Intravenous albumin infusion does not augment the response rate to a combination of exclusive enteral nutrition and intravenous steroids in acute severe ulcerative colitis: a randomized controlled trial.

INTRODUCTION: 30-40% patients with acute severe ulcerative colitis (ASUC) fail intravenous (IV) steroids requiring medical rescue therapy/colectomy. Low baseline albumin predicts steroid non-response, and exclusive enteral nutrition (EEN) has been shown to improve steroid response and albumin levels. Albumin infusion due to its anti-inflammatory and anti-oxidant properties might further improve steroid response in ASUC, which was evaluated in present study. METHODS: In this open-label randomized controlled trial, patients with ASUC were randomized in 1:1 ratio to albumin + standard of care (SOC) + EEN vs. SOC + EEN (Jan2021 - Feb2023). Both arms received 5 days of EEN with 400 mg IV hydrocortisone/day. Patients in albumin arm were administered 5 days of 20% w/v intravenous albumin (100 ml). Primary outcome was 1) steroid failure (need for rescue medical therapy or colectomy) and 2) proportion of patients with adverse events. RESULTS: Sixty-one patients (albumin-30, SOC-31)(mean age-31.6±0.4 years, male-57.4%), were included. Baseline characteristics were comparable. There was no difference in steroid failure between albumin and SOC arm(10/30(33.33 %) vs 13/31(41.94 %), p=0.49). No adverse events were reported with albumin infusions. Colectomy rate(10% vs 9.68%, P=1), response to salvage medical therapy (88.89% vs 76.92%, P=0.62) and median duration of hospitalization (10.5(7-16) vs 10(7-20), P=0.43) were also comparable. Long-term composite outcome of colectomy and re-admission rates was numerically higher in the albumin than SOC arm (37.04% vs 17.86%, p>0.05), although it did not reach statistical significance. CONCLUSION: There was no benefit of intravenous albumin infusion as an adjunct to IV steroids and EEN in patients with ASUC.

Effect of prostaglandin treatment on the estrus behaviour, follicular and luteal morphometry and serum hormone profile in sub-estrus buffaloes during non-breeding season.

Sub-estrus buffaloes do not exhibit estrus signs despite being cyclic contributing to extended service periods and inter-calving intervals causing significant economic loss. The present study described the effect of synthetic prostaglandin (PGF2α) on estrus behaviour, follicular and luteal morphometry, and serum estradiol (E2) and progesterone (P4) profile in sub-estrus buffaloes during the non-breeding season. The incidence of sub-estrus was 38.4% during the non-breeding season. The sub-estrus buffaloes (n = 33) were divided into two groups, viz., Control (n = 16) and PGF2α treatment (Inj. Cloprostenol 500 µg, i.m., n = 17). Estrus induction response was significantly greater in the treatment (100 vs. 18.75%, p < .001), and a relatively greater proportion of animals conceived in the treatment group (29.41 vs. 6.25%, p = .08). The time elapsed to induction of estrus and insemination following treatment was significantly lower in the treatment group than control. A significant increment in the follicle diameter (9.72 ± 0.45 vs. 13.00 ± 0.45 mm, P < .0001) and serum estradiol (E2) concentration (66.01 ± 11.92 vs. 104.9 ± 13.21 pg/mL, p = .003) observed at the post-treatment period in the PGF2α treatment group. At the same time, CL diameter was reduced significantly at a higher regression rate in the PGF2α treated buffaloes than those of control. Of the responded buffaloes, only 30% showed high-intensity estrus attributed to the expulsion of cervico-vaginal mucus (CVM), uterine tonicity, micturition, and mounting response by a teaser bull. From this study, it can be concluded that the administration of PGF2α could induce estrus in the sub-estrus buffaloes during the non-breeding season. Behavioural changes, along with sonographic observation of POF, regressing CL, and serum E2 and P4 concentration would be useful to determine the right time of insemination in sub-estrus buffaloes during non-breeding season.

Evaluation of in-feed supplementation of formic acid and thymol as non-antibiotic growth promoters and assessing their effect on antimicrobial resistant E.coli isolated in Turkey.

