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.

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.

Induction of innate immune memory via microRNA targeting of chromatin remodelling factors.

Prolonged exposure to microbial products such as lipopolysaccharide can induce a form of innate immune memory that blunts subsequent responses to unrelated pathogens, known as lipopolysaccharide tolerance. Sepsis is a dysregulated systemic immune response to disseminated infection that has a high mortality rate. In some patients, sepsis results in a period of immunosuppression (known as 'immunoparalysis')1 characterized by reduced inflammatory cytokine output2, increased secondary infection3 and an increased risk of organ failure and mortality4. Lipopolysaccharide tolerance recapitulates several key features of sepsis-associated immunosuppression5. Although various epigenetic changes have previously been observed in tolerized macrophages6-8, the molecular basis of tolerance, immunoparalysis and other forms of innate immune memory has remained unclear. Here we perform a screen for tolerance-associated microRNAs and identify miR-221 and miR-222 as regulators of the functional reprogramming of macrophages during lipopolysaccharide tolerization. Prolonged stimulation with lipopolysaccharide in mice leads to increased expression of miR-221 and mir-222, both of which regulate brahma-related gene 1 (Brg1, also known as Smarca4). This increased expression causes the transcriptional silencing of a subset of inflammatory genes that depend on chromatin remodelling mediated by SWI/SNF (switch/sucrose non-fermentable) and STAT (signal transducer and activator of transcription), which in turn promotes tolerance. In patients with sepsis, increased expression of miR-221 and miR-222 correlates with immunoparalysis and increased organ damage. Our results show that specific microRNAs can regulate macrophage tolerization and may serve as biomarkers of immunoparalysis and poor prognosis in patients with sepsis.

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.

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.

Class-Specific Relationship Between Use of Immunosuppressants and Risk for Community-Acquired Clostridioides difficile Infection.

BACKGROUND: Immunosuppressant exposure is associated with risk for Clostridioides difficile infection (CDI). It is unknown whether this risk is shared equally across immunosuppressant classes. METHODS: This was a retrospective cohort study. Adults were included if they were tested for community-acquired CDI (CA-CDI) by stool polymerase chain reaction within 72 hours of hospitalization between 2010 and 2019. The primary outcome was CA-CDI requiring hospitalization, defined as a positive stool test. The primary exposure was use of a home immunosuppressant, at any dose or duration, defined based on the medication reconciliation, and categorized as systemic steroids, calcineurin inhibitors, antimetabolites, anti-tumor necrosis factor-alpha agents, anti-CD20 antibody, and all others. RESULTS: A total of 10 992 hospitalized patients met criteria for the study including 1793 (16%) with CA-CDI; 23% used 1 or more immunosuppressant class. Among those immunosuppressed, 27% tested positive for CA-CDI compared with 22% among those who were not immunosuppressed (P < .01). After adjustment, calcineurin inhibitors (adjusted odds ratio [aOR], 1.19; 95% confidence interval [CI], 1.01-1.44) were associated with increased risk for CA-CDI. Risk for CA-CDI rose with multiple immunosuppressant classes: aOR, 1.22; aOR, 1.53; and aOR, 2.40 for 2, 3, and 4 classes, respectively. After excluding those with solid organ transplant, the relationship between use of calcineurin inhibitors and CDI increased (aOR, 2.21; 95% CI, 1.40-3.49). CONCLUSIONS: The greatest risk for CA-CDI was observed among patients using multiple classes of immunosuppressants and those using calcineurin inhibitors. Future studies should recognize that CDI risk differs based on immunosuppressant class.

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.

Proton Pump Inhibitor Prescribing and Monitoring Patterns Among Gastroenterology Practitioners.

