ABSTRACT
Functional gastrointestinal system disorders are common problems in practice. The most common symptoms are abdominal pain, gas, bloating, diarrhea, constipation, and a mixture of these, and similar symptoms can be seen in conditions such as inflammatory bowel disease, colorectal cancer, and celiac disease depending on the age of the patient, indicating the importance of differential diagnosis. The importance of patient management is shown by making a symptom-based diagnosis and making cost-effective, that is, limited advanced examinations. The pathophysiology of irritable bowel syndrome (IBS) is multifactorial, and stress is one of the leading triggers of IBS symptoms. Therefore, terminology will change to gut-brain interaction disorders in the future, and the patient-physician relationship has a special place in the treatment of functional bowel disorder. Dietary recommendation and medical treatment in IBS should be determined according to the predominant symptom and symptom severity. In addition to diet, some lifestyle changes can also be helpful in reducing IBS symptoms. Antispasmodics and antidepressants are not fast-acting. These drugs should be used for at least 2-4 weeks to see the efficacy of treatment. Drugs should be used according to the standard recommended duration and dose in intermittent treatments.
Subject(s)
Irritable Bowel Syndrome , Humans , Irritable Bowel Syndrome/therapy , Diagnosis, Differential , Antidepressive Agents/therapeutic use , Parasympatholytics/therapeutic use , Gastrointestinal Diseases/therapy , Gastrointestinal Diseases/etiology , Constipation/therapy , Constipation/etiologyABSTRACT
BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens. METHODS: We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP. RESULTS: We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054-3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose. CONCLUSIONS: Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens.
Subject(s)
Autoimmune Pancreatitis , Humans , Male , Middle Aged , Female , Retrospective Studies , Autoimmune Pancreatitis/drug therapy , Autoimmune Pancreatitis/diagnosis , Europe , Aged , Treatment Outcome , Adult , Steroids/therapeutic use , Steroids/administration & dosage , Aged, 80 and overABSTRACT
BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a popular weight loss procedure with potential effects on gastroesophageal reflux disease (GERD). However, research on the association between LSG and GERD using objective evaluation criteria, such as multichannel intraluminal impedance combined with pH testing (MII-pH), is limited. This study aimed to investigate the impact of LSG on GERD using MII-pH and current consensus guidelines. MATERIALS AND METHODS: It was conducted as a prospective clinical study on 33 patients who underwent LSG between January 2022 and August 2022. MII-pH and high-resolution manometry were performed preoperatively and 3 to 6 months postoperatively. GERD diagnosis was based on MII-pH results using the Lyon and Update Porto consensus guidelines. RESULTS: Postoperative MII-pH analysis revealed a significant increase in acid reflux time, acid exposure time, reflux index, esophageal clearance, total reflux time, and longest reflux period. Weak acid reflux episodes decreased, while Demeester score and alkaline reflux showed nonsignificant increases. Pathologic reflux significantly increased postoperatively based on MII-pH diagnosis. High-resolution manometry showed a significant increase in unsuccessful motility. CONCLUSION: Although the Demeester score calculation consists of 6 metrics, including acid exposure time, the acid exposure time is more specific in detecting pathologic reflux. Pathologic GERD increases significantly with LSG in the early period. Therefore, preoperative and postoperative endoscopy and MII-pH can provide valuable information regarding the need for closer follow-up after LSG.