With the rampant usage of antibiotics as growth promoters (AGPs) in poultry sector, there has been alarming concerns of antimicrobial resistant microbes such as Escherichia coli. Diversification of poultry farming due to consumer demand for safer products with higher protein content, turkey production is gaining popularity. Feed additives such as formic acid (FA) and thymol (TH) are effectively replacing AGPs due to their antimicrobial action. This directed the researchers to find alternatives to antibiotics such as thymol and formic acid because of their strong antimicrobial, anti-oxidative, digestive-stimulating properties. To assess the efficacy of FA and TH as growth promoters and their effect on the antimicrobial resistance (AMR) load, the current study (0-12 weeks) was conducted in CARI VIRAT turkey poults (n = 256; unsexed) those were randomly distributed into eight treatment groups: control(T1), AGP (T2), graded levels of FA (T3 to T5) @ 2.5, 5 and 7.5 ml/kg and TH (T6 to T8) @ 120, 240 and 350 mg/kg. Cloacal swab samples were collected at 0, 4th, 8th and 12th week interval and processed further for isolation, identification and assessment of resistance profile of E. coli. The final body weight, cumulative gain and FCR were significantly (p < 0.05) better for birds under supplementation. The Total plate count (TPC) and coliforms showcased a significant (p < 0.001) reduction in the FA and TH supplement groups as compared to control and AGP group. The resistance profile indicated E. coli isolates from AGP group with significantly (p < 0.001) highest resistivity against antibiotics (viz. chloramphenicol, tetracycline, nalidixic acid, chlortetracycline) while isolates from FA (T5) and TH (T8) groups were the least resistant. blaAmpC gene was significantly (p < 0.001) harbored in T2 isolates whereas least detected in T5 and T8. It was inferred that formic acid (7.5 ml/kg) and thymol (360 mg/kg) can effectively replace AGPs and lower AMR burden in poultry.

To Determine the Quality of Life in Indian Women After Peripartum Hysterectomy Using a Hindi Version of the SF-36 Questionnaire.

Objective: The objective of the study was to determine the quality of life in women after peripartum hysterectomy using a Hindi version of the SF-36 questionnaire. Background: There are long-term effects on quality of life in women after peripartum hysterectomy. The effects on physical, mental, and social functioning have a prolonged recovery. No studies have been done in Indian women after peripartum hysterectomy to evaluate quality of life. Methods: Patients who underwent peripartum hysterectomy from January 2017 to May 2021 were contacted to participate in the study. To determine the quality of life post-surgery, a Hindi version of the 36-item Short-Form Health Survey (SF-36) was used for a face-to-face personal interview-based assessment. The participants were divided into two groups based on the duration between surgery and the interview. The aggregate scores for the eight components of SF-36 were calculated, and responses were analyzed. Results: Out of the 138 post-hysterectomy women, 118 were enrolled in the study. Women who could not be contacted [14 (10.14%)] and those who died post-procedure [6 (4.35%)] were excluded. Out of the total, 43 assessed participants were within 2 years of surgery, and 75 were after 2 years of surgery. The group that was assessed after 2 years of surgery had a significantly lower quality of life in six, out of the eight aspects of SF-36 domains. Conclusion: Women after peripartum hysterectomy undergo a prolonged recovery phase with effects on physical, mental, and social functioning. A multi-disciplinary long-term follow-up including physiotherapy and psychotherapy is required and that should be guided by a dedicated clinical team.

Exclusive Enteral Nutrition Mediates Beneficial Gut Microbiome Enrichment in Acute Severe Colitis.

