Oral Anticoagulation in Patients with Chronic Liver Disease.

The administration of an anticoagulant in patients with liver disease (nonalcoholic steatohepatitis-NASH, nonalcoholic fatty liver disease-NAFLD, chronic hepatitis, or cirrhosis) who have an indication (atrial fibrillation, venous thrombosis, or pulmonary embolism) is challenging because there is an imbalance between thrombosis and bleeding. There is a need to focus our attention on preventing risk factors because diabetes, obesity, dyslipidemia, smoking, and sedentary behavior are risk factors for both NASH/NAFLD and AF, and these patients require anticoagulant treatment. Patients with advanced liver disease (Child-Pugh C) were excluded from studies, so vitamin K antagonists (VKAs) are still recommended. Currently, VKAs are recommended for other conditions (antiphospholipid syndrome, mitral valve stenosis, and mechanical valve prosthesis). Amongst the patients under chronic anticoagulant treatment, especially for the elderly, bleeding as a result of the improper use of warfarin is one of the important causes of emergency admissions due to adverse reactions. DOACs are considered to be efficient and safe, with apixaban offering superior protection against stroke and a good safety profile as far as major bleeding is concerned compared to warfarin. DOACs are safe in the Child-Pugh A and B classes (except rivaroxaban), and in the Child-Pugh C class are contraindicated. Given that there are certain and reliable data for chronic kidney disease regarding the recommendations, in liver function impairment more randomized studies must be carried out, as the current data are still uncertain. In particular, DOACs have a simple administration, minimal medication interactions, a high safety and effectiveness profile, and now a reversal agent is available (for dabigatran and idarucizumab). Patients are also statistically more compliant and do not require INR monitoring.

Risk Factors for Pancreatic Cancer in Patients with New-Onset Diabetes: A Systematic Review and Meta-Analysis.

(1) Background: Patients with new-onset diabetes (NOD) are at risk of pancreatic ductal adenocarcinoma (PDAC), but the most relevant additional risk factors and clinical characteristics are not well established. (2) Objectives: To compare the risk for PDAC in NOD patients to persons without diabetes. Identify risk factors of PDAC among NOD patients. (3) Methods: Medline, Embase, and Google Scholar were last searched in June 2022 for observational studies on NOD patients and assessing risk factors for developing PDAC. Data were extracted, and Meta-Analysis was performed. Pooled effect sizes with 95% confidence intervals (CI) were estimated with DerSimonian & Laird random effects models. (4) Findings: Twenty-two studies were included, and 576,210 patients with NOD contributed to the analysis, of which 3560 had PDAC. PDAC cases were older than controls by 6.14 years (CI 3.64-8.65, 11 studies). The highest risk of PDAC involved a family history of PDAC (3.78, CI 2.03-7.05, 4 studies), pancreatitis (5.66, CI 2.75-11.66, 9 studies), cholecystitis (2.5, CI 1.4-4.45, 4 studies), weight loss (2.49, CI 1.47-4.22, 4 studies), and high/rapidly increasing glycemia (2.33, CI 1.85-2.95, 4 studies) leading to more insulin use (4.91, CI 1.62-14.86, 5 studies). Smoking (ES 1.20, CI 1.03-1.41, 9 studies) and alcohol (ES 1.23, CI 1.09-1.38, 9 studies) have a smaller effect. (5) Conclusion: Important risk factors for PDAC among NOD patients are age, family history, and gallstones/pancreatitis. Symptoms are weight loss and rapid increase in glycemia. The identified risk factors could be used to develop a diagnostic model to screen NOD patients.

Dysregulation of miRNAs Targeting the IGF-1R Pathway in Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC), the most prevalent neoplastic lethal pancreatic disease, has a poor prognosis and an increasing incidence. The insulin-like growth factor-1 receptor (IGF-1R) signaling pathway is considered to be a contributing factor to the progression, metastasis, and therapy resistance of PDAC. Currently available treatment options for PDAC are limited, but microRNAs (miRNAs) may represent a new therapeutic strategy for targeting genes involved in the IGF-1R signaling pathway. METHOD: We investigated the expression levels of 21 miRNAs involved in the IGF-1R signaling pathway in pancreatic tissue from 38 patients with PDAC and 11 controls (five patients with chronic pancreatitis and six patients with normal pancreatic tissue). RESULTS: We found 19 differentially expressed miRNAs between the PDAC cases and the controls. In particular, miR-100-5p, miR-145-5p, miR-29c-3p, miR-9-5p, and miR-195-5p were exclusively downregulated in PDAC tissue but not in chronic pancreatitis or normal pancreatic tissues; both control types presented similar levels. We also identified miR-29a-3p, miR-29b-3p, and miR-7-5p as downregulated miRNAs in PDAC tissues as compared with normal tissues but not with pancreatitis tissues. CONCLUSIONS: We identified a panel of miRNAs that could represent putative therapeutic targets for the development of new miRNA-based therapies for PDAC.

