Real-world Effectiveness and Tolerability of Interferon-free Direct-acting Antiviral for 15,849 Patients with Chronic Hepatitis C: A Multinational Cohort Study.

Background and Aims: As practice patterns and hepatitis C virus (HCV) genotypes (GT) vary geographically, a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal. This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs, focusing on GT3 and GT6. Methods: We analyzed the sustained virological response (SVR12) of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific, North America, and Europe between 07/01/2014-07/01/2021. Results: The mean age was 62±13 years, with 49.6% male. The demographic breakdown was 91.1% Asian (52.9% Japanese, 25.7% Chinese/Taiwanese, 5.4% Korean, 3.3% Malaysian, and 2.9% Vietnamese), 6.4% White, 1.3% Hispanic/Latino, and 1% Black/African-American. Additionally, 34.8% had cirrhosis, 8.6% had hepatocellular carcinoma (HCC), and 24.9% were treatment-experienced (20.7% with interferon, 4.3% with direct-acting antivirals). The largest group was GT1 (10,246 [64.6%]), followed by GT2 (3,686 [23.2%]), GT3 (1,151 [7.2%]), GT6 (457 [2.8%]), GT4 (47 [0.3%]), GT5 (1 [0.006%]), and untyped GTs (261 [1.6%]). The overall SVR12 was 96.9%, with rates over 95% for GT1/2/3/6 but 91.5% for GT4. SVR12 for GT3 was 95.1% overall, 98.2% for GT3a, and 94.0% for GT3b. SVR12 was 98.3% overall for GT6, lower for patients with cirrhosis and treatment-experienced (TE) (93.8%) but ≥97.5% for treatment-naive patients regardless of cirrhosis status. On multivariable analysis, advanced age, prior treatment failure, cirrhosis, active HCC, and GT3/4 were independent predictors of lower SVR12, while being Asian was a significant predictor of achieving SVR12. Conclusions: In this diverse multinational real-world cohort of patients with various GTs, the overall cure rate was 96.9%, despite large numbers of patients with cirrhosis, HCC, TE, and GT3/6. SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent (>91%).

Diet Optimization in Inflammatory Bowel Disease: Impact on Disease Relapse and Inflammatory Markers. A 1-year Prospective Trial.

BACKGROUND AND AIMS: Recent research has shown that Western-style diets have been associated with an increased risk of inflammatory bowel diseases (IBD). Our aim was to examine the link between an anti-inflammatory diet and the maintenance of IBD remission, as well as to assess the potential therapeutic advantages of this dietary approach in preserving IBD remission. METHODS: The inclusion and exclusion criteria were applied to a total of 189 individuals with IBD, with 21 individuals not meeting the criteria. Therefore, 168 eligible patients were enrolled in the study and allocated to either an anti-inflammatory diet or a regular diet, based on their personal preference. RESULTS: A cohort of 168 IBD adult patients was recruited for the study: 88 patients with ulcerative colitis and 80 with Crohn's disease. The intervention group received an anti-inflammatory diet consisting of the removal of red and processed meat, fried foods, high-lactose foods, fast food, white bread, sugar, and vegetable oils rich in omega-6 for a period of 1 year. The clinical response was maintained in 80 patients (95.2%) in the intervention group and in 72 patients (85.7%) in the control group (p-value=0.036). Although not statistically significant, fecal calprotectin was higher in the control group than in the intervention group at follow-up. CONCLUSIONS: Patients who adhered to an anti-inflammatory diet exhibited a higher rate of maintenance of clinical remission. Furthermore, improvement in inflammation tests was observed in the intervention group, reinforcing the proposition that IBD is a lifestyle-related disease.

Sex and ethnic disparities in hepatitis B evaluation and treatment across the world.