GOALS: The aim was to quantify proton pump inhibitor (PPI) practice habits among gastroenterology (GI) practitioners. BACKGROUND: Reports of side effects have prompted patients and practitioners alike to discontinue PPI use. Emerging evidence-based literature on PPI risks and safety seek to guide practitioners, but the impact of this literature on PPI prescribing patterns has not been evaluated. STUDY: We performed an anonymous online survey of US GI practitioners across 6 academic and community affiliated medical centers. Demographic data including practice type and number of weekly gastroesophageal reflux disease patients seen were obtained. Survey questions evaluated practitioners' monitoring for PPI side effects, dose adjustments, and sources of information about PPI risks. RESULTS: The survey response rate was 60% (256/429). The majority of respondents were male (169, 66%) attending physicians (178, 70%) practicing general GI (63, 25%). There were 92 (36%) respondents who reported testing for PPI side effects at least once a year. Most respondents (143, 56%) reported discontinuing PPIs at least 50% of the time because of patients' concerns about PPI side effects. The majority of respondents reported getting their information regarding PPI safety from published journals (239, 98%) as well as colleagues (222, 91%). CONCLUSIONS: Despite best available evidence suggesting safety of long-term PPI use without routine monitoring, stopping PPIs and monitoring for potential side effects occurs frequently, even within a cohort of mostly academic GI practitioners. Alternative strategies are needed to improve adherence to best practices, especially since gastroenterologists often serve as PPI experts.

Inappropriateness of Proton Pump Inhibitors After Hospital Discharge Is Associated with Thirty-Day Hospital Readmission.

BACKGROUND AND AIMS: Concerns have been raised about the adverse effects of proton pump inhibitors (PPIs). Rather than PPIs themselves causing harm, we hypothesized that PPIs prescribed without appropriate indications would be associated with adverse outcomes compared to appropriately indicated PPIs. METHODS: Adult patients initiated on a new PPI during a hospitalization at our institution from 2014 to 2018 were analyzed. The primary outcome was all-cause 30-day readmission rate. The primary exposure was long-term appropriateness of PPI determined by the presence of prespecified diagnostic codes and discharge medications. Logistic regression modeling was used to estimate the odds of 30-day readmission in patients discharged on inappropriate compared to appropriate new PPIs. RESULTS: Of 84,236 patients admitted to our institution, 7745 (9.2%) were discharged on a new PPI, of which 5136 (66.3%) lacked an appropriately documented indication. Inappropriate PPIs were associated with 30-day hospital readmission after adjusting for other factors (adjusted odds ratio 1.30, 95% confidence interval 1.10-1.53). The excess risk associated with lack of appropriate documentation for PPIs in these patients was 44 readmissions per 1000 hospitalizations (95% confidence interval 21-67). CONCLUSIONS: Discharge on inappropriate PPIs was associated with 30-day hospital readmission compared to appropriate PPIs. The harm associated with inappropriate PPIs is not likely due to direct effects of PPIs because all patients in the study received PPIs. Rather, patients who receive inappropriate PPIs may have additional patient-specific factors that place them at increased risk for hospital readmission.

A Simple Emergency Department-Based Score Predicts Complex Hospitalization in Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Thirty percent of inflammatory bowel disease (IBD) patients hospitalized with flare require salvage therapy or surgery. Additionally, 40% experience length of stay (LOS) > 7 days. No emergency department (ED)-based indices exist to predict these adverse outcomes at admission for IBD flare. We examined whether clinical, laboratory, and endoscopic markers at presentation predicted prolonged LOS, inpatient colectomy, or salvage therapy in IBD patients admitted with flare. METHODS: Patients with ulcerative colitis (UC) or colonic involvement of Crohn's disease (CD) hospitalized with flare and tested for Clostridioides difficile infection (CDI) between 2010 and 2020 at two urban academic centers were studied. The primary outcome was complex hospitalization, defined as: LOS > 7 days, inpatient colectomy, or inpatient infliximab or cyclosporine. A nested k-fold cross-validation identified predictive factors of complex hospitalization. RESULTS: Of 164 IBD admissions, 34% (56) were complex. Predictive factors included: tachycardia in ED triage (odds ratio [OR] 3.35; confidence interval [CI] 1.79-4.91), hypotension in ED triage (3.45; 1.79-5.11), hypoalbuminemia at presentation (2.54; 1.15-3.93), CDI (2.62; 1.02-4.22), and endoscopic colitis (4.75; 1.75-5.15). An ED presentation score utilizing tachycardia and hypoalbuminemia predicted complex hospitalization (area under curve 0.744; CI 0.671-0.816). Forty-four of 48 (91.7%) patients with a presentation score of 0 (heart rate < 99 and albumin ≥ 3.4 g/dL) had noncomplex hospitalization. CONCLUSIONS: Over 90% of IBD patients hospitalized with flare with an ED presentation score of 0 did not require salvage therapy, inpatient colectomy, or experience prolonged LOS. A simple ED-based score may provide prognosis at a juncture of uncertainty in patient care.

