GSTM1 and GSTP1 Polymorphisms Affect Outcome in Colorectal Adenocarcinoma.

Background and Objectives: Despite improvements in screening programs, a large number of patients with colorectal cancer (CRC) are diagnosed in an advanced disease stage. Previous investigations imply that glutathione transferases (GSTs) might be associated with the development and progression of CRC. Moreover, the detoxification mechanism of oxaliplatin, which represents the first line of treatment for advanced CRC, is mediated via certain GSTs. The aim of this study was to evaluate the significance of certain GST genetic variants on CRC prognosis and the efficacy of oxaliplatin-based treatment. Materials and Methods: This prospective study included 523 patients diagnosed with CRC in the period between 2014 and 2016, at the Digestive Surgery Clinic, University Clinical Center of Serbia, Belgrade. Patients were followed for a median of 43.47 ± 17.01 months (minimum 1-63 months). Additionally, 109 patients with advanced disease, after surgical treatment, received FOLFOX6 treatment as a first-line therapy between 2014 and 2020. The Kaplan-Meier method was used to analyze cumulative survival, and the Cox proportional hazard regression model was used to study the effects of different GST genotypes on overall survival. Results: Individuals with the GSTM1-null genotype and the GSTP1 IleVal+ValVal (variant) genotype had significantly shorter survival when compared to referent genotypes (GSTM1-active and GSTP1 IleIle) (log-rank: p = 0.001). Moreover, individuals with the GSTM1-null genotype who received 5-FU-based treatment had statistically significantly shorter survival when compared to individuals with the GSTM1-active genotype (log-rank: p = 0.05). Conclusions: Both GSTM1-null and GSTP1 IleVal+ValVal (variant) genotypes are associated with significantly shorter survival in CRC patients. What is more, the GSTM1-null genotype is associated with shorter survival in patients receiving FOLOFOX6 treatment.

Clinical Indicators of Bone Deterioration in Alcoholic Liver Cirrhosis and Chronic Alcohol Abuse: Looking beyond Bone Fracture Occurrence.

Although previous studies indicated that chronic alcohol abuse (CAA) and alcoholic liver cirrhosis (ALC) are associated with increased bone fragility, understanding bone fragility determinants is still modest in these individuals. We used a comprehensive individualized clinical fracture risk assessment approach (vertebral osteodensitometry, femoral osteodensitometry and geometry, and serum bone turnover biomarkers) to compare adult male patients with ALC who have not previously had femoral or vertebral fractures (n = 39), patients with CAA (without liver cirrhosis, n = 78) who have not previously had femoral or vertebral fractures and healthy age- and sex-matched controls (n = 43). Our data suggested that intertrochanteric bone mineral density was significantly lower in ALC and CAA patients than in controls. Also, the trabecular bone score was considerably lower in ALC patients compared with CAA and control individuals. The most significant inter-group differences in femoral geometry were noted on the femoral shaft. Patients with ALC and CAA have a higher 10-year risk of major osteoporotic fractures compared to the controls. Analysis of bone turnover biomarkers showed increased osteoprotegerin and beta-C-terminal telopeptide serum concentrations and decreased insulin growth factor-1 concentrations in patients with ALC compared to CAA and control groups. Our data revealed that bone alterations are present in patients with ALC and CAA even if they did not sustain a nontraumatic bone fracture, but it is also indicative that current bone-assessing clinical methods are not entirely reliable. Thus, future studies should focus on developing a reliable integrative clinical tool that can be used to accurately predict and prevent bone fracture occurrences in patients with ALC and CAA.

The Importance of Artificial Intelligence in Upper Gastrointestinal Endoscopy.

Recently, there has been a growing interest in the application of artificial intelligence (AI) in medicine, especially in specialties where visualization methods are applied. AI is defined as a computer's ability to achieve human cognitive performance, which is accomplished through enabling computer "learning". This can be conducted in two ways, as machine learning and deep learning. Deep learning is a complex learning system involving the application of artificial neural networks, whose algorithms imitate the human form of learning. Upper gastrointestinal endoscopy allows examination of the esophagus, stomach and duodenum. In addition to the quality of endoscopic equipment and patient preparation, the performance of upper endoscopy depends on the experience and knowledge of the endoscopist. The application of artificial intelligence in endoscopy refers to computer-aided detection and the more complex computer-aided diagnosis. The application of AI in upper endoscopy is aimed at improving the detection of premalignant and malignant lesions, with special attention on the early detection of dysplasia in Barrett's esophagus, the early detection of esophageal and stomach cancer and the detection of H. pylori infection. Artificial intelligence reduces the workload of endoscopists, is not influenced by human factors and increases the diagnostic accuracy and quality of endoscopic methods.

