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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and objectives: One of the most frequent glomerular diseases in the pediatric population is represented by the idiopathic nephrotic syndrome (INS). The exact mechanisms mediating the disease are still unknown, but several genetic factors have been studied for possible implications. Cytokines are considered to play a pivotal role in mediating INS disease progression, interleukin-4 (IL-4) exhibiting particular interest. The objective of this research project was to investigate the association between two IL-4 gene single-nucleotide polymorphisms (SNPs) and INS susceptibility as well as response to steroid therapy, in a group of Romanian children. Materials and Methods: In total, 75 patients with INS and 160 healthy controls of Romanian origin were genotyped for IL-4 rs2243250/−590C/T and rs2070874/−34C/T using real-time polymerase chain reaction. Association tests were performed using the DeFinetti program and Plink 1.07 software and p-values < 0.05 were considered statistically significant. Results: The analysis of INS patients and controls revealed a similar genotype distribution of the studied SNPs. The minor T alleles were less frequent in the INS group, but not statistically significant (p = 0.1, OR = 0.68 and p = 0.2, OR = 0.74). Regarding the response to steroids, a low frequency of 590*T allele in steroid-resistant patients (7.7%), compared with steroid-sensitive patients (14%) and controls (17.5%), was obtained, but the difference did not reach the statistical significance threshold. The same result was obtained for −34C/T SNP. Conclusions: This is the first study examining the relationship between the IL-4 gene and INS susceptibility conducted in a European population, and particularly in Romania. The investigated SNPs were found to not be associated with disease susceptibility or response to the steroid treatment of pediatric INS. [ABSTRACT FROM AUTHOR]

Background: Bone impairment of multifactorial etiology is a common feature in inflammatory bowel disease (IBD). Body composition parameters, which might be selectively modified in these patients, are important determinants of bone strength. Our aim was to investigate the relationship between components of body composition and bone parameters in IBD patients. Methods: This is a cross-sectional, retrospective study including 80 IBD patients (43 women, 37 men). Lumbar spine (LS), femoral neck (FN) and whole body DXA scans were performed to analyze regional bone mineral density (BMD), as well as body composition, including appendicular skeletal muscle mass index (ASMI), total and visceral fat mass (VAT). Trabecular bone score (TBS) was assessed using iNsight Software. Results: Twenty (25%) IBD patients had inadequate LS-BMD z scores (<=−2DS). Lean mass (LM) was a significant determinant of LS-BMD, after adjusting for age, gender, BMI and fat mass (p < 0.01), while fat mass% remained associated with FN-BMD (p < 0.01). TBS correlated positively with BMI (r = 0.24, p < 0.05), LS-BMD (r = 0.56, p < 0.001), ASMI (r = 0.34, p < 0.001) and negatively with VAT/total fat% (r = −0.27, p < 0.05). Multivariate analysis showed that ASMI, LS-BMD (positively) and VAT/total fat% (negatively) were independently associated with TBS. Conclusions: In IBD patients, skeletal muscle mass and fat percentage and distribution are important factors associated with bone health. [ABSTRACT FROM AUTHOR]

