Applicability of Child-Turcotte-Pugh Score in Anticipating Post-ERCP Adverse Events in Patients With Cirrhosis: A Systematic Review and Meta-analysis.

Limited objective data exist on the comparison of post-endoscopic retrograde cholangiopancreatography (ERCP) complications in patients with cirrhosis based on the severity of the disease. We evaluated the effectiveness of the Child-Turcotte-Pugh (CTP) score system in anticipating the risk of post-ERCP complications in patients with cirrhosis. The PubMed, Scopus, Embase, and Cochrane databases were searched from inception through September 2022 to identify studies comparing post-ERCP complications in patients with cirrhosis based on CTP score. Odds ratios (ORs) and their associated 95% CIs were pooled using a random-effect model to calculate effect size. The reference group for analysis was the CTP class C patient group. Seven studies comprising 821 patients who underwent 1068 ERCP procedures were included. The CTP class C patient population exhibited a higher risk of overall post-ERCP adverse events compared with those with class A or B (OR: 2.87, 95% CI: 1.77-4.65, P = 0.00 and OR: 2.02, 95% CI: 1.17-3.51, P = 0.01, respectively). Moreover, CTP class B patients had a significantly higher complication rate than CTP class A patients (OR: 1.62, 95% CI: 1.04-2.53, P = 0.03). However, no statistically significant differences were found in the occurrence of specific types of complications, including bleeding, pancreatitis, cholangitis, perforation, or mortality across the three CTP groups. We demonstrated that the CTP classification system is a reliable predictor of ERCP complications in patients with cirrhosis. Consequently, caution should be exercised when performing ERCP in patients classified as CTP class C.

A comparison of career plans of gastroenterology fellows compared to fellows in other internal medicine subspecialties.

Background: The career trajectory of medical professionals, particularly in specialized fields like gastroenterology, can significantly impact healthcare and research. This study aimed to analyze career choices among gastroenterology fellows in the US and investigate the factors influencing these choices. Methods: We utilized data from the American Medical Association on internal medicine subspecialty fellows. The study examined career plans of gastroenterology fellows and compared them with those of other subspecialties. A chi-square test was performed to assess differences in career choices and practice settings. Results: Among gastroenterology fellows, 46% opted for private practice, 28% pursued further training, and 26% chose academia. Notably, gastroenterology fellows were more inclined toward private practice than their counterparts in other subspecialties (46.3% vs 38.4%) and were less likely to pursue academic careers (25.6% vs 30.7%). Conclusion: This study highlights a concerning trend among recent gastroenterology fellowship graduates favoring private practice over academic careers or additional training. To sustain and strengthen academic medicine in gastroenterology, interventions such as scholarships, mentorship programs, and loan repayment initiatives tailored to academic pursuits could play a crucial role.

Gastroenterology fellowship application and match trends in the United States over a 12-year period, 2010 to 2022.

Introduction: Gastroenterology has recently gained prominence as a competitive internal medicine subspecialty. The intense competition within the gastroenterology fellowship match (GFM) presents challenges for both applicants and programs, particularly in virtual interviews due to the COVID-19 pandemic. We analyzed the variables impacting GFM competitiveness to provide insights for prospective gastroenterologists and programs to enhance the match process. Methods: We used publicly available National Resident Matching Program (NRMP) data to examine applications and match data for internal medicine subspecialties from 2010 to 2022. We considered factors such as the number of positions, applicants, and programs, utilizing the specialty competitiveness ratio (SCR) to assess competitiveness. Annual growth rates for positions and applications and average annual growth rates were calculated. Correlation coefficients between annual salaries and SCR were computed using various compensation reports. Results: GFM's competitiveness has increased recently, evidenced by substantial growth in positions (4.61%) and applications (3.81%) since 2010. Gastroenterology ranked as the second-fastest growing specialty in positions and applications. In 2022, GFM ranked fourth in applications (974) and positions offered (616). Among internal medicine subspecialties, gastroenterology exhibited the highest SCR (1.58). Correlation analysis highlighted a positive link between SCR and compensation across specialties. Conclusion: The escalating competition within GFM necessitates an expansion of positions to address potential shortages. Complex factors, such as academic interest and financial considerations, require multifaceted strategies to ensure an adequate supply of gastroenterologists. Further research is warranted to examine the long-term consequences of this trend.