BACKGROUND: Exclusive enteral nutrition (EEN) supplementation of the standard of care (SOC) augments steroid responsiveness in patients with acute severe ulcerative colitis (ASUC). EEN is known to alter gut microbial composition. The present study investigates EEN-driven gut microbial alterations in patients with ASUC and examines their correlations with clinical parameters. METHODS: Stool samples from patients with ASUC (n = 44) who received either EEN-supplemented SOC (EEN group; n = 20) or SOC alone (SOC group; n = 24) for 7 days were collected at baseline (day 0) and postintervention (day 7). Microbiome analysis was carried out using 16S ribosomal RNA gene sequencing followed by data processing using QIIME2 and R packages. RESULTS: Seven-day EEN-conjugated corticosteroid therapy in patients with ASUC enhanced the abundances of beneficial bacterial genera Faecalibacterium and Veillonella and reduced the abundance of Sphingomonas (generalized linear model fitted with Lasso regularization with robustness of 100%), while no such improvements in gut microbiota were observed in the SOC group. The EEN-associated taxa correlated with the patient's clinical parameters (serum albumin and C-reactive protein levels). Unlike the SOC group, which retained its preintervention core microbiota, EEN contributed Faecalibacterium prausnitzii, a beneficial gut bacterial taxon, to the gut microbial core. EEN responders showed enhancement of Ligilactobacillus and Veillonella and reduction in Prevotella and Granulicatella. Analysis of baseline gut microbiota showed relative enhancement of certain microbial genera being associated with corticosteroid response and baseline clinical parameters and that this signature could conceivably be used as a predictive tool. CONCLUSIONS: Augmentation of clinical response by EEN-conjugated corticosteroid therapy is accompanied by beneficial gut microbial changes in patients with ASUC.

Exclusive enteral nutrition­supplemented corticosteroid therapy in acute severe ulcerative colitis (ASUC) is accompanied by the enrichment of beneficial gut microbial genera, which correlate negatively with the disease activity scores and objective inflammatory markers in ASUC. The baseline gut microbiota in ASUC associates with and may predict corticosteroid response.

Nanoparticle-based platforms for targeted drug delivery to the pulmonary system as therapeutics to curb cystic fibrosis: A review.

Cystic fibrosis (CF) is a genetic disorder of the respiratory system caused by mutation of the Cystic Fibrosis Trans-Membrane Conductance Regulator (CFTR) gene that affects a huge number of people worldwide. It results in difficulty breathing due to a large accumulation of mucus in the respiratory tract, resulting in serious bacterial infections, and subsequent death. Traditional drug-based treatments face hindered penetration at the site of action due to the thick mucus layer. Nanotechnology offers possibilities for developing advanced and effective treatment platforms by focusing on drugs that can penetrate the dense mucus layer, fighting against the underlying bacterial infections, and targeting the genetic cause of the disease. In this review, current nanoparticle-mediated drug delivery platforms for CF, challenges in therapeutics, and future prospects have been highlighted. The effectiveness of the different types of nano-based systems conjugated with various drugs to combat the symptoms and the challenges of treating CF are brought into focus. The toxic effects of these nano-medicines and the various factors that are responsible for their effectiveness are also highlighted.

A bis-calix[4]arene-supported [CuII16] cage.

Reaction of 2,2'-bis-p-tBu-calix[4]arene (H8L) with Cu(NO3)2·3H2O and N-methyldiethanolamine (Me-deaH2) in a basic dmf/MeOH mixture affords [CuII16(L)2(Me-dea)4(µ4-NO3)2(µ-OH)4(dmf)3.5(MeOH)0.5(H2O)2](H6L)·16dmf·4H2O (4), following slow evaporation of the mother liquor. The central core of the metallic skeleton describes a tetracapped square prism, [Cu12], in which the four capping metal ions are the CuII ions housed in the calix[4]arene polyphenolic pockets. The [CuII8] square prism is held together "internally" by a combination of hydroxide and nitrate anions, with the N-methyldiethanolamine co-ligands forming dimeric [CuII2] units which edge-cap above and below the upper and lower square faces of the prism. Charge balance is maintained through the presence of one doubly deprotonated H6L2- ligand per [Cu16] cluster. Magnetic susceptibility measurements reveal the predominance of strong antiferromagnetic exchange interactions and an S = 1 ground state, while EPR is consistent with a large zero-field splitting.

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.

A Comparative Study on Clinico-radiological Differentiation of Sino-nasal Squamous Cell Carcinoma (SCC) and Sino-nasal Non-Hodgkins Lymphoma (NHL).

