GI Complications Research Articles

Outcomes of Laparoscopic Partial Nephrectomy for small renal masses

Background: Due to the increased use of imaging modalities in daily medical practices, more and more small renal masses are detected. For these SRMs, nephron sparing procedures are more commonly opted rather than radical nephrectomy for the sake of preservation of renal function and proven similar oncological outcomes. This surgery has evolved from open, laparoscopic to Robot-assisted approaches. This article summarizes our institutional experience of laparoscopic partial nephrectomy. Materials and Methods: Patients with small renal masses who underwent laparoscopic partial nephrectomy at B.P. Koirala Memorial Cancer Hospital from January 2023 to June 2024 were retrospectively retrieved. Altogether 23 case notes fulfilled the criteria for analysis. All the demographic, preoperative, intraoperative, postoperative data were collected form the notes and plotted. All the issues within 30 days of surgery were defined as early complications. Clavein-Dindo Classification used for analysis. SPSS 25 software was used. Results: Twenty three patients underwent partial nephrectomy with lapascopic method. All were done trans-peritoneally. Average age of patient was 50.96±12.8 years with range of 33-76. Male were 14 and 9 were females. Average hospital stay was 8 days. The majority of patients after PN recovered well. Nonetheless, 8 developed postoperative complications. GI complications were 8.7%, infections related 13%, Wound related 8.7% and others. Two patients (8.3%) were required to undergo reoperation and nephrectomy for haematuria. Conclusion: Laparoscopic partial nephrectomy is a surgery with steep learning curve. As it requires advanced laparoscopic suturing skills, complications in early period was common. After maturity the complications are as par to open PN.

Postoperative Complications of Radical Cystectomy and Urinary Diversion using Clavein-Dindo Classification in Tertiary Care Hospital

Background: The gold standard treatment for muscle-invasive transitional cell carcinoma of the bladder is radical cystectomy (RC) with urine diversion. The mortality and morbidity rates ranged from 0 to 9.0% and 30 to 70%, respectively in various reports. Among various classifications of complications, the Clavien–Dindo classification (CDC) is applicable to most procedures for comprehensive surgical outcome assessment. The study will be helpful to identify the potential early postoperative complications and possibly minimize the morbidity and mortality of this surgery in the future. Materials and Methods: Prospective study of 60 patients with Bladder Cancer fulfilling the inclusion criteria who underwent radical cystectomy with urinary diversion was collected from January 2023 to June 2024 at B.P. Koirala Memorial Cancer Hospital. The various demographic data and perioperative parameters were recorded. The early complications defined as the complications during hospitalization or within 30 days of surgery were enlisted and then classified according to Clavein-Dindo Classification. Data were analyzed using SPSS 25 software. Results: Many patients, 56 (93.33%) patients had some form of postoperative complications of radical cystectomy with urinary diversion. Of these, GI complications were (41.7%), infections related (21.7%), Wound related (11.7%) and others. 23 (38.33%) patients had high grade (≥ Grade III) complications. The mortality rate was 6.7%. Conclusion: Radical cystectomy is complicated surgery involving at least 2 systems in the body ie genitourinary and Gastrointestinal systems. So it is associated with higher rate of morbidity.

Intra-Operative Hypotension is an Important Modifiable Risk Factor for Major Complications in Spinal Fusion Surgery.

Retrospective observational cohort. This study explores the impact of Intraoperative hypotension (IOH)on post-op complications for major thoracolumbar spine fusion procedures. IOH with mean arterial pressure (MAP) < 65mmHg is associated with post-op acute kidney injury (AKI) in general surgery. In spinal deformity surgery, IOH is a contributing factor to MEP changes and spinal cord dysfunction with deformity correction. 539 thoracolumbar fusion cases, > 6 surgical levels and > 3 hours duration were identified. Anesthetic/surgical data included OR time, fluid volume, blood loss, blood product replacement and use of vasopressors. Arterial-line based MAP data was collected at 1 min intervals. Cummulative duration of MAP < 65mmHg was recorded. IOH within the first hour of surgery vs. the entire case was determined. Post-op course and complications including SSI, GI complications, pulmonary complications, MI, DVT, PE, AKI and encephalopathy were noted. Cumulative complications were grouped as none, 1-2 complications, or >3 complications. There was a significant association between occurrence of complications and duration of IOH within the first hour of surgery (8.2 vs. 5.6 min, P<0.001) and across the entire procedure (28.1 vs. 19.3 min, P=0.008). This association persisted for individual major complications including SSI, acute respiratory failure, PE, ileus requiring NGT and post-operative cognitive dysfunction. Comparison of patients with 0 vs. 1-2 vs. 3 or more complications demonstrated that patients with 3 or more complications had a longer duration of IOH in the first hour of the surgery and that patients who had no complications received less vasopressor than patients who had 1-2 or 3 or more complications. This study identifies duration of IOH during the first hour of surgery as a previously unrecognized modifiable risk associated with major complications for multi-level lumbar fusion surgery.

