used drugs in the United States (U.S.). We aimed to determine the trends in use of PPIs among adults in the U.S. from 1999 through 2018, hypothesizing the trend would follow an inverted U-shaped curve, with a decline in recent years due to safety concerns. METHODS: Temporal trends in use of prescription PPIs were assessed using the 1999-2018 National Health and Nutrition Examination Survey (NHANES), a nationally representative cross-sectional survey of non-institutionalized U.S. civilians. Use of PPIs was defined as any use during the month preceding the survey. Descriptive statistics were produced and trends in PPI use were examined, stratified by sex, age, race, body mass index (BMI), and poverty level. RESULTS: Use of prescription PPIs increased from 4.1% of U.S. adults in 1999-2000 to 8.6% in 2017-2018 (p for trend <0.01). All of the increase was observed during the first half of the study period (4.6% increase from 1999 to 2008 vs. 0.5% decrease from 2009 to 2018) and almost all of it was among those aged 55 or more (8.6% increase among those aged ≥ 55 compared to 1.2% increase among those aged < 55, p for interaction based on age <0.01). CONCLUSIONS: Use of prescription PPIs increased from 1999 to 2008 and then plateaued through 2018. This rise was driven by increased usage among older NHANES respondents.

Antibiotic-Specific Risk for Community-Acquired Clostridioides difficile Infection in the United States from 2008 to 2020.

Antibiotic exposure is a crucial risk factor for community-acquired Clostridioides difficile infection (CA-CDI). However, the relative risks associated with specific antibiotics may vary over time, and the absolute risks have not been clearly established. This is a retrospective cohort study. Adults were included if they received an outpatient antibiotic prescription within the IBM MarketScan databases between 2008 and 2020. The primary exposure was an outpatient antibiotic prescription, and the receipt of doxycycline was used as the reference comparison. The primary outcome was CA-CDI, defined as the presence of an International Classification of Diseases (ICD) diagnosis code for CDI within 90 days of receiving an outpatient antibiotic prescription, and subsequent treatment for CDI. There were 36,626,794 unique patients who received outpatient antibiotics, including 11,607 (0.03%) who developed CA-CDI. Relative to doxycycline, the antibiotics conferring the highest risks for CA-CDI were clindamycin (adjusted odds ratio [aOR], 8.81; 95% confidence interval [CI], 7.76 to 10.00), cefdinir (aOR, 5.86; 95% CI, 5.03 to 6.83), cefuroxime (aOR, 4.57; 95% CI, 3.87 to 5.39), and fluoroquinolones (aOR, 4.05; 95% CI, 3.58 to 4.59). Among older patients with CA-CDI risk factors, nitrofurantoin was also associated with CA-CDI (aOR, 3.05; 95% CI, 1.92 to 4.84), with a smaller number needed to harm, compared to the fluoroquinolones. While clindamycin, cefuroxime, and fluoroquinolone use declined from 2008 to 2020, nitrofurantoin use increased by 40%. Clindamycin was associated with the greatest CA-CDI risk, overall. Among older patients with an elevated baseline risk for CA-CDI, multiple antibiotics, including nitrofurantoin, had strong associations with CA-CDI. These results may guide antibiotic selection and future stewardship efforts.

Gastrointestinal symptoms in COVID-19: the long and the short of it.

PURPOSE OF REVIEW: A large and growing number of patients have persistent gastrointestinal symptoms that they attribute to COVID-19. SARS-CoV-2, the virus that causes COVID-19, replicates within the gut and acute COVID-19 is associated with alteration of the gut microbiome. This article reviews recent observational data related to gastrointestinal symptoms in 'long COVID' and discusses pathophysiologic mechanisms that might explain persistent post-COVID gastrointestinal symptoms. RECENT FINDINGS: Gastrointestinal symptoms are present in half of the patients with acute COVID-19, persist 6 months after COVID-19 in 10-25% of patients, and are rated as the most bothersome symptom in 11% of all patients. These symptoms include heartburn, constipation, diarrhoea and abdominal pain and decline in prevalence with the passage of time. Long COVID gastrointestinal symptoms are associated with mental health symptoms (anxiety and depression) that predate COVID-19 and also with mental health symptoms that are concurrent, after recovery from COVID-19. The cause of long COVID gastrointestinal symptoms is unknown and hypotheses include the SARS-CoV-2 virus itself, which infects the gastrointestinal tract; COVID-19, which can be accompanied by gut microbiome changes, a profound systemic inflammatory response and critical illness; and/or effects of pandemic stress on gastrointestinal function and symptom perception, which may be unrelated to either SARS-CoV-2 or to COVID-19. SUMMARY: New, persistent gastrointestinal symptoms are commonly reported after recovery from COVID-19. The pathophysiology of these symptoms is unknown but likely to be multifactorial.

Decreased Gut Microbiome Tryptophan Metabolism and Serotonergic Signaling in Patients With Persistent Mental Health and Gastrointestinal Symptoms After COVID-19.

