IDDF2023-ABS-0032 Active inflammatory bowel disease is associated with severe covid-19: a systematic review and meta-analysis

IDDF2023-ABS-0032 Figure 1 IDDF2023-ABS-0032 Figure 2 IDDF2023-ABS-0032 Figure 3 IDDF2023-ABS-0032 Figure 4COVID-19 outcomes in moderate-severe vs mild or quiescent IBD[Figure omitted. See PDF]ConclusionsPatients with IBD, particularly UC had an increased risk of developing severe COVID-19. Active IBD is associated with adverse COVID-19 outcomes, and the risk is increased with the disease activity of IBD.

PLACEBO-CONTROLLED EFFICACY AND SAFETY OF UPADACITINIB THROUGH ONE YEAR IN PATIENTS WITH NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS

BackgroundUpadacitinib (UPA), a Janus kinase inhibitor, was effective and well tolerated in patients (pts) with non-radiographic axial spondyloarthritis (nr-axSpA) through 14 weeks (wks) of treatment.[1]ObjectivesThis analysis assessed the efficacy and safety of UPA vs placebo (PBO) through 1 year.MethodsThe SELECT-AXIS 2 nr-axSpA study included a 52-wk randomized, double-blind, PBO-controlled period. Enrolled adults had a clinical diagnosis of active nr-axSpA fulfilling the 2009 ASAS classification criteria, objective signs of inflammation based on MRI sacroiliitis and/or elevated C-reactive protein, and an inadequate response to NSAIDs. One-third of pts had an inadequate response to biologic DMARDs. Pts were randomized 1:1 to UPA 15 mg once daily or PBO. Concomitant medications, including NSAIDs, had to be kept stable through wk 52. The study protocol outlined that pts who did not achieve ASAS20 at any two consecutive study visits between wks 24 to 52 should receive rescue therapy with NSAIDs, corticosteroids, conventional synthetic/biologic DMARDs, or analgesics. Cochran-Mantel-Haenszel (CMH) test with non-responder imputation incorporating multiple imputation (NRI-MI) was used to handle missing data and intercurrent events for binary efficacy endpoints. Mixed-effect model repeated measures (MMRM) was used to assess continuous efficacy endpoints. NRI was used for binary endpoints after rescue and as observed analysis excluding data after rescue for continuous endpoints. Treatment-emergent adverse events (TEAEs) are reported through wk 52.ResultsOf the 314 pts randomized, 259 (82%;UPA, n=130;PBO, n=129) completed wk 52 on study drug. More pts achieved an ASAS40 response with UPA vs PBO from wks 14 to 52 with a 20% treatment difference at wk 52 (63% vs 43%;nominal P <.001;Figure 1). The proportion of pts achieving ASDAS inactive disease with UPA remained higher than PBO at wk 52 (33% vs 11%;nominal P <.0001;Figure 1). Consistent improvements and maintenance of efficacy were also seen across other disease activity measures. Between wks 24 and 52, fewer pts on UPA (9%) than PBO (17%) received rescue therapy. A similar proportion of pts in each treatment group had a TEAE (Table 1). Infections were the most common TEAE;the rates of serious infections and herpes zoster were higher with UPA vs PBO, although no new serious infections were reported from wks 14 to 52. COVID-19 events were balanced between treatment groups. No opportunistic infections, malignancy excluding non-melanoma skin cancer, adjudicated major adverse cardiovascular events, inflammatory bowel disease, or deaths were reported. Two pts (1.3%) on PBO had adjudicated venous thromboembolic events.ConclusionUPA showed consistent improvement and maintenance of efficacy vs PBO through 1 year across multiple disease activity measures. No new safety risks were identified with longer-term UPA exposure. These results continue to support the benefit of UPA in pts with active nr-axSpA.Reference[1]Deodhar A, et al. Lancet. 2022;400(10349):369–379.Table 1.Safety through week 52Event, n (%)PBO (n = 157)UPA 15 mg QD (n = 156)Any AE103 (66%)107 (69%)Serious AE6 (3.8%)6 (3.8%)AE leading to D/C4 (2.5%)6 (3.8%)COVID-19-related AE22 (14%)24 (15%)Deaths00Infection60 (38%)68 (44%) Serious infection1 (0.6%)2 (1.3%) Herpes zoster1 (0.6%)5 (3.2%)Malignancy other than NMSC00NMSC1 (0.6%)0Hepatic disorder7 (4.5%)6 (3.8%)Neutropenia1 (0.6%)8 (5.1%)MACE (adjudicated)00VTE (adjudicated)2 (1.3%)a0Uveitisb3 (1.9%)2 (1.3%)Inflammatory bowel disease00aBoth patients had non-serious events of deep vein thrombosis in the lower limb with risk factors including obesity and prior deep vein thrombosis in one patient and concomitant COVID-19 infection in the other patient.bThree events of uveitis occurred in each treatment group (among n = 3 patients in the PBO group and n = 2 patients in the UPA group);two events in the PBO group and one in the UPA group occurred in patients with a history of uveitis.AcknowledgementsAbbVie funded this study and participated in the study design, res arch, analysis, data collection, interpretation of data, review, and approval of the . All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Julia Zolotarjova, MSc, MWC, of AbbVie.Disclosure of InterestsFilip van den Bosch Speakers bureau: AbbVie, Amgen, Galapagos, Janssen, Lilly, Merck, MoonLake, Novartis, Pfizer, and UCB., Consultant of: AbbVie, Amgen, Galapagos, Janssen, Lilly, Merck, MoonLake, Novartis, Pfizer, and UCB., Atul Deodhar Consultant of: AbbVie, Amgen, Aurinia, BMS, Celgene, GSK, Janssen, Lilly, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, GSK, Lilly, Novartis, Pfizer, and UCB, Denis Poddubnyy Speakers bureau: AbbVie, Biocad, BMS, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB, Consultant of: AbbVie, Biocad, BMS, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, Lilly, MSD, Novartis, and Pfizer., Walter P Maksymowych Consultant of: AbbVie, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Novartis, Pfizer, and UCB, Employee of: Chief Medical Officer of CARE Arthritis Limited, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, and UCB, Employee of: Director of Imaging Rheumatology BV, Tae-Hwan Kim Speakers bureau: AbbVie, Celltrion, Kirin, Lilly, and Novartis., Mitsumasa Kishimoto Consultant of: AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi Sankyo, Eisai, Gilead, Janssen, Lilly, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, and UCB., Xenofon Baraliakos Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, and UCB, Consultant of: AbbVie, BMS, Chugai, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie and Novartis, Yuanyuan Duan Shareholder of: AbbVie, Employee of: AbbVie, Kristin D'Silva Shareholder of: AbbVie, Employee of: AbbVie, Peter Wung Shareholder of: AbbVie, Employee of: AbbVie, In-Ho Song Shareholder of: AbbVie, Employee of: AbbVie.