Unlocking Therapeutic Symphonies: Innovations in Clinical Decision Support for Drug-Disease Interactions in Kidney Transplantation

Introduction: Drug-disease interactions (DDSIs) are associated with increasing morbidity, mortality, and healthcare costs. These interactions are preventable if recognized and managed properly. Medication safety is critical in kidney transplant patients due to polypharmacy, co-morbidities, and susceptibility to adverse events. Clinical decision support systems (CDSSs) can play a key role therein. Therefore, this study aims to report on the process of developing an innovative, patient-centered, context-aware CDSS for managing DDSIs in kidney recipients.Material and Methods: Clinically important DDSIs were identified in the medications of patients at a kidney transplant outpatient clinic. Subsequently, rules for their detection and management were extracted based on pharmacology references and clinical expertise. A CDSS was developed and piloted following recommendations on medication CDSS design principles.Results: The knowledge base for this CDSS was developed with clinical context sensitivity. We defined priority levels for alerts, established associated display rules, and determined necessary actions based on the transplantation clinical workflow. The DDSI-CDSS correctly detected 37 DDSIs and displayed nine warnings and 28 cautionary alerts for the medications of 113 study patients (32.7% DDSI rate). The system fired three warnings for diltiazem in bradyarrhythmia, and two for each of the following medications and underlying diseases: aspirin in asthma, erythropoietin alfa in hypertension, and gemfibrozil in gall bladder disease. The potential consequences of the identified DDSIs were GI complications (17%), deterioration of the existing disease/condition (6.1%), and an increased risk of arrhythmias (2.6%), thrombosis (2.6%), and hypertension (1.7%). Complying with system alerts and recommendations would potentially prevent all these DDSIs.Conclusion: This study delineates the process of developing an evidence-based DDSI-CDSS for kidney transplantation, laying the groundwork for future advancements. Our results underscore the clinical significance of these interactions and emphasize the imperative for their accurate and timely detection, particularly in these vulnerable patients.

Gastrointestinal perforations induced by long-term non-steroidal anti-inflammatory drugs use: a case series analysis and discussion

Non-steroidal anti-inflammatory drugs (NSAIDS) are used in a wide range but may cause harm to the gastrointestinal mucosa, which leads to various complications. This study shows the impact of long term NSAID use on small and large intestine and presents 2 cases of patients with NSAID induced perforations. The first case involves a 62-year-old male patient with RA on long term Ibuprofen use, presented with abdominal pain, vomiting, and lower limbs pain. Laparotomy revealed a 5 mm perforation in the proximal jejunum. The second case, a male patient of 65 years of age using diclofenac without a prescription, which lead to a 4×4 cm sigmoid colon perforation. The comparison of both the cases presents a difference in examination and laboratory findings. Long-term NSAID use has been associated with various GI complications, including perforations. The case presents the importance of considering NSAID related complications, mainly in older patients and the persons with ulcers. Combining NSAIDS with other drugs, like misoprostol may minimize the risk of the GI complications. NSAIDs are also linked with cardiovascular events, and heart related issues. This study shows the need of careful NSAID prescription, with their association with preventable adverse effects. 30% of hospitalizations for adverse drug reactions are only by the NSAIDs. PPIs and H2 receptor antagonist are commonly used to protect the gastrointestinal mucosa which minimizes the occurrence of ulcers. Healthcare professionals should be careful particularly in case of high risk patients to minimize the NSAID related complications.

