SERUM PROCALCITONIN AS A PROGNOSTIC MARKER IN ACUTE SEVERE ULCERATIVE COLITIS: A PROSPECTIVE STUDY.

BACKGROUND: Procalcitonin may be increased in active ulcerative colitis (UC). We investigated the role of procalcitonin in predicting response in acute severe UC (ASUC). METHODS: Consecutive patients with ASUC diagnosed on basis of Truelove and Witts criteria were enrolled. Serum procalcitonin levels for consecutive patients were measured at admission and day 3. We assessed role of procalcitonin values at presentation and at day 3 in assessing response on day 3 (Oxford's criteria) and need for second line therapy (day 28). RESULTS: Of fifty patients (23 males, mean age: 35.98±13.8 years), 16 did not respond (day 3). Ten (20%) patients required second-line therapy. Baseline procalcitonin was significantly associated with response on day 3 (P=0.016). There was no association between day 1 or day 3 procalcitonin and need for second-line rescue therapy. CONCLUSION: Serial procalcitonin is not an effective biomarker for predicting outcomes or need for second line therapy in ASUC.

A procalcitonina sérica como marcador prognóstico na colite ulcerativa aguda / Serum procalcitonin as a prognostic marker in acute severe ulcerative colitis: a prospective study

ABSTRACT Background Procalcitonin may be increased in active ulcerative colitis (UC). We investigated the role of procalcitonin in predicting response in acute severe UC (ASUC). Methods Consecutive patients with ASUC diagnosed on basis of Truelove and Witts criteria were enrolled. Serum procalcitonin levels for consecutive patients were measured at admission and day 3. We assessed role of procalcitonin values at presentation and at day 3 in assessing response on day 3 (Oxford's criteria) and need for second line therapy (day 28). Results Of fifty patients (23 males, mean age: 35.98±13.8 years), 16 did not respond (day 3). Ten (20%) patients required second-line therapy. Baseline procalcitonin was significantly associated with response on day 3 (P=0.016). There was no association between day 1 or day 3 procalcitonin and need for second-line rescue therapy. Conclusion Serial procalcitonin is not an effective biomarker for predicting outcomes or need for second line therapy in ASUC.

RESUMO Contexto A procalcitonina pode estar aumentada em colite ulcerativa ativa. Investigamos o papel da procalcitonina na previsão de resposta na colite ulcerativa aguda grave. Métodos Foram inscritos pacientes consecutivos com colite ulcerativa aguda grave diagnosticados com base nos critérios de Truelove e Witts. Os níveis de procalcitonina sérica dos pacientes foram medidos consecutivamente na internação e no terceiro dia. Avaliamos o papel dos valores procalcitonina na apresentação e na avaliação da resposta no terceiro dia (critérios de Oxford) e necessidade de terapia de segunda linha (dia 28). Resultados Dos 50 pacientes (23 homens, idade média: 35,98±13,8 anos), 16 não responderam (terceiro dia). Dez pacientes (20%) necessitaram de terapia de segunda linha. A procalcitonina de linha de base foi significativamente associada à resposta no terceiro dia (P=0,016). Não houve associação entre o primeiro dia ou o terceiro dia de procalcitonina e necessidade de terapia de resgate de segunda linha. Conclusão A procalcitonina sérica não é um biomarcador eficaz para prever desfechos ou necessidade de terapia de segunda linha em colite ulcerativa aguda grave.

Oral Fluconazole Therapy in Patients With Active Ulcerative Colitis Who Have Detectable Candida in the Stool : A Double-Blind Randomized Placebo-controlled Trial.