IRF2BP2 mutation with autoimmune enteropathy, immune deficiency, and respiratory failure

Case history: We present the case of a 31-year-old Hispanic male with history of recurrent bronchiectasis, invasive aspergillosis, and severe persistent asthma, who is now status post lung transplant for end-stage lung disease. He initially presented at 7 years of age with diarrhea, failure to thrive, and nearly absent immunoglobulin levels (IgG < 33 mg/dL, IgA < 7 mg/dL, IgM = 11 mg/dL, IgE = 4 IU/dL) necessitating IVIG treatment. Small intestinal biopsy showed villous atrophy consistent with autoimmune enteropathy. Sweat chloride was reported as indeterminate (44 me/dL). Initial WBC, platelet, and T- and NK-cell counts were within normal range, and B-cell count and percentage were borderline low. Most recently, he was found to have increased immature B-cell count (CD21low), decreased memory B-cells, and poor pneumococcal vaccine antibody response. Patient has been hospitalized numerous times with increasingly severe bronchiectasis, pneumonitis, and COVID-19 infections twice despite vaccination, leading to respiratory failure and lung transplantation. Family history is negative for immune deficiency and lung diseases. Discussion(s): Of these 3 VUSs (see the table), the one in IRF2BP2 has the most pathogenic potential due to its autosomal dominant inheritance, its location in a conserved domain (Ring), and previous case reports of pathogenic variants at the same or adjacent alleles 1-3. Baxter et al reported a de novo truncating mutation in IRF2BP2 at codon 536 (c.1606CinsTTT), which is similar to our patient's mutation. This patient was noted to have an IPEX-like presentation, with chronic diarrhea, hypogammaglobulinemia, and recurrent infections. Variant Functional Prediction Score for our variant predicts a potentially high damage effect. There are 2 other case reports of heterozygous mutations in loci adjacent to this allele;one (c.1652G>A)2 with a similar clinical phenotype to our patient and the other (C.625-665 del)3 with primarily inflammatory features and few infections. Impact: This case highlights a variant in IRF2BP2 associated with severe hypogammaglobulinemia, recurrent pulmonary infections, and autoimmune enteropathy. [Table presented]Copyright © 2023 Elsevier Inc.