INTRODUCTION: An estimated 15%-29% of patients report new gastrointestinal (GI) symptoms after coronavirus-19 disease (COVID-19) while 4%-31% report new depressive symptoms. These symptoms may be secondary to gut microbiome tryptophan metabolism and 5-hydroxytryptamine (5-HT)-based signaling. METHODS: This study used specimens from 2 patient cohorts: (i) fecal samples from patients with acute COVID-19 who participated in a randomized controlled trial testing prebiotic fiber and (ii) blood samples from patients with acute COVID-19. Six months after recovering from COVID-19, both cohorts answered questions related to GI symptoms and anxiety or depression. Microbiome composition and function, focusing on tryptophan metabolism-associated pathways, and plasma 5-HT were assessed. RESULTS: In the first cohort (n = 13), gut microbiome L-tryptophan biosynthesis during acute COVID-19 was decreased among those who developed more severe GI symptoms (2.0-fold lower log activity comparing those with the most severe GI symptoms vs those with no symptoms, P = 0.06). All tryptophan pathways showed decreased activity among those with more GI symptoms. The same pathways were also decreased in those with the most severe mental health symptoms after COVID-19. In an untargeted analysis, 5 additional metabolic pathways significantly differed based on subsequent development of GI symptoms. In the second cohort (n = 39), plasma 5-HT concentration at the time of COVID-19 was increased 5.1-fold in those with GI symptoms alone compared with those with mental health symptoms alone ( P = 0.02). DISCUSSION: Acute gut microbiome-mediated reduction in 5-HT signaling may contribute to long-term GI and mental health symptoms after COVID-19. Future studies should explore modification of 5-HT signaling to reduce post-COVID symptoms.

A Prediction Model Incorporating Peripheral Eosinopenia as a Novel Risk Factor for Death After Hospitalization for Clostridioides difficile Infection.

BACKGROUND AND AIMS: Clostridioides difficile infection (CDI) is associated with a range of outcomes, and existing prediction models for death among patients with CDI are imprecise. Peripheral eosinopenia has been proposed as a novel risk factor for death among patients with CDI but has not been incorporated into prediction models. This study aimed to develop and validate a prediction model for death among patients hospitalized with CDI that incorporated peripheral eosinopenia. METHODS: Eosinopenia was defined as 0 eosinophils/µL on the soonest peripheral blood drawn within the 48-hour window of the CDI test (before or after). Adults were eligible for the study if they were hospitalized at any one of 3 large, unaffiliated hospital networks, tested positive for CDI by stool polymerase chain reaction, and received appropriate anti-CDI treatment. Patients were followed for all-cause death for up to 30 days. RESULTS: There were 4518 unique hospitalized adults with CDI included (2142 in the derivation cohort and 2376 in the validation cohort). All-cause 30-day mortality was 9% and 10% in the cohorts. In the validation cohort, the factors most strongly associated with death were eosinopenia (adjusted odds ratio [aOR] 2.49, 95% confidence interval [CI] 1.77-3.50), albumin <3 g/dL (aOR 3.26, 95% CI 2.13-3.49), and creatinine >1.5 mg/dL (aOR 2.55, 95% CI 1.86-3.49). A 6-variable clinical prediction model was developed that improved on existing classification schemes for CDI severity (area under the receiver operating characteristic curve of 0.75 vs 0.68). CONCLUSION: Among adults hospitalized with CDI, peripheral eosinopenia was associated with increased risk of all-cause 30-day mortality. A prediction model incorporating peripheral eosinopenia was developed to improve care for hospitalized patients with CDI through risk stratification.

Evaluation of the ASPEN guidelines for refeeding syndrome among hospitalized patients receiving enteral nutrition: A retrospective cohort study.

BACKGROUND: Until recently, refeeding syndrome (RFS) has lacked standardized diagnostic criteria. This study sought to (1) determine whether RFS, as operationalized in the 2020 American Society for Parenteral and Enteral Nutrition (ASPEN) guideline definition, is associated with adverse clinical outcomes and (2) identify key risk factors for RFS. METHODS: In this retrospective cohort study, adults hospitalized from 2015 to 2019 were included if they were ordered for enteral feeding during hospitalization. Data were collected for up to 30 days, and RFS was operationalized as per the ASPEN 2020 guidelines as a ≥10% (corresponding to mild RFS), ≥25% (moderate), and ≥50% (severe) decline in prefeeding serum phosphorus, magnesium, or potassium. The mortality associated with RFS was assessed, and risk factors for RFS were identified using multivariable logistic regression modeling. RESULTS: Of 3854 participants, 3480 (90%) developed mild RFS. Thirty-day mortality was higher in those without mild RFS (24%) than in those with mild RFS (18%) (P < 0.01). When RFS was reoperationalized as a 50% decline in electrolytes, 25% of patients developed RFS with a 20% 30-day mortality. Risk factors for development of RFS included renal failure, elevated creatinine, and low platelets; additionally, prefeeding serum phosphorus level was strongly associated with development of RFS (adjusted odds ratio, 6.09; 95% confidence interval, 4.95-7.49 for those in the highest tertile of prefeeding phosphorus compared with the lowest). CONCLUSION: The ASPEN operationalization of RFS as a decline in baseline electrolyte values was not associated with death. Prefeeding serum phosphorus level strongly predicted severe RFS.