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

Hepatic safety and efficacy of immunomodulatory drugs used in patients with autoimmune hepatitis.

BACKGROUND AND AIMS There is little data on the hepatic efficacy and safety of immunomodulatory drugs used in patients with autoimmune hepatitis (AIH), despite their established use in dermatology, rheumatology and inflammatory bowel diseases (IBD). Our aim was to collect real-life data on the experience of expert centres in treating AIH patients with these drugs, considered unconventional for AIH management. METHODS Online survey among hepatology centres being part of the European Reference Network on Hepatological Diseases (ERN RARE-LIVER). RESULTS 25 AIH patients have been reported. Ten were female, median age at diagnosis was 28 years; median follow-up was 17 months. All had initially received AIH-standard treatment. AIH-unconventional treatment was initiated for concomitant autoimmune diseases in 15 cases: nine for IBD (five vedolizumab and four ustekinumab), and one each for following diseases: autoinflammatory syndrome (tocilizumab), chronic urticaria (omalizumab), rheumatoid arthritis (abatacept), psoriasis (guselkumab), psoriatric arthritis (secukinumab, followed by ustekinumab) and alopecia (ruxolitinib). Three patients were treated with immunomodulatory drugs for side effects of previous treatments, including two patients with IBD treated with vedolizumab and ustekinumab, respectively, and one treated with belimumab. At the end of follow-up, 13 patients were in complete biochemical response, the patient on omalizumab had a relapse, and four patients with concomitant IBD had insufficient response. Seven patients were treated for lack of biochemical remission, of whom six with belimumab, all initially reaching complete biochemical response, but five relapsing during follow-up; and one with secukinumab, having concomitant rheumatoid arthritis and ankylosing spondylitis, reaching complete biochemical response. Only the patient on abatacept received unconventional treatment as monotherapy. Side effects were reported in two patients on belimumab: one recurrent soft tissue infections, one fatigue and arthralgia. CONCLUSION Among 25 AIH patients who were treated with immunomodulatory drugs for different reasons, the majority had a fovorable course, relapse was frequent in difficult-to-treat patients who received belimumab, and four with concomitant IBD had insufficient response

Sport-Related Portal Vein Thrombosis: An Unusual Complication

Portal vein thrombosis (PVT) is an uncommon condition usually associated with hypercoagulable states or liver cirrhosis. PVT due to sports-related injuries is rarely reported and, to the best of our knowledge, only two cases have been reported thus far. Brazilian jiu-jitsu (BJJ) is a form of martial arts and is considered very safe with minimal risk for injury. It has growing popularity worldwide. Here, we report the first case of PVT secondary to abdominal trauma related to the practice of (BJJ) in an otherwise healthy 32-year-old man with no other traditional risk factors for PVT

Gastrointestinal Tract Disorders in Older Age

Considering an increase in the life expectancy leading to a rise in the elderly population, it is important to recognize the changes that occur along the process of aging. Gastrointestinal (GI) changes in the elderly are common, and despite some GI disorders being more prevalent in the elderly, there is no GI disease that is limited to this age group. While some changes associated with aging GI system are physiologic, others are pathological and particularly more prevalent among those above age 65 years. This article reviews the most important GI disorders in the elderly that clinicians encounter on a daily basis. We highlight age-related changes of the oral cavity, esophagus, stomach, small and large bowels, and the clinical implications of these changes. We review epidemiology and pathophysiology of common diseases, especially as they relate to clinical manifestation in elderly. Details regarding management of specific disease are discussed in detail if they significantly differ from the management for younger groups or if they are associated with significant challenges due to side effects or polypharmacy. Cancers of GI tract are not included in the scope of this article

Epidemiology and risk factors for multi-drug resistant hospital-acquired urinary tract infection in patients with liver cirrhosis: single center experience in Serbia

Abstract Background Cirrhosis-associated immune dysfunction syndrome (CAIDS) has been identified in patients with liver cirrhosis (LC), predisposing them to a wide variety of infections. In patients with LC, healthcare-associated infections involving multi-drug resistant (MDR) bacteria have increased significantly over the last decades. Among them, hospital-acquired urinary tract infections (HA-UTI) are the most common. This study aimed to investigate the rates of antimicrobial resistance among patients with LC and HA-UTI and to determine risk factors associated with their development among patients hospitalized in tertiary care facility in Serbia. Methods This retrospective study included 65 hospitalized patients with LC who had developed HA-UTI. We examined the epidemiology of these infections concerning resistance to the most commonly used antimicrobials and patient-specific risk factors associated with HA-UTI development by MDR pathogens. Results The most frequently isolated organisms were Enterococcus spp. (n = 34, 52.3%), Klebsiella spp. (n = 10, 15.4%), and E.coli (n = 6, 9.2%). Thirty-five isolates (53.8%) were identified as MDR, and 30 (46.2%) were non-MDR.We found a statistically significant difference in the distribution of MDR and non-MDR strains, based on Gram staining, with the majority of Gram-negative pathogens being MDR (p = 0.005). We identified age ≥ 65 years (p = 0.007), previous use of cephalosporins as empiric therapy (p = 0.042), and the presence of hepatic encephalopathy (p = 0.011) as independent risk factors for the development of MDR UTIs. Conclusion This is the first study from Serbia and the Balkans concerning the changing epidemiology of MDR UTI in patients with LC. Our study showed that more than half of HA-UTI was caused by MDR and the most common pathogen was Enterococcus spp. The overall resistance to ceftriaxone was 92%. Our findings underscore the need for institutions to individualize protocols for treatment of hospital-acquired infections, particularly in immunocompromised populations

<i>GSTM1</i> and <i>GSTP1</i> 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

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

Background and Aim. Differentiating iron deficiency anemia (IDA) from anemia of chronic disease (ACD) in patients with inflammatory bowel disease (IBD) represents a clinical challenge. Hepcidin is a polypeptide synthetized in the liver, and iron levels or inflammation mostly regulate hepcidin production. Our aim was to determine serum hepcidin levels in patients with inflammatory bowel disease (IBD) as well to investigate whether hepcidin levels correlate with disease activity. Material and Methods. A case-control study was preformed among newly diagnosed IBD patients and same number age- and sex-matched healthy controls. All patients underwent a total ileocolonoscopy. Complete blood count was obtained in addition to inflammatory markers (CRP, erythrocyte sedimentation rate-ESR). Serum levels of hepcidin were determined with commercially available enzyme-linked immunosorbent assay (DRG Instruments Marburg, Germany). Serum iron, TIBC, and UIBC were assessed with an electrochemiluminesence immunoassay, and soluble transferrin receptor (sTfR) was assessed using an immunoturbidimetric method. Mayo score and CDAI, respectively, were calculated for each patient. Statistical analyses were performed using the SPSS software version 20.0 for Windows. Results. There was a high statistically significant difference between IBD patients and controls in levels of hepcidin (P0.05). 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

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