BACKGROUND: There is an emerging role of fungal dysbiosis in the pathogenesis of inflammatory bowel disease. Prevalence of Candida in patients with active ulcerative colitis (UC) and the effect of fluconazole therapy in reducing disease activity of UC are not known. PATIENTS AND METHODS: All consecutive consenting patients with active UC defined as Mayo score ≥3 were evaluated for presence of Candida by stool culture and predictors for presence of Candida were identified. Those who had evidence of Candida in the stool were randomized to receive oral fluconazole 200 mg daily or placebo for 3 weeks along with standard medical therapy. Patients were assessed by clinical, sigmoidoscopy, and laboratory parameters at baseline and at 4 weeks. The primary outcome was clinical and endoscopic response at 4 weeks defined by a 3-point reduction in Mayo score. Secondary outcomes were reduction in fecal calprotectin, histologic response, and adverse events. RESULTS: Of the 242 patients with active UC, 68 (28%) patients had Candida in stool culture. Independent predictors for presence of Candida in patients with active UC were partial Mayo score of ≥3 and steroid exposure. Among those with Candida on stool culture (n=68), 61 patients fulfilled eligibility criteria and were randomized to receive fluconazole (n=31) or placebo (n=30). Three-point reduction in Mayo score though was numerically higher in the fluconazole group than the placebo group but was not statistically significant [5 (16.1%) vs. 1 (3.33%); P =0.19]. Postintervention median Mayo score was lower in fluconazole than placebo group [4 (3, 5) vs. 5 (4, 6); P =0.034]. Patients in fluconazole group had more often reduction in fecal calprotectin [26 (83.9%) vs. 11 (36.7%); P =0.001] and histologic scores [23 (74.1%) vs. 10 (33.3%); P =0.001] compared with placebo. All patients were compliant and did not report any serious adverse event. CONCLUSION: Candida colonization is found in 28% of patients with UC. Steroid exposure and active disease were independent predictors for the presence of Candida . There was no statistically significant difference in the number of patients who achieved 3-point reduction in Mayo score between 2 groups. However, clinical, histologic, and calprotectin levels showed significant improvement in fluconazole group.

TPMT and NUDT15 polymorphisms in thiopurine induced leucopenia in inflammatory bowel disease: a prospective study from India.

BACKGROUND: Polymorphisms in thiopurine methyltransferase (TPMT) and Nudix hydrolase-15 (NUDT15) have been implicated as the predominant cause of thiopurine induced leukopenia in the Western countries and East Asia respectively. Exact role of these polymorphisms in South Asian population with inflammatory bowel disease (IBD) is uncertain. METHODS: We included consecutive patients with IBD who were initiated on thiopurines at a center in North India. The dosage of thiopurines was titrated using regular monitoring of hemogram and liver function tests. Three TPMT polymorphisms (c.238 G > C, c.460 G > A, and c.719A > G) and one NUDT15 polymorphism (c.415 C > T) were assessed. Comparison regarding incidence of leukopenia and maximum tolerated thiopurine dosage was performed between those with wild polymorphism and those with TPMT and NUDT15 polymorphisms, respectively. RESULTS: Of the 119 patients (61 males, mean age 36.8 ± 13.5 years), 105 (88.2%) had ulcerative colitis and 14 (11.8%) had Crohn's disease. Leukopenia was noted in 33 (27.7%), gastrointestinal intolerance in 5 (4.2%) and pancreatitis in 2 (1.6%). TPMT polymorphisms were detected amongst five patients of whom 1 developed leukopenia. NUDT15 polymorphism was noted in 13 patients of whom 7 had leukopenia. The odds of developing leukopenia in TPMT polymorphism were non-significant (0.77, 95% CI:0.0822 to 7.2134, P = 0.819) but were significantly higher in those with NUDT15 polymorphism (3.5933, 1.1041 to 11.6951, P value: = 0.0336). CONCLUSION: NUDT15 polymorphism was more frequent than TPMT polymorphisms and was associated with thiopurine induced leukopenia. However, the tested polymorphisms account for only 24.2% of the risk of thiopurine induced leukopenia.

FDG-PET-CT Enterography Helps Determine Clinical Significance of Suspected Ileocecal Thickening: A Prospective Study.