Relationship Between Body Composition and Death in Patients with COVID-19 Differs Based on the Presence of Gastrointestinal Symptoms.

BACKGROUND: Patients with SARS-CoV-2 who present with gastrointestinal symptoms have a milder clinical course than those who do not. Risk factors for severe COVID-19 disease include increased adiposity and sarcopenia. AIMS: To determine whether body composition risk factors are associated with worse outcomes among patients with gastrointestinal symptoms. METHODS: This was a retrospective study of hospitalized patients with COVID-19 who underwent abdominal CT scan for clinical indications. Abdominal body composition measures including skeletal muscle index (SMI), intramuscular adipose tissue index (IMATI), visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), visceral-to-subcutaneous adipose tissue ratio (VAT/SAT ratio), and liver and spleen attenuation were collected. The association between body composition measurements and 30-day mortality was evaluated in patients with and without gastrointestinal symptoms at the time of positive SARS-CoV-2 test. RESULTS: Abdominal CT scans of 190 patients with COVID-19 were evaluated. Gastrointestinal symptoms including nausea, vomiting, diarrhea, or abdominal pain were present in 117 (62%). Among patients without gastrointestinal symptoms, those who died had greater IMATI (p = 0.049), less SMI (p = 0.010), and a trend toward a greater VAT/SAT ratio. Among patients with gastrointestinal symptoms, those who died had significantly greater IMATI (p = 0.025) but no differences in other measures. CONCLUSIONS: Among patients with COVID-19, those without gastrointestinal symptoms showed the expected associations between mortality and low SMI, high IMATI, and trend toward higher VAT/SAT ratio, but those with gastrointestinal symptoms did not. Future studies should explore the mechanisms for the altered disease course in patients with COVID-19 who present with gastrointestinal symptoms.

Disease Course and Outcomes of COVID-19 Among Hospitalized Patients With Gastrointestinal Manifestations.

BACKGROUND & AIMS: Our understanding of outcomes and disease time course of COVID-19 in patients with gastrointestinal (GI) symptoms remains limited. In this study we characterize the disease course and severity of COVID-19 among hospitalized patients with gastrointestinal manifestations in a large, diverse cohort from the Unites States. METHODS: This retrospective study evaluated hospitalized individuals with COVID-19 between March 11 and April 28, 2020 at two affiliated hospitals in New York City. We evaluated the association between GI symptoms and death, and also explored disease duration, from symptom onset to death or discharge. RESULTS: Of 2804 patients hospitalized with COVID-19, the 1,084 (38.7%) patients with GI symptoms were younger (aOR for age ≥75, 0.59; 95% CI, 0.45-0.77) and had more co-morbidities (aOR for modified Charlson comorbidity score ≥2, 1.22; 95% CI, 1.01-1.48) compared to those without GI symptoms. Individuals with GI symptoms had better outcomes, with a lower likelihood of intubation (aHR, 0.66; 95% CI, 0.55-0.79) and death (aHR, 0.71; 95% CI, 0.59-0.87), after adjusting for clinical factors. These patients had a longer median disease course from symptom onset to discharge (13.8 vs 10.8 days, log-rank p = .048; among 769 survivors with available symptom onset time), which was driven by longer time from symptom onset to hospitalization (7.4 vs 5.4 days, log-rank P < .01). CONCLUSION: Hospitalized patients with GI manifestations of COVID-19 have a reduced risk of intubation and death, but may have a longer overall disease course driven by duration of symptoms prior to hospitalization.

