Upper gastrointestinal bleeding from primary aortoesophageal fistula in a patient with aneurism of the thoracoabdominal aorta: Case report and literature review.

Key Clinical Message: Upper gastrointestinal bleeding due to primary aortoesophageal fistula is a rare clinical condition burdened with high mortality rate. However, the outcomes are closely related to the level of clinical awareness, the complementary and multidisciplinary approach during the diagnostic workup, and the selected treatment option. Abstract: We present an atypical case of an aneurysm of the thoracoabdominal aorta complicated with primary aortoesophageal fistula (AEF). A 55-year-old male with no previous diseases, presented with prolonged and intense back pain and upper gastrointestinal bleeding. The gastroscopy detected an unusual culprit lesion in the distal esophagus resembling an esophageal wall defect, and the computed tomography revealed an aneurysm of the thoracoabdominal aorta, remarkable surrounding hematoma, and active contrast extravasation. Despite the urgent surgical repair, a lethal outcome occurred. AEF patients require high clinical awareness and complementary multidisciplinary approach in order to provide a rapid diagnosis and optimal treatment.

Case report: Rapidly progressive neurocognitive disorder with a fatal outcome in a patient with PU.1 mutated agammaglobulinemia.

Introduction: PU.1-mutated agammaglobulinemia (PU.MA) represents a recently described autosomal-dominant form of agammaglobulinemia caused by mutation of the SPI1 gene. This gene codes for PU.1 pioneer transcription factor important for the maturation of monocytes, B lymphocytes, and conventional dendritic cells. Only six cases with PU.MA, presenting with chronic sinopulmonary and systemic enteroviral infections, have been previously described. Accumulating literature evidence suggests a possible relationship between SPI1 mutation, microglial phagocytic dysfunction, and the development of Alzheimer's disease (AD). Case description: We present a Caucasian female patient born from a non-consanguineous marriage, who was diagnosed with agammaglobulinemia at the age of 15 years when the immunoglobulin replacement therapy was started. During the following seventeen years, she was treated for recurrent respiratory and intestinal infections. At the age of 33 years, the diagnosis of celiac-like disease was established. Five years later progressive cognitive deterioration, unstable gait, speech disturbances, and behavioral changes developed. Comprehensive microbiological investigations were negative, excluding possible infective etiology. Brain MRI, 18FDG-PET-CT, and neuropsychological testing were suggestive for a diagnosis of a frontal variant of AD. Clinical exome sequencing revealed the presence of a novel frameshift heterozygous variant c.441dup in exon 4 of the SPI1 gene. Despite intensive therapy, the patient passed away a few months after the onset of the first neurological symptoms. Conclusion: We describe the first case of PU.MA patient presenting with a rapidly progressive neurocognitive deterioration. The possible role of microglial dysfunction in patients with SPI1 mutation could explain their susceptibility to neurodegenerative diseases thus highlighting the importance of genetic testing in patients with inborn errors of immunity. Since PU.MA represents a newly described form of agammaglobulinemia, our case expands the spectrum of manifestations associated with SPI1 mutation.

Metabolic Associated Fatty Liver Disease (MAFLD) and COVID-19 Infection: An Independent Predictor of Poor Disease Outcome?

Background and Objectives: Early reports on COVID-19 infection suggested that the SARS-CoV-2 virus solely attacks respiratory tract cells. As the pandemic spread, it became clear that the infection is multiorganic. Metabolic associated fatty liver disease (MAFLD) is a chronic liver disease strongly associated with insulin resistance and diabetes. The aim of this study was to assess a possible interplay between MAFLD and COVID-19 infection and its implication in COVID-19 outcome. Materials and Methods: A retrospective observational study, including 130 COVID-19 positive patients was conducted. MAFLD diagnosis was made based on the International Consensus criteria. Patients were divided into two groups, group A (MAFLD) and group B (nonMAFLD). Anthropometric and laboratory analysis were obtained. COVID-19 severity was assessed using the NEWS2 score. Disease outcome was threefold and regarded as discharged, patients who required mechanical ventilation (MV), and deceased patients. Results: MAFLD prevalence was 42%, 67% of patients were discharged, and 19% needed MV. Mortality rate was 14%. MAFLD patients were significantly younger (p < 0.001), and had higher body mass index (p < 0.05), respiratory rate (p < 0.05) and systolic blood pressure (p < 0.05) than nonMAFLD patients. Regarding metabolic syndrome and inflammatory markers: group A had significantly higher glycemia at admission (p = 0.008), lower HDL-c (p < 0.01), higher triglycerides (p < 0.01), CRP (p < 0.001), IL-6 (p < 0.05) and ferritin (p < 0.05) than group B. MAFLD was associated with more prevalent type 2 diabetes (p = 0.035) and hypertension (p < 0.05). MAFLD patients had a more severe disease course (NEWS2 score, 6.5 ± 0.5 vs. 3 ± 1.0, p < 0.05). MAFLD presence was associated with lower patient discharge (p < 0.01) and increased need for MV (p = 0.024). Multiple regression analysis showed that BMI (p = 0.045), IL-6 (p = 0.03), and MAFLD (p < 0.05) are significant independent risk factors for a poor COVID-19 outcome. Conclusions: The prevalence of MAFLD is relatively high. MAFLD patients had a more severe COVID-19 clinical course and worse disease outcome. Our results imply that early patient stratification and risk assessment are mandatory in order to avoid poor outcomes.