BACKGROUND & AIMS: Oral antiviral therapy with nucleos(t)ide analogues (NAs) for chronic hepatitis B (CHB) is well-tolerated and lifesaving, but real-world data on utilization are limited. We examined rates of evaluation and treatment in patients from the REAL-B consortium. METHODS: This was a cross-sectional study nested within our retrospective multinational clinical consortium (2000-2021). We determined the proportions of patients receiving adequate evaluation, meeting AASLD treatment criteria, and initiating treatment at any time during the study period. We also identified factors associated with receiving adequate evaluation and treatment using multivariable logistic regression analyses. RESULTS: We analyzed 12,566 adult treatment-naïve patients with CHB from 25 centers in 9 countries (mean age 47.1 years, 41.7% female, 96.1% Asian, 49.6% Western region, 8.7% cirrhosis). Overall, 73.3% (9,206 patients) received adequate evaluation. Among the adequately evaluated, 32.6% (3,001 patients) were treatment eligible by AASLD criteria, 83.3% (2,500 patients) of whom were initiated on NAs, with consistent findings in analyses using EASL criteria. On multivariable logistic regression adjusting for age, sex, cirrhosis, and ethnicity plus region, female sex was associated with adequate evaluation (adjusted odds ratio [aOR] 1.13, p = 0.004), but female treatment-eligible patients were about 50% less likely to initiate NAs (aOR 0.54, p <0.001). Additionally, the lowest evaluation and treatment rates were among Asian patients from the West, but no difference was observed between non-Asian patients and Asian patients from the East. Asian patients from the West (vs. East) were about 40-50% less likely to undergo adequate evaluation (aOR 0.60) and initiate NAs (aOR 0.54) (both p <0.001). CONCLUSIONS: Evaluation and treatment rates were suboptimal for patients with CHB in both the East and West, with significant sex and ethnic disparities. Improved linkage to care with linguistically competent and culturally sensitive approaches is needed. IMPACT AND IMPLICATIONS: Significant sex and ethnic disparities exist in hepatitis B evaluation and treatment, with female treatment-eligible patients about 50% less likely to receive antiviral treatment and Asian patients from Western regions also about 50% less likely to receive adequate evaluation or treatment compared to Asians from the East (there was no significant difference between Asian patients from the East and non-Asian patients). Improved linkage to care with linguistically competent and culturally sensitive approaches is needed.

Diagnosis and Medical Treatment of Acute and Chronic Idiopathic Pouchitis in Inflammatory Bowel Disease.

Despite the decreased rates in inflammatory bowel disease (IBD) colectomies due to high advances in therapeutic options, a significant number of patients still require proctocolectomy with ileal pouch-anal anastomosis (IPPA) for ulcerative colitis (UC). Pouchitis is the most common complication in these patients, where up to 60% develop one episode of pouchitis in the first two years after UC surgery with IPAA with severe negative impact on their quality of life. Acute cases usually respond well to antibiotics, but 15% of patients will still develop a refractory disease that requires the initiation of advanced immunosuppressive therapies. For chronic idiopathic pouchitis, current recommendations suggest using the same therapeutic options as for IBD in terms of biologics and small molecules. However, the available data are limited regarding the effectiveness of different biologics or small molecules for the management of this condition, and all evidences arise from case series and small studies. Vedolizumab is the only biologic agent that has received approval for the treatment of adult patients with moderately to severely active chronic refractory pouchitis. Despite the fact that IBD treatment is rapidly evolving with the development of novel molecules, the presence of pouchitis represents an exclusion criterion in these trials. Recommendations for the approach of these conditions range from low to very low certainty of evidence, resulting from small randomized controlled trials and case series studies. The current review focuses on the therapeutic management of idiopathic pouchitis.

Alcoholic Acute Pancreatitis, a Retrospective Study about Clinical Risk Factors and Outcomes-A Seven-Year Experience of a Large Tertiary Center.

(1) Background: Alcohol consumption is one of the main causes of acute pancreatitis. (2) Material and Methods: In this unicentric retrospective cohort study, we selected 1855 patients from the Bucharest Acute Pancreatitis Index (BUC-API) who presented with acute pancreatitis. We investigated correlations between Alcoholic Acute Pancreatitis (AAP) and the rate of complications, cost, length of hospitalization and rate of recurrence. (3) Results: We found a moderately strong association between AAP and recurrence (p < 0.01) and observed that the disease is likelier to evolve with pseudocysts and walled-off necrosis than other forms of AP. Patients with AAP are less likely to have a morphologically normal pancreas than patients suffering from AP of other causes (p < 0.01), but a low probability of requiring intensive care unit admission (p < 0.01) significantly lowers daily cost (Md = 154.7 EUR compared to Md = 204.4 EUR) (p < 0.01). (4) Conclusions: This study's data show that patients with AAP have a greater rate of pseudocyst occurrence, lower intensive care unit admittance rate and lower cost of hospitalization than patients with AP of other causes. Typical Sketch: A middle-aged male tobacco smoker with recurrent AP, lower risk of in-hospital mortality and complications such as pseudocysts; treated in a gastroenterological ward and discharged at-will.