A81 GASTROINTESTINAL (GI) FEATURES OF HYPERMOBILE EHLERS-DANLOS SYNDROME (HEDS) AND HYPERMOBILITY SPECTRUM DISORDER (HSD): A SCOPING REVIEW

Abstract Background Ehlers-Danlos syndromes (EDS) are a varied group of hereditable connective tissue disorders (HCTD) typified by skin, joint and vascular features, along with less well-recognized features of chronic pain, immunological dysfunction and chronic GI symptoms. The latest EDS classification (2017) lists 13 EDS types and 19 genetic factors but there is no identified genetic basis for hEDS, the most common type and the most-commonly associated with GI symptoms. There is a need for robust data on the prevalence of GI symptoms and diagnoses in hEDS and HSD. Aims To investigate the extent of evidence on GI symptom prevalence and methods used to establish GI diagnoses in patients with hEDS and HSD. Methods Following the JBI (Joanna Briggs Institute) guide for scoping reviews, a systematic search of Ovid Medline, Embase and Cochrane Library retrieved scoping and systematic reviews, published in English (1974 – Sept 2023), reporting GI symptom prevalence, assessment and complications in EDS or HSD. Abstracts of identified papers were reviewed by NC &amp; DB and discrepancies resolved by YY &amp; DA. As a scoping review, it required no statistical comparisons. Results Duplicate screening of 410 abstracts yielded 10 papers that met inclusion criteria: 1 scoping and 9 systematic reviews. Four systematic reviews reported GI surgical issues related to vascular EDS; none was evaluated further. Two papers reported, specifically, on GI symptoms in patients with postural tachycardia syndrome or eating disorders, some of whom had hEDS or HSD and two papers reported on multiple GI and non-GI symptoms associated with fibromyalgia or functional somatic symptoms. The final 2 papers reported on multiple GI and non-GI symptoms in patients with HSD or multiple EDS types, limited in the latter case to papers published after the latest EDS classification (2017). In general, GI symptoms were characterised as IBS-like symptoms (Rome III or Rome IV) or as typical GI symptoms but without using a validated symptom questionnaire. Conclusions There are few data on GI symptom prevalence in hEDS or HSD and no standardised methods for identifying or characterizing GI symptoms or function in hEDS. The evaluation of GI function and symptoms in EDS is hampered by the absence of a definitive genetic or diagnostic test for hEDS or HSD and by changes in EDS classification over the last 50 years. There is a need for targeted systematic reviews of the prevalence of various GI symptoms in hEDS individuals and of relevant diagnostic methods, to guide further research into the causes of GI dysfunction in hEDS or HSD. Funding Agencies None

Gastrointestinal complications in pediatric lung transplant recipients: Incidence, risk factors, and effects on patient outcomes.

Gastrointestinal (GI) complications in lung transplant recipients can occur any time during the post-operative period, leading to prolonged morbidity and mortality. Despite the negative association between GI complications and patient outcomes, little is known about their incidence and risk factors for their development in pediatric lung transplant recipients. We performed a retrospective chart review at one pediatric tertiary center to describe the frequency of GI complications in lung transplant recipients. We identified potential risk factors for the diagnosis of gastroparesis, gastroesophageal reflux disease (GERD) and aspiration in the post-transplant period. Lastly, we investigated the association of these complications with mortality and graft survival. 84.3% of lung transplant recipients experienced at least one GI complication in the post-transplant period. Gastroparesis (52.9%), GERD (41.2%), and oropharyngeal dysphagia/laryngeal penetration (33.3%) were the most common complications diagnosed. Post-operative opioid exposure was a risk factor for gastroparesis, with the odds increasing 3.0% each day a patient was prescribed opioids (p = .021). The risk of death or retransplant in individuals who experienced gastroparesis was 2.7 times higher than those not diagnosed with gastroparesis (p = .027). Exposure to opioids in the post-operative period is a risk factor for gastroparesis and a prolonged hospitalization placed patients at risk for aspiration. Gastroparesis was associated with increased patient mortality and graft failure, while aspiration and GERD had no effect on long term outcomes. Future prospective studies investigating the relationship between opioid use and the development of a gastroparesis are necessary to improve patient outcomes.