The Role of Endothelial Dysfunction in the Pathogenesis of Pregnancy-Related Pathological Conditions: A Review.

In the recent decades, endothelial dysfunction (ED) has been recognized as a significant contributing factor in the pathogenesis of many pathological conditions. In interaction with atherosclerosis, hypercholesterolemia, and hypertension, ED plays a crucial role in the pathogenesis of coronary artery disease, chronic renal disease, and microvascular complications in diabetes mellitus. Although ED plays a significant role in the pathogenesis of several pregnancy-related disorders such as preeclampsia, HELLP syndrome, fetal growth restriction, and gestational diabetes mellitus, the exact pathogenetic mechanisms are still a matter of debate. The increased prevalence of these entities in patients with preexisting vascular diseases highlights the essential pathological role of the preexisting ED in these patients. The abnormal uteroplacental circulation and the release of soluble factors from the ischemic placenta into the maternal bloodstream are the main causes of the maternal ED underlying the characteristic preeclamptic phenotype. Besides the increased risk for maternal and fetal poor outcomes, the preexisting ED also increases the risk of development of future cardiovascular diseases in these patients. This study aimed to look deeper into the role of ED in the pathogenesis of several pregnancy-related hypertensive and liver diseases. Hopefully, it could contribute to improvement of the awareness, knowledge, and management of these conditions and also to the reduction of the adverse outcomes and additional long-term cardiovascular complications.

Current Trends in the Management of Helicobacter pylori Infection in Serbia: Preliminary Results from the European Registry on H. pylori Management.

BACKGROUND: Helicobacter pylori (H. pylori) is the most common chronic bacterial infection. Treatment effectiveness remains a subject of debate considering bacterial antimicrobial resistance. Our aim was to analyze the diagnostic methods and eradication treatments for H. pylori infection in Serbia. METHODS: An observational multicenter prospective study was conducted in Serbia, as part of the European Registry on H. pylori Management (Hp-EuReg). Demographics, treatment indication, diagnostic methods, previous eradication attempts, and treatment were collected at AEG-REDCap e-CRF. Modified intention-to-treat (mITT) and per-protocol (PP) effectiveness analyses were performed. Safety, compliance, and bacterial antimicrobial resistance rates were reported. Data were quality checked. RESULTS: Overall, 283 patients were included, with a mean age of 55 ± 15 years. Dyspepsia (n = 214, 77%) was the most frequent treatment indication, and histology (n = 144, 51%) was the most used diagnostic method. Overall eradication rate was 95% (PP) and 94% (mITT). Most prevalent first-line therapy was quadruple PPI + clarithromycin + amoxicillin + metronidazole, with a 96% effectiveness (p < 0.001). Second-line main treatment choice was triple amoxicillin + levofloxacin, with a 95% effectiveness (p < 0.05). Single-capsule Pylera® was the most prescribed third-line therapy, with 100% effectiveness (p < 0.05). Longer treatment duration was associated with a higher eradication rate in first-line therapy (p < 0.05). Clarithromycin and quinolone resistance rates in first-line were 24% and 8.3%, respectively. The overall adverse events' incidence rate was 13.4%, and therapy compliance was 97%. CONCLUSIONS: Considering the high eradication rate, 14-day non-bismuth quadruple concomitant therapy is a reasonable first-line choice, while quinolone-based therapy and single-capsule Pylera® should be considered as rescue therapy options.

Fatal gastrointestinal bleeding associated with acute pancreatitis as a complication of Covid-19: a case report.

