Background: Fatigue significantly affects health-related quality of life (HRQoL) in patients with immune thrombocytopenia (ITP). However, the interplay between fatigue and cytokines in ITP remains poorly understood. Methods: This study included 100 patients with persistent or chronic ITP who had not received ITP-directed therapy in the previous 8 weeks and 50 age-matched healthy controls. Fatigue and HRQoL were assessed using the Functional Assessment of the Chronic Illness Therapy (FACIT) scale. Concurrently, plasma levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, IL-17, and interferon-gamma (IFN-γ) were measured via enzyme-linked immunosorbent assay (ELISA). Results: ITP patients had significantly lower total FACIT scores [median 146 (range 59–160]) and fatigue subscale scores [median 45 (range 9–52]) than controls [155 (149–159) and 49 (44–52), respectively; both p < 0.001]. IL-12 levels were significantly elevated in patients (313.2 vs. 95.5 pg/mL; p < 0.001) and showed a significant negative correlation with FACIT scores (Spearman’s ρ = –0.272, p = 0.007). Multivariate analysis revealed that female sex, longer disease duration among patients with chronic ITP (> 24 months), and elevated IL-12 levels were independently associated with greater fatigue and poorer HRQoL. Conclusions ITP is associated with significant fatigue and HRQoL impairment, with IL-12 emerging as a potential immunological marker linked to this symptom burden.

Clinical outcomes after fixation of distal humerus intraarticular fractures are directly related to the quality of reduction. The use of three-dimensional (3D)-printed fracture models can benefit preoperative planning to ensure good reduction. This review aims to determine if surgery performed with 3D printing assistance are faster and result in fewer complications and improved clinical outcomes than conventional methods. We also outline the benefits and drawbacks of this novel technique in surgical management of distal humerus fractures. Methods: A systematic literature search was carried out in various electronic databases. Search results were screened based on title and abstract. Data from eligible studies were extracted into spreadsheets. Meta-analysis was performed using appropriate computer software. Results: Three randomized controlled trials with 144 cases were included in the final analysis. The 3D-printed group had significantly shorter mean operating time (mean difference, 16.25 minutes; 95% confidence interval [CI], 12.74–19.76 minutes; P<0.001) and mean intraoperative blood loss (30.40 mL; 95% CI, 10.45–60.36 mL; P=0.005) compared with the conventional group. The 3D-printed group also tended to have fewer complications and a better likelihood of good or excellent outcomes as per the Mayo elbow performance score, but this did not reach statistical significance. Conclusions: Three-dimensional-printing-assisted surgery in distal humerus fractures has several benefits in reduced operating time and lower blood loss, indirectly decreasing other complications such as infection and anemia-related issues. Future good-quality studies are required to conclusively demonstrate the benefits of 3D printing in improving clinical outcomes. Level of evidence: I.

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.

Background/Aims: Infliximab (IFX) has been used to induce and maintain remission in patients with severe steroid-refractory ulcerative colitis (UC). Long-term use of biologics in developing countries is limited by high cost and frequent side effects. An optimal maintenance strategy in these patients needs to be established. Methods: A retrospective analysis of maintenance of clinical remission with combination of azathioprine (AZA) and 5-aminosalicylates (5-ASA) in patients with severe steroidrefractory UC where IFX (5 mg/kg intravenously at weeks 0, 2, 6) had been used only as an induction therapy was done at 2 centers in India. Primary outcome was the proportion of patients maintaining corticosteroid-free sustained clinical remission (SCR) at the end of study period. Rates of relapse and cost of therapy were also analyzed. Results: Of the 137 patients who received rescue IFX induction therapy, 77 (56.2%) achieved clinical remission (mean age 34.81 ± 13.32 years, 68.83% males, median follow-up 4 years, range 3 months to 6 years) and were included. Cumulative corticosteroid-free SCR was maintained in 68%, 59%, 42%, and 35% patients at 1, 2, 4, and 6 years respectively. Sixty-seven relapses were observed in 33 patients. Majority of the relapses (45/67, 67.16%) occurred within first 2 years of follow-up. Two relapses were managed with re-induction with IFX, one required colectomy, whereas all other responded to repeat course(s) of corticosteroids. Annual per capita maintenance therapy with 5-ASA and AZA was cheaper by US$ 4,526 compared to maintaining remission with IFX. Conclusions Clinical remission achieved with IFX induction therapy in severe steroid-refractory UC can be sustained over long time with a combination of AZA and 5-ASA.