Sylimarin Versus Essential Phospholipids in Metabolic Associated Steatotic Liver Disease (MASLD) - A Prospective Comparative Randomized Trial.

Introduction:Metabolic dysfunction-associated steatotic liver disease (MASLD) is an entity with a growing incidence but only a few pharmacological options. In Romania, the prevalence of MASLD has been increasing, while that of viral hepatitis has been decreasing. The purpose of this study is to compare two supplements for the treatment of MASLD. Methods:Between January 2020 and May 2022, 90 patients with MASLD were randomized to receive either silymarin 150 mg b.i.d (45 subjects) or essential phospholipids (EPLs) 825 mg b.i.d. (45 subjects) for six months. All study participants received recommendations for lifestyle and diet modifications. Assessment of the severity of steatosis and liver fibrosis was performed using FibroScan® with controlled attenuated parameter (CAP) at the beginning and end of treatment. Results:A total of 68 patients completed the trial. The two groups were statistically comparable in terms of clinical, biological and FibroScanR parameters. Aspartate transferase (AST) decreased from a median of 40 to 28 IU/L in the EPL arm (compared to 25→¨25.5 IU/L in the silymarin arm) (p-value=0.11) and alanine transaminase (ALT) decreased from 46 to 37.5 IU/L (compared to 31→30 IU/L) (p-value = 0.38). Plasma cholesterol levels also decreased significantly in the EPL group (218→189.5 mg/dL) compared to the silymarin arm (217→209 mg/dL) (p = 0.01). At the end of treatment, liver stiffness decreased by 0.7 KPa (6.9→6.2 KPa) in the EPL group but increased by 2.3 KPa (7.2→9.5 KPa) in the silymarin group (p = 0.1). The reduction in hepatic steatosis was comparable between the two groups: it decreased by 5% of the initial value. Conclusion:In our study, a six-month treatment with EPLs was superior to silymarin in MASLD patients because it succeeded in improving both laboratory parameters and liver fibrosis, as estimated by FibroScan®.

Paradoxical Psoriasis Induced by Ustekinumab: A Comprehensive Review and Case Report.

Ustekinumab (UST), a biologic agent targeting interleukin-12 and interleukin-23, is widely used in the management of psoriasis and Crohn's disease. Despite its efficacy, there have been instances of paradoxical psoriasis induction or exacerbation in some patients during UST therapy. This paper offers a comprehensive review of reported cases of UST-induced paradoxical psoriasis, including a case from our clinic. We focus on a 39-year-old female patient with a history of long-standing Crohn's disease who developed a psoriasiform rash, as confirmed by biopsy, while undergoing UST treatment. The patient's clinical journey, from initial diagnosis through the complexities of treatment adjustments due to various complications including drug-induced lupus and the subsequent onset of psoriatic manifestations, provides insight into the challenges encountered in the clinical management of such cases. This review emphasizes the necessity for clinicians to recognize the possibility of paradoxical psoriasis in patients receiving UST treatment and calls for further research to better understand this phenomenon and devise effective management strategies.

Impact of Dietary Patterns in Inflammatory Bowel Disease Subtypes Versus Healthy Subjects: a Retrospective Cohort Study.

