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Background : Kawasaki disease (KD) is the most common cause of acquired heart disease in developed countries. KD is increasingly being reported from India; however, studies involving the large number of patients are few. Methods : All children presenting to the center from January 2017 to December 2019, diagnosed to have KD, were retrospectively included in the study. Clinical and laboratory profiles, including echocardiograms, were reviewed. Factors contributing to intravenous immunoglobulin (IVIg) refractoriness and the development of coronary artery abnormalities (CAA) were assessed. Results : A total of 39 children with KD presented to the center during the study. While 32 received initial treatment at our center, seven were referred after the initial IVIg infusion. The age range was 2 months to 11 years (mean 42.15 ± 38.51 months). More than two-thirds of the cohort was male (n = 27/39). Mucosal involvement was the commonest clinical abnormality for the group, followed by rash. Hemoglobin was significantly lower in the group with coronary artery involvement (P = 0.001). CAA (61.5%), incomplete KD, and atypical features were much more common in infants compared to the rest. Refractoriness to treatment was significantly more common in infants (P = 0.029). Conclusions : A significant proportion of infants with KD had cardiac involvement. Infants were more likely to have IVIg-resistant disease.

BackgroundSolid organ transplant recipients have heightened risk for diffuse large B cell lymphoma (DLBCL). The role of donor-recipient HLA mismatch and recipient HLA type on DLBCL risk are not well established.MethodsWe examined 172 231 kidney, heart, pancreas, and lung recipients transplanted in the United States between 1987 and 2010, including 902 with DLBCL. Incidence rate ratios (IRRs) were calculated using Poisson regression for DLBCL risk in relation to HLA mismatch, types, and zygosity, adjusting for sex, age, race/ethnicity, year, organ, and transplant number.ResultsCompared with recipients who had 2 HLA-DR mismatches, those with zero or 1 mismatch had reduced DLBCL risk, (zero: IRR, 0.76, 95% confidence interval [95% CI], 0.61-0.95; one: IRR, 0.83; 95% CI, 0.69-1.00). In stratified analyses, recipients matched at either HLA-A, -B, or -DR had a significantly reduced risk of late-onset (>2 years after transplantation), but not early-onset DLBCL, and there was a trend for decreasing risk with decreasing mismatch across all 3 loci (P = 0.0003). Several individual recipient HLA-A, -B, -C, -DR, and -DQ antigens were also associated with DLBCL risk, including DR13 (IRR, 0.74; 95% CI, 0.57-0.93) and B38 (IRR, 1.48; 95% CI, 1.10-1.93), confirming prior findings that these 2 antigens are associated with risk of infection-associated cancers.ConclusionsIn conclusion, variation in HLA is related to susceptibility to DLBCL, perhaps reflecting intensity of immunosuppression, control of Epstein-Barr virus infection among transplant recipients or chronic immune stimulation.

Previous studies have suggested that kidney donors may have abnormalities of mineral and bone metabolism typically seen in chronic kidney disease. This may have important implications for the skeletal health of living kidney donors and for our understanding of the pathogenesis of long-term mineral and bone disorders in chronic kidney disease. In this prospective study, 182 of 203 kidney donors and 173 of 201 paired normal controls had markers of mineral and bone metabolism measured before and at 6 and 36 months after donation (ALTOLD Study). Donors had significantly higher serum concentrations of intact parathyroid hormone (24.6% and 19.5%) and fibroblast growth factor-23 (9.5% and 8.4%) at 6 and 36 months, respectively, as compared to healthy controls, and significantly reduced tubular phosphate reabsorption (-7.0% and -5.0%) and serum phosphate concentrations (-6.4% and -2.3%). Serum 1,25-dihydroxyvitamin D3 concentrations were significantly lower (-17.1% and -12.6%), while 25-hydroxyvitamin D (21.4% and 19.4%) concentrations were significantly higher in donors compared to controls. Moreover, significantly higher concentrations of the bone resorption markers, carboxyterminal cross-linking telopeptide of bone collagen (30.1% and 13.8%) and aminoterminal cross-linking telopeptide of bone collagen (14.2% and 13.0%), and the bone formation markers, osteocalcin (26.3% and 2.7%) and procollagen type I N-terminal propeptide (24.3% and 8.9%), were observed in donors. Thus, kidney donation alters serum markers of bone metabolism that could reflect impaired bone health. Additional long-term studies that include assessment of skeletal architecture and integrity are warranted in kidney donors.

