ABSTRACT
BACKGROUND: The differentiation between intestinal tuberculosis (ITB) and Crohn's disease (CD) remains a challenge, particularly in areas where tuberculosis is highly prevalent. Previous studies have identified features that favour one diagnosis over the other. The aim of the study was to determine the accuracy of a standardized protocol in the initial diagnosis of CD versus ITB. METHODS: All patients with suspected ITB or CD were prospectively recruited. A standardized protocol was applied, and the diagnosis was made accordingly. The protocol consists of history and examination, ileocolonoscopy with biopsies, and tuberculosis workup. The diagnosis of probable ITB was made based on at least one positive finding. All other patients were diagnosed as probable CD. Patients were treated either with anti-tubercular therapy or steroids. Reassessment was then carried out clinically, biochemically, and endoscopically. In patients with suboptimal response, the treatment was either switched or escalated depending on the reassessment. RESULTS: 164 patients were recruited with final diagnosis of 30 (18.3%) ITB and 134 (81.7%) CD. 1 (3.3%) out of 30 patients with ITB was initially treated as CD. 16 (11.9%) out of 134 patients with CD were initially treated as ITB. The initial overall accuracy for the protocol was 147/164 (89.6%). All patients received the correct diagnosis by 12 weeks after reassessment. CONCLUSION: In our population, most patients had CD rather than ITB. The standardized protocol had a high accuracy in differentiating CD from ITB.
Subject(s)
Crohn Disease , Tuberculosis, Gastrointestinal , Humans , Crohn Disease/pathology , Tuberculosis, Gastrointestinal/diagnosis , Tuberculosis, Gastrointestinal/drug therapy , Tuberculosis, Gastrointestinal/epidemiology , Biopsy , Diagnosis, Differential , AlgorithmsABSTRACT
INTRODUCTION: Small intestinal bacterial overgrowth (SIBO) is prevalent in irritable bowel syndrome (IBS), but its' association with other functional gastrointestinal disorders (FGIDs) is less certain. This study aimed to explore SIBO in a multi-racial Asian population with various FGIDs compared to non-FGID controls. METHODOLOGY: Consecutive Asian adults with Rome III diagnosed common FGIDs (functional dyspepsia/FD, IBS and functional constipation/FC) and non-FGID controls were subjected to glucose breath testing, with hydrogen (H2) and methane (CH4) levels determined. RESULTS: A total of 244 participants (FGIDs n = 186, controls n = 58, median age 45 years, males 36%, Malay ethnicity 76%) were recruited. FGIDs had a higher prevalence trend of SIBO compared to controls (16% FGIDs vs. 10% controls, p = 0.278) with 14% in FD, 18% in IBS and 17% in FC. Compared to controls, SIBO was associated with diarrhoea-predominant IBS (IBS-D) (24% vs. 10%, P = 0.050) but not with other types of FGIDs. IBS-D remained an independent predictor of SIBO (OR = 2.864, 95% CI 1.160-7.071, p = 0.023) but not PPI usage nor history of diabetes (both p > 0.050) at multivariate analysis. Compared to controls, SIBO in IBS-D was associated with an elevated H2 level (≥ 20 ppm from baseline) (18% vs. 3%, p = 0.017), but not CH4 levels (≥ 10 ppm) (9% vs. 7%, p = 0.493). In addition, no difference was found in the prevalence of methane-positive SIBO between chronic constipation (constipation-predominant IBS and FC) compared to controls (9% vs. 7%, P = 0.466). CONCLUSION: SIBO is prevalent amongst multi-ethnic Asian adults with and without FGIDs. Amongst various FGIDs, only IBS-D is significantly associated with SIBO.
Subject(s)
Irritable Bowel Syndrome , Adult , Breath Tests , Case-Control Studies , Constipation/diagnosis , Constipation/epidemiology , Humans , Intestine, Small/microbiology , Irritable Bowel Syndrome/diagnosis , Irritable Bowel Syndrome/epidemiology , Irritable Bowel Syndrome/microbiology , Male , Methane , Middle AgedABSTRACT
OBJECTIVES: In Malaysia, the prevalence of Helicobacter pylori resistance to clarithromycin is increasing. This study aimed to determine mutations in the 23S rRNA domain V directly using bacterial DNA extracted from gastric biopsy specimens with a urease-positive result. METHODS: A 1085-bp fragment of 23S rRNA domain V from samples of 62 treatment-naïve patients with H. pylori infection was amplified by PCR with newly designed primers, followed by sequencing. RESULTS: Of the 62 cases, 42 patients were treated with clarithromycin-based triple therapy and 20 patients were treated with amoxicillin and proton pump inhibitor only; both therapies showed successful eradication rates of 70-73.8%. Sequencing analysis detected 37 point mutations (6 known and 31 novel) with prevalences ranging from 1.6% (1/62) to 72.6% (45/62). A2147G (aka A2143G) appears to be associated with a low eradication rate [40% (2/5) failure rate and 13.3% (6/45) treatment success rate], supporting its role as a clinically significant point mutation. T2186C (aka T2182C) was found in 71.1% (32/45) and 80% (4/5) of treatment success and failure cases, respectively, suggesting that the mutation is clinically insignificant. The eradication success rate in patients with the novel T2929C mutation was decreased three-fold (6.7%; 3/45) compared with the failure rate (20%; 1/5), suggesting that it may play an important role in clarithromycin resistance, thus warranting further study. CONCLUSION: This study identified multiple known and novel mutations in 23S rRNA domain V through direct sequencing. Molecular detection of clarithromycin resistance directly on biopsies offers an alternative to conventional susceptibility testing.