Lower Gastrointestinal Bleeding in Patients with Liver Cirrhosis: Prevalence, Outcomes, and Correlation with MELD Score in an Indian Tertiary Care Facility

Background: Lower gastrointestinal bleeding (LGIB) is responsible for 25 percent of overall GI bleeding patients in the general population. In the US, the LGIB incidence is thought to be 21–27/100,000 per year, while the rate of hospitalization is thought to be 20–30/100,000 per year. According to reports, 2–4% of patients hospitalized with LGIB die. Despite the fact that upper GI complications associated with portal hypertension have received a lot of attention, few studies have explored lower GI complications. Objective: To study the prevalence and 28-day outcome of patients hospitalized with lower gastrointestinal bleeding in liver cirrhosis and its correlation with the model for end-stage liver disease (MELD). Method: A single center-based cross-sectional study was conducted for a duration of eighteen months. The main source of data is from patients hospitalized at the Department of General Medicine and Department of Medical Gastroenterology at the Institute of Medical Sciences and SUM hospital, with a minimum of 100 cases. Results: Out of 100 patients, internal hemorrhoids were observed in 50 patients, external hemorrhoids were found only in 1 patient, and rectal varices were present in 17 patients. The MELD score for the 28th day outcome was found to be 21.85 on follow-up. It was 27.0 in discharged patients by the 28th day. Conclusions: An essential element of the condition, portal hypertension, appears to be responsible for the poor prognosis.

Characteristics, incidence, and outcomes of gastrointestinal complications post cardiac surgery in a quaternary referral centre: A retrospective study

BackgroundGastrointestinal (GI) complications after cardiac surgery are associated with high morbidity and mortality. Early identification and treatment of GI complications could improve patient outcomes. ObjectivesThe objective of this study was to ascertain the incidence, risk factors, and clinical outcomes of GI complications following cardiac surgery. MethodsA retrospective single-centre cohort study of adult patients undergoing cardiac surgery in an Australian quaternary cardiothoracic surgical referral centre was conducted from November 2012 to March 2020. Preoperative, intraoperative, and postoperative characteristics were compared between patients who did and did not develop GI complications. Data are presented as n (%). Between-group comparisons were analysed using Chi-square and Fisher's exact tests (where n < 6) for categorical variables and Wilcoxon rank-sum test for continuous variables. ResultsOf the 4417 patients who underwent cardiac surgery, 95 (2.2%) patients developed a total of 100 GI complications, with the most common being paralytic ileus (n = 22/100, 22%). Baseline characteristics and preoperative factors associated with GI complications included an age of >70 years (GI complication vs no GI complication: 55.8% vs 37.6%; p = 0.000), preexisting diabetes (49.5% vs 34.5%; p = 0.002), and a creatinine level >200 mcg/ml (11.6% vs 3.7%; p = 0.000). Intra-operative factors included a cardiopulmonary bypass time >120 min (28.4% vs 15.5%; p < 0.01). Postoperatively, developing a GI complication was associated with return to theatre (36.8% vs 13.9%; p < 0.01) and new stroke, pneumonia, and acute kidney injury (all p < 0.01). Patients with a GI complication had a higher intensive care unit and hospital mortality (7.4% vs 1.1%, and 13.6% vs 1.4%, respectively), and a longer intensive care unit and hospital stay (5.5 vs 2.3 days, and 24.0 vs 10.3 days). ConclusionsMultiple risk factors associated with GI complications in cardiac surgery patients were identified. These provide potential targets to support the early detection and management of GI complications to reduce morbidity and mortality in these patients.