Objectives:Inflammatory bowel diseases (IBD) have been associated with multiple environmental factors, including diet. A dietary pattern characterized by low fiber content, high fat content and high carbohydrate content has been linked to the development of IBD. The objective of the current investigation is to examine the potential link between dietary patterns and the occurrence of IBD and to investigate whether there are any differences in relation to the type of IBD and specific food groups. Material and methods:We conducted an observational retrospective comparative study using three cohorts: 89 Crohn's disease (CD) patients, 40 ulcerative colitis (UC) patients and 64 healthy subjects. All participants underwent structured interviews and were required to complete a questionnaire regarding their dietary habits either prior to the onset of IBD or within the last year for control subjects. Results:A higher proportion of CD patients reported a higher rate of salt intake (71.9% vs. 53.1%, p-value = 0.043), sweetened beverages (38.2% vs. 17.2%, p-value=0.022), processed meat (66.3% vs. 40.6%, p-value=0.007), fatty meat (50.6% vs. 28.1%, p-value=0.021), fried foods (47.2% vs. 9.4%, p-value<0.001) and mayonnaise (21.3% vs. 6.2%, p-value=0.032) and a lower intake of nuts and seeds (20.2% vs. 43.8%, p-value=0.004) and yogurt (23.6% vs. 43.8%, p-value=0.030) compared to healthy subjects. Compared to controls, in the UC group there was a higher consumption of salt (85% vs. 53.1%, p-value=0.003), sweetened beverages (47.5% vs. 17.2%, p-value=0.005), fatty meat (55% vs. 28.1%, p-value=0.025) and fried foods (55% vs. 9.4%, p-value<0.001) and a lower intake of nuts and seeds (10% vs. 43.8%, p-value=0.001). Conclusion:Diet patterns before the onset of the disease are similar in patients with Crohn's disease and patients with ulcerative colitis: increased consumption of sweetened beverages, processed and fatty meat, fried food, salt, store-bought ice cream, and mayonnaise, and decreased intake of seeds, nuts, and yogurt.

Treatment Outcomes of Sofosbuvir/Velpatasvir/Voxilaprevir in Direct-Acting Antiviral-Experienced Hepatitis C Virus Patients: A Systematic Review and Meta-Analysis.

About 5% of chronic hepatitis C (CHC) patients experienced treatment failure with direct-acting antiviral (DAA) treatment. The global data on the practice and treatment outcomes of Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) in DAA-experienced CHC patients remains sparse. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of SOF/VEL/VOX as a salvage treatment in DAA-experienced CHC patients. We searched five electronic databases from inception to 31 January 2023. The study outcomes were SVR12 and treatment-related adverse effects, with subgroup analysis performed based on genotype, cirrhosis, HCC, prior SOF/VEL exposure, and region. We identified and analyzed data from 24 studies (2877 DAA-experienced CHC patients); 17.2% had prior SOF/VEL exposure, 25% received ribavirin with SOF/VEL/VOX, and 42% had pre-treatment resistance-associated substitution (RAS) testing performed. Eastern Mediterranean had a higher pooled SVR12 than the America and Europe regions (p < 0.05). Predictors of SOF/VEL/VOX failure were genotype 3, active HCC, baseline cirrhosis, and prior SOF/VEL. Baseline RAS mutation and ribavirin supplementation were not associated with higher SVR12. Treatment discontinuation because of drug-related adverse events was uncommon (10 studies, 0.2%). In summary, SOF/VEL/VOX is efficacious and safe for retreatment in DAA-experienced CHC patients, even with RAS mutation. Our findings support SOF/VEL/VOX as a first-line rescue treatment for DAA-experienced CHC patients.

Interleukin-4 Gene Polymorphisms in Romanian Patients with Inflammatory Bowel Diseases: Association with Disease Risk and Clinical Features.

1. INTRODUCTION: Multiple cytokines have been studied for their role in the propagation of the inflammatory process related to inflammatory bowel diseases (IBD), but the role of interleukin-4 remains controversial. The aim of this study was to evaluate the role of two IL-4 gene single nucleotide polymorphisms (SNPs) in disease susceptibility and phenotypic expression. 2. MATERIALS AND METHODS: A group of 160 patients with IBD (86CD/74UC) and 160 healthy controls were genotyped for IL-4 rs2243250/-590C/T and rs2070874/-34C/T using real-time polymerase chain reaction with TaqMan assay. 3. RESULTS: The analysis of IBD patients and controls revealed a significantly reduced frequency of the minor allele T of both SNPs in CD patients (p = 0.03, OR 0.55 and p = 0.02, OR 0.52) and for the entire IBD group (p = 0.01, OR 0.57 and p = 0.01, OR 0.55). Haplotype analysis identified the most frequent haplotype (rs2243250/rs2070874 CC) associated with a high risk for developing IBD (either UC or CD) (p = 0.003). IBD patients with extraintestinal manifestations had significantly increased frequency of the minor alleles T. We also found an association between the presence of allele C of rs2070874 and response to antiTNF treatment. 4. CONCLUSIONS: This is the first study to investigate the IL-4 gene's relation to IBD susceptibility conducted in Romania. Both SNPs were found to be associated with disease susceptibility and phenotypic features, such as extraintestinal manifestations and response to antiTNF agents.