Characteristics and Outcomes of Endoscopies before and during the COVID-19 Pandemic in New York.

INTRODUCTION: The COVID-19 pandemic drastically changed hospital workflows. This study aimed to characterize differences in gastrointestinal endoscopies in the New York metropolitan region before, during, and after the first wave of the pandemic. METHODS: Across 3 hospitals, we compared demographics, indications, and yield of endoscopies before and after March 16, 2020, the date on which elective procedures were canceled, as well as a recovery period for 5 months after they were resumed. RESULTS: A total of 9,401 procedures before and 332 procedures during the first wave were performed. Females comprised 57 and 44% of patients (p < 0.01), respectively. There was a decline in the proportion of Black (15 vs. 7%, p < 0.02) and Hispanic patients (29 vs. 16%, p < 0.02) undergoing outpatient procedures. There was a significant rise in urgent indications such as bleeding and jaundice. There was an increase in the diagnostic yield of all esophagogastroduodenoscopies for bleeding (p < 0.01) and of outpatient endoscopic ultrasounds for malignancy (p = 0.01), but no increase in yield of inpatient colonoscopy for bleeding. A review of 7,475 procedures during the recovery period showed a return to many nonurgent indications, but still showed decreased proportions of Hispanic and male patients compared to the prepandemic period. DISCUSSION/CONCLUSION: Lower proportions of Black and Hispanic patients underwent outpatient endoscopies during and after the first wave. The proportion of procedures done for emergent indications and their diagnostic yield increased during the pandemic, suggesting a higher threshold to perform endoscopy. In resource-sparing conditions, clinicians should pay attention to thresholds to perform colonoscopy for bleeding and to racial disparities in outpatient healthcare access.

Patients with More Severe IBD Get Clostridioides difficile Rather than Clostridioides difficile Increasing the Severity of IBD.

BACKGROUND: Inflammatory bowel disease (IBD) patients who have Clostridioides difficile infection (CDI) have worse outcomes. AIMS: We aimed to determine whether such outcomes are the result of CDI or whether CDI occurs in patients who have more severe IBD. METHODS: This was a retrospective study of patients hospitalized for ≥ 2 IBD flares from 2010 to 2019. The primary outcome was time to IBD flare between hospitalizations. First, time to flare was compared between patients who were hospitalized for a flare complicated by CDI and subsequently for a CDI-negative flare (cohort A, denoted +/-) versus patients who were hospitalized for two CDI-negative flares (cohort B, -/-). Second, time between flares was compared within the subset of cohort A patients who had three flares (cohort C, -/+/-) before and after CDI. RESULTS: Time between flares was a median of 4 months (IQR 1-9) among 51 cohort A patients versus 12 months (IQR 6-38) among 51 cohort B patients (log-rank P < 0.01). In contrast, the median time between flares was similar within cohort C before and after CDI (log-rank P = 0.54). At time of the second IBD flare, patients in cohort A (+/-) were more likely to have moderate or severe disease compared to patients in cohort B (-/-). CONCLUSIONS: Patients with prior CDI had shorter time to subsequent IBD flare relative to their CDI-negative counterparts. This is not likely due to CDI itself because there was no difference in time between flares before versus after acquiring CDI. Rather, patients who acquire CDI may have more severe IBD.

Type II Achalasia Is Increasing in Prevalence.