Prognostic and diagnostic scoring models in acute alcohol-associated hepatitis: A review comparing the performance of different scoring systems.

Alcohol-associated hepatitis (AAH) is a severe form of liver disease caused by alcohol consumption. In the absence of confounding factors, clinical features and laboratory markers are sufficient to diagnose AAH, rule out alternative causes of liver injury and assess disease severity. Due to the elevated mortality of AAH, assessing the prognosis is a radical step in management. The Maddrey discriminant function (MDF) is the first established clinical prognostic score for AAH and was commonly used in the earliest AAH clinical trials. A MDF > 32 indicates a poor prognosis and a potential benefit of initiating corticosteroids. The model for end stage liver disease (MELD) score has been studied for AAH prognostication and new evidence suggests MELD may predict mortality more accurately than MDF. The Lille score is usually combined to MDF or MELD score after corticosteroid initiation and offers the advantage of assessing response to treatment a 4-7 d into the course. Other commonly used scores include the Glasgow Alcoholic Hepatitis Score and the Age Bilirubin international normalized ratio Creatinine model. Clinical AAH correlate adequately with histologic severity scores and leave little indication for liver biopsy in assessing AAH prognosis. AAH presenting as acute on chronic liver failure (ACLF) is so far prognosticated with ACLF-specific scoring systems. New artificial intelligence-generated prognostic models have emerged and are being studied for use in AAH. Acute kidney injury (AKI) is one possible complication of AAH and is significantly associated with increased AAH mortality. Predicting AKI and alcohol relapse are important steps in the management of AAH. The aim of this review is to discuss the performance and limitations of different scoring models for AAH mortality, emphasize the most useful tools in prognostication and review predictors of recurrence.

Transjugular Intrahepatic Portosystemic Shunt With or Without Gastroesophageal Variceal Embolization for the Prevention of Variceal Rebleeding: A Systematic Review and Meta-Analysis.

Background: The role of variceal embolization (VE) during transjugular intrahepatic portosystemic shunt (TIPS) creation for preventing gastroesophageal variceal rebleeding remains controversial. Therefore, we performed a meta-analysis to compare the incidence of variceal rebleeding, shunt dysfunction, encephalopathy, and death between patients treated with TIPS alone and those treated with TIPS in combination with VE. Methods: We performed a literature search using PubMed, EMBASE, Scopus, and Cochrane databases for all studies comparing the incidence of complications between TIPS alone and TIPS with VE. The primary outcome was variceal rebleeding. Secondary outcomes include shunt dysfunction, encephalopathy, and death. Subgroup analysis was performed based on the type of stent (covered vs. bare metal). The random-effects model was used to calculate the relative risk (RR) with the corresponding 95% confidence intervals (CIs) of outcome. A P value < 0.05 was considered statistically significant. Results: Eleven studies with a total of 1,075 patients were included (597: TIPS alone and 478: TIPS plus VE). Compared to the TIPS alone, the TIPS with VE had a significantly lower incidence of variceal rebleeding (RR: 0.59, 95% CI: 0.43 - 0.81, P = 0.001). Subgroup analysis revealed similar results in covered stents (RR: 0.56, 95% CI: 0.36 - 0.86, P = 0.008) but there was no significant difference between the two groups in the subgroup analysis of bare stents and combined stents. There was no significant difference in the risk of encephalopathy (RR: 0.84, 95% CI: 0.66 - 1.06, P = 0.13), shunt dysfunction (RR: 0.88, 95% CI: 0.64 - 1.19, P = 0.40), and death (RR: 0.87, 95% CI: 0.65 - 1.17, P = 0.34). There were similarly no differences in these secondary outcomes between groups when stratified according to type of stent. Conclusions: Adding VE to TIPS reduced the incidence of variceal rebleeding in patients with cirrhosis. However, the benefit was observed with covered stents only. Further large-scale randomized controlled trials are warranted to validate our findings.

Ischemic Reperfusion Injury After Liver Transplantation: Is There a Place for Conservative Management?