Accidental Sewing Pin Ingestion by a Tailor: A Case Report and Literature Review.

Foreign body ingestion is a frequently encountered emergency in healthcare institutions. It mostly affects pediatric populations, although it can also affect adults with developmental delays, those with psychiatric diseases, drug abusers, and prisoners. Endoscopy is a diagnostic and treatment method for suspected foreign body ingestion. In this article, we discuss a 45-year-old tailor who swallowed a sewing pin while at work. The abdominal X-ray showed a needle-shaped metal shadow in the stomach region. During an upper endoscopy, it was discovered that a sewing pin with a sharp edge was stuck in the pylorus. The sewing pin was extracted endoscopically, and the patient was discharged the same day in good condition. Since the estimated risk of complications of foreign body ingestion in the adult population is about 35%, and the most common complications include impaction, laceration, bleeding, or perforation of the gastrointestinal wall, endoscopic or surgical removal is necessary. This also emphasizes the importance of a careful endoscopic evaluation of some at-risk occupations for foreign body ingestion with or without gastrointestinal complaints.

Hematological Indices Are Useful in Predicting Complications of Liver Cirrhosis.

BACKGROUND: Liver cirrhosis is the final stage of chronic liver disease. We aimed to evaluate non-invasive scores as predictors of complications and outcome in cirrhotic patients. METHODS: A total of 150 cirrhotic patients were included. Models for end-stage liver disease (MELD), albumin-bilirubin (ALBI) score, neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MoLR), and neutrophil-lymphocyte-albumin ratio (NLA) scores were tested in relation to the development of complications and mortality using receiver operating characteristic (ROC) curves. RESULTS: The ROC curve analysis showed (area under the curve) AUC values of NLR, NLA, ALBI, and MELD of 0.711, 0.730, 0.627, and 0.684, respectively, for short-term mortality. MELD, ALBI, and NLA scores showed a statistically significant correlation with hepatic encephalopathy (p = 0.000 vs. 0.014 vs. 0.040, respectively), and the MELD cut-off value of 16 had a sensitivity of 70% and a specificity of 52% (AUC: 0.671, 95% CI (0.577-0.765)). For the assessment of the presence of ascites, the AUC values for NLA and MoLR were 0.583 and 0.658, respectively, with cut-offs of 11.38 and 0.44. CONCLUSIONS: MELD, ALBI, and NLA are reliable predictors of hepatic encephalopathy. NLA and MoLR showed a significant correlation with the presence of ascites, and MELD, ALBI, NLR, and NLA have prognostic value to predict 30-day mortality in cirrhotic patients.

The Quality of Life After Liver Transplantation-The First Experience from Serbia.

Background: Liver transplantation (LT) is the most effective treatment for patients with end-stage liver disease, which dramatically effects patient's quality of life (QoL). The aim of this study was to evaluate the impact of socio-demographic and clinical factors on different QoL domains of patients who underwent orthotopic LT. Methods: A cross-sectional study included a total of 43 patients who underwent a LT from 2013 to 2018. Socio-demographic and clinical data were recorded in each patient. The QoL was estimated using two validated questionnaires: 36-Item Short Form Health Survey (SF-36) and Chronic Liver Disease Questionnaire (CLDQ). Results: Male patients obtained significantly higher scores than women, in the domains of general health perception (83.2 ± 16.3 vs. 71.0 ± 18.4; t = 2.229, p = .031) and physical component summary (69.0 ± 7.2 vs. 62.0 ± 11.4; t = 2.451, p = .019). There were no significant differences in other domains of SF-36 and CLDQ. Etiology of the underlying liver disease and the presence of post-transplant complications showed no effect on score values of SF-36 and CDLQ domains (p < .05). Time from LT showed negative medium correlation with role limitations due to physical health problems (S = -0.417, p = .005), while no other significant correlations were noted in other items of SF-36 and CLDQ. Conclusions: Men had higher scores in the domain of general health perception and physical component summary following LT than women. With the increase in time from LT, patients experience a decrease in limitations due to physical health problems. The audit and improvement of QoL is an essential part of the individualized long-term health-care approach to LT patients.