Clinical manifestations of Covid-19 vary widely among patients. Recent studies suggest that up to 15% of patients with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections develop gastrointestinal symptoms. The location of virus-host cell receptors angiotensin-converting enzyme 2 and transmembrane serine protease 2 has an important role in the pathophysiology and presentation of disease. They are expressed in the respiratory tract, as well as other organs and tissues including exocrine and endocrine pancreatic cells. These cells are therefore a possible target for the virus, which could explain the relationship between SARS-CoV-2 infection and pancreatic injury. We report a disastrous collateral effect of the Covid-19 pandemic on a 33-year-old man with chronic renal insufficiency and asymptomatic SARS-CoV-2 infection, who developed acute pancreatitis. Inflammation progressed rapidly toward necrosis and the development of a peripancreatic pseudoaneurysm which subsequently ruptured, causing death.

Diagnostic Value of Non-invasive Scoring Systems in the Prediction of Esophageal Varices in Patients with Liver Cirrhosis-Single Center Experience.

Background and Objectives: Upper endoscopy is considered the gold standard for screening and diagnosis of esophageal varices (EV). Non-invasive methods for predicting EV have become a research hotspot in recent years. The aim of this study was to assess the role of non-invasive scores in predicting the presence of EV in patients with liver cirrhosis, and to determine the value of these scores in predicting the outcome of patients with cirrhosis presenting with acute variceal bleeding. Materials and Methods: A total of 386 patients with liver cirrhosis were included. The model for end-stage liver disease (MELD), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AST/ALT), AST to platelet ratio index (APRI), fibrosis-4-index (FIB-4), fibrosis index (FI), King's Score, albumin-bilirubin (ALBI) score, and platelet-albumin-bilirubin (PALBI) score were calculated. The discriminatory capacities of the examined scores in predicting the presence of esophageal varices were tested using receiver operating characteristic (ROC) curves. Results: The ROC curve analysis showed (area under the curve) AUC values of ALBI and PALBI of 0.603, and 0.606, respectively, for the prediction of EV. APRI, MELD, PALBI, King's, FIB-4, and ALBI scores showed statistically significant correlation with EV bleeding (p < 0.05). AUC of APRI and MELD for predicting EV bleeding were 0.662 and 0.637, respectively. The AUC value of MELD in short-term mortality was 0.761. Conclusions: ALBI and PALBI scores had modest diagnostic accuracy of EVs in liver cirrhosis. APRI and MELD can be used as a reference index for the EV bleeding, and MELD score is best associated with short-term outcome in cirrhotic patients.

Interplay between chronic hepatitis B and atherosclerosis: Innovative perspectives and theories.

Elaboration of carotid atherosclerosis in the setting of hepatitis B virus (HBV) infection should emphasize the significance of extrahepatic manifestations of the infection pathogenesis. Diverse processes comprise the pathoevolution of HBV infection, rendering it a multi-systemic disease in its essence. Our work not only exemplified atherosclerosis as an often-underestimated contributor to the severity of HBV infection but has also highlighted the bidirectional relationship between the two. Therefore, it is suggested that HBV-induced inflammation is one of the root causes of atherosclerosis, which in turn has a consequent effect on the severity of the chronic infection disease state, creating a vicious cycle. Additionally, we coupled prior data with the current concepts of HBV infection to postulate intriguing perspectives and theories.

Dyspepsia Challenge in Primary Care Gastroenterology.

BACKGROUND: The purpose of this review is to take a deep dive into general problems and challenges of diagnosis and treatment of patients with symptoms of dyspepsia in primary care practice. SUMMARY: Primary care physicians become acquainted with a broad range of clinical problems and therefore require a wide span of knowledge in taking care of patients from their first medical examination within the health care system. Dyspepsia and Helicobacter pylori infection are two of the most frequent reasons of digestive-related health care issues, despite that in primary care practice, current recommendations for diagnosis and differential therapy are often not implemented. The "test-and-treat" strategy is the initial management of the condition, reserving gastroscopy for patients refractory to symptomatic treatment and for patients presenting with any of the following alarm signs: age of above 55, dysphagia, anemia, weight loss, frequent vomiting, family history of GI malignancy, or a physical examination with key pathological findings. KEY MESSAGES: Examination and treatment of dyspepsia symptoms is the diagnostic and therapeutic challenge dictated by organizational and economic potentials of the health system, professional resources, and primary health care capabilities to accept and treat patients with dyspepsia and to properly refer those with alarm symptoms and findings indicative of organic disease to a gastroenterologist.

Enhanced Liver Fibrosis Score as a Biomarker for Vascular Damage Assessment in Patients with Takayasu Arteritis-A Pilot Study.