Non-alcoholic fatty liver disease in diabetes mellitus patients on chronic hemodialysis - A case series addressing cardiovascular and mortality risks.

Non-alcoholic fatty liver disease (NAFLD) has an important role in the pathogenesis of cardiovascular diseases in the population with diabetes and it is highly prevalent in end-stage renal disease (ESRD) patients. This case series describes NAFLD associated factors and survival in type 2 diabetes patients (T2DM) who have ESRD treated with hemodialysis. NAFLD prevalence in patients with T2DM and ESRD is 69.2%. A high number of patients (15 out of 18) have obesity evaluated by calculating body mass index (BMI) and bioimpedance measurements. Patients with NAFLD have higher cardiovascular mortality risk, 13 of 18 patients were already diagnosed with coronary heart disease, 6 of 18 had cerebrovascular disease, and 6 of 18 had peripheral artery disease. Fourteen patients were treated with insulin, two patients with sitagliptin (renal adjusted dose of 25mg/day) and two patients with medical nutrition therapy, with an HbA1c ranging from 4.4 to 9.0%. After one-year follow-up 7 of 18 patients died, the causes having roughly equal proportions: myocardial infarction, SARS-CoV2 infection, and pulmonary edema. In conclusion, our population of type 2 diabetic patients with ESRD in hemodialysis had a prevalence of ultrasound-diagnosed NAFLD of 69.2%. Also, this population had a high death rate at one-year follow-up, cardiovascular causes being among the most common.

Role of an Exclusion Diet (Reduced Disaccharides, Saturated Fats, Emulsifiers, Red and Ultraprocessed Meats) in Maintaining the Remission of Chronic Inflammatory Bowel Diseases in Adults.

Background and Objectives: Inflammatory bowel diseases are a main focus in current research, with diet being an emerging therapeutic line due to its links in both onset and progression. A Western-style diet high in processed foods, food additives, red meat, and animal fat has been linked to a higher risk of developing IBD. The aim of this study was to establish an association between an anti-inflammatory exclusion diet and maintenance of remission in IBD. Also, we assessed the efficacy and safety of this diet compared to a non-dietary group and the possible therapeutic effect of this diet in the maintenance of IBD remission. Materials and Methods: A total of 160 patients with IBD were screened for inclusion, but 21 did not met the inclusion criteria. Thus, 139 patients were assigned to either an exclusion diet or a regular diet according to their choice. Results: Clinical remission after six months was maintained in the exclusion diet arm (100%). In the control arm, four patients had clinically active disease (one patient with UC and three with CD), and 90 patients maintained the clinical remission state (95.7%) (p-value = 0.157). Regarding biochemical markers, ESR at baseline was higher in the exclusion diet arm: 29 (5-62) versus in the control arm 16 (4-48) (p-value = 0.019), but six months after, the groups were similar (p-value = 0.440). Conclusions: Patients who followed an exclusion diet maintained clinical remission more frequently. However, the threshold for statistical significance was not achieved. There was also a trend of improvement in inflammation tests in the intervention group.

HLA Genotyping in Romanian Adult Patients with Celiac Disease, their First-degree Relatives and Healthy Persons.