BACKGROUND: Three manometric subtypes of achalasia were defined in the Chicago Classification approximately 10 years ago: type I (aperistalsis), type II (pan-pressurization), and type III (spastic). Since the widespread use of this classification scheme, the evolving prevalence of these subtypes has not been elucidated. We aim to determine the prevalence of each subtype a decade after the adoption of the Chicago Classification. METHODS: This is a retrospective cohort analysis of patients diagnosed with achalasia on high-resolution manometry (HRM) at two major academic medical centers between 2015 and 2018. Patients were excluded if they had a diagnosis of another esophageal motility disorder, previously treated achalasia, or foregut surgery. Demographic data, manometric subtype, and esophageal dilatation grade on endoscopy were obtained. Prevalence of achalasia subtypes was compared with a published historical control population (2004-2007). Fischer's exact and t tests were used for analysis. RESULTS: Of 147 patients in the contemporary cohort and 99 in the historical control cohort, the prevalence of type I achalasia was 8% versus 21%, type II 63% versus 50%, and type III 29% versus 29%, respectively (p = 0.01). The mean age in our population was 58 years compared to 57 years in the historical control, and the proportion of men 48% versus 47%, respectively (p = 0.78). Mean endoscopic dilatation grade in the contemporary cohort was 1.5 for type I patients, 0.9 for type II, and 0.4 for type III, compared with 1.5, 0.6, and 0.4, respectively. Overall mean dilatation grade was 0.8 in our cohort versus 0.7 in the historical control (p = 0.58). CONCLUSION: The prevalence of type II achalasia was significantly greater and prevalence of type I significantly less in our patient population compared to our predefined historical control. Other characteristics such as age and sex did not appear to contribute to these differences. Histopathological evidence has suggested that type II achalasia may be an earlier form of type I; thus, the increased prevalence of type II achalasia may be related to earlier detection of the disease. The adoption of HRM, widespread use of the Chicago Classification, and increased disease awareness in the past decade may be contributing to these changes in epidemiology.

Prevalence of Clostridioides difficile and Other Gastrointestinal Pathogens in Patients with COVID-19.

BACKGROUND: Gastrointestinal symptoms are common in patients with COVID-19, but prevalence of co-infection with enteric pathogens is unknown. AIMS: This study assessed the prevalence of enteric infections among hospitalized patients with COVID-19. METHODS: We evaluated 4973 hospitalized patients ≥ 18 years of age tested for COVID-19 from March 11 through April 28, 2020, at two academic hospitals. The primary exposure was a positive COVID-19 test. The primary outcome was detection of a gastrointestinal pathogen by PCR stool testing. RESULTS: Among 4973 hospitalized individuals, 311 were tested for gastrointestinal infections (204 COVID-19 positive, 107 COVID-19 negative). Patients with COVID-19 were less likely to test positive compared to patients without COVID-19 (10% vs 22%, p < 0.01). This trend was driven by lower rates of non-C.difficile infections (11% vs 22% in COVID-19 positive vs. negative, respectively, p = 0.04), but not C. difficile infection (5.1% vs. 8.2%, p = 0.33). On multivariable analysis, infection with COVID-19 remained significantly associated with lower odds of concurrent GI infection (aOR 0.49, 95% CI 0.24-0.97), again driven by reduced non-C.difficile infection. Testing for both C.difficile and non-C.difficile enteric infection decreased dramatically during the pandemic. CONCLUSIONS: Pathogens aside from C.difficile do not appear to be a significant contributor to diarrhea in COVID-19 positive patients.

Characteristics and Outcomes of Patients Undergoing Endoscopy During the COVID-19 Pandemic: A Multicenter Study from New York City.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the practice of endoscopy, but characteristics of COVID patients undergoing endoscopy have not been adequately described. AIMS: To compare findings, clinical outcomes, and patient characteristics of endoscopies performed during the pandemic in patients with and without COVID-19. METHODS: This was a retrospective multicenter study of adult endoscopies at six academic hospitals in New York between March 16 and April 30, 2020. Patient and procedure characteristics including age, sex, indication, findings, interventions, and outcomes were compared in patients testing positive, negative, or untested for COVID-19. RESULTS: Six hundred and five endoscopies were performed on 545 patients during the study period. There were 84 (13.9%), 255 (42.2%), and 266 (44.0%) procedures on COVID-positive, negative, and untested patients, respectively. COVID patients were more likely to undergo endoscopy for gastrointestinal bleeding or gastrostomy tube placement, and COVID patients with gastrointestinal bleeding more often required hemostatic interventions on multivariable logistic regression. COVID patients had increased length of stay, intensive care unit admission, and intubation rate. Twenty-seven of 521 patients (5.2%) with no or negative COVID testing prior to endoscopy later tested positive, a median of 13.5 days post-procedure. CONCLUSIONS: Endoscopies in COVID patients were more likely to require interventions, due either to more severe illness or a higher threshold to perform endoscopy. A significant number of patients endoscoped without testing were subsequently found to be COVID-positive. Gastroenterologists in areas affected by the pandemic must adapt to changing patterns of endoscopy practice and ensure pre-endoscopy COVID testing.