Surveillance for SARS-CoV-2 in Norway Rats (Rattus norvegicus) from Southern Ontario

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from wildlife has raised concerns about spillover from humans to animals, the establishment of novel wildlife reservoirs, and the potential for future outbreaks caused by variants of wildlife origin. Norway rats (Rattus norvegicus) are abundant in urban areas and live in close proximity to humans, providing the opportunity for spillover of SARS-CoV-2. Evidence of SARS-CoV-2 infection and exposure has been reported in Norway rats. We investigated SARS-CoV-2 infection and exposure in Norway rats from Southern Ontario, Canada. From October 2019 to June 2021, 224 rats were submitted by collaborating pest control companies. The majority of samples were collected in Windsor (79.9%;n = 179), Hamilton (13.8%;n = 31), and the Greater Toronto Area (5.8%;n = 13). Overall, 50.0% (n = 112) were female and most rats were sexually mature (55.8%;n = 125). Notably, 202 samples were collected prior to the emergence of variants of concern (VOC) and 22 were collected while the Alpha variant (B.1.1.7) was the predominant circulating VOC in humans. Nasal turbinate (n = 164) and small intestinal (n = 213) tissue samples were analyzed for SARS-CoV-2 RNA by RT-PCR. Thoracic cavity fluid samples (n = 213) were tested for neutralizing antibodies using a surrogate virus neutralization test (sVNT) (GenScript cPass);confirmatory plaque reduction neutralization test (PRNT) was conducted on presumptive positive samples. We did not detect SARS-CoV-2 RNA in any samples tested. Two out of eleven samples positive on sVNT had neutralizing antibodies confirmed positive by PRNT (1 : 40 and 1 : 320 PRNT70);both were collected prior to the emergence of VOC. It is imperative that efforts to control and monitor SARS-CoV-2 include surveillance of rats and other relevant wildlife species as novel variants continue to emerge.

Liver biomarkers for prognosis in COVID-19

The novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).Mortality attributable to COVID-19 remains considerably high, with case fatality rates as high as 8-11%. Early medical intervention in patients who are seriously and critically ill with COVID-19 reduces fatal outcomes. Thus, there is an urgent need to identify biomarkers that could help clinicians determine which patients with SARS-CoV-2 infection are at a higher risk of developing the most adverse outcomes, which include intensive care unit (ICU) admission, invasive ventilation, and death. In COVID-19 patients experiencing the most severe form of the disease, tests of liver function are frequently abnormal and liver enzymes are found to be elevated. For this reason, we examine the most promising liver biomarkers for COVID-19 prognosis in an effort to help clinicians predict the risk of ARDS, ICU admission, and death at hospital admission. In patients meeting hospitalization criteria for COVID-19, serum albumin < 36 g/L is an independent risk factor for ICU admission, with an AUC of 0.989, whereas lactate dehydrogenase (LDH) values > 365 U/L accurately predict death with an AUC of 0.943.The clinical scores COVID-GRAM and SOFA that include measures of liver function such as albumin, LDH, and total bilirubin are also good predictors of pneumonia development, ICU admission, and death, with AUC values ranging from 0.88 to 0.978.Thus, serum albumin and LDH, together with clinical risk scores such as COVID-GRAM and SOFA, are the most accurate biomarkers in the prognosis of COVID-19.Copyright © 2021 Sociedad Medica del Hospital General de Mexico. Published by Permanyer.

Effects of Porcine deltacoronavirus on the transduction pathway of the innate immune signal

Porcine deltacoronavirus (PDCOV) is a new type of pig intestinal coronavirus, which targets pig small intestinal epithelial cells to cause severe enteritis. After infecting the host, PDCoV finishes its proliferation in the host cell by antagonism or escape the innate immune signaling transduction pathway. In order to understand the action mechanism of PDCOV 0n the congenital immune signal transduction pathways, this paper reviews the effects of PDCOV on RLR, Jak-STAT, MAPK and mitochondrial signaling pathway to clarify the relationship between PDCOV and host innate immune signaling transduction pathways in order to provide help for the prevention and treatment of PDCOV infection.