BackgroundThe probability of liver transplant and death on the waiting list in the United States varies greatly by donation service area (DSA) due to geographic differences in availability of organs and allocation of priority points, making it difficult for providers to predict likely outcomes after listing. We aimed to develop an online calculator to report outcomes by region and patient characteristics.MethodsUsing the Scientific Registry of Transplant Recipients database, we included all prevalent US adults aged 18 years or older waitlisted for liver transplant, examined on 24 days at least 30 days apart over a 2-year period. Outcomes were determined at intervals of 30 to 365 days. Outcomes are reported by transplant program, DSA, region, and the nation for comparison, and can be shown by allocation or by laboratory model for end-stage liver disease (MELD) score (6-14, 15-24, 25-29, 30-34, 35-40), age, and blood type.ResultsOutcomes varied greatly by DSA; for candidates with allocation MELD 25-29, the 25th and 75th percentiles of liver transplant probability were 30% and 67%, respectively, at 90 days. Corresponding percentiles for death or becoming too sick to undergo transplant were 5% and 9%. Outcomes also varied greatly for candidates with and without MELD exception points.ConclusionsThe waitlist outcome calculator highlights ongoing disparities in access to liver transplant and may assist providers in understanding and counseling their patients about likely outcomes on the waiting list.

We previously reported that tacrolimus (TAC) trough blood concentrations for African American (AA) kidney allograft recipients were lower than those observed in white patients. Subtherapeutic TAC troughs may be associated with acute rejection (AR) and AR-associated allograft failure. This variation in TAC troughs is due, in part, to differences in the frequency of the cytochrome P450 CYP3A5*3 allele (rs776746, expresses nonfunctional enzyme) between white and AA recipients; however, even after accounting for this variant, variability in AA-associated troughs is significant. We conducted a genomewide association study of TAC troughs in AA kidney allograft recipients to search for additional genetic variation. We identified two additional CYP3A5 variants in AA recipients independently associated with TAC troughs: CYP3A5*6 (rs10264272) and CYP3A5*7 (rs41303343). All three variants and clinical factors account for 53.9% of the observed variance in troughs, with 19.8% of the variance coming from demographic and clinical factors including recipient age, glomerular filtration rate, anticytomegalovirus drug use, simultaneous pancreas-kidney transplant and antibody induction. There was no evidence of common genetic variants in AA recipients significantly influencing TAC troughs aside from the CYP3A gene. These results reveal that additional and possibly rare functional variants exist that account for the additional variation.

Abstract Objectives Ambulatory‐care‐sensitive conditions (ACSCs) represent emergency department (ED) visits and hospital admissions that might have been avoided through earlier primary care intervention. We characterize the current frequency and cost of ACSCs among older adults (≥65 years of age) in the ED. Methods This study is a retrospective analysis of Centers for Medicare and Medicaid Services (CMS) national claims data distributed by the Research Data Assistance Center, a CMS contractor based at the University of Minnesota. We analyzed outpatient ED‐based national claims data for visits made by traditional fee‐for‐service (FFS) Medicare beneficiaries in 2016. ACSCs were identified according to the Agency for Healthcare Research and Quality's Prevention Quality Indicators criteria, which require that the ACSC be the primary diagnosis for the visit. Analysis was done in Alteryx and R. Results We documented nearly 1.8 million ACSC ED visits in 2016, finding that ≈10.6% of all ED visits by older adult FFS Medicare beneficiaries were associated with an ACSC. ACSC ED visits resulted in admission more often (39.7%) than non‐ACSC ED visits (23.9%). Notably, 83% of patients with short‐term complications from diabetes were admitted. Conclusions ED visits for a primary diagnosis of an ACSC highlight opportunities to improve access to preventive care, particularly earlier recognition and treatment of patients’ deteriorating conditions that could have potentially precluded the need for the ED visit. An opportunity exists to leverage ED‐based initiatives during an ACSC ED visit to support appropriate community and care transitions of these high‐risk patients.