BACKGROUND: Ileocecal thickening (ICT) on imaging could result from diverse etiologies but may also be clinically insignificant. AIM: Evaluation of role of combined 2-deoxy-2-fluorine-18-fluoro-D-glucose(18F-FDG)-positron emission tomography and computed tomographic enterography (PET-CTE) for determination of clinical significance of suspected ICT. METHODS: This prospective study enrolled consecutive patients with suspected ICT on ultrasound. Patients were evaluated with PET-CTE and colonoscopy. The patients were divided into: Group A (clinically significant diagnosis) or Group B (clinically insignificant diagnosis) and compared for various clinical and radiological findings. The two groups were compared for maximum standardized uptake values of terminal ileum, ileo-cecal valve, cecum and overall. RESULTS: Of 34 patients included (23 males, mean age: 40.44 ± 15.40 years), 12 (35.3%) had intestinal tuberculosis, 11 (32.4%) Crohn's disease, 3 (8.8%) other infections, 1 (2.9%) malignancy, 4 (11.8%) non-specific terminal ileitis while 3 (8.8%) had normal colonoscopy and histology. The maximum standardized uptake value of the ileocecal area overall (SUVmax-ICT-overall) was significantly higher in Group A (7.16 ± 4.38) when compared to Group B (3.62 ± 9.50, P = 0.003). A cut-off of 4.50 for SUVmax-ICT-overall had a sensitivity of 70.37% and a specificity of 100% for prediction of clinically significant diagnosis. Using decision tree model, the SUVmax-ICT with a cut-off of 4.75 was considered appropriate for initial decision followed by the presence of mural thickening in the next node. CONCLUSION: PET-CTE can help in discrimination of clinically significant and insignificant diagnosis. It may help guide the need for colonoscopy in patients suspected to have ICT on CT.

Adjuvant use of combination of antibiotics in acute severe ulcerative colitis: A placebo controlled randomized trial.

OBJECTIVES: Evaluation of a combination of antibiotics as an adjuvant therapy in acute severe ulcerative colitis (ASUC). METHODS: Patients with ASUC were randomized to either infusions of placebo or intravenous ceftriaxone and metronidazole in addition to standard care. Primary outcome was response on day three according to Oxford's criteria. Secondary outcome measures included changes in partial Mayo score, CRP levels, fecal calprotectin (day three), and need for second-line therapy, hospital stay, and mortality (day 28). RESULTS: Fifty patients (25 in each group, median age: 33 years, 23 males) were included. The number of patients with fulminant disease in the antibiotic group were 16 (64%) as compared to 7 (28%) in the standard of care group. Complete response on day three was attained by 7 (28%) in the antibiotic and 6 (24%) standard of care group (p = 1.00). Three patients from the antibiotic group underwent colectomy and three received intravenous cyclosporine whereas four patients in the standard of care group received cyclosporine (p = 0.725). There was no significant difference in change in CRP, Partial Mayo score, and fecal calprotectin between the two groups on day three. CONCLUSION: Combination of intravenous ceftriaxone and metronidazole did not improve outcomes in ASUC.Acronym: AAASUC trialRegistration Number: CTRI/2019/03/018196 and NCT03794765.

Serial measurements of faecal calprotectin may discriminate intestinal tuberculosis and Crohn's disease in patients started on antitubercular therapy.

BACKGROUND: Response to antitubercular therapy (ATT) is often used to differentiate intestinal tuberculosis (ITB) from Crohn's disease. Role of non-invasive biomarkers to predict mucosal response to ATT is unclear. MATERIALS AND METHODS: A prospective study to compare faecal calprotectin and serum C-reactive protein (CRP) levels at diagnosis, 2 and 6 months of ATT in patients with suspected ITB started on ATT was done. The patients were eventually divided into two groups: ITB or alternative diagnosis (OTH). Decline of calprotectin and CRP levels was used to compute area under the receiver operating characteristic (AUROC) to predict mucosal healing at 2 months. RESULTS: Thirty-seven patients (mean age: 34.95 ± 16.35 years, 23 males) were included and 28 (75.67%) were diagnosed as ITB while nine (24.32%) had alternative diagnosis (OTH). The median faecal calprotectin values of ITB and OTH groups at baseline, 2 months and 6 months were 216 and 282 µg/g (P = 0.466), 43 and 216 µg/g (P = 0.003), and 26 and 213 µg/g (P < 0.001), respectively. The median CRP values at baseline, 2 months and 6 months were 18 and 30 mg/L (P = 0.767), 4.7 and 15 mg/L (P = 0.025), and 3 and 10.85 mg/L (P = 0.068), respectively. The AUROC of percent decline in faecal calprotectin and serum CRP at 2 months for mucosal healing were 0.8287 [95% confidence inteval (CI) 0.6472-1] and 0.6018 (95% CI 0.4079-0.7957), respectively. CONCLUSION: Faecal calprotectin can help in assessing response to therapy in suspected ITB patients started on empirical ATT.