Nutrition Strategies Pre-infection, during, and Post-infection with Coronavirus Disease

Coronavirus disease is a serious viral infection that is characterized by severe inflammation and lymphopenia. The virus attacks many organs causing acute respiratory distress and malfunctioning of the organs leading to death. Through strengthening of the innate immune system, a balanced diet plays a critical role in defense against bacterial and viral diseases. A healthy diet before, during and after an infection can lessen the severity of the symptoms and speed up the recovery of damaged cells. Due to the Mediterranean diet's high concentration of bioactive polyphenols, which have antioxidant, anti-inflammatory, and antithrombic properties, numerous studies have suggested that it is a preventative dietary strategy against many diseases including coronavirus disease. Nutrition and herbal plants play a key role to enhance the immunity of people to protect and fight against coronavirus. Diet rich in antioxidants and phytochemicals represents perfect barrier to the virus through elevation of the innate immunity of the body. In addition, gut microbiota including prebiotics, probiotics, and synbiotics were found to enhance immunity to reduce the symptoms of the disease during infection. Protein-rich foods and honey bee products reported significant role during and post-coronavirus infection. This review presents updated information from original pre-clinical and clinical researches, and review articles as well to expose the nutritive strategies including breastfeeding benefits to infants pre-infection, during, and post-infection with coronavirus.Copyright © 2023, Scientific Foundation SPIROSKI. All rights reserved.

Surgical treatment of acute intestinal obstruction in the infectious department environment for covid-19 patients.

Surgical care in a mono-hospital for patients with COVID-19 leads to a number of organisational problems due to the lack of specialised departments. The article presents the experience of surgical treatment in a mono-hospital obtained from one and a half years of work in this mode. In total, approximately 400 surgeries were performed. The experience of treatment of 7 patients with acute intestinal obstruction has been summarised. In the abdominal cavity, a significant number of hematomas of varied localisation were found under the parietal and visceral peritoneum, as well as in the subcutaneous fat. This is possibly associated with anticoagulant therapy included in the treatment regimen for patients with COVID-19 according to the methodical recommendations by the Ministry of Health of the Russian Federation. As an illustration, a successful case of treating COVID-19 patient with strangulated hernia of the abdominal white line complicated by acute intestinal obstruction is presented.Copyright © 2022, Krasnoyarsk State Medical University. All rights reserved.

Whipple's Disease, An Overlooked Diagnosis

Whipple disease is a rare multisystem inflammatory disease. Because fewer than 1000 reported cases have been described, clinical experience with this disorder is sparse. We are reporting a case of a 46-year-old man who presented with fever, weight loss, and polyarthralgia for 2 months, and 1 month of diarrhea. The patient was thoroughly investigated for collagen diseases and COVID-19, with no definite diagnosis. A therapeutic trial by immunosuppressive drugs provided partial remission followed by a marked rebound of the symptoms. His occult blood in stool was positive and subsequent upper endoscopy with proximal small intestinal biopsies showed the pathological features of Whipple's disease. The patient showed a dramatic improvement following treatment with ceftriaxone and trimethoprim-sulfamethoxazole. Despite the rarity of Whipple's disease, its course mimics many rheumatological diseases, inflammatory bowel disease, and COVID-19 disease. It should always be a part of the differential diagnosis of obscure polyarthralgia and chronic diarrhea.Copyright © 2023 The Author(s).

Gastrointestinal symptoms and disorders related to COVID-19. Lessons learned from gastroenterologists

COVID-19 is mainly a respiratory illness caused by the SARS-CoV-2 but can also lead to GI symptoms. The primary host receptor which mediates the mechanism as SARS-CoV-2 enters the cell is the ACE2 receptor. Therefore, GI symptoms can be common in COVID-19, and in some cases, they are the first manifestation even before fever and respiratory symptoms. In addition, the liver function tests alteration often is related to a worse prognosis. The exact incidence of GI symptoms is a matter of debate. Moreover, wide variation concerning GI symptoms frequency exists, but the predominant ones seem to be diarrhea, anorexia, nausea, vomiting, and abdominal pain or discomfort.This review summarizes the most relevant findings of COVID-19 on the digestive system, including the liver, biliary tract, pancreas, the most common GI symptoms, and the atypical clinical GI manifestations.Copyright © 2022 Sociedad Medica del Hospital General de Mexico. Published by Permanyer.

IDDF2023-ABS-0156 Poor tolerance of bowel preparation for index colonoscopy decreases surveillance rate in high-risk adenoma removal patients