Subject(s)
Gastroesophageal Reflux , Laparoscopy , Humans , Prospective Studies , Electric Impedance , Esophageal pH Monitoring/methods , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/etiology , Gastroesophageal Reflux/surgery , Gastrectomy/methods , Manometry , Hydrogen-Ion Concentration , Laparoscopy/methodsABSTRACT
Crohn's disease is an inflammatory, autoimmune disorder that predominantly affects the intestines but can also affect extraintestinal organs. Certain neurological conditions, such as autoimmune encephalitis, can develop along with this disease. In this case report, we present a case of anti-glutamic acid decarboxylase (GAD) antibody-associated autoimmune encephalitis that occurred shortly after the diagnosis of Crohn's disease and was unrelated to the treatment and nutritional deficiencies. After a significant weight loss (24 kg) and persistent diarrhea, the patient was diagnosed with Crohn's disease by colonoscopy and biopsy. Within two weeks after the diagnosis, he experienced altered consciousness and memory impairment, followed by a rapid deterioration in consciousness and respiratory distress, leading to intubation and admission to the intensive care unit. His brain MRI revealed asymmetrical diffuse cortical diffusion restrictions, hyperintense signals on fluid-attenuated inversion recovery (FLAIR) sequences, and diffuse pachymeningeal contrast enhancement involving both cingulate gyri, bilateral insular cortices, amygdalae, hippocampi, and the right precuneus. Analysis of cerebrospinal fluid (CSF) revealed a slight elevation of CSF proteins, and the patient tested positive for serum anti-GAD antibodies. The patient responded favorably to a seven-day course of intravenous methylprednisolone, five days of intravenous immunoglobulin (IVIG), and oral corticosteroids. Subsequent treatment consisted of monthly IVIG, azathioprine, and vedolizumab, resulting in no neurologic sequelae except mild amnesia. A follow-up MRI at three months showed a nearly complete disappearance of the lesions. This is the first reported case of anti-GAD-associated encephalitis occurring in the presence of Crohn's disease.
ABSTRACT
Background and Aim: Radioembolization (RE) is a one of the palliative treatments that have been used to down stage and/or increase the survival time in intermediate-advanced stages of HCC. We aimed to evaluate the clinical impact of RE and the clinical use of the albumin-bilirubin (ALBI) score as a predictor for survival in HCC patients. Materials and Methods: Fifty-nine unresectable hepatocellular carcinoma (HCC) patients were enrolled. RE was performed in 28 of them (group 1) and 31 patients were followed up in the natural course (NC) (group 2). Patients were classified according to the Child-Pugh score (only cirrhotic patients), Barcelona clinic liver cancer (BCLC) staging, and ALBI scores were also calculated. Results: All patients in Group 1 were cirrhotic and their BCLC stages were as follows: 60.7% stage B and 39.3% stage C. In Group 2, 83.9% of patients were cirrhotic and their BCLC stages were as follows: 9.7% stage B, 51.6% stage C, and 38.7% stage D. Mortality rates were 82% and 100% in Groups 1 and 2, respectively. The median overall survival (OS) was 13.5 months (95% CI: 10.4-16.6 months) and 4.5 months (95% CI: 3.5-5.5 months) in Groups 1 and 2, respectively (p=0.000). When RE was applied to patients with ALBI Grade 1 and 2, the median OS was statistically higher than in the NC group, respectively (p<0.001, p<0.001). Conclusion: RE is an effective treatment method at the advanced stages of HCC. The ALBI score is a more useful and practical than the other prognostic tools.
ABSTRACT
Capsule endoscopy, in clinical use since the 2000s, has disrupted the diagnosis of various small bowel diseases, especially obscuregastrointestinal bleeding. An overview of information on indications, contraindications, patient management, and patient preparationfor capsule endoscopy, which allows the evaluation of the entire gastrointestinal tract, will be helpful for both referrers and capsuleendoscopy. This review critically considers current evidence on the optimal clinical use of capsule endoscopy and addresses areas in the "gray zone."
Subject(s)
Capsule Endoscopy , Endoscopy, Gastrointestinal , Intestinal Diseases , Intestine, Small , Humans , Gastrointestinal Hemorrhage/diagnosis , Intestinal Diseases/diagnosisABSTRACT
OBJECTIVE: The purpose of this study was to evaluate the relationship of IL28B rs12979860 and rs8099917 polymorphisms with the clinical, histological, and virological outcomes of patients with chronic hepatitis B (CHB) also the treatment responses of patients who received Nucleos(t)ide analogs (NAs) therapy. METHODS: This study included 152 CHB patients who were underwent liver parenchymal biopsy. The IL28B rs12979860 and rs8099917 polymorphism were genotyped using the TaqMan assay. RESULTS: The IL28B rs12979860 CC and IL28B rs8099917 TT were identified as the genotypes with the highest frequency in all patients. On the other hand, IL28B rs12979860 TT and IL28B rs8099917 GG were the genotypes with the lowest frequency. The frequency of IL28B rs8099917 TG genotype was significantly different between patients with hepatitis B, who has histologically defined liver cirrhosis and no-fibrosis (p=0.02). In addition, a statistically significant correlation was found between the presence of IL28B rs8099917 G allele and virological unresponsiveness to NAs treatments in CHB patients (p=0.028). CONCLUSION: The presence of the IL28B rs8099917 G allele in CHB patients might be associated with the risk of developing cirrhosis and virological unresponsiveness to NAs treatments.