Historic. A 59-year-old patient, a chronic ethanol user, without any medical history, presents with hematemesis and abdominal pain. Methods. The level of hemoglobin was 8.2 g/dL, without any other biological modification. The emergency upper digestive endoscopy revealed a large clot that almost completely occupied the esophageal and gastric lumen, up to the duodenal angle. Endoscopic re-evaluation at 24 hours: esophagus and stomach with free lumen, gastric body with extrinsic compression on the posterior face towards the greater curvature and intensely edematous mucosa at that level. Abdominal ultrasound revealed multiple calcifications at the level of the pancreatic head and body and at the level of the tail of the pancreas, a cystic formation of approximately 5 cm was visualized, with a pulsed Doppler signal. CEUS:hyperinhancement in the center of the lesion and lack of contrast in the periphery, an aspect that was maintained in the portal and parenchymal phases. The abdominal CT showed a corporeo-caudal pancreatic pseudoaneurysm of the splenic artery with dimensions of 65 mm, with parietal thrombosis with a stratified appearance, affecting about 40% of the lumen, with contrast extravasation, in direct contact with the posterior gastric wall. Results. The suspicion of upper digestive hemorrhage secondary to a fistula between the pseudo-aneurysm of the splenic artery and the stomach was raised, but also the possibility of a wirsungorrhagia, given the direct contact of the lesion with the pancreatic tail. Abdominal angiography with angioplasty was performed, secondary to the extravasation of the contrast substance at the level of the splenic artery with a 3/18 mm Bentley type stent graft, with an optimal result, without extravasation of contrast. Diagnosis. Upper gastrointestinal hemorrhage secondary to a splenic artery pseudoaneurysm. Chronic ethanolic pancreatitis. Conclusions. Bleeding from splenic artery pseudoaneurysm is a rare and often fatal cause of gastrointestinal bleeding The most common causes are pancreatitis and abdominal trauma. In pancreatitis, pancreatic enzymes can cause vascular necrosis and rupture of elastic tissue, leading to pseudoaneurysm formation. Another way can be through pseudocysts (41% of patients with pseudoaneurysms), In this patient's case, the pseudoaneurysm most likely occurred secondary to a pseudocyst that eroded the splenic artery, with intracystic hemorrhage, which led to a localized hemorrhage and not to a hemoperitoneum, and subsequently to the digestive tract, transgastric or through the main pancreatic duct. After stent placement by angiography, the patient had a favorable evolution at ultrasound reevaluation at 1 month, with remission of the lesion. [ABSTRACT FROM AUTHOR]

Aims. Among the non-invasive methods of evaluation in cirrhotic patients, the shear wave elastography (2D-SWE) method has been used to quantify the stiffness in chronic liver disease with good accuracy. Several studies have shown that each complication of cirrhosis is associated with a certain amount of liver stiffness. The objective of the study we performed was to quantify the use of elastography (liver and spleen) in predicting the risque and the grade of gastro-esophageal varices in patients diagnosed with hepatic cirrhosis. Methods. We used the GE Logiq E9/E10 ultrasound system for 34 pacients. We excluded the pacients with liver neoplasia, infiltrative liver disease, acute virale hepatitis and obstructive cholestasis. The value cutt-off used for liver stiffness was >11.88 kPa (>1.99 m/s), correspondent for F4 Metavir. The procedure was realized after 4 hours of fasting, intercostal at 1.5-2 cm below liver and spleen capsule avoiding vessels. Six measurements were obtained for each patient. The results were compared with upper digestive endoscopy. Results. We performed liver elastography for 34 patients known with liver cirrhosis, 94.2% due to ethanol consumption, of which 29.4% (n:10) were female and 70.5% (n:24) were male. We compared the degree of esophageal varices with the value of elastography. Elastography can differentiate patients without esophageal varices from patients with moderate (p value=0.072) or large esophageal varices (p value=0.013), but it cannot differentiate between patients without esophageal varices and those with small esophageal varice (p value=0.8249). However, there was a lack of correlation between the elastographic values of the spleen and the degree of esophageal varices (p value= 0.5860). Conclusions. The results obtained are indicating that 2D-SWE of the liver can be used for ruling-out varices needing treatment in patients with cACLD, knowing that the presence of varices and especially of varices needing treatment indicates distinct prognostic stages in patients with compensated ACLD (cACLD). [ABSTRACT FROM AUTHOR]