IDDF-2023-ABS-0156 Table 1Association between Tolerance of BP for index colonoscopy and surveillance rateTolerance of BP for index colonoscopy Surveillance rate% (n/N) Total 67% (127/186) 1. Very intolerable 47% (9/19) 2. Intolerable 48% (10/21) 3. Neither tolerable nor intolerable 76% (55/72) 4. Tolerable 71% (22/31) 5. Very tolerable 72% (31/43) P for trend test 0.04 IDDF2023-ABS-0156 Table 2Risk factors of non-compliance of surveillance colonoscopy by multivariate regression analysis Multivariate OR (95%CI) p value Age,/1-year increase 1.04 (1.03-1.05) 0.001 Male sex 1.13 (0.85-1.52) 0.40 BMI,/1-kg/m2 increase 1.05 (0.96-1.15) 0.28 Family history of CRC 0.93 (0.16-5.25) 0.92 Low education 0.92 (0.39-2.15) 0.90 Comorbidities 1.05 (0.51-2.13) 0.90 Low tolerance of BP for colonoscopy 2.45 (1.11-5.41) 0.006 Absence of primary care physician 4.63 (1.60-13.4) 0.001 BMI: body mass index, CRC: colorectal cancer, BP: bowel preparation IDDF2023-ABS-0156 Table 3The reasons of non-compliance surveillance colonoscopyReasons of non-compliance surveillance colonoscopy n, (%) Total 62 (100%) Not knowing about follow-up intervals 4 (6%) Having no symptoms 15 (24%) Fear of examination Pain during colonoscopy 1 (2%) Embarrassment during colonoscopy 0 (0%) Bowel preparation for colonoscopy 17 (28%) Over sedation during colonoscopy 2 (3%) Old age/severe illness for surveillance 10 (16%) Having no time 10 (16%) Having no money 1 (2%) Fear of Covid-19 infection 2 (3%) IDDF2023-ABS-0156 Figure 1ConclusionsOur findings highlight the need for improvement of the surveillance colonoscopy rate, especially for patients who had poor tolerance to BP on index colonoscopy and no gastroenterology visit. Providing a well-tolerated BP regimen may lead to an increase in surveillance colonoscopy compliance.

Natural Evolution of Porcine Epidemic Diarrhea Viruses Isolated from Maternally Immunized Piglets

Simple SummaryDuring the long-term co-evolution of the virus and the host, even closely related vaccines may emerge with incomplete protective immunity due to the mutations or deletions of amino acids at specific antigenic sites. The mutation of PEDV was accelerated by the recombination of different strains and the mutation of the strains adapting to the environment. These mutations either cause immune escape from conventional vaccines or affect the virulence of the virus. Therefore, researching and developing new vaccines with cross-protection through continuous monitoring, isolation and sequencing are important to determine whether their genetic characteristics are changed and to evaluate the protective efficacy of current vaccines. The porcine epidemic diarrhea virus (PEDV) can cause severe piglet diarrhea or death in some herds. Genetic recombination and mutation facilitate the continuous evolution of the virus (PEDV), posing a great challenge for the prevention and control of porcine epidemic diarrhea (PED). Disease materials of piglets with PEDV vaccination failure in some areas of Shanxi, Henan and Hebei provinces of China were collected and examined to understand the prevalence and evolutionary characteristics of PEDV in these areas. Forty-seven suspicious disease materials from different litters on different farms were tested by multiplex PCR and screened by hematoxylin-eosin staining and immunohistochemistry. PEDV showed a positivity rate of 42.6%, infecting the small and large intestine and mesenteric lymph node tissues. The isolated strains infected Vero, PK-15 and Marc-145 multihost cells and exhibited low viral titers in all three cell types, as indicated by their growth kinetic curves. Possible putative recombination events in the isolates were identified by RDP4.0 software. Sequencing and phylogenetic analysis showed that compared with the classical vaccine strain, PEDV SX6 contains new insertion and mutations in the S region and belongs to genotype GIIa. Meanwhile, ORF3 has the complete amino acid sequence with aa80 mutated wild strains, compared to vaccine strains CV777, AJ1102, AJ1102-R and LW/L. These results will contribute to the development of new PEDV vaccines based on prevalent wild strains for the prevention and control of PED in China.

A Case Series Analysis of Intestinal Ischemia in Covid- 19 Pandemic

Introduction: Coronavirus disease-2019 (COVID-19) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has caused a global health crisis. Initially considered a respiratory tract pathogen, it can cause multiple organ dysfunction. It has also been described to predispose to venous and arterial thromboembolism;however, limited published data is available regarding mesenteric thrombosis COVID-19. Clinicians should be aware of the life-threatening situation in COVID-19 patients. Method(s): A case series analysis of 9 patients admitted and managed under department of operation over a duration of 13 months from September 2020 to September 2021 Results: Out of the total of 9 cases of intestinal ischemia, 3 were COVID-19 positive (rapid antigen, RT PCR or CORADS 4 or higher), overall mortality being 55.5% and patients with COVID- 19 were found to have 100% mortality in the study. Mortality in conservatively managed patients was 100%, Mortality in surgically managed patients was 42.8%. Pre operative acidosis, hypoxia and hypotension were found to be important determinants of outcome of the disease. Conclusion(s): Treatment of COVID - 19 and intestinal Ischemia should go simultaneously and in line with the latest evidence based guidelines of COVID 19, Patients who survive an acute event are likely to die of other complications related to the COVID-19 like ARDS, Disseminated Intravascular Coagulation etc that could have predisposed them to intestinal ischemia. Perioperative acidosis, hypoxia and hypotension are important determinants of the outcome of the course of the disease.