ABSTRACT
BACKGROUND: One-third of all extraintestinal manifestations are mucocutaneous findings in patients with Crohn's disease and there is a relationship between some risk factors. Our aim is to evaluate factors associated with mucocutaneous manifestations in our cohort of patients with Crohn's disease with a follow-up duration of up to 25 years. METHODS: In the study, 336 patients with Crohn's disease who were followed up between March 1986 and October 2011 were included. The demographic characteristics, Crohn's disease-related data, and accompanying mucocutaneous manifestations were recorded. The cumulative probability of mucocutaneous extraintestinal manifestations and possible risk factors were analyzed. RESULTS: Oral and skin involvement were detected in 109 (32%) and 31 (9.2%) patients, respectively. The cumulative probability of developing oral and skin manifestations were 43.2% and 20.3%, respectively. Cox regression analysis showed that female gender (odds ratio: 3.28, 95% CI: 1.51-7.14, P = .003) and corticosteroid use (odds ratio: 7.88, 95% CI: 1.07-57.97, P = .043) are independently associated with the development of skin manifestations, while family history (odds ratio: 3.59, 95% CI: 2.18-5.93, P < .001) and inflammatory-type disease (odds ratio: 1.776, 95% CI: 1.21-2.61, P = .004) were independently associated with the development of oral ulcers. CONCLUSION: Mucocutaneous extraintestinal manifestations are associated with female gender, corticosteroid use, family history, and disease type in a large cohort of patients with Crohn's disease. Defining the specific relationships of immune-mediated diseases will help to better understand the pathogenesis of Crohn's disease and associated mucocutaneous manifestations and to use more effective treatments.
Subject(s)
Crohn Disease , Humans , Female , Crohn Disease/complications , Crohn Disease/pathology , Cohort Studies , Risk Factors , Odds Ratio , Adrenal Cortex HormonesABSTRACT
Background and Aim: Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC). Circulating cell-free DNA (cfDNA) methylation of tumor suppressor genes are emerging potential biomarkers in HCC. We aimed to evaluate the cfDNA methylation status of RASSF1 and CDKN2AIP genes in patients with liver cirrhosis (LC) with or without HCC caused by HBV. Materials and Methods: A total of 47 patients with HBV cirrhosis were included in the study. Patients were divided into two groups: HCC and LC (HCC+LC, n=22) and HBV cirrhosis only (LC, n=25). cfDNA was isolated from the plasma samples of the patients. Methylation analysis was performed for RASSF1 and CDKN2AIP genes. Results: Mean methylation percentage of CDKN2AIP gene was 0.001±0.004% in the HCC+LC group and 0.008±0.004 % in the LC only group. The mean methylation percentage of RASSF1 gene was 5.1±16.1% in the HCC+LC group and 9.7±25.9% in the LC only group. The methylation rate of CDKN2AIP was significantly lower in the HCC+LC group (p=0.027). A positive correlation was found with the absence of cfDNA methylation of CDKN2AIP gene in the presence of HCC (R=0.667, p=0.018). Conclusion: cfDNA methylation of CDKN2AIP and RASSF1 genes may provide important diagnostic information regarding the development of HCC in the setting of HBV cirrhosis.