(1) To compare clinical presentations between sinonasal non-Hodgkins Lymphoma (NHL) and sino-nasal Squamous cell carcinoma (SCC). (2) To compare computed tomographic (CT) scan findings between sino-nasal NHL and sino-nasal SCC. (1) Design: Retrospective Comparative study. (2) Setting: tertiary care hospital. (3) Subjects: patients with histologically proven primary maxillary tumors (NHL and SCC). (4) Method: (a) Patients: medical records between March 2013 to March 2018 were examined and patients with histologically proven primary maxillary tumors (NHL and SCC) were included in the study. (b) CT imaging: unenhanced and contrast enhanced images were obtained for all patients. Unenhanced CT images were reconstructed using bone and soft tissue algorithm. (c) Image Assessment: Predominant growth patterns of the tumors were noted from the CT images. Sino-nasal NHL: 8 men and 3 women; Sino-nasal SCC: 19 men and 5 women. Mean age of the NHL and SCC patients were 66.18 y and 64.88 y respectively. Nasal obstruction, diplopia/blurred vision, nasal/cheek pain and cranial nerve palsies were significantly more common presentation among sino-nasal NHL patients (p values of 0.0053, 0.0014, 0.0089 and 0.0089 respectively). Permeative growth pattern was significantly higher among NHL patients (54.54%) (p value = 0.026) whereas SCCs showed significant destructive growth pattern (83.33%) (p value = 0.0009). Intra-tumoral necrosis was significantly higher in SCC patients (87.5%) (p value = < 0.0001). Nasal obstruction, diplopia/blurred vision, nasal/cheek pain and cranial nerve palsies were the predominant presenting features in sino-nasal NHL patients. In CT imaging, Sino-nasal SCCs showed predominantly destructive growth pattern and intra-tumoral necrosis whereas permeative growth was predominant feature of sino-nasal NHL.

Stringent screening strategy significantly reduces reactivation rates of tuberculosis in patients with inflammatory bowel disease on anti-TNF therapy in tuberculosis endemic region.

BACKGROUND: Anti-tumor necrosis factor (anti-TNF) therapy use in patients with inflammatory bowel disease (IBD) leads to an increased risk of tuberculosis (TB) reactivation despite latent tuberculosis (LTB) screening, especially in TB endemic regions. AIM: We evaluated the effect of stringent screening strategy and LTB prophylaxis on TB reactivation. METHODS: We performed an ambispective comparison between patients who received anti-TNF therapy after January 2019 (late cohort) and between Jan 2005 and Jan 2019 (early cohort). Late cohort patients were subjected to stringent screening criteria which included all: history of past TB/recent contact with active TB, chest X-ray, CT (computed tomography) chest, IGRA (interferon-gamma release assay), TST (tuberculin skin test), and if any positive were given chemoprophylaxis. A cohort comparison was done to evaluate for risk reduction of TB following the stringent screening strategy. RESULTS: One hundred seventy-one patients (63: ulcerative colitis/108: Crohn's disease, mean age diagnosis: 28.5 ± 13.4 years, 60% males, median follow-up duration after anti-TNF: 33 months [interquartile range: 23-57 months]) were included. Among the 112 in the early cohort, 29 (26%) underwent complete TB screening, 22 (19.6%) had LTB, 10 (9%) received chemoprophylaxis, and 19 (17%) developed TB. In comparison, in the late cohort, 100% of patients underwent complete TB screening, 26 (44%) had LTB, 23 (39%) received chemoprophylaxis, and only 1(1.7%) developed TB (p < 0.01). On survival analysis, patients in early cohort had a higher probability of TB reactivation compared with the late cohort (HR: 14.52 (95% CI: 1.90-110.61 [p = 0.01]) after adjusting for gender, age at anti-TNF initiation, concomitant immunosuppression, anti-TNF doses, and therapy escalation. CONCLUSION: The high risk of TB reactivation with anti-TNF therapy in TB endemic regions can be significantly mitigated with stringent LTB screening and chemoprophylaxis.

Characterization of organophosphate pesticide sorption of potato peel biochar as low cost adsorbent for chlorpyrifos removal.