An unusual case of hereditary transthyretin-related amyloidosis and ulcerative colitis in a young Indian girl.

Hereditary transthyretin (TTR) amyloidosis is a multisystem disorder caused by extracellular amyloid deposition, usually presenting with neurological and cardiovascular involvement. Gastrointestinal involvement, if present, is usually in the form of motility symptoms like diarrhea, constipation, or diarrhea alternating with constipation. Presentations mimicking ulcerative colitis without other system involvement are rare. Here we present a case of a young female from northern India, who presented with blood-admixed diarrhea without any feature of any other system involvement. She was diagnosed and treated as ulcerative colitis for two years with ambivalent response, although the compliance to therapy was also poor. She was re-evaluated when she presented with recurrence of symptoms and new onset dysphagia. On evaluation, she was diagnosed as hereditary transthyrtetin related amyloidosis.

Utility of tissue Xpert-Mtb/Rif for the diagnosis of intestinal tuberculosis in patients with ileocolonic ulcers.

INTRODUCTION: Data on the use of Xpert Mtb/Rif for the diagnosis of intestinal tuberculosis is sparse. We report on the utility of Xpert Mtb/Rif testing for diagnosis of intestinal tuberculosis (ITB) in patients with ileocecal ulcers. METHODOLOGY: We performed a retrospective analysis of patients with ileocecal ulcers and suspected to have ITB and in whom testing of intestinal tissue for Xpert Mtb/Rif was performed. The patients were divided into two groups: those with a final diagnosis of intestinal tuberculosis and those with other diagnosis. These patients were compared for clinical features and presentation. The sensitivity, specificity, positive predictive value, and negative predictive value of Xpert Mtb/Rif for the diagnosis of ITB were calculated. RESULTS: Of the 40 patients studied, 23 were women and the mean age was 32.92 ±â€„12.78 years. Abdominal pain was present in 33 (88.5%) patients and diarrhea in 12 (30%). A total of 25 patients had underlying ITB whereas 15 patients had other diagnoses (Crohn's disease, amebiasis, nonspecific ileitis, etc.). The sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of GeneXpert-Mtb/Rif was 32% (CI: 14.95-53.50%), 100% (78.2-100), 46.88% (40.27-53.59%), 100 & 57.50 (40.89-72.89%) respectively. CONCLUSION: A positive GeneXpert-Mtb/Rif helps in the diagnosis of ITB, but the sensitivity is low.

Esophageal manometry, esophagogastroduodenoscopy, and duodenal mucosal histopathology in systemic sclerosis.

BACKGROUND AND AIM: Systemic sclerosis (SSc) is known to involve the gastrointestinal (GI) tract, resulting in dysmotility, gastroesophageal reflux disease, and mucosal changes causing significant morbidity. The study aimed to assess esophageal motility and duodenal mucosal changes in SSc. METHODS: This is a prospective, cross-sectional, single-center study of 23 patients with SSc diagnosed on the basis of standard criteria. Clinical details including the GI symptoms were recorded. All of them underwent esophagogastroduodenoscopy with duodenal biopsy, and 21 underwent esophageal manometry. RESULTS: Regurgitation, heartburn, and dysphagia were seen in 19 (82%), 16 (69%), and 10 (43%) patients, respectively. On endoscopy, 19 patients (83%) showed changes of reflux esophagitis (4 had grade C esophagitis), and 3 had esophageal candidiasis. Of the 21 patients who underwent esophageal manometry, 13 (62%) had absent peristalsis, 6 (28%) had ineffective peristalsis, and 10 (48%) had hypotensive lower esophageal sphincter (LES). Duodenal biopsy showed partial villous atrophy in 9 (39%) patients, increased intraepithelial lymphocytes in 18 (78%), and excess of mononuclear inflammatory cells in lamina propria in 21 (91%). Partial villous atrophy was seen more commonly in those with abnormal esophageal peristalsis and a hypotensive LES. CONCLUSION: Most of the patients with SSc had esophageal dysmotility in the form of absent peristalsis, ineffective esophageal peristalsis, and hypotensive LES. Histology of descending duodenum demonstrated partial villous atrophy and chronic inflammatory infiltrates in most of the patients with SSc.