Manometric changes of the esophagus in morbidly obese patients.

This prospective study aimed to determine the manometric pattern and the prevalence of esophageal dysmotility in 79 morbidly obese patients selected for laparoscopic sleeve gastrectomy. After clinical evaluation and upper gastrointestinal endoscopy, high-resolution esophageal manometry was performed. The esophageal peristalsis, lower esophageal sphincter (LES) basal pressure, and LES relaxation were evaluated. Demographic data showed a predominance of females (55.70%) and both females and males were in the 5th decade of life. In addition, approximately 3/4 of the patients (78.48%) were from the urban zone. The mean body mass index of the patients was 46.40±6.0069 kg/m2, with a maximum of 61 kg/m2. The LES basal pressure was normal in 59.49% of the patients, with a mean value of 31.40±18.43 mmHg. LES basal hypertonia was observed in 26.58%, and LES hypotonia in 13.93% of patients; 46.84% (37 patients) had abnormal manometric findings: 24.05% (19 patients) had EGJ outflow obstruction, 12.66% (10 patients) ineffective esophageal motility, 3.8% (3 patients) distal esophageal spasm, 3.8% (3 patients) Jackhammer esophagus, 2 cases were suggestive for type 2 achalasia but in asymptomatic patients. Ineffective esophageal motility was not associated with diabetes mellitus type 2 or erosive esophagitis according to our data. Hiatal hernia (HH) was manometrically diagnosed in 23 patients (29.11%). Preoperative high-resolution esophageal manometry in obese patients demonstrated a high prevalence of motility disorders, but in asymptomatic patients, thus in the future, we require more studies and larger cohorts to better appreciate the clinical impact.

Impact of laparoscopic sleeve gastrectomy on esophageal physiology.

Introduction. Laparoscopic sleeve gastrectomy (LSG) is a popular weight loss surgery technique, but the impact on esophageal physiology and esophagogastric junction is still debatable. The aim of our study was to evaluate the manometric changes of the lower esophageal sphincter (LES) after LSG in order to indicate LES manometry pre- procedure. Methods. In a prospective study we evaluated clinically, with upper gastrointestinal endoscopy, and high-resolution esophageal manometry 45 morbidly obese patients before, and 6-12 months after LSG. Results. The BMI (body mass index) decreased from 46.28±5.79 kg/m2 to 32.28±4.65 kg/m2 postoperatively (p <0.01), with a reduction of ~14 kg/m2 of BMI, 39.9 (±11.9) kg body weight and 29.9 (± 6.2)% of the TWL (Total Weight Loss index), in a median interval of 7.9 months. Gastroesophageal reflux disease (GERD) prevalence increased from 17.8% to 31.1% postoperatively, with new GERD onset in 22.2%, but mild symptomatology (the median GERD-HRQL score increased from 1.56 to 2.84 points). Postoperatory reflux was associated with lower esophageal sphincter (LES) hypotonia, shortening of LES length and IIGP (increased intragastric pressure). Hiatal hernia repair rate was 17.8%, and proton pump inhibitor consumption 20%. After weight loss, the 10 cases of esophagitis discovered preoperatively cured, but 3 patients were diagnosed with de novo esophagitis. The prevalence of manometric dysmotility after LSG was 28.9%, lower than before surgery (44.4%). Conclusion. Even if GERD remains the main limitation of LSG, the high-resolution esophageal manometry has proved useful and should be implemented in morbidly obese evaluation protocol, to better select the bariatric procedure.

EUS-through-the-needle microbiopsy forceps in pancreatic cystic lesions: A systematic review.

Pancreatic cystic lesions (PCLs) are being increasingly encountered in clinical practice, and sometimes, they can represent a diagnostic challenge. Recently, a through-the-needle micro forceps biopsy (MFB) device was introduced in the endosonography practice to facilitate EUS-guided sampling of PCLs. The aim was to perform a systematic review of studies evaluating the technical aspects, safety, and efficacy of the EUS-guided MFB for PCLs. A literature search was performed in three major databases, PubMed, Embase, and Web of Science in September 2019 using the search terms: "through-the-needle," "biopsy forceps," "microforceps," "endoscopic ultrasound," and "endosonography." Case reports and case series with <10 patients were excluded from the analysis. Altogether nine studies reporting on 463 patients were included in our systematic review. The mean age of the patients was 68.3 years, with a slight female predominance (60.9%). Most of the cysts were located in the body/tail of the pancreas (61.2%), with an overall mean size of 33 mm. The technical success of EUS-guided MFB was reported in 98.5%. The tissue acquisition yield reported was 88.2%, and the diagnostic accuracy was 68.6%. Adverse events were reported in 9.7%. EUS-guided MFB is technically feasible, safe, and has a high diagnostic accuracy for PCLs.