Background & Aims: The sofosbuvir (SOF) / velpatasvir (VEL) / voxilaprevir (VOX) combination has been evaluated in more than 800 patients enrolled in phase II and phase III studies, where it demonstrated excellent safety and efficacy, achieving overall sustained viral response (SVR) rates of more than 95%. We aimed to assess the efficacy and safety of SOF/VEL/VOX in a real-world study, including patients previously treated for genotype 1b hepatitis C virus (HCV) infection that did not obtain a sustained viral response with previous direct-acting antivirals (DAAs) therapy. Methods: In Romania, through a nationwide government-funded program in 2019-2020, 213 patients with chronic hepatitis C non-responders to previous DAAs therapy, received treatment with SOF/VEL/VOX 400/100/100 mg/day for 12 weeks. We performed a retrospective longitudinal study that included 143 individuals who were treated in Bucharest, Iași, Craiova and Constanța clinics, all with genotype 1b HCV infection. Efficacy was assessed by the percentage of patients achieving SVR 12 weeks post-treatment (SVR12). Serious adverse events (SAE) were registered. Results: Our cohort comprised 53% males with a median age of 60 years (27÷77); 47% were pre-treated with ombitasvir/paritaprevir/ritonavir+dasabuvir ± ribavirin, 40% with ledipasvir/SOF, 13% with elbasvir/grazoprevir. 42% of patients associated co-morbidities, 45% had compensated liver cirrhosis, 2% had treated hepatocellular carcinoma (HCC) and 1% had hepatitis B virus co-infection. SVR by intention to treat was reported in 139/143 (97.2%) and per protocol in 141/143 (98.6%). No predictive factors for SVR were identified. Rate of liver decompensation in patients with cirrhosis was 6% and was statistically associated in multivariate analysis with Child-Pugh score (p<0.01) and with severe steatosis (p=0.004). Occurrence of new HCC was reported in 3.6% of all patients with cirrhosis and was associated with poor liver function [higher Child-Pugh score (p=0.001) and low albumin levels (p=0.02)]. Serious adverse events related to therapy were reported in 1/143(0.7%). Conclusions: SOF/VEL/VOX was highly efficient in our population of patients with a 97.2% SVR. Liver decompensation occurred in 6% of cirrhotic patients at SVR, related to hepatic dysfunction. [ABSTRACT FROM AUTHOR]

Background and aims. For the 8-week OPrD regimen, real world data are insufficient. This study aims to compare the efficacy of the two types of regimens (12-week versus 8-week) in a real world cohort of patients with genotype 1b. Material and methods. We analysed a multicentric retrospective cohort enrolling 1436 patients who started HCV therapy in 2018-2019. Liver fibrosis was staged in all subjects by Fibromax. Efficacy was assessed by the percentage of patients achieving SVR 12 weeks post-treatment (SVR12). Results. Out of the 1436 analysed patients, 112 received 8 weeks therapy and 1324 received 12 weeks. In this cohort the proportion of male patients was 25.2%, the median age 61 years, 28.2% were interferon pre-treated, and the rate of co-morbidities was 47%. 42% of the subjects had F2 fibrosis, 29% F1 fibrosis, 16% F3 and 12% F4. The SVR rate was comparable in both groups of patients (97% in those treated with OPrD 12 weeks vs 96.4% in those that received OPrD 8 weeks) (by intention-to-treat). In the 12 weeks arm, the drop-out rate was 0.8% and the rate of severe adverse events was 1%, while in the arm of 8 weeks therapy there were no severe adverse events reported and no drop-out (p = 0.25). The only predictive factor for non-response in both treatment arms was the male sex. Conclusions. OPrD 8 weeks proved to be highly efficient in our patients with a 96.4% SVR. No serious adverse events and no drop out were reported. [ABSTRACT FROM AUTHOR]