Background/Aims: The national registry for inflammatory bowel disease (IBD) was designed to study epidemiology and prescribing pattern of treatment of IBD in India. Methods: A multicenter, cross-sectional, prospective registry was established across four geographical zones of India. Adult patients with ulcerative colitis (UC) or Crohn’s disease (CD) were enrolled between January 2014 and December 2015. Information related to demographics; disease features; complications; and treatment history were collected and analyzed. Results: A total of 3,863 patients (mean age, 36.7 ± 13.6 years; 3,232 UC [83.7%] and 631 CD [16.3%]) were enrolled. The majority of patients with UC (n = 1,870, 57.9%) were from north, CD was more common in south (n = 348, 55.5%). The UC:CD ratio was 5.1:1. There was a male predominance (male:female = 1.6:1). The commonest presentation of UC was moderately severe (n = 1,939, 60%) and E2 disease (n = 1,895, 58.6%). Patients with CD most commonly presented with ileocolonic (n = 229, 36.3%) inflammatory (n = 504, 79.9%) disease. Extraintestinal manifestations were recorded among 13% and 20% of patients in UC and CD respectively. Less than 1% patients from both cohorts developed colon cancer (n = 26, 0.7%). The commonly used drugs were 5-aminosalicylates (99%) in both UC and CD followed by azathioprine (34.4%). Biologics were used in only 1.5% of patients; more commonly for UC in north and CD in south. Conclusions The national IBD registry brings out diversities in the 4 geographical zones of India. This will help in aiding research on IBD and improving quality of patient care.

Background/Aims: Exclusive enteral nutrition (EEN), an established modality for pediatric Crohn’s disease (CD) is seldomly utilized in adults. The present study reports the outcome of EEN in adult CD patients at a tertiary care hospital in India. Methods: This was a retrospective analysis of CD patients who received EEN as a sole modality/adjunct to other treatment. The primary and secondary outcomes changed in Crohn’s Disease Activity Index (CDAI), and clinical response (decline in CDAI > 70), respectively, at 4 and 8 weeks. Subgroup analysis evaluated response across different phenotypes, EEN formulations and prior treatment. Linear mixed effect model was created to assess the predictors of EEN response. Results: Thirty-one CD patients received EEN over median duration of 4 weeks (range, 2–6 weeks). CDAI showed a significant improvement post EEN at 4 (baseline 290 [260–320] vs. 240 [180–280], P= 0.001) and 8 weeks (baseline 290 [260–320] vs. 186 [160–240], P= 0.001), respectively. The cumulative clinical response rates at 4 and 8 weeks were 37.3% and 80.4% respectively. The clinical response rates at 8 weeks across B1 (n = 4), B2 (n = 18) and B3 (n = 9) phenotypes were 50%, 78.8% and 100% respectively (log-rank test, P= 0.093). The response rates at 8 weeks with polymeric (n = 8) and semi-elemental diet (n = 23) were 75% and 82.6%% respectively (log-rank test, P= 0.49). Baseline CDAI (odds ratio, 1.008; 95% confidence interval, 1.002–1.017; P= 0.046) predicted response to EEN. Conclusions EEN was effective in inducing clinical response across different phenotypes of CD. Baseline disease activity remained the most important predictor of clinical response to EEN.