Is mucosa-associated lymphoid tissue lymphoma an infectious disease? Role of Helicobacter pylori and eradication antibiotic therapy (Review).

Mucosa-associated lymphoid tissue lymphoma (MALT) is seldom considered a diagnosis hypothesis in symptomatic patients. These lymphomas present as a main risk factor for chronic gastritis due to Helicobacter pylori infection. H. pylori leads to chronic inflammation, producing lymphoid tissue in the stomach mucosa (MALT) possibly leading to malignant transformation. Even though H. pylori remains one of the most important factors in the development of MALT lymphoma, it is not mandatory in the evolution of MALT lymphoma since high-grade lymphomas present a lower prevalence of H. pylori. The prevalence of H. pylori is indirectly proportional with the progression into the gastric wall. Mucosal and submucosal MALT lymphomas have a higher prevalence of the bacteria. However, genetic factors remain a risk factor especially if eradication treatment fails. Even though a low percentage of MALT lymphomas are H. pylori-negative, some respond to antibiotic eradication treatment. This can be explained either by the immunomodulatory effect of antibiotics or by other infectious sources such as Helicobacter heilmannii and Campylobacter jejuni (small bowel lymphoma). Treatment in MALT gastric lymphoma was a breakthrough since it was the first time in oncology where tumours were cured by antibiotic therapy, leading us to wonder if MALT lymphomas are infectious disease or not?

Effect of a New Synergistic Combination of Low Doses of Acetylsalicylic Acid, Caffeine, Acetaminophen, and Chlorpheniramine in Acute Low Back Pain.

The present paper continues a more complex research related to the increased synergism in terms of both anti-inflammatory and analgesic effect obtained by the addition of chlorpheniramine (CLF) to the common acetylsalicylic acid (ASA), acetaminophen (PAR), and caffeine (CAF) combination. This synergistic effect was previously highlighted both in vitro in rat models and in vivo in the treatment of migraine. The aim of the research was to further evaluate the analgesic effect of a synergistic low-dose ASA-PAR-CAF-CLF combination in the treatment of low back pain, in a parallel, multiple-dose, double-blind, active controlled clinical trial. A number of 89 patients with low back pain of at least moderate intensity were randomly assigned to receive Algopirin® (ALG), a combinational product containing 125 mg ASA, 75 mg PAR, 15 mg CAF, and 2 mg CLF, or PAR 500 mg, a drug recognized by American Pain Society as "safe and effective" in the treatment of low back pain. One tablet of the assigned product was administered three times a day for seven consecutive days. The patients evaluated their pain level using a Visual Analog Scale prior to administration, and at 1, 2, 4, and 6 h after the morning dose. Time course of effect was similar in structure and size for both treatments. Pain relief appeared rapidly and steadily increased over 4 h after drug administration. Differential pain curves of ALG and PAR were very similar and comparable with the previously determined ALG analgesia pattern in migraine. Differences between the daily mean pain scores were not statistically significant for the two treatments. Similar results were obtained for the Sum of Pain Intensity Differences (SPID) for 0-4 h and 0-6 h intervals as well as for the time course of the proportion of patients with at least 30% and at least 50% pain relief. In conclusion, in spite of very small doses of active components, ALG proved equally effective to the standard low back pain treatment and therefore a viable therapeutic alternative, mainly for patients with gastrointestinal and hepatic sensitivity. Trial Registration: www.ClinicalTrials.gov, identifier EudraCT No.: 2015-002314-74.

Usefulness of virtual chromoendoscopy in the evaluation of subtle small bowel ulcerative lesions by endoscopists with no experience in videocapsule.

BACKGROUND AND STUDY AIMS: In videocapsule endoscopy examination (VCE), subtle variations in mucosal hue or pattern such as those seen in ulcerations can be difficult to detect, depending on the experience of the reader. Our aim was to test whether virtual chromoendoscopy (VC) techniques, designed to enhance the contrast between the lesion and the normal mucosa, could improve the characterization of ulcerative mucosal lesions. PATIENTS AND METHODS: Fifteen trainees or young gastroenterologists with no experience in VCE were randomly assigned to evaluate 250 true ulcerative and 100 false ulcerative, difficult-to-interpret small bowel lesions, initially as white light images (WLI) and then, in a second round, with the addition of one VC setting or again as WLI, labeling them as real lesions or artifacts. RESULTS: On the overall image evaluation, an improvement in lesion characterization was observed by adding any chromoendoscopy setting, especially Blue mode and FICE 1, with increases in accuracy of 13 % [95 %CI 0.8, 25.3] and 7.1 % [95 %CI - 17.0, 31.3], respectively. However, when only false ulcerative images were considered, with the same presets (Blue mode and FICE 1), there was a loss in accuracy of 10.7 % [95 %CI - 10.9, 32.3] and 7.3 % [95 %CI - 1.3, 16.0], respectively. The interobserver agreement was poor for both readings. CONCLUSIONS: VC helps beginner VCE readers correctly categorize difficult-to-interpret small bowel mucosal ulcerative lesions. However, false lesions tend to be misinterpreted as true ulcerative with the same presets. Therefore care is advised in using VC especially under poor bowel preparation.