Abstract 16830: Feasibility and Safety of Intracardiac Echocardiography Guidance in Mitral Transcatheter Edge-to-Edge Repair: Analysis of the National Inpatient Sample Data From 2015 to 2020

Introduction: Data on use of ICE guidance in TEER procedure is limited to case reports and small case series. Our study aims to assess the feasibility, safety, utilization patterns and clinical outcomes of mitral TEER procedure with ICE guidance using a nationally representative real-world cohort of patients.Hypothesis: There is no difference between ICE-guided TEER and TEE-guided TEER in the clinical outcomes and complications. Methods: This study used the National Inpatient Sample database from quarter 4 of 2015 to 2020. We used a propensity-matched analysis and adjusted odds ratios for in-hospital outcomes/complications. A P value of &lt;0.05 was considered significant. Results: A total of 38,770 weighted cases of mitral TEER were identified. Of the included patients 665 patients underwent ICE-guided TEER while 38,105 had TEE-guided TEER. There were no differences in the in-hospital mortality between both groups (2.5% vs. 3.0%, p=0.58). Adjusted odds of in-hospital mortality (aOR 0.83, 95%CI [0.42-1.64]) were not significantly different. There were no differences in periprocedural complications including cardiac (aOR 0.85, 95%CI [0.54-1.35]), bleeding (aOR 1.45, 95%CI [0.93-2.33]), respiratory (aOR 0.88, 95%CI [0.61-1.25]), and renal (aOR 0.89, 95%CI [0.66-1.20]) complications between patients undergoing ICE-guided versus TEE-guided TEER. There was no difference in GI complications between both groups (aOR 1.11, 95%CI [0.46-2.70]). The adjusted length of stay was less among ICE-guided TEER (median: 1 vs. 2, p&lt;0.01) with no differences in costs of hospitalization ($137,312 vs. $153,773, p=0.06), Conclusions: In conclusion, ICE-guided mitral TEER is safe when compared with TEE guided TEER with no significant differences in in-hospital mortality, cardiac, bleeding, respiratory, and renal complications. The length of stay in ICE group is shorter as compared with the TEE group.

S3997 An Unusual Presentation of GI Complication Related to Immune Checkpoint Inhibitor Therapy

S3997 An Unusual Presentation of GI Complication Related to Immune Checkpoint Inhibitor Therapy

1058 Jejunal or Ileal Exocrine Drainage in Pancreas Transplantation?

Abstract Aim Pancreas transplantation (PT) is performed for restoration of endocrine function in type 1 diabetes mellitus with amelioration of diabetic complications. However, PT can have serious complications requiring salvage pancreatectomy and surgical approaches should be carefully considered. Anastomoses to jejunum or ileum are most often employed. We compare outcomes between these techniques. Method A retrospective analysis was performed on simultaneous pancreas and kidney transplants (SPK) at Manchester University Hospitals NHS Foundation Trust between 2013 and 2015. Follow up was completed until 2020. Results 86 SPK were performed. 59.2% were male with mean age of 41.5yo (SD±8.4). 72.4% (n = 55) were donors after brain death and 98.7% (n = 75) were receiving first PT. 43 SPK were performed with ileal anastomosis, 33 jejunal. There were no significant differences in demographics of recipients, donors, immunosuppression regimens, overall patient and graft survival and frequency of GI complications. Length of hospital stay was higher with ileal anastomosis (median 14 v 19 days, p&amp;lt;0.05), as was cold ischaemic time (median 8:48 v 9:31 hours, p&amp;lt;0.05). Three patients required salvage pancreatectomy and loop ileostomy formation with multi-organ support and prolonged ITU stay. Conclusions Long term outcomes between groups were comparable in this cohort. Catastrophic complications occur in the minority requiring salvage surgery. Here more occurred with ileal anastomosis, but this approach allows graft pancreatectomy and formation of loop ileostomy, avoiding a more proximal stoma in a clinically unstable patient. Further powered studies are required to rigorously examine the impact of enteric anastomosis site.

Outcomes of Incidental Appendectomy During Ovarian Operations in a National Pediatric Cohort