HbA1c levels at presentation do not impact the clinical presentation or outcomes in abdominal tuberculosis.

Background: The relationship between diabetes mellitus and tuberculosis (TB) has received increasing attention, and diabetes may be associated with poor outcomes in pulmonary TB. Clinical relevance of HbA1c measurement in abdominal TB is unknown. Methods: We did a retrospective study of consecutive patients diagnosed with abdominal TB and treated with antitubercular therapy for 6 months. Patients were categorized as those with normal HbA1c (<5.7%) or those having elevated HbA1c (≥5.7%). The patients' baseline characteristics, their mode of presentation, type of abdominal TB, and their outcomes after treatment were retrieved and compared. Results: Of 84 patients included in the final analysis, the mean age was 35.52 years and 50% were male. While 19 patients had a confirmed diagnosis, 65 patients were diagnosed as probable abdominal TB. Of the 84 patients, 60 patients (71.43%) had a normal HbA1c and 24 patients (28.57%) had an elevated HbA1c. Those with elevated HbA1c were older in age (47.00 ± 13.98 vs. 30.93 ± 13.91; P < 0.001), and there were more males (75.0% vs. 40.0%; P = 0.004) as compared to the normal HbA1c group. However, other parameters such as their presenting features, pattern of abdominal TB, extra-abdominal involvement, outcomes after treatment, and need of intervention (surgery and dilatation) were comparable between both the groups. Conclusion: Presence of prediabetes or diabetes does not seem to impact the clinical presentation or outcomes in patients with abdominal TB.

Extra-abdominal involvement is associated with antitubercular therapy-related hepatitis in patients treated for abdominal tuberculosis.

AIM OF THE STUDY: Incidence and predictors of antitubercular therapy (ATT)-related hepatitis in abdominal tuberculosis are not known. The aim of the study was to identify the incidence and predictors of ATT-induced hepatitis in abdominal tuberculosis. MATERIAL AND METHODS: A retrospective analysis of patients who received ATT for suspected abdominal tuberculosis with complete follow-up was done. We excluded patients with underlying chronic or acute liver disease necessitating an alteration in the usual ATT at start. We recorded the occurrence of ATT-induced hepatitis and compared patients with and without ATT hepatitis for any predictors of ATT-induced hepatitis. RESULTS: Of 163 patients, 22 were excluded (17 missing information, 5 chronic liver disease). One hundred and forty-one patients (mean age: 34.33 ±15.18 years, males: 72) were included. The Mantoux test was positive in 78; 1 had HIV and 32 had an abnormal chest X-ray. Six patients had an alternative diagnosis and 11 needed surgery. Forty-nine (34.8%) had extra-abdominal involvement. Ten patients (7.1%) developed ATT-induced hepatitis. Patients with extra-abdominal tubercular involvement had a greater risk of developing ATT-induced hepatitis (p-value 0.003). None of the other parameters including hematological tests, liver function tests and biochemical parameters were different between the two groups. CONCLUSIONS: Seven percent of patients treated for abdominal tuberculosis developed ATT hepatitis. Presence of extra-abdominal involvement was associated with ATT hepatitis.

Tubercular colitis masquerading as ischemic colitis: An unusual presentation.

