Serum albumin is the strongest predictor of anti-tumor necrosis factor nonresponse in inflammatory bowel disease in resource-constrained regions lacking therapeutic drug monitoring

Background/Aims@#Evidence on predictors of primary nonresponse (PNR), and secondary loss of response (SLR) to anti-tumor necrosis factor (anti-TNF) agents in inflammatory bowel disease is scarce from Asia. We evaluated clinical/biochemical/molecular markers of PNR/SLR in ulcerative colitis (UC) and Crohn’s disease (CD). @*Methods@#Inflammatory bowel disease patients treated with anti-TNF agents (January 2005–October 2020) were ambispectively included. Data concerning clinical and biochemical predictors was retrieved from a prospectively maintained database. Immunohistochemistry for expression of oncostatin M (OSM), OSM receptor (OSM-R), and interleukin-7 receptor (IL-7R) were done on pre anti-TNF initiation mucosal biopsies. @*Results@#One-hundred eighty-six patients (118 CD, 68 UC: mean age, 34.1±13.7 years; median disease duration at anti-TNF initiation, 60 months; interquartile range, 28–100.5 months) were included. PNR was seen in 17% and 26.5% and SLR in 47% and 28% CD and UC patients, respectively. In CD, predictors of PNR were low albumin (P<0.001), postoperative recurrence (P=0.001) and high IL-7R expression (P<0.027) on univariate; and low albumin alone (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.03–0.28; P<0.001) on multivariate analysis respectively. Low albumin (HR, 0.31; 95% CI, 0.15–0.62; P=0.001) also predicted SLR. In UC, predictors of PNR were low albumin (P<0.001), and high C-reactive protein (P<0.001), OSM (P<0.04) and OSM-R (P=0.07) stromal expression on univariate; and low albumin alone (HR, 0.11; 95% CI, 0.03–0.39; P=0.001) on multivariate analysis respectively. @*Conclusions@#Low serum albumin at baseline significantly predicted PNR in UC and PNR/SLR in CD patients. Mucosal markers of PNR were high stromal OSM/OSM-R in UC and high IL-7R in CD patients.

Interferon-gamma release assay has poor diagnostic accuracy in differentiating intestinal tuberculosis from Crohn’s disease in tuberculosis endemic areas

Background/Aims@#Intestinal tuberculosis (ITB) and Crohn’s disease (CD) frequently present with a diagnostic dilemma because of similar presentation. Interferon-gamma release assay (IGRA) has been used in differentiating ITB from CD, but with sparse reports on its diagnostic accuracy in tuberculosis endemic regions and this study evaluated the same. @*Methods@#Patients with definitive diagnosis of ITB (n=59) or CD (n=49) who underwent IGRA testing (n=307) were retrospectively included at All India Institute of Medical Sciences, New Delhi (July 2014 to September 2021). CD or ITB was diagnosed as per standard criteria. IGRA was considered positive at >0.35 IU/mL.Relevant data was collected and IGRA results were compared between ITB and CD to determine its accuracy. @*Results@#Among 59 ITB patients (mean age, 32.6±13.1 years; median disease duration, 1 year; male, 59.3%), 24 were positive and 35 tested negative for IGRA. Among 49 CD patients (mean age, 37.8±14.0; median disease duration, 4 years; male, 61.2%), 12 were positive and 37 tested negative for IGRA. Hence, for diagnosing ITB, IGRA showed a sensitivity, specificity, positive and negative predictive values of 40.68%, 75.51%, 66.67%, and 51.39%, respectively. The area under the curve of IGRA for ITB diagnosis was 0.66 (95% confidence interval, 0.55–0.75). In a subset (n=64), tuberculin skin test (TST) showed sensitivity, specificity, positive and negative predictive values of 64.7%, 73.3%, 73.3%, and 64.71%, respectively. IGRA and TST were concordant in 38 (59.4%) patients with κ=0.17. @*Conclusions@#In a tuberculosis endemic region, IGRA had poor diagnostic accuracy for differentiating ITB from CD, suggesting a limited value of IGRA in this setting.