Body Mass Index and Risk for Intubation or Death in SARS-CoV-2 Infection : A Retrospective Cohort Study.

BACKGROUND: Obesity is a risk factor for pneumonia and acute respiratory distress syndrome. OBJECTIVE: To determine whether obesity is associated with intubation or death, inflammation, cardiac injury, or fibrinolysis in coronavirus disease 2019 (COVID-19). DESIGN: Retrospective cohort study. SETTING: A quaternary academic medical center and community hospital in New York City. PARTICIPANTS: 2466 adults hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection over a 45-day period with at least 47 days of in-hospital observation. MEASUREMENTS: Body mass index (BMI), admission biomarkers of inflammation (C-reactive protein [CRP] level and erythrocyte sedimentation rate [ESR]), cardiac injury (troponin level), and fibrinolysis (D-dimer level). The primary end point was a composite of intubation or death in time-to-event analysis. RESULTS: Over a median hospital length of stay of 7 days (interquartile range, 3 to 14 days), 533 patients (22%) were intubated, 627 (25%) died, and 59 (2%) remained hospitalized. Compared with overweight patients, patients with obesity had higher risk for intubation or death, with the highest risk among those with class 3 obesity (hazard ratio, 1.6 [95% CI, 1.1 to 2.1]). This association was primarily observed among patients younger than 65 years and not in older patients (P for interaction by age = 0.042). Body mass index was not associated with admission levels of biomarkers of inflammation, cardiac injury, or fibrinolysis. LIMITATIONS: Body mass index was missing for 28% of patients. The primary analyses were conducted with multiple imputation for missing BMI. Upper bounding factor analysis suggested that the results are robust to possible selection bias. CONCLUSION: Obesity is associated with increased risk for intubation or death from COVID-19 in adults younger than 65 years, but not in adults aged 65 years or older. PRIMARY FUNDING SOURCE: National Institutes of Health.

Does Addition of Intravenous Metronidazole to Oral Vancomycin Improve Outcomes in Clostridioides difficile Infection?

BACKGROUND: Guidelines recommend adding intravenous (IV) metronidazole to oral vancomycin for fulminant Clostridioides difficile infection (CDI). In this study, we compared dual therapy with IV metronidazole and vancomycin vs vancomycin monotherapy. We assessed prevalence of use and effectiveness of dual therapy in nonfulminant and fulminant CDI. METHODS: This was a 2-center retrospective study conducted from 2010 to 2018. Adult inpatients were included if they had a positive C. difficile polymerase chain reaction (PCR) performed on an unformed stool and received vancomycin within 2 days of testing. Patients were classified as having received dual therapy if IV metronidazole was given within the same time window, and otherwise classified as vancomycin monotherapy. The primary outcome was death or colectomy within 90 days after the index test. Logistic regression modeling was used to adjust for CDI severity and other established predictors of CDI outcomes. CDI recurrence was examined as a secondary outcome, adjusting for death as a competing risk. RESULTS: The study included 2114 patients (dual therapy, 993; monotherapy, 1121); 23% met the primary outcome. There was no association between dual therapy and the primary outcome (adjusted odds ratio [aOR], 1.07; 95% confidence interval [CI], .79-1.45), which remained true when the analysis was restricted to patients with fulminant CDI (aOR, 1.17; 95% CI, .65-2.10). There was also no association between dual therapy and CDI recurrence. CONCLUSIONS: Dual therapy with IV metronidazole and vancomycin was common for nonfulminant and fulminant CDI but was not associated with improved outcomes compared with vancomycin alone.