Ischemic reperfusion injury (IRI) after liver transplantation is a common cause of early allograft dysfunction with high mortality. The purpose of this case report series is to highlight an unusual clinical course in which complete recovery can occur following the identification of severe hepatic IRI post-transplantation and the implications of this finding on management strategies in patients with IRI post-transplant. Here, we include three cases of severe IRI following liver transplantation that are putatively resolved without retransplantation or definitive therapeutic intervention. All patients recovered until their final follow-up visits to our institution and developed no significant complications from their injury throughout the course of patient care by our institution after discharge from the hospital.

Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis.

Little is known about how interactions of diet, intestinal stem cells (ISCs), and immune cells affect early-stage intestinal tumorigenesis. We show that a high-fat diet (HFD) reduces the expression of the major histocompatibility complex class II (MHC class II) genes in intestinal epithelial cells, including ISCs. This decline in epithelial MHC class II expression in a HFD correlates with reduced intestinal microbiome diversity. Microbial community transfer experiments suggest that epithelial MHC class II expression is regulated by intestinal flora. Mechanistically, pattern recognition receptor (PRR) and interferon-gamma (IFNγ) signaling regulates epithelial MHC class II expression. MHC class II-negative (MHC-II-) ISCs exhibit greater tumor-initiating capacity than their MHC class II-positive (MHC-II+) counterparts upon loss of the tumor suppressor Apc coupled with a HFD, suggesting a role for epithelial MHC class II-mediated immune surveillance in suppressing tumorigenesis. ISC-specific genetic ablation of MHC class II increases tumor burden cell autonomously. Thus, HFD perturbs a microbiome-stem cell-immune cell interaction that contributes to tumor initiation in the intestine.

Rise of sodium-glucose cotransporter 2 inhibitors in the management of nonalcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in the Western world. It is more prevalent in male gender, and with increasing age, obesity, and insulin resistance. Besides weight loss, there are limited treatment options. The use of anti-diabetic medications has been studied with mixed results. In this review, we discuss the use of anti-diabetic medications in the management of NAFLD with a specific focus on sodium-glucose cotransporter 2 inhibitors. We shed light on the evidence supporting their use in detail and discuss limitations and future directions.

A quality improvement project to reduce overutilization of blood tests in a teaching hospital.

Objective: In hospitals, physicians-in-training are major contributors to the burden of tests ordered, increasing cost and resource utilization. We implemented an intervention to discourage overutilization of the complete blood count (CBC) and the basic metabolic panel (BMP). Methods: An intervention was designed, comprising education on high-value care and burden of over-testing, encouragement of competition, and use of positive reinforcement. The intervention was monitored by a test index determined by dividing the total number of a specific laboratory test ordered for a patient by the total number of hospital days. Results: Following a 6-month intervention, the mean CBC index decreased from 1.56 ± 0.02 to 1.45 ± 0.03 (p < 0.001), and the BMP index, from 1.35 ± 0.02 to 1.14 ± 0.03 (p < 0.001). There was significant interaction between the intervention and the slope of the BMP index trend (p = 0.03), but not the CBC index trend. The intervention had no impact on hospital length of stay and mortality. Conclusion: This quality improvement intervention is an effective approach to reducing overutilization of laboratory tests.

Gut organoids: mini-tissues in culture to study intestinal physiology and disease.

In vitro, cell cultures are essential tools in the study of intestinal function and disease. For the past few decades, monolayer cellular cultures, such as cancer cell lines or immortalized cell lines, have been widely applied in gastrointestinal research. Recently, the development of three-dimensional cultures known as organoids has permitted the growth of normal crypt-villus units that recapitulate many aspects of intestinal physiology. Organoid culturing has also been applied to study gastrointestinal diseases, intestinal-microbe interactions, and colorectal cancer. These models are amenable to CRISPR gene editing and drug treatments, including high-throughput small-molecule testing. Three-dimensional intestinal cultures have been transplanted into mice to develop versatile in vivo models of intestinal disease, particularly cancer. Limitations of currently available organoid models include cost and challenges in modeling nonepithelial intestinal cells, such as immune cells and the microbiota. Here, we describe the development of organoid models of intestinal biology and the applications of organoids for study of the pathophysiology of intestinal diseases and cancer.