Evaluating ground glass opacities (GGO) in the COVID-19 era. Do autoantibodies help?

INTRODUCTION: COVID-19 is an infectious disease, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and there have been outbreaks worldwide. The presentation may include unspecific and mild symptoms, myalgia, headaches, high fever, dry cough, severe dyspnea and acute respiratory distress syndrome (ARDS). CASE STUDY: We present a rare case of microscopic polyangiitis (MPA) with interstitial lung disease and without renal involvement misdiagnosed as COVID-19. CONCLUSIONS: Differential diagnosis of COVID-19 is extremely important, and must be correctly identified in order to proceed with correct treatment.

Genetic Aspects of Micronutrients Important for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC) are complex diseases whose etiology is associated with genetic and environmental risk factors, among which are diet and gut microbiota. To date, IBD is an incurable disease and the main goal of its treatment is to reduce symptoms, prevent complications, and improve nutritional status and the quality of life. Patients with IBD usually suffer from nutritional deficiency with imbalances of specific micronutrient levels that contribute to the further deterioration of the disease. Therefore, along with medications usually used for IBD treatment, therapeutic strategies also include the supplementation of micronutrients such as vitamin D, folic acid, iron, and zinc. Micronutrient supplementation tailored according to individual needs could help patients to maintain overall health, avoid the triggering of symptoms, and support remission. The identification of individuals' genotypes associated with the absorption, transport and metabolism of micronutrients can modify future clinical practice in IBD and enable individualized treatment. This review discusses the personalized approach with respect to genetics related to micronutrients commonly used in inflammatory bowel disease treatment.

Autoimmune and immunoserological markers of COVID-19 pneumonia: Can they help in the assessment of disease severity.

Background: Immune dysregulation and associated inefficient anti-viral immunity during Coronavirus Disease 2019 (COVID-19) can cause tissue and organ damage which shares many similarities with pathogenetic processes in systemic autoimmune diseases. In this study, we investigate wide range autoimmune and immunoserological markers in hospitalized patients with COVID-19. Methods: Study included 51 patients with confirmed Severe Acute Respiratory Syndrome Coronavirus 2 infection and hospitalized due to COVID-19 pneumonia. Wide spectrum autoantibodies associated with different autoimmune inflammatory rheumatic diseases were analyzed and correlated with clinical and laboratory features and pneumonia severity. Results: Antinuclear antibodies (ANA) positivity was found in 19.6%, anti-cardiolipin IgG antibodies (aCL IgG) in 15.7%, and anti-cardiolipin IgM antibodies (aCL IgM) in 7.8% of patients. Positive atypical x anti-neutrophil cytoplasmic antibodies (xANCA) were detected in 10.0% (all negative for Proteinase 3 and Myeloperoxidase) and rheumatoid factor was found in 8.2% of patients. None of tested autoantibodies were associated with disease or pneumonia severity, except for aCL IgG being significantly associated with higher pneumonia severity index (p = 0.036). Patients with reduced total serum IgG were more likely to require non-invasive mechanical ventilation (NIMV) (p < 0.0001). Serum concentrations of IgG (p = 0.003) and IgA (p = 0.032) were significantly lower in this group of patients. Higher total serum IgA (p = 0.009) was associated with mortality, with no difference in serum IgG (p = 0.115) or IgM (p = 0.175). Lethal outcome was associated with lower complement C4 (p = 0.013), while there was no difference in complement C3 concentration (p = 0.135). Conclusion: Increased autoimmune responses are present in moderate and severe COVID-19. Severe pneumonia is associated with the presence of aCL IgG, suggesting their role in disease pathogenesis. Evaluation of serum immunoglobulins and complement concentration could help assess the risk of non-invasive mechanical ventilation NIMV and poor outcome.

Intestinal Ultrasonography as a Tool for Monitoring Disease Activity in Patients with Ulcerative Colitis.