ABSTRACT
BACKGROUND AND AIM: This study aimed to detect mutations in the HBV S gene and evaluate their relationship to occult hepatitis B virus (HBV) infection (OBI). METHODS: The study included 32 patients with negative serum HBsAg and HBV DNA who underwent liver biopsy due to different clinical indications defined as the OBI group and 32 patients who underwent liver biopsy due to chronic hepatitis B (CHB) as the comparison group. The HBV S gene region was amplified by Nested PCR, and Sanger sequencing was performed. RESULTS: At least one amino acid (aa) mutation was detected in the major hydrophilic region (MHR) of the HBV S gene in 14/32 (43.75%) of the patients with OBI and 8/32 (25.0%) with CHB. The genotype of all patients with OBI and CHB was HBV/D. Although 9 (28.1%) of the cases with OBI had sub-genotype HBV/D3, none of the patients with CHB had sub-genotype HBV/D3. Unlike patients with CHB, L15*, D33N, Q51P, V63F, L91I, P108S, T115I, P120L, T125M, Q129H, T189I, L216F, P217L mutations were detected in the HBV S gene in OBI cases. Also, P127T aa polymorphism was frequently detected. Mutation frequency in the HBV S gene in the major hydrophilic region (MHR) was higher in patients with OBI with sub-genotypes HBV/D3 and D2 than those with HBV/D1 and those with serotype HBV/ayw3 compared to those with HBV/ayw2 (p < 0.05). CONCLUSIONS: Sub-genotypic-specific mutation patterns were seen in the "a" determinant region and T helper cell epitopes of HBsAg, especially in the C-terminus domain; this may be associated with OBI.
Subject(s)
Hepatitis B Surface Antigens , Hepatitis B virus , Hepatitis B , DNA, Viral/chemistry , Genotype , Hepatitis B Surface Antigens/genetics , Hepatitis B virus/genetics , Hepatitis B, Chronic , Humans , MutationABSTRACT
BACKGROUND: Cyclosporine is a rescue treatment alternative to avoid colectomy in corticosteroid refractory acute severe ulcerative colitis. In this study, we aimed to evaluate the long-term efficacy and safety of cyclosporine therapy in acute severe ulcerative colitis patients. METHODS: Acute severe ulcerative colitis (basal Lichtiger score > 10) patients who did not respond to 40 mg intravenous methylpredniso- lone therapy after 3-5 days were included in the study. The presence of clinical response and remission was assessed at 1st week, 1st, 6th, and 12th month according to the Lichtiger index. RESULTS: In this study, 40 patients, whose steroid refractory acute severe ulcerative colitis and basal Lichtiger score > 10 points were enrolled. The median disease duration was 49.3 months (2-204). All patients received cyclosporine for 132 ± 78 days (7-270). Clinical response was obtained on seventh day in 82.5%. The clinical response rates of the first and sixth months were 72.5% and 62.5%, respectively. A total of 17/40 (42.5%) patients underwent colectomy within 1 year. In the patients who underwent colectomy, the basal LS (14.2 ± 1.9 vs 12.3 ± 1.7) (P = .002) was higher and the basal hemoglobin value (11.8 ± 2.3 vs 10.1 ± 1.5) (P = .037) was lower than those who did not undergo colectomy. CONCLUSION: Our findings suggest that cyclosporine treatment may be successfully and safely used in steroid refractory acute severe ulcerative colitis patients. Cyclosporine is a drug that has recently started to come up again with the introduction of new maintenance treatments. Especially in patients who develop a loss of response to infliximab therapy, or where infliximab therapy is contraindicated, or who have azathioprine intolerance, or are unresponsive.