Subject(s)
Helicobacter pylori , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Clarithromycin/pharmacology , Clarithromycin/therapeutic use , Drug Resistance, Bacterial , Helicobacter pylori/genetics , Humans , Malaysia/epidemiology , Mutation , RNA, Ribosomal, 23S/geneticsSubject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/therapeutic use , Alanine/therapeutic use , COVID-19 , Compassionate Use Trials , Coronavirus Infections/complications , Humans , Pandemics , Pneumonia, Viral/complications , SARS-CoV-2 , Treatment OutcomeABSTRACT
A 33-year-old man was referred with hyperosmotic symptoms of 4 weeks. Clinical examination showed palpable hepatomegaly and no stigmata of liver disease. Findings were random glucose 16.6 mmol/L, HbA1c 12.4%, triglyceride 6.2 mmol/L, normal LFTs and ultrasound liver: increased echogenicity. Management consisted of dietician referral and commencement of metformin 500 mg bd, diamicron MR 60 mg od, and fenofibrate 145 mg od. He was non-compliant, complaining of "heaviness of head" after consuming oral diabetic agents, without symptoms of hypoglycemia. Treatment was switched to Kombiglyze XR (saxaglipitin 5 mg + metformin 1000 mg) and empagliflozin 25 mg od. He presented 1 week later with generalised pruritus with ALT 307 IU/L and serum GGT 808 IU/L. Following this, a percutaneous liver biopsy was performed, revealing steatohepatitis and marked intra-hepatic cholestasis. Kombiglyze XR was withheld, with resolution of LFTs to baseline. Phenotypes of liver injury are categorised according to R value, defined as ratio ALT/ULN:ALP/ULN. R value of ≥5:hepatocellular injury, ≤2:cholestatic injury, 2-5:mixed-type injury. Here, R value points toward mixed type (R = 3.203). Hepatotoxicity in patients with NASH is difficult to diagnose, based on laboratory parameters. Liver histology was useful in indicating additional changes apart from NASH, causing liver derangement. The Rousal Uclaf Causality Assessment Method is a scoring method to determine the probability of drug induced liver injury. RUCAM score for this case was 6 (probable adverse drug reaction). Hepatotoxicity from saxagliptin not been reported prior. Clinicians need to be more vigilant, particularly in patients with NASH.
ABSTRACT
BACKGROUND: Some studies have suggested that chronic Helicobacter pylori (HP) infection can aggravate the neurodegenerative process in Parkinson's disease (PD), and targeted intervention could potentially modify the course of this disabling disease. We aimed to study the impact of HP infection on motor function, gastrointestinal symptoms, and quality of life in a large cohort of PD patients. METHODS: 102 consecutive PD patients underwent (13)C urea breath testing and blinded evaluations consisting of the Unified Parkinson's Disease Rating Scale (UPDRS) including "On"-medication motor examination (Part III), objective and quantitative measures of bradykinesia (Purdue Pegboard and timed gait), Leeds Dyspepsia Questionnaire, and PDQ-39 (a health-related quality of life questionnaire). RESULTS: 32.4% of PD patients were HP-positive. HP-positive patients were older (68.4 ± 7.3 vs. 63.8 ± 8.6 years, P = 0.009) and had worse motor function (UPDRS Part III 34.0 ± 13.0 vs. 27.3 ± 10.0, P = 0.04; Pegboard 6.4 ± 3.3 vs. 8.0 ± 2.7 pins, P = 0.04; and timed gait 25.1 ± 25.4 vs. 15.5 ± 7.6 s, P = 0.08). In the multivariate analysis, HP status demonstrated significant main effects on UPDRS Part III and timed gait. The association between HP status and these motor outcomes varied according to age. Gastrointestinal symptoms and PDQ-39 Summary Index scores did not differ between the two groups. CONCLUSIONS: This is the largest cross-sectional study to demonstrate an association between HP positivity and worse PD motor severity.
Subject(s)
Helicobacter Infections/physiopathology , Helicobacter pylori/pathogenicity , Parkinson Disease/microbiology , Parkinson Disease/physiopathology , Age Factors , Aged , Aged, 80 and over , Breath Tests , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Quality of Life , Severity of Illness Index , Spectrophotometry, Infrared , Statistics, Nonparametric , Surveys and QuestionnairesABSTRACT
BACKGROUND: Recent studies reported a high prevalence of small intestinal bacterial overgrowth (SIBO) in Parkinson's disease (PD), and a possible association with gastrointestinal symptoms and worse motor function. We aimed to study the prevalence and the potential impact of SIBO on gastrointestinal symptoms, motor function, and quality of life in a large cohort of PD patients. METHODS: 103 Consecutive PD patients were assessed using the lactulose-hydrogen breath test; questionnaires of gastrointestinal symptoms and quality of life (PDQ-39); the Unified PD Rating Scale (UPDRS) including "on"-medication Part III (motor severity) score; and objective and quantitative measures of bradykinesia (Purdue Pegboard and timed test of gait). Patients and evaluating investigators were blind to SIBO status. RESULTS: 25.3% of PD patients were SIBO-positive. SIBO-positive patients had a shorter mean duration of PD (5.2 ± 4.1 vs. 8.1 ± 5.5 years, P = 0.007). After adjusting for disease duration, SIBO was significantly associated with lower constipation and tenesmus severity scores, but worse scores across a range of "on"-medication motor assessments (accounting for 4.2-9.0% of the variance in motor scores). There was no association between SIBO and motor fluctuations or PDQ-39 Summary Index scores. CONCLUSIONS: This is the largest study to date on SIBO in PD. SIBO was detected in one quarter of patients, including patients recently diagnosed with the disease. SIBO was not associated with worse gastrointestinal symptoms, but independently predicted worse motor function. Properly designed treatment trials are needed to confirm a causal link between SIBO and worse motor function in PD.