Background/Aims: The national registry for inflammatory bowel disease (IBD) was designed to study epidemiology and prescribing pattern of treatment of IBD in India. Methods: A multicenter, cross-sectional, prospective registry was established across four geographical zones of India. Adult patients with ulcerative colitis (UC) or Crohn’s disease (CD) were enrolled between January 2014 and December 2015. Information related to demographics; disease features; complications; and treatment history were collected and analyzed. Results: A total of 3,863 patients (mean age, 36.7 ± 13.6 years; 3,232 UC [83.7%] and 631 CD [16.3%]) were enrolled. The majority of patients with UC (n = 1,870, 57.9%) were from north, CD was more common in south (n = 348, 55.5%). The UC:CD ratio was 5.1:1. There was a male predominance (male:female = 1.6:1). The commonest presentation of UC was moderately severe (n = 1,939, 60%) and E2 disease (n = 1,895, 58.6%). Patients with CD most commonly presented with ileocolonic (n = 229, 36.3%) inflammatory (n = 504, 79.9%) disease. Extraintestinal manifestations were recorded among 13% and 20% of patients in UC and CD respectively. Less than 1% patients from both cohorts developed colon cancer (n = 26, 0.7%). The commonly used drugs were 5-aminosalicylates (99%) in both UC and CD followed by azathioprine (34.4%). Biologics were used in only 1.5% of patients; more commonly for UC in north and CD in south. Conclusions The national IBD registry brings out diversities in the 4 geographical zones of India. This will help in aiding research on IBD and improving quality of patient care.

Background/Aims: Exclusive enteral nutrition (EEN), an established modality for pediatric Crohn’s disease (CD) is seldomly utilized in adults. The present study reports the outcome of EEN in adult CD patients at a tertiary care hospital in India. Methods: This was a retrospective analysis of CD patients who received EEN as a sole modality/adjunct to other treatment. The primary and secondary outcomes changed in Crohn’s Disease Activity Index (CDAI), and clinical response (decline in CDAI > 70), respectively, at 4 and 8 weeks. Subgroup analysis evaluated response across different phenotypes, EEN formulations and prior treatment. Linear mixed effect model was created to assess the predictors of EEN response. Results: Thirty-one CD patients received EEN over median duration of 4 weeks (range, 2–6 weeks). CDAI showed a significant improvement post EEN at 4 (baseline 290 [260–320] vs. 240 [180–280], P= 0.001) and 8 weeks (baseline 290 [260–320] vs. 186 [160–240], P= 0.001), respectively. The cumulative clinical response rates at 4 and 8 weeks were 37.3% and 80.4% respectively. The clinical response rates at 8 weeks across B1 (n = 4), B2 (n = 18) and B3 (n = 9) phenotypes were 50%, 78.8% and 100% respectively (log-rank test, P= 0.093). The response rates at 8 weeks with polymeric (n = 8) and semi-elemental diet (n = 23) were 75% and 82.6%% respectively (log-rank test, P= 0.49). Baseline CDAI (odds ratio, 1.008; 95% confidence interval, 1.002–1.017; P= 0.046) predicted response to EEN. Conclusions EEN was effective in inducing clinical response across different phenotypes of CD. Baseline disease activity remained the most important predictor of clinical response to EEN.

The study was conducted for quantitive determination of macronutrients, micronutrients and heavy metals present in Spilanthes acmella Hutch and Dalz, a traditionally used important medicinal plant. The results illustrated the presence of substantial amounts of essential nutrient elements in different parts of the plant. K and Mg were detected in the range between 36.35 ± 1.01 to 67.78 ± 1.33 g/kg and 2.17 ± 0.13 to 7.02 ± 0.84 g/kg of DWS respectively. While the essential micronutrients Fe, Na, Mn, Zn and Cu were detected in the range between 62.62 ± 12.72 to 856.95 ± 76.61 mg/kg, 365.47 ± 23.84 to 633.03 ± 38.12 mg/kg, 51.66 ± 7.77 to 186.33 ± 13.92 mg/kg, 41.87 ± 2.85 to 53.89 ± 3.79 mg/kg and 18.49 ± 2.07 to 48.71 ± 4.89 mg/kg of DWS respectively. Besides, heavy metals (Cd, Ni and Pb) detected in some of the plant samples were beyond the maximum permissible limit (MPL) of FAO/WHO for herbal medicines. The concentrations of the essential nutrient elements except zinc were significantly different in different parts of the plant (p < 0.001). Further variation in the concentrations of the elements in the plant was observed with respect to seasonal changes and geographical conditions. Nevertheless the findings corroborate ethnomedicinal significance of the plant and signify the possibilibity of utilizing its standardized products for preparation of food supplements as well as multidimensional therapeutic herbal medicines.