IntroductionThe utility of incidental appendectomy (IA) during many ovarian operations has not been evaluated in the pediatric population. This study sought to compare outcomes after ovarian surgery with IA in the pediatric population. MethodsFemales (≤20 y old) undergoing ovarian surgeries (oophorectomy, detorsion and/or drainage) were identified from the Nationwide Readmissions Database (2016-2018). Those with appendicitis were excluded. A propensity score-matched analysis (PSMA) with 46 covariates (demographics, comorbidities, hospitalization factors, etc.) was performed between those receiving ovarian surgery with or without IA. ResultsThere were 13,202 females (median age 17 [IQR 14-20] y old) who underwent oophorectomy (90%), detorsion (26%), and/or ovarian drainage (13%). There were more episodes of torsion in the PSMA cohort receiving ovarian surgery alone (17% versus 10% IA; P = 0.016), while other indications (ovarian mass, cyst) were similar. Open (66% versus 34% laparoscopic) IAs were more frequent. Length of stay (LOS) was longer for those undergoing IA (3 [2-4] versus 2 [2-4] days ovarian surgery alone; P < 0.001). There was a higher rate of postoperative GI complications in the IA cohort. Subgroup analysis of those undergoing laparoscopic operations demonstrated no difference in LOS or postoperative complications between patients undergoing IA or not. ConclusionsThese data indicate that IA in pediatric ovarian operations is associated with longer LOS and higher GI postoperative complications. However, laparoscopic IA was not associated with higher cost, complications, LOS, or readmissions. This suggests that IA performed during ovarian surgeries in select patients may be cost-effective and worthy of future study.

Safety and tolerability of immune checkpoint inhibitor (CPI) use in advanced hepatocellular carcinoma (aHCC) with Child-Pugh (CP) class B and C.

e14676 Background: The vast majority of HCC cases occur in the setting of liver cirrhosis. Patients with decompensated cirrhosis CHILD-Pugh Class B and C (CPB and CPC) are usually excluded from clinical trials. Here we report the safety and tolerability of CPI in patients with CPB/CPC. Methods: A retrospective chart review was performed of all patients with aHCC who received therapy with CPI from 1/2019 to 12/2022 at our institution. Patients with CP class B and C were included in this study. Safety endpoints included rates of immune-related adverse events (irAEs), grade ≥3 adverse events (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 5.0]), duration of treatment with CPI and overall survival (OS) were reported. Results: We performed this retrospective chart review of 60 patients with aHCC who were treated with CPI at our institution. A total of 22 patients with CPB and CPC at the time of CPI initiation were included, 86.4% with CPB (n=19) and 13.6% with CPC (n=3). Median age was 68 (range 40-82). Amongst patients with CPB, 10 patients (45.4%) had CP score 7 (CP7) and 9 patients (40.9%) had CP score 8 or 9. Single agent nivolumab was the most common CPI used, followed by pembrolizumab and combination of ipilimumab and nivolumab, 38.4%, 27.3% and 13.6% respectively. Any grade irAEs were reported in 54.5% of patients (n=12).9% of patients (n=2) had grade ≥3 irAEs. In the CP7 subgroup, the rate of irAEs reported was 40% and no grade ≥3 irAEs were observed. In contrast, 55.5% of patients with CP 8 and 9 experienced irAEs and of those, 11.1% had grade ≥3 irAEs (n=1). In the CPC subgroup, 2 out of 3 patients reported irAEs (75%), one with a grade 4 irAE. GI complications(n=5) were the most common irAEs reported, followed by endocrine (n=4) and dermatologic complications (n=3). The median time on treatment was 1.63 months (95% CI,1.08-2.99). The median overall survival from the time of CPI initiation was 3.7 months (95% CI, 1.97-9.79). Conclusions: Immunotherapy has an acceptable safety and toxicity profile in aHCC patients with CP7. Higher rate of irAEs were observed in patients with CP ≥8. Further studies are warranted to evaluate the safety of CPI in patients with CP ≥8. We reported shorter duration of treatment with CPI and shorter OS in real world practice compared with those reported in the CheckMate 040 trial.[Table: see text]

Novel RAG2 Mutation in a Patient with Leaky Severe Combined Immunodeficiency

T and B lymphocytes development and function are highly dependent on Recombination Activating Genes (RAG) 1 and 2. RAG mutations result in different degree of T and B cell impaired function, broad clinical manifestations, and immunological manifestations. Pathogenic mutations cause severe combined immunodeficiency (SCID) phenotype, while hypomorphic mutations are responsible for leaky or partial SCID.&#x0D; Here, we described a 4-year-old girl who had a persistent diarrhea, recurrent infection and vomiting. Although physicians were suspicious about autoimmune enteropathy, her molecular report showed a homozygous and novel RAG2 mutation in its core domain. The number of CD4 T cells and IgA level were lower than normal ranges. Lack of IgA brought about different GI complications. Our patient died finally because of the liver and gallbladder failure.