Background: Ultrasonography is a noninvasive, inexpensive, and widely available diagnostic tool. In the last two decades, the development of ultrasound techniques and equipment has significantly increased the usage of intestine ultrasound (US) in the assessment of the gastrointestinal tract in patients with inflammatory bowel disease (IBD). Although current guidelines suggest routine utilization of US in patients with Crohn's disease, data regarding US usage in ulcerative colitis are still scarce. We aimed to assess the reliability of intestinal ultrasonography in the assessment of disease activity and extension of patients with ulcerative colitis. Methods: Fifty-five patients with a histologically confirmed diagnosis of ulcerative colitis, treated at University Clinical Center of Serbia in the period from 2019 to 2022 were included in this retrospective observational study. The data were obtained from the patient's medical records including history, laboratory, US, and endoscopy findings. US examined parameters were as following: bowel wall thickness (BWT), presence of fat wrapping, wall layer stratification, mesenteric hypertrophy, presence of enlarged mesenteric lymph nodes, and absence or presence of ascites. Results: Our results suggest that there is a strong correlation of BWT and colonoscopy findings regarding disease extension (r = 0.524, p=0.01, p < 0.05). Furthermore, our results have shown a statistically significant correlation of BWT with the Mayo endoscopic score (r = 0.434, p=0.01, p < 0.05), disease activity score (r = 0.369,p=0.01, p < 0.05), degree of ulcerative colitis burden of luminal inflammation (r = 0.366, p=0.01, p < 0.05), and Geboes index (r = 0.298, p=0.027, p < 0.05). Overall accuracy of US for disease extension and activity was statistically significant (p < 0.05). Conclusions: Our results suggest that US is a moderately accurate method for the assessment of disease activity and localization in patients with UC.

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.

Abnormal Liver Blood Tests: Hepatologist Approach.

BACKGROUND: Available data suggest that the prevalence of chronic liver disease (CLD) and primary liver cancer is rising in Europe and represents a major public health problem. Predictions are showing that these trends will continue to rise in the upcoming years. SUMMARY: Alcohol-related liver disease, nonalcohol fatty liver disease, and viral hepatitis B and hepatitis C are the leading causes of liver cirrhosis and primary liver cancer in Europe. Drug-induced liver injury represents a major cause of acute hepatitis, while liver transplantation is the second most common solid organ transplantation in the world. Patients with CLD have increasing rates of hospitalization, longer hospital stays, and more adverse outcomes compared to the other chronic conditions. Direct targeting of risk factors can prevent complications of advanced liver disease and improve outcome. Patients with CLD should be referred to a hepatologist for assessment of the stage of liver disease, for specific treatment and screening for hepatocellular carcinoma. Moreover, patients with unknown etiology of abnormal liver blood tests should be referred to a hepatologist for assessment of liver disease, as well as for prevention and treatment of complications of cirrhosis and/or portal hypertension. Key Messages: CLD is amenable to prevention and treatment, while disease management strategies need to improve in order to reduce the burden of liver disease and deaths due to end-stage liver diseases.

Jaundice as a Diagnostic and Therapeutic Problem: A General Practitioner's Approach.

BACKGROUND: Jaundice is a common clinical finding in clinical practice of hepatologists and general practitioners. It occurs when serum bilirubin levels exceed 3 mg/dL. SUMMARY: In this review, we summarize the pathophysiological mechanism of jaundice, clinical approach to the patient with jaundice, and laboratory and imaging techniques. Clinical presentation of jaundice manifests through yellow skin and sclera coloration. Evaluation of every patient includes detailed medical history and examination. In the laboratory, evaluation of enzymes of hepatic inflammation as well as cholestatic enzymes with serum bilirubin must be included. Additional laboratory analysis and imaging modalities are needed in order to differentiate jaundice etiology. Moreover, imaging is available and needed in further evaluation, and treatment is dependent on the underlying cause. KEY MESSAGES: In this review, we will outline the pathophysiological mechanism of jaundice, clinical approach to the patient with jaundice, and diagnostic and treatment approach to these patients.

Recommendations for the diagnosis and management of transthyretin amyloidosis with gastrointestinal manifestations.

Transthyretin amyloid (ATTR) amyloidosis is an adult-onset, rare systemic disorder characterized by the accumulation of misfolded fibrils in the body, including the peripheral nerves, the heart and the gastrointestinal tract. Gastrointestinal manifestations are common in hereditary (ATTRv) amyloidosis and are present even before the onset of the polyneuropathy in some cases. Delays in diagnosis of ATTRv amyloidosis with gastrointestinal manifestations commonly occur because of fragmented knowledge among gastroenterologists and general practitioners, as well as a shortage of centers of excellence and specialists dedicated to disease management. Although the disease is becoming well-recognized in the societies of Neurology and Cardiology, it is still unknown for most gastroenterologists. This review presents the recommendations for ATTRv amyloidosis with gastrointestinal manifestations elaborated by a working group of European gastroenterologists and neurologists, and aims to provide digestive health specialists with an overview of crucial aspects of ATTRv amyloidosis diagnosis to help facilitate rapid and accurate identification of the disease by focusing on disease presentation, misdiagnosis and management of gastrointestinal symptoms.