Celiac Disease Phenotype in Clinically Diagnosed Romanian Adults and Children.

BACKGROUND: Once considered a disease of childhood, celiac disease (CD) is now seen quite frequently in adults also, but with different and various clinical presentation. Little data is currently available about pediatric and adult CD features in Romanian patients. METHODS: 38 newly-diagnosed CD patients (17 adults and 21 children) were recruited for this study. The two groups (adult and pediatric) were compared regarding demographic, clinical, serologic and histological data. RESULTS: Regarding demographic data, female gender was predominant in both groups (71% and 67% respectively). Median age was 42 (range 23-83) in the adult CD group and 4 (1-17) in the pediatric CD group. Classic presentation was more frequently seen in children than adults (62% vs. 53%). Altered liver function tests, anemia and iron deficiency were more prevalent in the pediatric group. Children with CD also had higher titers of tTG antibodies (81% over 200 U/l, compared to 29% adults) and a higher frequency of destructive histology on small bowel biopsy (95% Marsh>3a, compared to 76% adults). CONCLUSION: Significant differences in pediatric and adult CD were seen in our study cohort, regarding clinical, laboratory and histological parameters. CD manifests differently in children and adults.

Severe Refractory Anemia in Primary Intestinal Lymphangiectasia. A Case Report.

BACKGROUND: Primary intestinal lymphangiectasia (Waldmann's disease) is a rare disease characterized by dilated lymphatics in the small bowel leading to an exudative enteropathy with lymphopenia, hypoalbuminemia and hypogammaglobulinemia. CASE PRESENTATION: We report the case of a 23 year-old male who presented with chronic anemia and in whom primary intestinal lymphangiectasia was diagnosed. A low-fat diet along with nutritional therapy with medium-chain triglyceride supplementation improved the protein-losing enteropathy, but did not solve the anemia. Octreotide was also unsuccessful, and after attempting angiographic embolization therapy, limited small bowel resection together with antiplasmin therapy managed to correct the anemia and control the exudative enteropathy. CONCLUSIONS: Although primary intestinal lymphangiectasia is usually adequately managed by nutritional therapy, complications such as anemia can occur and can prove to be a therapeutic challenge.

Fingertip rapid point-of-care test in adult case-finding in coeliac disease.

BACKGROUND: Coeliac disease (CD), due to its protean clinical manifestation, is still very under diagnosed in adults and delays in diagnosis may take years and even decades. Simple tools to find cases in primary care may help to identify patients for further diagnostic tests. We have evaluated the usefulness of an on site rapid fingertip whole blood point-of-care test (POCT) for such a purpose. METHODS: As CD is known to run within families, we tested 148 healthy relatives of 70 Romanian index cases with biopsy-proven CD (87% of all first-degree family members, median age 36 years) for the presence of circulating autoantibodies. In addition to performing the POCT (which measures blood erythrocyte self-TG2-autoantibody complexes) on site, blood was drawn for later evaluations of serum IgA-class endomysial antibodies (EMA). EMA-positive sera were further tested for transglutaminase 2 antibodies (TG2-IgA). All serological parameters were analyzed blindly in a centralized laboratory that had no knowledge of the on site POCT result. Endoscopic small intestinal biopsies was recommended for all POCT- or EMA-test positive subjects. RESULTS: In on site testing the POCT was positive in 12/148 first-degree relatives (8%) and all these subjects were also serum EMA-positive. A positive EMA test was found only in one other subject. All remaining 135 healthy first-degree relatives were negative for both POCT and EMA. Four subjects positive for both POCT and EMA were negative for TG2-IgA. Ten out of thirteen of the antibody-positive subjects agreed to undergo endoscopy. The POCT was found to be positive in 8/9 first-degree relatives having coeliac-type mucosal lesions of grade Marsh 2 (n = 3) or Marsh 3 (n = 6). The three POCT-positive subjects not agreeing to undergo endoscopy were also both EMA- and TG2-IgA-positive. CONCLUSION: The fingertip whole blood rapid POCT might fulfill the unmet need for a simple and cheap case-finding biomarker for early detection and presumptive diagnosis of CD. Confirmatory studies are warranted in adult case-finding in specialized outpatient clinics and in primary care.