Successful Management of Malakoplakia in a Patient Combined Variable Immunodeficiency

Malakoplakia is a rare tumor-like inflammatory condition often affecting the urogenital and gastrointestinal tract of immunocompromised individuals. Malakoplakia is posited to be secondary to impaired macrophages with an inability to phagocyte bacteria completely. The resulting inflammation may trigger CVID-associated enteropathy. Treatment is challenging, often requiring prolonged antibiotics, and reducing immunosuppression.Our patient is a 45-year-old female with heterozygous TNFRSF13B c.310T>C common variable immunodeficiency (CVID). She has granulomatous lymphocytic interstitial lung disease (GILD), CVID-enteropathy in remission, immune thrombocytopenia requiring splenectomy, and chronic norovirus shedding. She was on mycophenolate mofetil, immunoglobulin replacement, and trimethoprim/sulfamethoxazole prophylaxis.She presented with two months history of progressive diarrhea, weight loss, and abdominal pain. Stool calprotectin was 131 uG/G. GI pathogen panel was only positive for Norovirus. Endoscopy showed intraepithelial lymphocytosis and villus blunting (seen on previous scopes). Colonoscopy demonstrated rectal polyps, submucosal atypical lymphoid proliferation, abundant histiocytes with Michaelis-Gutman bodies, positive calcium deposits with Von-Kossa stain, consistent with malakoplakia, with no evidence of malignancy.We started ciprofloxacin 500 milligrams twice daily, Vitamin C, oral immunoglobulin, and probiotics. We continued mycophenolate mofetil to avoid GLILD flares. Diarrhea resolved several weeks after starting ciprofloxacin. However, attempts to wean ciprofloxacin led to recurrence of diarrhea. She completed nine months of ciprofloxacin, after which calprotectin normalized, and repeat scopes showed no evidence of malakoplakia; diarrhea did not recur after stopping ciprofloxacin.We highlight a rare CVID GI complication that successfully responded to a prolonged course of antibiotics. Balancing immune suppression with worsening malakoplakia requires vigilant diagnostic and therapeutic decision-making. Malignancy surveillance will be warranted.

Applying patient personalized organoid model system to understand complex GI manifestations in cystic fibrosis disease

Background: Stem cell-derived organotypic culture has become a revolutionary tool in transforming care for patients with multiple GI-disorders. Cystic fibrosis is a deadly genetic disorder with multiple GI complications, such as Distal intestinal obstruction syndrome (DIOS), chronic constipation, Gastroesophageal reflux disease (GERD), and in some cases pancreatitis, caused by loss of function mutations in the gene that encodes for the cystic fibrosis transmembrane conductance regulator (CFTR) chloride/bicarbonate ion channel. Due to genetic and environmental influences, CF patients exhibit large phenotypic variation. These factors make clinical trials difficult and largely impractical due to limited and heterogenous patient pools, and additionally, the benefit of approved small-molecule CF therapy in a large number of rare mutation patients is not known. Moreover, critical questions of whether CFTR contributes to the development of intestine and how it contributes to GI-related issues remain unanswered. Results: In this study, we performed a comprehensive bench-side study using in vitro patient enteroids and in vivo mice implanted Human Intestinal Organoids (HIOs) to test highly effective CFTR modulators -Ivacaftor response for a rare CF mutation patient. Based on the positive Ivacaftor response in the enteroids, the patient was enrolled in N=1 clinical trial and showed improved GI outcomes upon Ivacaftor treatment. HIO implantation model allowed in vivo modulator dosing and provided an elegant human organ-based demonstration of bench-to-bedside testing of modulator effects. Additionally, using the CF HIO model the role of CFTR function in the maturation of human intestine was reported for the first time. In HIOs derived from a stop mutation CF patient and CFTR-corrected HIOs as control, we performed single cell RNAseq analysis to generate a molecular map of GI-cell type specific transcriptomic alterations and identify key targetable pathways relevant to stop mutations in CFTR for which currently there is no small molecule therapy. Conclusion: In all, we demonstrate that these models effectively serve to translate data from the lab to the clinic and back so that patient specific therapies could be validated, or new therapies be devised. Additionally, single-cell RNA sequencing in patient HIOs will provide useful insights into cell population specific and transcriptomic level alterations that are associated with abnormalities in GI function in CF. Nothing to disclose This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A Patient with Acute Necrotizing Fasciitis after a Total Knee Replacement: A Case Report