Background & Aims: Therapeutic targets in ulcerative colitis (UC) have evolved over time from clinical remission to biological and endoscopic remission. Histologic remission remains a debatable outcome due to lack of data regarding its impact on long-term evolution. The development of histologic activity scores has brought standardization. We aimed to identify mucosal markers differentiating histological inflammation from histological remission in UC patients. Methods: The gene expression levels of 84 genes associated with inflammatory bowel diseases have been analyzed in 43 colonic mucosa samples from 30 patients with UC. The gene expression levels have been correlated with histological inflammation score of Geboes. Patients with endoscopic remission were divided by histological activity into two groups and molecular results were compared in order to identify differences in the mucosal gene expression. Results: We found a significant Pearson correlation (p<0.001 and r>0.5) between the Geboes score and the expression of 29 genes, whereas negative correlation (p<0.001 and r<-0.50) was observed with two genes in the entire UC cohort. In the subgroup of patients with endoscopic remission three transcripts: formyl-peptide receptor 1 (FPR1), matrix metalloproteinases 1 (MMP1) and mucine 1 (MUC1) were significantly up-regulated in patients with histological inflammation compared to patients with histologic remission. Conclusion: Our study further emphasizes the importance of histological assessment when endoscopic mucosal healing is present, as FPR1, MMP-1 and MUC1 were all significantly upregulated in patients with histological alterations. [ABSTRACT FROM AUTHOR]

Aims. An 84-year-old patient with a history of high blood pressure presented to the emergency room with lower abdominal pain and haematochezia. Methods. Clinical:hemodynamically stable. Biological: WBC 32700/microL, Hb=8.1 g/dL, PLT = 321 000/microL, INR=1.23, CRP = 292 mg/L. CTscan: no contrast extravasation in the digestive tract, infrarenal aortic aneurysm (130 mm cranio-caudal), with parietal thrombus plus a retroaortic abscess with stenosis of the inferior vena cava. Vascular surgery consultation: no surgical indication ->admission to the gastroenterology department. Emergency upper GI endoscopy: adherent clot in the fornix, stasis fluid. 60 cm rectosigmoidoscopy: mucosal lesions suggestive of ischemic colitis. Reevaluation after 12 h: WBC = 26 000/microL, hemoglobin = 7.1 g/dL Results. Re-evaluation of the CT-scan: suspicion of an aorto-duodenal fistula. Second upper GI endoscopy: gastric mucosa, bulb and D2 lined with fresh blood. On withdrawal, an infrapapillary lesion suggestive for an aortoenteric fistula. Duodenoscopesecond look:an erosion with a diameter of 10 mm with a deep punctate hole: most likely aortoenteric fistula. The patient was transferred to cardio-vascular surgery: double-layer duodenorrhaphy and aorto-aortic interposition of a silver Dacron prosthesis were done. Conclusion. The particularity of the case was represented by the rare cause of haemorrhage with difficult diagnosis. The approach and treatment required a multidisciplinary team and a good collaboration. The patient was discharged after 17 days with a good general condition. [ABSTRACT FROM AUTHOR]

Aims. Variceal bleeding is a common and severe cause of hospitalization in cirrhotic patients. We analyzed how the COVID-19 waves modified the outcome of the patients compared to COVID-19 extra-wave intervals. Methods. We retrospectively included all patients hospitalized between March 2020 and December 2021 for variceal bleeding. They were separated in 2 categories: hospitalizations during COVID-19 extrawaves period and the COVID-19 waves. Variables like sex, age, hemoglobin at presentation, endoscopic timing, hemostatic methods, transfusion necessity, duration of hospitalization and mortality were analyzed. Results. Out of 76 patients (2020-2021), 20patients were hospitalized during the COVID-19 waves. The median age did not differ significantly across groups (61 years [IQR: 52-65] vs 58years [IQR: 44-64]), 59 patients being male and 17 being female. The number of admissions for variceal bleeding and gastroscopy requirement and timing were similar regardless of the studied period (p > 0.05). Median hemoglobin admission values were significantly lower in the following subgroups: patients in whom gastroscopy was performed in less than 6 hours or more than 12 hours (p = 0.045) and patients requiring PRBC transfusion (p = 0.018). There were also no differences in duration of hospitalization and mortality between the two studied periods (p>0.05). Conclusions. The number of patients remained relatively constant in both periods. We found no differences in the management and outcomes of patients with variceal bleeding throughout the COVID pandemic. Our results might be influenced by the low number of patients and need confirmation on larger cohorts. [ABSTRACT FROM AUTHOR]