Collection

All the plants are having medicinal values and thus are used traditionally in many diseasesfrom ancient times. One of such useful plant is Aerva lanata commonly known as “Bhui” which is awoody, prostate or succulent, perennial herb from the Amaranthaceae family, found in open forest onmountains, slopes, disturbed ground and deserted areas(1). The plant has been screened for diuretic,antidiabetic, anti-inflammatory and hepatoprotective activity (2) (3). According to the literature referredthe pharmacognostical studies of this plant have not been reported yet, therefore the presentinvestigation is planned to study the pharmacognostical and phytochemical aspects of Aerva lanata. Inthe present research article the pharmacognostical study i.e. morphological, microscopical, chemical &chromatographic analysis of plant Aerva lanata was carried out. This study provides the standardizationparameters important for the characterization & identification of the plant. The information will beuseful for the traditional medicine practitioners & establishing literature regarding the plant.Microscopic studies shows upper epidermis is straight walled, single layered containing trichomesbelow the epidermis collenchyma cellular layers are present which can be characterized by thickcellulosic deposition. Cells contain calcium oxalate crystals (in small amount) and starch. Vascularbundles present in spongy tissues. Physiochemical analysis shows Total ash, Acid insoluble ash, Watersoluble ash, Sulphated ash values as 10.01%, 2.01%, 4.92% and 4.82% respectively. Other parameterslike Alcohol soluble extractive value, Water soluble extractive value, Loss on drying and swelling indexare found to be 20%, 24%, 8% and 6.42%. Fluorescence study and preliminary phytochemical tests arealso performed. Thin layer chromatographic studies showing presence of carbohydrates, steroids,flavonoids and tannins at Rf values of 0.88, 0.86, 0.92 and 0.86 respectively.

Analytical Method Development And Its Validation For Estimation Of Chlorhexidine Gluconate

In the present work, Independent method was developed for estimation of Chlorhexidine Gluconate, Metronidazole benzoate,Lignocaine Hydrochloride, and Salicylic Acid in bulk and dosage form by UV-Visible Spectrophotometry. In this method the determination ofmaximum absorbance (λmax) of the drugs were found to be 259 nm, 285.8 nm, 263 nm and 304 nm. The validation parameters were studiedaccording to ICH guidelines. On the basis of % agreement criteria, therefore Average % agreement found to be 100.05 at 259 nm, 99.32 at285.8 nm, 100.001 at 304 nm and 99.70 at 263 nm. Specificity study shows the good agreement with results, indicating that excipients did notinterfere with the analyte. Repeatability study showed a % R.S.D of 0.2486 at 259 nm, 0.2605 at 285.8 nm, 0.403174 at 304 nm and 0.880817at 263 nm for Chlorhexidine Gluconate, Metronidazole benzoate, Lignocaine Hydrochloride, and Salicylic Acid. Thus it is concluded that theanalytical technique has a good repeatability precision as R.S.D are less than 5.3% (Specified) and less than 2% (desired). So it can be said thatthe proposed method is precise. Intraday study were showed a % R.S.D of 1.246918, 0.984763, 0.775939 and 1.022045 respectively forChlorhexidine Gluconate, Metronidazole benzoate, Lignocaine Hydrochloride, and Salicylic Acid. So it can be said that the proposed method isprecise. Interday study were showed a % R.S.D of 1.358486, 0.829325, 1.273356 and 0.968196 respectively for Chlorhexidine Gluconate,Metronidazole benzoate, Lignocaine Hydrochloride, and Salicylic Acid. So it can be said that the proposed method is precise. Limit of detectionwere found to be 0.097, 0.117, 0.010 and 0.074 g/ml at 259, 285.8, 304and 263 nm. Limit of quantification were found to be 0.29, 0.35, 0.030and 0.418 g/ml at 259, 285.5 304, and 263nm. The accuracy of the methods was proved by performing recovery studies in availableformulations. Since the % recovery 98.07 to 101.28 at 259 nm, 98.29 to 101.02 at 285.8 nm, 99.99 to 101.25 at 304nm and 99.10 to 101.78 at263nm are within the desirable confidence interval of 98-102%. So it can be said that the proposed method is accurate. The percent meanrecovery is 98.46, 101.42 (1:3), 98.20 and 99.78% of labeled amount, which is within specified limits of 98-102%. It can be said that proposedmethod can satisfactory be applied for analysis of Chlorhexidine Gluconate, Metronidazole benzoate, Lignocaine Hydrochloride, and SalicylicAcid in dosage form. The developed method is precise, accurate and do not suffer from any interference due to common excipients. It isevident from this study that the developed method is simple, sensitive, specific, precise and accurate and economic. Hence it can be employedfor routine analysis in quality control laboratories.