Bacteremia in patients with liver cirrhosis in the era of increasing antimicrobial resistance: single-center epidemiology.

INTRODUCTION: Liver cirrhosis is commonly associated with bacterial infections, which contribute to unfavorable outcome. This study aimed to investigate the epidemiology of bacteremia and patterns of antibiotic resistance in patients with cirrhosis, factors associated with multidrug-resistant infection, and predictors of mortality. METHODOLOGY: This retrospective single-center study included patients with cirrhosis treated between January 2016 and December 2018. Data were collected from the patients' medical records. The severity of liver disease was determined using the Child-Pugh, Model for End-Stage Liver Disease-Na, Chronic Liver Failure-Consortium Acute-on-Chronic Liver Failure, and Chronic Liver Failure-Consortium Acute Decompensation scores. RESULTS: A total of 85 patients with cirrhosis and bacteremia were included (male: 82.4%, mean age 60.3 ± 9.4 years). The etiology of cirrhosis was mainly alcoholism (87.1%). After 30 days, lethal outcome occurred in 44.7% of the patients. The most commonly isolated pathogens were Enterococcus spp. (31.8%), methicillin-sensitive Staphylococcus aureus (15.3%), and Escherichia coli (14.1%), while 37.3% of all isolated microorganisms were multi-drug resistant. Multi-drug resistant infection [odds ratio (OR): 6.198, 95% confidence interval (CI): 2.326-17.540, p = 0.006] and neutrophil-to-lymphocyte ratio (OR = 1.181, 95% CI = 1.043-1.337, p = 0.009) are independent predictors of mortality. The aforementioned scores, which represent the extent of hepatic insufficiency, are significantly higher in patients with multi-drug resistant isolates, while multi-drug resistant bacteremia was more common in patients with more advanced liver disease. CONCLUSIONS: Multi-drug resistant bacteremia is more common in patients in whom liver disease is more severe and is a major independent predictor of mortality.

Hepcidin Is a Reliable Marker of Iron Deficiency Anemia in Newly Diagnosed Patients with Inflammatory Bowel Disease.

RESULTS: There was a high statistically significant difference between IBD patients and controls in levels of hepcidin (P < 0.01). Namely, serum hepcidin levels were significantly higher in the control group. There was no statistically significant correlation of serum hepcidin with CRP, Mayo score, or CDAI, respectively (P > 0.05). However, we have found a statistically significant negative correlation of sTfR and TIBC with hepcidin (P < 0.01). CONCLUSION: Results of our study suggest that hepcidin is a reliable marker of IDA in patients with IBD, and it could be used in routine clinical practice when determining adequate therapy in these patients.

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.

Correlation of Patient-Reported Outcome (PRO-2) with Endoscopic and Histological Features in Ulcerative Colitis and Crohn's Disease Patients.

METHODS: A cross-sectional study was conducted in consecutive newly diagnosed patients with inflammatory bowel disease in a tertiary care referral center. The initial evaluation included patient-reported outcome for stool frequency subscore and rectal bleeding. Endoscopic activity was determined using the Mayo scoring system for ulcerative colitis and the Simple Endoscopic Score for Crohn's disease. Histopathological activity was assessed using a validated numeric scoring system. RESULTS: We included 159 patients (63 Crohn's disease with colonic involvement and 96 with ulcerative colitis). We found significant correlation between the Mayo endoscopic subscoring system and histology activity in ulcerative colitis, while no correlation was found in patients with Crohn's disease. Patient-reported outcome showed inverse correlation with endoscopic and histological activity in Crohn's disease (r s = -0.67; r s = -0.72), while positive correlation was found in ulcerative colitis (r s = 0.84; r s = 0.75). Interpretation and Conclusions. Patient-reported outcome is a practical and noninvasive tool for assessment of disease activity in ulcerative colitis patients but not in Crohn's disease.