Ultrabright fluorescent cellulose acetate nanoparticles for imaging tumors through systemic and topical applications.

Cellulose acetate (CA), viscose, or artificial silk are biocompatible human-benign derivatives of cellulose, one of the most abundant biopolymers on earth. While various optical materials have been developed from CA, optical CA nanomaterials are nonexistent. Here we report on the assembly of a new family of extremely bright fluorescent CA nanoparticles (CA-dots), which are fully suitable for in vivo imaging / targeting applications. CA-dots can encapsulate a variety of molecular fluorophores. Using various commercially available fluorophores, we demonstrate that the fluorescence of CA-dots can be tuned within the entire UV-VIS-NIR spectrum. We also demonstrate excellent specific targeting of tumors in vivo, when injected in blood in zebrafish (xenograft model of human cervical epithelial cancer), and unusually strong ex-vivo topical labeling of colon cancer in mice utilizing CA folate-functionalized nanoparticles.

Data on ultrabright fluorescent cellulose acetate nanoparticles for imaging tumors through systemic and topical applications.

Characterization data of fluorescent nanoparticles made of cellulose acetate (CA-dots) are shown. The data in this article accompanies the research article "Ultrabright fluorescent cellulose acetate nanoparticles for imaging tumors through systemic and topical applications" [1]. The measurements and calculation of brightness of individual CA-dots are presented. The description of conjugation procedure Pluronic F127-Folic Acid copolymer and folic acid is shown. Identification of composition of CA dots using Raman and absorbance spectroscopy is demonstrated. The methods for image analysis of efficiency of CA-dot targeting of epithelial tumors xenografted in zebrafish is presented.

Hemodialysis for treatment of levofloxacin-induced neurotoxicity.

Levofloxacin, a third-generation fluoroquinolone antibiotic, is rarely associated with neurotoxicity. Patients with advanced kidney disease are particularly vulnerable to this adverse effect. We present two elderly patients with kidney failure who developed levofloxacin-induced neurotoxicity, which was successfully treated with frequent hemodialysis, resulting in the full resolution of their symptoms. Neurotoxicity is a well-known side effect of fluoroquinolone antibiotics. Postulated mechanisms include inhibition of the gamma-aminobutyric acid A receptors and activation of the excitatory N-methyl-D-aspartate receptors. Risk factors include older age, kidney disease, pre-existing neurological disorders, and drug-drug interactions. While management of levofloxacin-induced neurotoxicity includes discontinuation of the drug and supportive care, hemodialysis is not recommended, despite available pharmacokinetic data in support of its dialyzability. The successful use of hemodialysis for the treatment of levofloxacin-induced neurotoxicity observed in our two patients with kidney failure should be further considered for rapid resolution of this rare fluoroquinolone-related adverse effect in patients with impaired kidney function.

Rituximab for retroperitoneal fibrosis due to IgG4-related disease: A case report and literature review.

Retroperitoneal fibrosis (RPF) is a progressive fibroinflammatory disease that can be complicated by urinary obstruction. RPF can be the only manifestation of IgG4-related disease (IgG4-RD). Treatment of IgG4-related RPF is challenging and mostly consists of long-term glucocorticoids leading to significant side effects and treatment intolerance. Recent exploration of the role of rituximab as a B-cell depleting therapy in the treatment of IgG4-RD provides therapeutic potential as a well-tolerated alternative to glucocorticoids. We present a case of IgG4-related RPF for which rituximab was instituted as a steroid-sparing treatment strategy. Following 4 doses, kidney function partially recovered, and the disease went into remission. We discuss the potential merit of rituximab for the treatment of patients with IgG4-related RPF.

Phenotypic Variability of c.436delC DCAF17 Gene Mutation in Woodhouse-Sakati Syndrome.