There has been a growing interest in the scientific world in the production of biochar from natural organic wastes as potential sustainable precursors for bioremediation. Potato peel biochar was produced by slow pyrolysis method under oxygen-limited conditions and used as bio adsorbent in bioremediation of commercial pesticide having Chlorpyrifos as an active component. Chlorpyrifos is an organophosphate pesticide, highly neurotoxic, and primarily targets the central nervous system of pests and insects. The excess residues of chlorpyrifos are hazardous to environmental flora and fauna. Chlorpyrifos was treated against biochar at varying physical parameters and further optimized by using response surface methodology through Box-Behnken design (BBD). 72.06% of pesticide removal was observed post 24 h of treatment against a pesticide concentration of 1346.85 µg/ml with a biochar concentration of 1.04 mg/ml under room temperature at pH 5.04. Biochar was characterized by proximate and ultimate analysis, FTIR, and SEM-EDX. Characterization by SEM-EDX showed the surface morphology and minerals on the peel and biochar. Microgram of potato peel shows pores of larger size than biochar having many cavities with different dimensions. In the plant system, growth morphology, nutritional status, polyphenols, total antioxidant content, and free radical scavenging activity were assessed. Enhancement in presence of biochar was recorded in growth morphology and plant biomolecules including photosynthetic pigments. Better translocation of the nutrient is recorded in biochar treated plants, as evidenced by the low amount of carbohydrate and protein in treated leaves. Biocompatibility assessment of chlorpyriphos in fish erythrocytes showed 43.26% hemolysis by pesticide-treated biochar. The practical use of this approach can also be best utilized if applied to those geographical regions where the soil pH is acidic. Biochar is a marketable bio-product, which can have a positive impact in agriculture, industries, and the energy sector creating a bio-based economy with reduced environmental pollution.

Differential prevalence of pathobionts and host gene polymorphisms in chronic inflammatory intestinal diseases: Crohn's disease and intestinal tuberculosis.

BACKGROUND AND OBJECTIVES: Crohn's disease (CD) and Intestinal tuberculosis (ITB) are chronic inflammatory ulcero-constrictive intestinal diseases with similar phenotype. Although both are disease models of chronic inflammation and their clinical presentations, imaging, histological and endoscopic findings are very similar, yet their etiologies are diverse. Hence, we aimed to look at differences in the prevalence of pathobionts like adherent-invasive Escherichia coli (AIEC), Listeria monocytogenes, Campylobacter jejuni and Yersinia enterocolitica in CD and ITB as well as their associations with host-associated genetic polymorphisms in genes majorly involved in pathways of microbial handling and immune responses. METHODS: The study cohort included 142 subjects (69 patients with CD, 32 with ITB and 41 controls). RT- PCR amplification was used to detect the presence of AIEC, L. monocytogenes, C. jejuni, and Y. enterocolitica DNA in colonic mucosal biopsies. Additionally, we tested three SNPs in IRGM (rs13361189, rs10065172, and rs4958847), one SNP in ATG16L1 (rs2241880) and one SNP in TNFRSF1A (rs4149570) by real-time PCR with SYBR green from peripheral blood samples in this cohort. RESULTS: In patients with CD, AIEC was most frequently present (16/ 69, 23.19%) followed by L. monocytogenes (14/69, 20.29%), C. jejuni (9/69, 13.04%), and Y. enterocolitica (7/69, 10.14%). Among them, L. monocytogenes and Y. enterocolitica were significantly associated with CD (p = 0.02). In addition, we identified all the three SNPs in IRGM (rs13361189, rs10065172, and rs4958847), one SNP in ATG16L1 (rs2241880) and TNFRSF1A (rs4149570) with a significant difference in frequency in patients with CD compared with ITB and controls (p<0.05). CONCLUSION: Higher prevalence of host gene polymorphisms, as well as the presence of pathobionts, was seen in the colonic mucosa of patients with CD as compared to ITB, although both are disease models of chronic inflammation.

Budget impact of capmatinib for adults with metastatic non-small cell lung cancer harboring a MET exon 14 skipping mutation in the United States.