Tuberculosis is a common clinical problem which can involve virtually any organ and mimic a multitude of clinical conditions. Colonic tuberculosis is a type of intestinal tuberculosis which involves the colon and mimics inflammatory bowel disease. Occasionally, it is also confused with colonic malignancy. We report the case of a young female who presented with abdominal pain, bleeding per rectum. Abdominal X-ray showed evidence of thumb-printing. A possibility of ischemic colitis was entertained. However, further investigation unraveled the presence of tubercular colitis. The patient improved with anti-tubercular therapy. Colonic tuberculosis can mimic a number of clinical entities and should be considered in differential diagnosis of colonic lesions in endemic areas.

Telmisartan-induced sprue-like enteropathy: a case report and a review of patients using non-olmesartan angiotensin receptor blockers.

Recent studies have identified sprue-like illness associated with the use of the antihypertensive agent olmesartan medoxomil. However, whether this condition is specific to the use of olmesartan or is associated with the use of drugs belonging to the class of "sartans" remains to be clarified. A 45-year-old woman with chronic kidney disease along with hypothyroidism and hypertension presented with chronic diarrhea and significant weight loss. Endoscopy of the upper gastrointestinal tract showed scalloping and grooving of the duodenum, and histopathological examination showed subtotal villous atrophy. She was on telmisartan for hypertension, which was discontinued. Subsequently, diarrhea ameliorated dramatically, and she regained weight. To our knowledge, this is the first study to report telmisartan-associated sprue-like enteropathy. Further, we have reviewed the cases of patients with sprue-like enteropathy caused by valsartan, irbesartan, and eprosartan.

Prevalence and clinical impact of vitamin D deficiency on abdominal tuberculosis.

BACKGROUND: Vitamin D is recognised to have multiple actions, including role in immune modulation. The prevalence and impact of vitamin D deficiency (VDD) in abdominal tuberculosis is unknown. METHODS: We report the prevalence and clinical impact of VDD in patients with abdominal tuberculosis. The patients were divided into two groups: VDD (<20 ng/ml) or vitamin D sufficient (VDS) (⩾20 ng/ml). Groups were compared for extent (abdominal alone or extra-abdominal also) of disease and pattern of involvement (intestinal, peritoneal or both) and inflammatory response [serum C-reactive protein (CRP)]. RESULTS: Of 63 patients, 53 had complete data (mean age: 36.3 ± 14.43, 31 males). Fourty-five (84.9%) patients had VDD and mean VD levels were 11.1 ± 10.1 ng/ml. Of 8 patients with VDS, 1 (12.5%) had extra-abdominal involvement while 13 (28.9%) with VDD had extra-abdominal involvement (p = 0.066). The mean CRP in patients with VDD was 42.9 ± 34.9 mg/dl vis-a-vis 105.38 ± 64.8 in VDS (p ⩽ 0.05). All seven patients with both intestinal and peritoneal involvement had VDD. CONCLUSION: VDD is common in abdominal tuberculosis and may be associated with more extensive involvement albeit a reduced inflammatory response.

Multiplex PCR for rapid diagnosis of gastrointestinal tuberculosis.

BACKGROUND: Rapid and specific diagnosis of gastrointestinal tuberculosis (GITB) is of utmost importance. AIM: To evaluate Multiplex PCR (MPCR) using MPB64 and IS6110 primers specific for M. tuberculosis for rapid diagnosis of GITB. MATERIALS AND METHODS: MPCR was performed on colonoscopy biopsy specimens on 11 GITB confirmed (culture/AFB/histopathology was positive), 29 GITB suspected and 30 Non GITB (control group) patients. RESULTS: MPB64 PCR had sensitivity and specificity of 90% and 100% for confirmed GITB cases. In 29 clinically diagnosed but unconfirmed GITB cases, MPCR was positive in 72.41%. MPCR was negative in all control group patients. The overall sensitivity and specificity of microscopy, culture, histopathology and MPCR was 5%, 2% 20% and 77.5% and 100%, 100%, 100% and 100% respectively. CONCLUSION: MPCR has good sensitivity and specificity in diagnosing gastrointestinal tuberculosis.