General Surgery Resident Case Numbers During the Covid-19 Pandemic

Introduction: The COVID-19 pandemic has had widespread effects on the healthcare system. For trainees, one particular detriment has been the cancellation of elective operations, reducing clinical experience and procedural volumes. Measures instituted to combat the pandemic have resulted in decreased cancellation of elective cases to varying degrees. The aim of this study is to evaluate the ongoing effect of the pandemic on resident operative volume. Method(s): Operative case numbers of general surgical graduates in 2019, 2020, and 2021 were extracted from the Accreditation Council for Graduate Medical Education case logs. Data included mean total cases/graduate and means for individual case types. Data was considered by overall number of cases and cases performed as surgeon chief. Analysis of variance was employed to compare groups with p<0.05 considered significant. Result(s): Mean total major cases differed significantly among groups with reduced volume noted for 2020 graduates but no difference in volume between 2019 and 2021 graduates (1070.5+/-150 vs 1054.8+/-155 vs 1074.1+/-164, p=0.0041). This same pattern was noted for surgeon chief total cases (288.6+/-69 vs 264.4+/-67 vs 286.2+/-73, p<0.0001) as well as several major general surgery subcategories including cases involving the stomach, small intestine, large intestine, biliary system, among others. Conclusion(s): Despite continued reduction in and alteration of elective surgery practice, improved pandemic measures have allowed for increased surgical volume. This has translated to increased operative experience for graduating surgical trainees that are comparable to case numbers that preceded the pandemic. Ramifications for the 2020 graduating cohort as well subsequent cohorts require continued evaluation.

Intestinal microbiota, pain, dementia

The review is dedicated the interconnection between neurodegenerative diseases, chronic pain and gut microbiota's structure and function. The gut microbiota's role in gut-brain axis, neuroimmune interaction is considered. The modern data about gut dysbiosis in Alzheimer disease, Parkinson disease, osteoarthrosis, neuropathic pain in COVID infection, muscular-skeletal pain in fibromyalgia, irritable bowel syndrome et cetera are provided. The gut microbiota's modification by means of pre and probiotics in combination with medicines and diet modification can be used for the treatment of chronic pain and dementia.Copyright © T.M. MANEVICH.

Coronavirus murine hepatitis virus strain 3 induces intestinal injury via caspase 3 dependent apoptosis

Background: Diarrhea was typical symptoms of the coronavirus disease 2019 (COVID-19). However, the underlying mechanism had not been fully understood. Aim(s): The study aimed to explore the mechanism of intestinal injury during COVID-19 in a coronavirus murine hepatitis virus strain 3 (MHV-3) induced acute mouse model. Method(s): MHV-3 induced acute infection Balb/cJ mice model was established. Intestine samples were collected at indicated time points as 0 h, 24 h, 48 h and 60 h post infection. The mRNA and protein expression of IL1b, TNFalpha, IL6, caspase 3 and cleaved caspase 3 were examined by real-time quantitative PCR (qPCR) and western blot respectively. The intestine injury and apoptosis were measured by HE staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Moreover, Z-DEVD-FMK (caspase 3 inhibitor) pre-treated MHV-3 infection mice model were established, in which the apoptosis of intestine was evaluated as well. Meanwhile, the murine intestinal cell MODE-K was infected by MHV-3 in vitro for evaluation of virus induced apoptosis. Result(s): Post MHV-3 infection, the histopathology of intestine tissue showed extraordinary injury with time dependence, as well as high level of TUNEL positivity. The mRNA levels of inflammatory cytokine IL1b, TNFalpha and IL6 were significantly increased. The protein expressions of caspase 3 and cleaved caspase 3 in the intestine was found significantly elevated from 24 to 48 h post MHV-3 infection. Z-DEVD-FMK pretreatment inhibited caspase 3 and cleaved caspase 3 expression and decreased TUNEL positivity. Meanwhile, alleviated gut injury and inhibited TNFalpha expression were observed. In vitro treated by MHV-3, intestinal cell line MODE-K showed nine-fold increase of apoptosis by comparison with saline treated ones. The expressions of apoptosis crucial protein caspase3 and cleaved caspase3 significantly elevated, as well as TNFalpha. Conclusion(s): Coronavirus murine hepatitis virus strain 3 induces intestinal injury via caspase 3 dependent apoptosis, which might shed light on the treatment of intestinal complications in COVID-19.