BACKGROUND AND AIMS: Celiac disease is characterized by an inappropriate T-cell-mediated response to gluten in small bowel in genetically predisposed individuals, carriers of the DQ2 and/or DQ8 haplotypes of the human leukocyte antigen. The aim of our study was to asses HLA typing in adult patients with celiac disease, in their first degree relatives and in a healthy control group. METHODS: We conducted a prospective observational study on three cohorts: 117 patients diagnosed with celiac disease, 41 first-degree relatives of celiac patients and 57 asymptomatic healthy volunteers. Low resolution HLA typing for DQ alleles was performed in all study subjects with DNA extracted from peripheral blood, using SSP HLA-DQB1 kit (Innotrain Diagnostik GmbH, Germany).  Next Generation Sequencing (NGS) was used only in 18 patients for typing confirmation of DQB1 and DQA1 loci and whole gene sequencing. RESULTS: Prevalence of HLA-DQ2 was significantly higher in the CD group compared to the healthy subjects group (95.6% vs 29.8%, p <0.001), with no statistically significant differences in HLA-DQ8 and combined HLA-DQ2/DQ8 prevalences.Several HLA DQA1 and DQB1 alleles (HLA-DQA1* 05:01, HLA-DQB1*02:01, HLA-DQB1*02:02) and haplotypes (DQA1*02:01-DQB1*02:02,DQA1*05:01-DQB1*02:01) were strongly associated with celiac disease in our group: OR 4.28, 4.28, 4.67 and 5.43 and 4.28 respectively. Predominantly, patients presented with typical symptoms and iron deficiency anemia. 95.5% of them had histological Marsh type modifications ≥3a. A relatively poor response to gluten-free diet was observed and 9.4% developed complications (refractory celiac disease, enteropathy-associated T cell lymphoma, intestinal adenocarcinoma), with a death rate of 6.8%. 23% associated other autoimmune diseases.Screening adherence for 1st degree relatives was very low: only 16%. Familial screening diagnosed 4 cases of asymptomatic celiac disease. 32 relatives (78%) had HLA-DQ2 haplotype, 5 carried HLA-DQ8, 4 didn't carry any risk haplotype. CONCLUSIONS: This study demonstrated a higher prevalence of the HLA-DQ2 genotype in patients with celiac disease compared to the healthy population but not of HLA-DQ8 or combined HLA-DQ2/DQ8. Alleles HLA-DQA1* 05:01, HLA-DQB1*02:01, HLA-DQB1*02:02 and haplotypes (DQA1*02:01-DQB1*02:02,DQA1*05:01-DQB1*02:01) were strongly associated with celiac disease in our cohort.

Clostridioides Difficile Enteritis: Case Report and Literature Review.

BACKGROUND: Clostridioides Difficile is a well-known pathogen causing diarrhea of various degrees of severity through associated infectious colitis. However, there have been reports of infectious enteritis mainly in patients with ileostomy, causing dehydration through high-output volume; Case presentation: We report the case of a 46-year-old male patient, malnourished, who presented with high-output ileostomy following a recent hospitalization where he had suffered an ileo-colic resection with ileal and transverse colon double ostomy, for stricturing Crohn's disease. Clostridioides Difficile toxin A was identified in the ileal output confirming the diagnosis of acute enteritis. Treatment with oral Vancomycin was initiated with rapid reduction of the ileostomy output volume; Conclusion: We report a case of Clostridioides Difficile enteral infection as a cause for high-output ileostomy, successfully treated with oral Vancomycin. We also review the existing literature data regarding this specific localized infection.

Mucosal gene expression profile of stricturing Crohn's disease: A preliminary study.

Intestinal strictures are an important complication of Crohn's disease (CD), with ~40% of patients developing symptomatic obstruction within 10 years of diagnosis. However, there is a paucity of research examining the mechanisms driving the development of fibrotic strictures in CD. The present study aimed to identify the mucosal markers associated with stricturing complications by examining the differences in the gene expression profiles of two patient cohorts: Patients diagnosed with inflammatory CD (n=12) and patients with stricturing CD (n=9). For each patient, a paired sample of inflamed and uninflamed mucosa was isolated and assessed by quantitative PCR using a large panel of genes associated with inflammatory bowel disease. The presents study revealed a significantly increased level of four genes in the mucosa of patients with strictures compared with the inflammatory pattern of the disease: Formyl-peptide receptor 1 [P=0.019; fold change (FC)=11.6], C-C chemokine receptor type 1 (P=0.035; FC=5.44), IFN-γ-inducible protein 10 (P=0.037; FC=3.8) and C-C chemokine ligand 25 (P=0.048; FC=3.56). The augmented expression of these four genes in the CD stricturing phenotype, if confirmed in larger cohorts of patients, could help elucidate the mechanisms leading to disease-associated complications.