AIMS: To estimate the budget impact of adding capmatinib, the first FDA approved MET inhibitor, to a US commercial or Medicare health plan for patients with metastatic non-small cell lung cancer (mNSCLC) whose tumors have a mutation that leads to MET exon 14 (METex14) skipping. METHODS: Target population size was estimated using published epidemiology data. Clinical data were obtained from the GEOMETRY mono-1 capmatinib trial and published trials. Treatments in the market mix included crizotinib, pembrolizumab, ramucirumab, and chemotherapy. Uptake of capmatinib and testing rates were based on market research. All costs (drug acquisition and administration, pre-progression, progression, terminal care, adverse event, and testing) were estimated based on public sources (2020 USD). RESULTS: The number of patients eligible for capmatinib in the first three years was estimated to be 2-3 in a hypothetical 1 million member commercial plan and 34-44 in a hypothetical 1 million member Medicare plan each year. The estimated total budget impact ranged from $9,695 to $67,725 for a commercial plan and $141,350 to $985,695 for Medicare. With capmatinib included, a marginal per member per month budget impact was estimated (commercial: $0.0008 to $0.0056; Medicare: $0.0118 to $0.0821). Capmatinib inclusion resulted in lower medical costs (commercial: -$0.0003 to -$0.0007; Medicare: -$0.0037 to -$0.0106), partially offsetting increased drug costs ($0.0011 to $0.0064; $0.0154 to $0.0928, respectively), and were primarily driven by reductions in progression and terminal care costs (-$0.0003 to -$0.0009; -$0.0037 to -$0.0125, respectively). The results were most sensitive to capmatinib market share, capmatinib price, and treatment duration. LIMITATIONS: Certain assumptions were applied to the model to account for inputs with limited evidence. CONCLUSIONS: The estimated budget impact of including capmatinib for mNSCLC with a METex14 skipping mutation is minimal, and the increased drug costs were partially offset by savings in AEs, and progression-related and terminal care costs.

Therapeutic apheresis in ABO-incompatible kidney and liver transplantation: A single-center experience of 50 patients.

ABO antigens play an important role in solid organ transplantation. Desensitization for ABO incompatibility offers patients awaiting transplant a larger donor pool. The aim of this study was to assess outcome of desensitization using the institutional preconditioning protocol in ABO-incompatible solid organ transplants. A retrospective analysis of ABO-incompatible solid organ transplants between October 2015 and June 2018, at a tertiary healthcare center was performed. The preconditioning regimen consisted of immunosuppression and therapeutic apheresis (TA). Pre- and post-TA titers were performed, until a target titer of 8 or below was achieved, at which transplant was performed. Follow-up data till 1 year was analyzed. A total of 50 ABO-incompatible solid organ transplantations, including 14 liver transplants and 36 renal transplants were analyzed. The median baseline anti-A and anti-B titers were 192 and 256, respectively. A total of 150 therapeutic plasma exchange (TPE) procedures were performed for renal transplant recipients; 19 TPE and eight immunoadsorption procedures (five preoperative and three intraoperative) were performed for liver transplant recipients. Five (10%) patients experienced minor adverse events. Biopsy revealed antibody-mediated rejection was observed in three cases in the immediate posttransplant phase and in three (6.67%) cases over 1 year. There was one death due to transplant-associated thrombotic microangiopathy. Graft survival for renal transplant was 100% and death-censored graft survival for liver transplant was 100%. Despite difficulties, ABO-incompatible transplants can be performed without antibody-mediated rejection with the use of an appropriate protocol.

Clinical outcome of living donor kidney transplantation across simultaneous ABO and HLA incompatibility: Single center experience of first ten cases.

BACKGROUND AND AIMS: Preconditioning using different protocols has been tested to prevent antibody mediated rejection (ABMR) individually for ABO and HLA incompatibility. However, simultaneous presence of both barriers is still less explored. The aim of this study was to report outcomes of institutional desensitization protocol in renal transplant recipients with simultaneous ABO and HLA incompatibility. MATERIALS AND METHODS: This was a retrospective study conducted from October 2015 to December 2018. All patients with a clinical diagnosis of dialysis dependent chronic kidney disease (CKD), who were prospective coexistent HLA and ABO incompatible renal transplant recipients were included in the study. Patients were followed up and graft function and patient survival was assessed at 1 y from the date of transplant. RESULTS: Median and mode baseline anti-A titers were 64, while median and mode baseline anti-B titers were 256. All recipients were discharged by tenth postoperative day. None of the patients had any bleeding complications. Post transplant infection rate was found to be 20 %. A total of 54 therapeutic plasma exchange (TPE) procedures were performed before transplant and 8 were performed after transplant. Graft survival and patient survival was 100 % at 3, 6, 9, and 12 months. Range and mean follow-up period was 15-42 months and 23 months respectively. Mean glomerular filtration rate (GFR) at 1 y using the CKD-EPI equation was 85.25 ± 13.76 mL/min. Biopsy proven ABMR was observed in one case only which was managed with TPE and immunosuppression. CONCLUSION: Simultaneous ABO and HLA incompatibility in renal transplant recipients can be managed successfully with adequate preconditioning and careful monitoring.