BACKGROUND Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive genetic condition that was first described in 1983. Since its original description, approximately 50 cases have been reported with various clinical signs and symptoms. Characteristics include progressive neurologic deterioration with extrapyramidal involvement and polyendocrinopathy most notable for hypogonadism starting in early adolescence. Clinical presentation is variable, and a subset of patients may have additional features, such as premature aging, alopecia, distinctive facial features, cognitive impairment, or deafness. CASE REPORT We illustrate the phenotypic variability of 5 patients with WSS due to the previously reported homozygous single nucleotide deletion c.436delC in the DCAF17 gene, identified in 2008. Despite identical genetic alteration, our 5 patients had various clinical features among them and compared with previously reported cases with the same pathogenic mutation. CONCLUSIONS The phenotypic variability of WSS due to c.436delC founder mutation may have a wider range than previously recognized.

The effect of geometric isomerism on the anticancer activity of the monofunctional platinum complex trans-[Pt(NH3)2(phenanthridine)Cl]NO3.

A trans-DDP based monofunctional phenanthridine Pt(ii) complex was synthesized and characterized. Its anticancer activity was studied in vitro on a panel of human cancer cell lines and mouse intestinal cancer organoids. This complex displays significant antitumor properties, with a different spectrum of activity than that of classic bifunctional cross-linking agents like cisplatin.

Colonoscopy-based colorectal cancer modeling in mice with CRISPR-Cas9 genome editing and organoid transplantation.

Most genetically engineered mouse models (GEMMs) of colorectal cancer are limited by tumor formation in the small intestine, a high tumor burden that limits metastasis, and the need to generate and cross mutant mice. Cell line or organoid transplantation models generally produce tumors in ectopic locations-such as the subcutaneous space, kidney capsule, or cecal wall-that do not reflect the native stromal environment of the colon mucosa. Here, we describe detailed protocols to rapidly and efficiently induce site-directed tumors in the distal colon of mice that are based on colonoscopy-guided mucosal injection. These techniques can be adapted to deliver viral vectors carrying Cre recombinase, CRISPR-Cas9 components, CRISPR-engineered mouse tumor organoids, or human cancer organoids to mice to model the adenoma-carcinoma-metastasis sequence of tumor progression. The colonoscopy injection procedure takes ∼15 min, including preparation. In our experience, anyone with reasonable hand-eye coordination can become proficient with mouse colonoscopy and mucosal injection with a few hours of practice. These approaches are ideal for a wide range of applications, including assessment of gene function in tumorigenesis, examination of tumor-stroma interactions, studies of cancer metastasis, and translational research with patient-derived cancers.

Native coronary artery thrombosis in the setting of heparin-induced thrombocytopenia: a case report.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a rare complication of heparin therapy. Its pathogenesis includes thrombotic events that can rarely affect the coronary arteries. CASE SUMMARY: We report a 67-year-old woman who presented with extensive lower extremities deep venous thrombosis. After being treated with heparin, she developed an ST-elevation myocardial infarction secondary to an acute thrombus formation. The patient's platelets dropped within 6 days from the procedure and her heparin-PF4 IgG antibody and serotonin release assay were positive confirming the diagnosis of HIT. DISCUSSION: Prothrombotic states, such as HIT, are associated with increased risk for coronary thrombosis and ischaemia. Heparin-induced thrombocytopenia can cause coronary complications usually in previously disrupted coronary vessels and bypass grafts. Here, we demonstrate that spontaneous thrombosis can occur in a previously untreated native coronary artery in a patient with HIT.

Corrigendum: In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis.

This corrects the article DOI: 10.1038/nbt.3836.

In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis.

In vivo interrogation of the function of genes implicated in tumorigenesis is limited by the need to generate and cross germline mutant mice. Here we describe approaches to model colorectal cancer (CRC) and metastasis, which rely on in situ gene editing and orthotopic organoid transplantation in mice without cancer-predisposing mutations. Autochthonous tumor formation is induced by CRISPR-Cas9-based editing of the Apc and Trp53 tumor suppressor genes in colon epithelial cells and by orthotopic transplantation of Apc-edited colon organoids. ApcΔ/Δ;KrasG12D/+;Trp53Δ/Δ (AKP) mouse colon organoids and human CRC organoids engraft in the distal colon and metastasize to the liver. Finally, we apply the orthotopic transplantation model to characterize the clonal dynamics of Lgr5+ stem cells and demonstrate sequential activation of an oncogene in established colon adenomas. These experimental systems enable rapid in vivo characterization of cancer-associated genes and reproduce the entire spectrum of tumor progression and metastasis.