Diarrhea as an Independent Risk Factor for COVID-19 Severity and Inpatient Mortality

Introduction: Multiple meta-analyses have shown that over 15% patients with COVID-19 have at least one gastrointestinal complaint, most commonly diarrhea. The effects on the gastrointestinal system are thought to be mediated by the high expression of angiotensin-converting enzyme 2 (ACE2) and cellular serine proteases (TMPRSS2) in enterocytes, which cause altered intestinal permeability. The purpose of this study was to determine the incidence of diarrhea as it relates to COVID-19 infection and to determine if having concomitant diarrhea had a significant impact on disease course. Method(s): A retrospective chart review of 164,730 patients in a hospital system who were older than 18 years of age and had a positive SARS-CoV-2 test from March 2020 to February 2022 was completed. Diarrhea was determined using ICD code or patient's symptoms. Patients with confounding variables such as IBD, IBS, Celiac, Clostridium difficile, and pancreatic insufficiency were excluded. Demographic clinical characteristics and outcomes, including inpatient admission and mortality, were compared in patients with and without diarrhea. The Mann-Whitney test and Fisher's exact or Chi-square test was used for continuous and categorical variables respectively and multivariate logistic regression was used to evaluate for significant differences in disease outcome between the two groups. (Table) Results: Of the 164,730 patients included, 14,648 (8.89%) had diarrhea at the time of SARS-CoV-2. 6,748/33,464 (20.16%) of inpatient admissions were associated with diarrhea. On multivariate analysis, diarrhea was an independent risk factor for inpatient hospitalization (OR 2.39, CI 95% 2.28-2.51, P, 0.001) and inpatient mortality (OR 1.15, CI 96% 1.06-1.26, P= 0.001) after controlling for age, gender, race, comorbidities that could impact patient outcome, use of immunomodulators and outpatient antibiotics. Conclusion(s): These findings show that, even with controlling for comorbidities with COVID-19, diarrhea was an independent factor for predicting inpatient mortality and inpatient admission in general. Patients who had diarrhea and COVID-19 were sicker, having more comorbid conditions than those without diarrhea in our cohort. Attention should be given to not only respiratory complaints of COVID-19, but also gastrointestinal complaints, as they are an indicator of poor prognosis and mortality.

Acute Pancreatitis Following a Lower Extremity Angioplasty

Introduction: Acute pancreatitis affects a significant population globally. Usual etiologies are gallstones, alcohol, hypertriglyceridemia, medications;less frequent are trauma, hypercalcemia, infections, toxins, ischemia, anatomic anomalies, vasculitis, and idiopathic. Pancreatitis post coronary intervention is an uncommon cause with only 19 published cases in the last two decades. Being cognizant of this etiology is important given the increasing number of patients undergoing angiography. Case Description/Methods: An 81-year-old female with hypertension, diabetes, peripheral arterial disease, prior cholecystectomy underwent left lower extremity angioplasty at an outside center. Within a few hours, she started having severe epigastric pain radiating to her back, nausea, vomiting and loose bloody stool. She presented to the emergency department 24 hours after symptom onset. Epigastric tenderness was present on exam. Labs revealed leukocytosis (24,450/muL), elevated lipase (1410 U/L), elevated creatinine (1.3 mg/dL), lactate (3.1 mmol/L), calcium 9.4 mg/dL and triglycerides 161 mg/dL. Incidentally, found to be positive for COVID-19. Normal common bile duct diameter seen on sonogram. CT angiogram of the abdomen/pelvis showed acute pancreatitis, duodenal and central small bowel enteritis (Figure). She was not on any medications known to cause pancreatitis and denied alcohol use. Patient improved with analgesics and intravenous fluids. She had no recurrence of bloody stools and hemoglobin remained stable. On day 4, she was able to tolerate a regular diet, and leukocyte count and creatinine normalized. Patient did not have any COVID respiratory symptoms, and was discharged. Discussion(s): Given the temporal association to angioplasty and no other identifiable cause, acute pancreatitis was presumed to be due to the contrast used during angioplasty. Other possibilities included cholesterol embolism but no peripheral signs of cholesterol embolism were seen. Patient was an asymptomatic COVID-19 case. Although, there are case series of pancreatitis due to COVID, those were found in very sick symptomatic patients. On review of literature, cholesterol embolism was identified as a definite cause only on autopsy or laparotomy (Table). Other possible mechanisms are: high viscosity of the contrast media leading to ischemia and necrosis, contrast causing NF-kB activation followed by epithelial damage, and vasospasm. Pancreatitis after coronary angiography is rare, nonetheless, an important differential especially if there is a temporal relationship.