Unsterile injection equipment associated with HIV outbreak and an extremely high prevalence of HCV-A case-control investigation from Unnao, India.

The integrated counseling and testing center (ICTC) located in the district hospital, Unnao in the northern state of Uttar Pradesh (UP), India witnessed an increased detection of HIV among its attendees in July 2017. Subsequently, health camps were organized by the UP State AIDS Control Society in the villages and townships contributing to such detection. We conducted a case-control study to identify factors associated with this increased detection; 33 cases and 125 controls were enrolled. Cases were individuals, detected HIV sero-reactive during November 2017-April 2018 from three locations namely Premganj, Karimuddinpur and Chakmeerapur in the Bangarmau block of the district of Unnao. Controls hailed from the same geographical setting and tested HIV sero-nonreactive either in health camps or at ICTC centers from where the cases were detected. Misclassification bias was avoided by confirming HIV sero-status of both cases as well as controls prior to final analysis. Study participants were interviewed on various risk practices and invasive treatment procedures. They were also tested for HIV and other bio-markers reflecting unsafe injecting and sexual exposures such as hepatitis B surface antigen (HBsAg), anti-HCV antibody (HCV Ab), anti-herpes simplex-2 Immunoglobulin G (HSV-2 IgG) and rapid plasma regain (RPR) test for syphilis. Secondary data analysis on three time points during 2015 through 2018 revealed a rising trend of HIV among attendees of the ICTCs (ICTC-Hasanganj, ICTC-Unnao district hospital and ICTC- Nawabganj) catering to the entire district of Unnao. While there was a seven fold rise of HIV among ICTC attendees of Hasanganj (χ2 value for trend 23.83; p < 0.001), the rise in Unnao district hospital was twofold (χ2 value for trend 4.37; p < 0.05) and was tenfold at ICTC-Nawabganj (χ2 value for trend 5.23; p < 0.05) indicating risk of infection prevailing throughout the district. Primary data was generated through interviews and laboratory investigations as mentioned above. The median age of cases and controls was 50 year (minimum 18 -maximum 68; IQR 31-57) and 38 year (minimum 18 -maximum 78; IQR 29-50) respectively. Thirty six percent of the cases and 47% of controls were male. A significantly higher proportion of cases (85%) had HCV Ab compared to controls (56%; OR 4.4, 95% CI 1.5-12.1); none reported injection drug use. However, cases and controls did not differ significantly regarding presence of HSV-2 IgG (6% versus 8% respectively). Neither any significant difference existed between cases and controls in terms of receiving blood transfusion, undergoing invasive surgical procedures, tattooing, tonsuring of head or skin piercing. In multivariate logistic regression model, 'unsafe injection exposure during treatment-seeking'(AOR 6.61, 95% CI 1.80-24.18) and 'receipt of intramuscular injection in last five years' (AOR 7.20, 95% CI 1.48-34.88) were independently associated with HIV sero-reactive status. The monophyletic clustering of HIV sequences from 14 cases (HIV-1 pol gene amplified) indicated a common ancestry. Availability of auto-disabled syringes and needles, empowerment of the local communities and effective regulatory practices across care settings would serve as important intervention measures in this context.

Femoral shaft fracture following oil massage in neonates: a single-centre experience.

Femoral shaft fractures following oil massage in newborns are very rare. We describe our observations at a tertiary centre in northern India. Three such cases encountered during the study period from July 2014 to June 2019 were evaluated. Sociocultural details, neonatal illnesses, mode of delivery, history of child abuse, type of fracture and management were recorded and analysed. All patients had a mid-shaft fracture after forceful oil massage by caring grandmothers. They all had complete union of fractures by the end of four weeks. This case series shows that mid-shaft fracture femur in neonates has excellent long-term prognosis, but the practice of oil massage needs to be modulated.