Relevance of HLA gene polymorphisms in Romanian patients with chronic renal insufficiency undergoing renal transplantation.

BACKGROUND: Chronic renal insufficiency (CRI) is a global public health problem with a high incidence in the Romanian population. In this study, we aimed to investigate genomic HLA polymorphisms in Romanian patients with CRI waiting for kidney transplantation. To determine the existence of a potential strong link between certain HLA polymorphisms and CRI, we also looked at HLA specificity combinations within the same locus or even different loci, referring to randomly inherited allelic combinations rather than potential haplotypes. METHODS: A total of 2199 patients with CRI on the kidney transplantation waiting list were included. A total of 2786 healthy individuals were included as controls. Both patients and controls were assessed for both HLA I and class II genes. HLA genes were typed using the low-resolution method polymerase chain reaction sequence-specific primer. RESULTS: Certain class I and class II HLA allele groups, genotypes and haplotypes were significantly more frequent in patients with CRI than in the control individuals (eg B* 40 (p ≤ .001, pc ≤ .001), C* 12 (p ≤ .001, pc ≤ .001), DRB1*14 (p = .0022, pc = .04), C*12,- (p < .001, pc < .001), A*01-C*15 (p = .0003, pc = .03) and A*02-C*12 (p = .0005, pc = .0486)). CONCLUSIONS: HLA gene polymorphisms could be clinically relevant CRI-associated genetic profiles in Romanian patients with CRI.

Rare Clinical Association between Clostridioides difficile Infection and Ischemic Colitis: Case Report and Literature Review.

Background and Objectives: Gut microbiota plays an important role in the wellbeing of the host through different interactions between microflora constituents. In certain instances, Clostridioides difficile may pullulate, causing infection with associated colitis that may vary in terms of severity from mild disease to severe colitis, with increased associated mortality due to its complications. However, there are few literature data regarding the association between Clostridioides difficile and ischemic colitis. Case report: We report the case of a 30-year-old male patient, overweight, with impending dehydration, who presented with hematochezia and colicky abdominal pain, with positive fecal tests for the detection of Clostridioides difficile infection and endoscopic appearance suggesting ischemic colitis in the sigmoid and left colon, confirmed by computed tomography and histology. The patient was treated with oral Vancomycin, with resolution of symptoms, and was reevaluated through colonoscopy eight weeks after discharge, with endoscopic mucosal normalization and histological scarring process on biopsy samples. Conclusion: We report one of the few cases in the literature of ischemic colitis associated with Clostridioides difficile infection, with resolution of clinical, endoscopic, and histologic changes after specific treatment with oral Vancomycin suggesting a possible association between the two diseases. We also review the existing literature data regarding this comorbid association.

Extrahepatic cholangiocarcinoma: Current status of endoscopic approach and additional therapies.

The prognosis of patients with advanced or unresectable extrahepatic cholangiocarcinoma is poor. More than 50% of patients with jaundice are inoperable at the time of first diagnosis. Endoscopic treatment in patients with obstructive jaundice ensures bile duct drainage in preoperative or palliative settings. Relief of symptoms (pain, pruritus, jaundice) and improvement in quality of life are the aims of palliative therapy. Stent implantation by endoscopic retrograde cholangiopancreatography is generally preferred for long-term palliation. There is a vast variety of plastic and metal stents, covered or uncovered. The stent choice depends on the expected length of survival, quality of life, costs and physician expertise. This review will provide the framework for the endoscopic minimally invasive therapy in extrahepatic cholangiocarcinoma. Moreover, additional therapies, such as brachytherapy, photodynamic therapy, radiofrequency ablation, chemotherapy, molecular-targeted therapy and/or immunotherapy by the endoscopic approach, are the nonsurgical methods associated with survival improvement rate and/or local symptom palliation.