Lactulose Works in the Large Bowel: But How Does It Improve Hepatic Encephalopathy in a Patient Without a Large Bowel?

Introduction: Lactulose is a non-absorbable disaccharide which acts in the large bowel, and is commonly used in the treatment of hepatic encephalopathy. We present an interesting case of altered mental status due to hepatic encephalopathy successfully managed with lactulose in a patient with history of total colectomy. Case Description/Methods: A 67-year-old male with non-alcoholic cirrhosis and inflammatory bowel disease (IBD) post total proctocolectomy with a continent ileostomy known as a Kock-pouch (K-pouch) presented to the hospital with flu like symptoms and altered mental status. He was subsequently found to be positive for COVID-19. At the time of initial evaluation, the patient was obtunded with an elevated ammonia level of 91 umol/L. Colorectal surgery was consulted as the patient was not able to empty his K-pouch. Recently, he complained of inability to catheterize and with bleeding from the stoma. Initial catheterization with a Water's tube yielded 400 cc of effluent. Nasogastric tube was placed through which he was receiving lactulose 30 mg q8 hours. The patient's mental status improved within 24 hours. The patient ultimately underwent flexible pouchoscopy with endoscopic dilation and placement of a 22 French mushroom catheter for decompression of the K-pouch. Discussion(s): Lactulose is a non-absorbable disaccharide composed of galactose and fructose. The small intestine does not have the enzymes required to breakdown lactulose so it reaches the large bowel in its original form. In the large bowel, it is metabolized by colonic bacteria into monosaccharides and then to volatile fatty acids, hydrogen and methane. Lactulose decreases both the production and absorption of ammonia mainly through the presence of gut bacteria. The question arises as to how lactulose decreased ammonia levels in this patient without a large bowel. One proposed mechanism is the translocation of bacteria normally found in the large bowel to the small intestine. Small Intestinal Bacterial Overgrowth (SIBO), is a condition causing an increased number of bacteria in the small intestine. Patients with IBD and structural abnormalities are at increased risk of developing SIBO. Lactulose is commonly used in the diagnosis through the administration of lactulose and subsequent measurements of hydrogen and methane gas in expired air. This condition, in our patient with history of ulcerative colitis and colectomy, is a proposed mechanism of the efficacy of lactulose in the treatment of hepatic encephalopathy.

Holy Foley: Iatrogenic Duodenal Obstruction From a Make-Shift Gastrostomy Tube

Introduction: Enteral feeding is a physiologic process of providing adequate nutrition and has been shown to improve both mortality and quality of life in patients with inadequate oral intake. Improved critical care medicine and recent wave of Coronavirus Disease 2019 (COVID-19) has left us with a large proportion of patients needing alternative enteral nutrition. Although rare, intussusception is an important differential for patients presenting with acute abdominal pain post makeshift percutaneous endoscopic gastrostomy (PEG) tube placement. Case Description/Methods: A 58-year-old male was admitted to the hospital for coffee ground emesis over three days accompanied with epigastric pain. He had right sided hemiparesis secondary to cerebrovascular accident with PEG tube for enteral nutrition. Examination was significant for epigastric tenderness with normal bowel sounds. PEG tube aspiration revealed bile-tinged fluid. Significant labs included white blood cell count of 11,600 /mm3, hemoglobin 10.2 g/dL, and lactic acid of 2.3 mmol/L. A computerized tomography of the abdomen with IV contrast showed a small segment duodeno-duodenal intussusception at the horizontal segment around the distal end of the tube was noted (Figure A). An urgent esophagogastroduodenoscopy (EGD) revealed a Foley catheter acting as a makeshift PEG tube extending across the pylorus into the duodenum. The distal tip of the Foley catheter was visualized with an inflated balloon seen in the third portion of the duodenum (Figure B) The inflated catheter balloon acted as a lead point causing intussusception in a ball-valve effect. The balloon was deflated, and the catheter was replaced (Figure C) with a 20 Fr PEG tube. Discussion(s): Gastric outlet obstruction is an uncommon complication reported in few cases caused by migration of the gastrostomy tube. Rarely this migrating gastrostomy tube can invaginate the duodenum or the jejunum causing intussusception. Only handful of cases have been reported in the literature. Patients usually present with epigastric pain, vomiting or rarely hematemesis. CT scan of the abdomen is the investigation of choice. Amidst the pandemic and supply shortage, Foley catheters have been deemed as a viable alternative to gastrostomy tubes and are being used more often. It is important to recognize this rare complication and use of balloon catheter should raise further suspicion. Timely endoscopic intervention can help avoid bowel necrosis and surgical intervention.