Subject(s)
Colitis, Ulcerative , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Cyclosporine/therapeutic use , Humans , Immunosuppressive Agents/therapeutic use , Infliximab , Steroids/therapeutic useABSTRACT
BACKGROUND: Patients with Crohn's disease experience major deterioration in work productivity and quality of life. We aimed to provide the long-term effects of anti-tumor necrosis factor agents on work productivity and activity impairment and quality of life in patients with Crohn's disease using the Inflammatory Bowel Disease Questionnaire and the Short-Form Health Survey-36. METHODS: Patients with Crohn's disease and initiated an anti-tumor necrosis factor treatment were included and followed up for 12 months in this observational study. RESULTS: A total of 106 patients were included in this study, and 64.2% of the patients were males. Mean [± standard deviation] age was 36.8 [± 10.9] years. At baseline, mostly perianal fistulas [65.7%] were observed [n = 23]. Intestinal stenosis was detected in 34.9% of the patients [n = 37], and most of the stenosis was located in the ileum [70.6%] followed by the colon [20.6%]. Extraintestinal symp- toms were observed in 24 patients [22.6%]. Most frequent extraintestinal symptom was arthritis with 71.4% [n = 15]. Mean time from first symptom to initiation of anti-tumor necrosis factor treatment was 6.3 [± 5.0] years. Improvements in work productivity and activ- ity impairment scores throughout 12 months were -24.1% [P = .003] for work time missed, -18.0% [P = .006] for impairment at work, -8.5% [P = .160] for overall work impairment, and -17.0% [P < .001] for daily activity impairment. Similarly, significant improvements [P < .001] were detected in all components of the Inflammatory Bowel Disease Questionnaire when compared to baseline. Statistically sig- nificant improvements [P < .05] were detected for all components of Short-Form Health Survey-36 except for mental health [P = .095]. CONCLUSION: Our study indicates the significant improvement in work productivity and activity impairment and quality of life of patients with Crohn's disease who receive long-term anti-tumor necrosis factor treatment.
Subject(s)
Crohn Disease , Constriction, Pathologic , Crohn Disease/drug therapy , Crohn Disease/psychology , Female , Humans , Male , Quality of Life , Treatment Outcome , Tumor Necrosis Factor-alpha , TurkeyABSTRACT
Irritable bowel syndrome with diarrhoea (IBS-D) and functional diarrhoea (FDr) are the two major functional bowel disorders characterized by diarrhoea. In spite of their high prevalence, IBS-D and FDr are associated with major uncertainties, especially regarding their optimal diagnostic work-up and management. A Delphi consensus was performed with experts from 10 European countries who conducted a literature summary and voting process on 31 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation criteria. Consensus (defined as >80% agreement) was reached for all the statements. The panel agreed with the potential overlapping of IBS-D and FDr. In terms of diagnosis, the consensus supports a symptom-based approach also with the exclusion of alarm symptoms, recommending the evaluation of full blood count, C-reactive protein, serology for coeliac disease, and faecal calprotectin, and consideration of diagnosing bile acid diarrhoea. Colonoscopy with random biopsies in both the right and left colon is recommended in patients older than 50 years and in presence of alarm features. Regarding treatment, a strong consensus was achieved for the use of a diet low fermentable oligo-, di-, monosaccharides and polyols, gut-directed psychological therapies, rifaximin, loperamide, and eluxadoline. A weak or conditional recommendation was achieved for antispasmodics, probiotics, tryciclic antidepressants, bile acid sequestrants, 5-hydroxytryptamine-3 antagonists (i.e. alosetron, ondansetron, or ramosetron). A multinational group of European experts summarized the current state of consensus on the definition, diagnosis, and management of IBS-D and FDr.
Subject(s)
Gastroenterology , Irritable Bowel Syndrome , Bile Acids and Salts/therapeutic use , Diarrhea/diagnosis , Diarrhea/etiology , Diarrhea/therapy , Gastrointestinal Agents/therapeutic use , Humans , Irritable Bowel Syndrome/diagnosis , Irritable Bowel Syndrome/epidemiology , Irritable Bowel Syndrome/therapyABSTRACT
Occult hepatitis B infection (OBI) is defined by the persistence of the hepatitis B virus (HBV) genome in the liver of individuals testing negative for hepatitis B surface antigen (HBsAg). Hepatitis B core antibody (anti-HBc) is the serological marker that indicates HBV exposure. The impact of anti-HBc and OBI on patients with chronic hepatitis C remains unclear. The aim of the present study was to determine the prevalence of anti-HBc and OBI and to evaluate their impact on the clinical and pathological outcomes of patients with chronic hepatitis C. The study included 59 HBsAg-negative chronic hepatitis C patients who underwent a liver parenchymal biopsy. The presence of HBV DNA was investigated using an in-house nested PCR method. OBI was detected in 16 (27.1%) of the 59 cases and also in 10 (62.5%) of 22 (37.3%) anti-HBc-positive patients. None of the patients had positive serum HBV DNA. OBI was associated with the presence of anti-HBV antibodies (P < 0.05). There was also an association between anti-HBc positivity and the activity grades and fibrosis stages of the liver and also a prevalence of liver steatosis (P < 0.05). Positive anti-HBc results may predict OBI and may also be associated with the progression of liver injury in HBsAg-negative patients with chronic hepatitis C. Therefore, it is suggested that patients with chronic hepatitis C should be screened for anti-HBc positivity, and anti-HBc-positive patients should be carefully evaluated for disease progression.