Takayasu Arteritis (TA) is characterized by granulomatous panarteritis, vessel wall fibrosis, and irreversible vascular impairment. The aim of this study is to explore the usefulness of the Enhanced Liver Fibrosis score (ELF), procollagen-III aminoterminal propeptide (PIIINP), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and hyaluronic acid (HA) in assessing vascular damage in TA patients. ELF, PIIINP, TIMP-1, and HA were measured in 24 TA patients, and the results were correlated with the clinical damage indexes (VDI and TADS), an imaging damage score (CARDS), and disease activity scores (NIH and ITAS2010). A mean ELF score 8.42 (±1.12) and values higher than 7.7 (cut-off for liver fibrosis) in 21/24 (87.5%) of patients were detected. The VDI and TADS correlated significantly to ELF (p < 0.01). Additionally, a strong association across ELF and CARDS (p < 0.0001), PIIINP and CARDS (p < 0.001), and HA and CARDS (p < 0.001) was observed. No correlations of the tested biomarkers with inflammatory parameters, NIH, and ITAS2010 scores were found. To our knowledge, this is the first study that suggests the association of the serum biomarkers PIIINP, HA, and ELF score with damage but not with disease activity in TA patients. The ELF score and PIIINP may be useful biomarkers reflecting an ongoing fibrotic process and quantifying vascular damage.

Perineural invasion as a prognostic factor in patients with stage I-III rectal cancer - 5-year follow up.

BACKGROUND: Rectal cancer (RC) is one of the most common diagnosed cancers, and one of the major causes of cancer-related death nowadays. Majority of the current guidelines rely on TNM classification regarding therapy regiments, however recent studies suggest that additional histopathological findings could affect the disease course. AIM: To determine whether perineural invasion alone or in combination with lymphovascular invasion have an effect on 5-years overall survival (OS) of RC patients. METHODS: A prospective study included newly diagnosed stage I-III RC patients treated and followed at the Digestive Surgery Clinic, Clinical Center of Serbia, between the years of 2014-2016. All patients had their diagnosis histologically confirmed in accordance with both TMN and Dukes classification. In addition, the patient's demographics, surgical details, postoperative pathological details, differentiation degree and their correlation with OS was investigated. RESULTS: Of 245 included patients with stage I-III RC, lymphovascular invasion (LVI) was identified in 92 patients (38%), whereas perineural invasion (PNI) was present in 46 patients (19%). Using Kaplan-Meier analysis for overall survival rate, we have found that both LVI and PNI were associated with lower survival rates (P < 0.01). Moreover when Cox multiple regression model was used, LVI, PNI, older age, male gender were predictors of poor prognosis (HR = 5.49; 95%CI: 2.889-10.429; P < 0.05). CONCLUSION: LVI and PNI were significant factors predicting worse prognosis in early and intermediate RC patients, hence more aggressive therapy should be reserved for these patients after curative resection.

Multiple Myeloma Associated Intestinal Amyloidosis: Intestinal Pseudoobstruction Falsely Considered as an Ascites.

INTRODUCTION: Amyloidosis is a group of diseases pathohistologically diagnosed by characteristic extracellular deposition of an abnormal fibrillary protein (i.e. amyloid) into organs, leading to organ dysfunction secondary to destruction of normal tissue architecture. METHODS: Case-report of a 44 year-old female, presenting with massive abdominal distension clinically suspected of ascites. RESULTS: On admission, the patient was complaining of nausea, vomiting, abdominal pain, distension and bloating associated with weight loss and diarrhoea. Her prior medical history revealed a treatment naïve viral hepatitis C (HCV) infection with normal liver tests. She was on long term haemodialysis due to end-stage renal disease. Based on clinical, laboratory and radiology findings we established the diagnosis of light chain amyloidosis associated with multiple myeloma, complicated with amyloid bowel depositions and intestinal pseudo-obstruction. On imaging, diffuse liver enlargement was seen. Liver biopsy could have rendered the possible cause of hepatomegaly, but patient's noncompliance hindered the answer whether liver involvement was the consequence of a chronic hepatitis due to HCV infection or amyloid accumulation. Unfortunately, consequent patient's death prevented specific treatment implementation. CONCLUSION: Patients with multiple myeloma and obscure abdominal complaints should be worked up for amyloidosis. Intestinal pseudo-obstruction due to amyloidosis can imitate in certain instances ascites hence complicating diagnostic algorithm. In such complex clinical cases, close collaboration between surgeon, gastroenterohepatologist and haematologist is necessary.