A prospective, observational study for optimization of antibody screening in pretransfusion compatibility testing.

CONCLUSIONS: Despite known use of antibody screening (AS), it has not been adopted uniformly across blood centers in India. Many centers in India are currently using a type and hold policy with subsequent antihuman globulin (AHG) crossmatch when blood units are requested. The main aim of this study was to assess the benefits of a type and screen (TS) policy in which blood grouping and AS are performed simultaneously during the first hospital visit. If the AS is negative, subsequent requests for blood units would require an immediate spin test (IST) crossmatch with release of blood units, followed by an AHG crossmatch. This prospective, observational study was conducted at a tertiary health care center between July 2014 and December 2018 and included only Indian patients. Blood grouping and AS were performed during the first hospital visit on a total of 22,888 patients; the majority of patients were from hemato-oncology and blood marrow transplant, hepatology and liver transplant, cardiothoracic vascular surgery, and medical intensive care units. Demographic parameters were evaluated for risk of alloimmunization, and a record of the same was maintained. Depending on the AS results, a further course of action was chosen. Clinically significant alloantibodies were detected in 145 patients, and autoantibodies were detected in 53 patients. Alloantibodies were mainly against Rh and Kell blood group antigens. A significantly higher proportion of patients in the AS+ group required blood transfusion when compared with the AS- group. In cases wherein the IST crossmatch was compatible but AHG crossmatch was not, follow-up did not demonstrate any clinical or laboratory evidence of hemolysis. AS is a safe, efficient, and beneficial tool for pretransfusion compatibility testing in both AS+ and AS- patients. With a TS policy, AHG crossmatch can be omitted in AS- patients without compromising safety.

Blood component administration to multiple myeloma patients treated with daratumumab: suggesting a novel approach with use of 0.1 M dithiothreitol.

CONCLUSIONS: Storage of dithiothreitol (DTT)-treated red blood cells (RBCs) leads to hemolysis. The aim of this study was to compare 0.1 M DTT with 0.2 M DTT treatment of RBCs and to share our experience of providing components to seven patients on daratumumab (DARA). This prospective, observational study included patients who required RBC transfusion within 6 months of DARA administration. All patients underwent a baseline serologic evaluation followed by a repeat evaluation after DARA administration. In addition, use of 0.1 M DTT was compared with 0.2 M DTT in terms of concordance of results, hemolysis with storage of treated RBCs, and ease of use. A total of 22 RBC requisitions were received for seven patients. Antibody screen was positive for one patient (anti-C) at baseline; it was panreactive for all patients after DARA. Concordance of results between the two concentrations was 98.5 percent. Laboratory personnel found results obtained with use of 0.1 M DTT-treated RBCs easy to interpret. Supernatant hemoglobin was found to be significantly greater for 0.2 M DTT-treated RBCs at the sixth day of storage. In conclusion, component administration to patients on DARA can be done without delay if adequate policies and procedures are in place. Use of 0.1 M DTT-pretreated RBCs can be used to avoid delay in transfusion and reduce the burden on the laboratory of weekly preparation of 0.2 M DTT-treated RBCs.

DeSUMOylase SENP7-Mediated Epithelial Signaling Triggers Intestinal Inflammation via Expansion of Gamma-Delta T Cells.

Inflammatory bowel disease (IBD) is a complex autoimmune disorder recently shown to be associated with SUMOylation, a post-translational modification mechanism. Here, we have identified a link between epithelial deSUMOylases and inflammation in IBD. DeSUMOylase SENP7 was seen to be upregulated specifically in intestinal epithelial cells in both human IBD and a mouse model. In steady state, but not IBD, SENP7 expression was negatively regulated by a direct interaction and ubiquitination by SIAH2. Upregulated SENP7 in inflamed tissue displayed a distinct interactome. These changes led to an expansion of localized proinflammatory γδ T cells. Furthermore, in vivo knockdown of SENP7 or depletion of γδ T cells abrogated dextran sulfate sodium (DSS)-induced gut inflammation. Strong statistical correlations between upregulated SENP7 and high clinical disease indices were observed in IBD patients. Overall, our data reveal that epithelial SENP7 is necessary and sufficient for controlling gut inflammation, thus highlighting its importance as a potential drug target.