Subject(s)
Hepatitis B, Chronic , Hepatitis B , Hepatitis C, Chronic , DNA, Viral/analysis , Hepatitis B/epidemiology , Hepatitis B Antibodies , Hepatitis B Surface Antigens , Hepatitis B virus/genetics , Hepatitis B, Chronic/epidemiology , Hepatitis C, Chronic/epidemiology , Humans , PrevalenceABSTRACT
BACKGROUND: Colorectal cancer is one of the most commonly diagnosed types of cancer worldwide. An early diagnosis and detection of colon cancer and polyp can reduce mortality and morbidity from colorectal cancer. Even though there are a variety of options in screen- ing tests, the question remains on which test is the most effective for the early detection of colorectal cancer. In this prospective study, we aimed to develop a simple, useful, effective, and reliable scoring system to detect colon polyp and colorectal cancer. METHODS: We enrolled 6508 subjects over the age of 18 from 16 centers, with colonoscopy screening. The age, smoking status, alcohol consumption, body mass index, polyp incidence, polyp size, number and localization, and pathologic findings were recorded. RESULTS: The age, male gender, obesity, smoking, and family history were found as independent risk factors for adenomatous polyp. We have developed a new scoring system which can be used for these factors. With a score of 4 or above, we found the following: sensitivity 81%, specificity 40%, positive predictive value 25.68%, and negative predictive value 89.84%, for adenomatous polyp detection; and sensitivity 96%, specificity 39%, positive predictive value 3.35%, negative predictive value 99.29%, for colorectal cancer detection. CONCLUSION: Even though the first colorectal cancer screening worldwide is generally performed for individuals over 50 years of age, we recommend that screening for colorectal cancer might begin for those under 50 years of age as well. Individuals with a score ≥ 4 must be included in the screening tests for colorectal cancer.
Subject(s)
Adenomatous Polyps , Colonic Polyps , Colorectal Neoplasms , Adenomatous Polyps/diagnosis , Adult , Colonic Polyps/diagnosis , Colonic Polyps/pathology , Colonoscopy , Colorectal Neoplasms/pathology , Early Detection of Cancer , Humans , Male , Middle Aged , Prospective Studies , Risk FactorsABSTRACT
Tryptophan metabolism in the tumor microenvironment exerts immunosuppressive effects by affecting the anti-tumor functions of immune cells. The immunosuppressive roles of tryptophan and tryptophan metabolites and their effects on the FOXP3 gene, highly expressed in regulatory T cells (Tregs), are remarkable. Our study aimed to investigate the relation between tryptophan metabolism and the transcription factor FOXP3 gene in colorectal cancer (CRC). Patients with CRC (n = 159) and controls (n = 112) were included in the study. The FOXP3 rs3761548 variant genotyping from the isolated genomic DNA was performed by PCR-RFLP. FOXP3 gene expression was determined by Q-PCR in RNAs isolated from resected tissues at the same time. Serum tryptophan, kynurenine, kynurenic acid levels of the cases were determined by HPLC. In serum samples with CRC, tryptophan level was 14.32 ± 1.09 µmol/L, kynurenine level was 1.33 ± 0.02 µmol/L, and the kynurenic acid level was 0.01 ± 0.001 µmol/L. The level of tryptophan was found to be low in CRC compared to control (p < .001). In cases with CRC, CC genotype (p = .048) and C allele (p = .012) frequency for FOXP3 rs3761548 were higher than the control group. It was found that the expression level of the FOXP3 gene was approximately 44 times higher in the advanced tumor stage (T3 + T4) than in the early tumor stage (T1 + T2) (p = .021).We suggest that there may be a possible relationship among serum TRP, TRP metabolites (KYN, KYNA) levels, FOXP3 gene expression, and FOXP3 gene variants in CRC pathogenesis.