Necrotizing fasciitis is a relatively rare and serious fatal soft-tissue infection that is characterized by a rapidly spreading bacterial infection located in the subcutaneous tissues. We report a 59-year-old man who was diagnosed with acute necrotizing fasciitis, following a primary total knee replacement. He received primary total knee replacement that was uneventful and smooth intraoperatively. An immediate high fever was reported in the next few days, with several complications, confirming a diagnosis of necrotizing fasciitis. The most effective treatment for this disease is a rapid primary diagnosis and surgical debridement. Gold standard treatment includes intravenous therapy, such as antibiotics, surgical debridement, and intensive care. As a result of possible GI complications that triggered necrotizing fasciitis, the patient underwent flap reconstruction. This report's aim is to review the comprehensive treatment, management, and experience of necrotizing fasciitis, highlighting the roles with a multidisciplinary care team for improving the condition of this patient.

Derivation and validation of a risk prediction score for nonsteroidal anti-inflammatory drug-related serious gastrointestinal complications in the elderly.

Few studies have quantified the impact of risk factors on GI complications in elderly nonsteroidal anti-inflammatory drug (NSAID) users. This study aimed to develop and validate a risk prediction score for severe GI complications to identify high-risk elderly patients using NSAID. We used the following two Korean claims datasets: customized data with an enrolment period 2016-2017 for model development, and the sample data in 2019 for external validation. We conducted a nested case-control study for model development and validation. NSAID users were identified as the elderly (≥65 years) who received NSAIDs for more than 30 days. Serious GI complications were defined as hospitalizations or emergency department visits, with a main diagnosis of GI bleeding or perforation. We applied the logistic least absolute shrinkage and selection operator (LASSO) regression model for variable selection and model fitting. We identified 8176 cases and 81 760 controls with a 1:10 matched follow-up period in the derivation cohort. In the external validation cohort, we identified 372 cases from 254 551 patients. The risk predictors were high-dose NSAIDs, nonselective NSAID, complicated GI ulcer history, male sex, concomitant gastroprotective agents, relevant co-medications, severe renal disease and cirrhosis. Area under the receiver operating characteristic curve was 0.79 (95% confidence interval, 0.77-0.81) in the external validation dataset. The prediction model may be a useful tool for reducing the risk of serious GI complications by identifying high-risk elderly patients.

Chronic active Epstein-Barr virus infection involving gastrointestinal tract with hemophagocytic lymphohistiocytosis

Chronic active EBV infection (CAEBV) is a lymphoproliferative disorder of T- or NK-cell type in Asian countries. CAEBV involving the gastrointestinal tract (GI CAEBV) is a rare condition with poor prognosis that may rapidly progress with hemophagocytic lymphohistiocytosis (HLH) and life-threatening complications such as GI bleeding and/or perforation. The approach to CAEBV with GI tract involvement (GI CAEBV) is still an unmet clinical need. In this case series study, we summarized the clinical features, treatment, and prognosis of seven cases of GI CAEBV with HLH, particularly focusing on its prognosis and the possible salvage therapy combining surgery, novel therapeutic agents, and/or autologous(auto-) hematopoietic stem cell transplantation (HSCT) based on successful cases from our center. GI CAEBV is often misdiagnosed as inflammatory bowel diseases and certain infections. The key to its early recognition is the integrative consideration of its systemic manifestation, serum virology, endoscopic, and imaging findings along with pathology. Surgical intervention should not be hesitated when life-threatening GI complications occur. Resection of the involved bowel segment is an effective way of controlling bleeding and reducing tumor burden. In addition to upfront allogeneic HSCT, new therapeutic modalities including PD-1 antibody and auto-HSCT may be effective in certain patients.