Subject(s)
Colorectal Neoplasms , Kynurenine , Colorectal Neoplasms/genetics , Forkhead Transcription Factors/genetics , Humans , Kynurenic Acid , Kynurenine/metabolism , Tryptophan , Tumor MicroenvironmentABSTRACT
Introduction: There are limited data about the safety of tenofovir disoproxil fumarate (TDF) in chronic renal failure (CRF). In this study, we aimed to evaluate the safety and efficacy of TDF in renal transplant recipients and hemodialysis patients with chronic hepatitis B (CHB) during long-term follow-up. Material and methods: CHB patients undergoing hemodialysis (group 1), renal transplant recipients (group 2) and patients with normal renal function were included in the study. All patients were treated with TDF for at least 6 months. The groups were compared with regards to safety and efficacy. HBV-DNA levels were studied using a Cobas-TaqMan 96 system. Results: A total of 217 patients with CHB (group 1: 8 patients, group 2: 9 patients, group 3: 200 patients) were enrolled in this study. The frequency of clinical adverse effects was significantly higher in groups 1 and 2compared with group 3 (37.5% vs. 11.1% vs. 0.5%, respectively, p < 0.001). However, no patients discontinued the drug due to the adverse effects. Serum creatinine levels were similar at baseline and at the end of follow-up in groups 1 and 2 (6.5 ±1.8 mg/dl and 6.9 ±1.5 mg/dl; 1.3 ±0.2 and 1.4 ±0.4 mg/dl, respectively, p < 0.05). HBV-DNA negativity rates were comparable at the 12th month and at the end of follow-up (50-83% for group 1, 60-67% for group 2 and 70-75% for group 3, respectively, p > 0.05). Conclusions: Clinical adverse effects of TDF were more common in patients with CRF in comparison with patients without CRF. However, the occurrence of adverse effects did not necessitate discontinuation of the drug. TDF was safe and effective for this group of patients.
ABSTRACT
BACKGROUND: The severe acute respiratory syndrome coronavirus 2 virus was found to have effects not only in the lungs but also in many different organs. We aimed to evaluate the management of our patients with inflammatory bowel disease in this pandemic, the incidence of coronavirus disease 2019 in terms of clinical, medical treatment, and features of inflammatory bowel disease, and to investigate the effects of the severe acute respiratory syndrome coronavirus 2 on this particular group of patients. METHODS: During the coronavirus disease 2019 pandemic, 207 patients who had inflammatory bowel disease for at least 6 months were questioned for coronavirus disease 2019 at their outpatient clinic admissions, and their medical records were evaluated prospectively. RESULTS: Of the 207 patients, 146 had Crohn's disease. The mean disease duration was determined as 118.15 ± 72.85 months. Of the patients, 127 (61.4%) were using mesalazine, 110 (53.1%) azathioprine, and 148 (71.5%) biological agents. It was found that 66 (31.9%) patients changed their medications during the coronavirus disease 2019 pandemic. As a medication change, anti-Tumor Necrosis Factor (TNF) dose was observed to be omitted most frequently at a rate of 80%. Diarrhea was present in 20.8%, abdominal pain in 20.3%, nausea in 10.6%, anorexia in 13.5%, and weight loss in 15.9% of the patients. Twelve (5.79%) patients were diagnosed with coronavirus disease 2019. Lung involvement was present in 11 (91.7%) of the patients diagnosed with coronavirus disease 2019. Of the patients diagnosed and not diagnosed with coronavirus disease 2019, 75% vs. 71.6% were using biological agents (P = .80), respectively. Half of the patients diagnosed with coronavirus disease 2019 were active in terms of inflammatory bowel disease at the time of diagnosis, and 2 of these patients were severely active. CONCLUSION: The incidence of coronavirus disease 2019 infection in patients with inflammatory bowel disease was not different from the general population during the severe acute respiratory syndrome coronavirus 2 pandemic. Coronavirus disease 2019 infection does not progress with poor prognosis in patients with inflammatory bowel disease who receive immunosuppressive therapy including biological agents.