Background and Introduction:This study was conducted to evaluate the morphology of cataract and relation to age in patients presenting to a health camp held at kashele, a village located in Maharashtra. Aims and objectives: The aim and objective of this study was to study the morphology of age related cataract in patients presenting to a rural eye camp in Maharashtra. Materials and Methods: The study was a cross-sectional study conducted on a rural population of Kashele village in Raigad district of Maharashtra.All 560 patients who visited ophthalmology OPD in the health camp conducted at Kashele were screened for cataract. One hundred fifty patients who had cataract were selected for the study. Comprehensive eye checkup was done in these patients at a medical college. The grading of the lens was conducted using the Lens Opacification Classification System (LOCS) III with the help of standard set of photographs of LOCS grading mounted next to the slit lamp. Results and Conclusion: A total of 201 eyes(67%) out of300 had nuclear sclerosis cataract of different grades.One hundred forty-nine eyes(49.66%) out of 300 had cortical cataract. Fifty-nine eyes(19.66%)out of 300had posterior sub capsular cataract. A total of 13 eyes(4.33%) out of 300 had mature cataract or a total cataract. Highest proportion of patients was in the age group of 45-50 (24%).

Image fusion is a technique that combines two source images to generate more informative target image. It plays a vital role in medical image investigation, military, navigation, etc. visible images offer efficient texture detail with high spatial resolution. In contrast, based on the radiation difference infrared images are able to differentiate target from their background. There are many algorithms that helps in preserving the edges of image like Bilateral filter, anisotropic diffusion (ADF). This paper integrates Anisotropic Diffusion and Karhunen-Loeve (KL)Transformation with discrete wavelet transform (DWT). In proposed Method, DWT decomposes into four sub-bands. ADF is applied on approximation sub-band and absolute maximum selection is applied on other three sub-bands. ADF decomposes the image into detailed layer and base layer. Base layer and Detailed layer are calculated using Kl- Transformation and linear combination respectively. Once fusion is done, inverse DWT is applied on all sub-bands. The experimental outcomes depict that the offered approach result with sharp edges of the image. The proposed algorithm is evaluated on standard dataset Like Duine_Sequence, Tree_sequence, Street dataset. Standard metrics like Average Gradients and Spatial Frequency metrics are used to evaluate the performance of the image.

Introduction Anti-Black racism has strong roots in American health care and medical education. While curricula on social determinants of health are increasingly common in medical training, curricula directly addressing anti-Black racism are limited. Existing frameworks like the Presence 5 framework for humanism in medicine can be adapted to develop a novel workshop that promotes anti-racism communication. Methods We performed a literature review of anti-racism collections and categorized anti-racism communication practices using the Presence 5 framework to develop the Presence 5 for Racial Justice Workshop. Implementation included an introductory didactic, a small-group discussion, and a large-group debrief. Participants evaluated the workshop via an online survey, and we analyzed the resulting qualitative feedback. Results A total of 17 participants took part in two workshops, with nine of the participants responding to the evaluation survey. Themes that emerged from survey responses included strengths of and improvements for the workshop structure (protected time for anti-racism discussion, dialogue between learners and faculty) and content (specific phrases and language, practicing self-reflection). Discussion The workshop provides participants with a semistructured discussion around the five anti-racism communication practices. Barriers to implementation include incorporating the workshop into existing curricula and ensuring diverse learners. Barriers to evaluating the workshop include the low survey response rate. Recommendations to improve the workshop include using case-based discussion and varying the workshop structure according to institutional needs. Next steps include an implementation study to evaluate the acceptability, feasibility, and effectiveness of the workshop.

BackgroundPeople with drug-resistant tuberculosis (DR-TB) are known to suffer from many mental-health disorders. This study aims to describe the proportion of patients diagnosed with psychiatric comorbidities, the different psychiatric diagnoses made, and treatment outcomes among DR-TB patients with or without psychiatric comorbidity and initiated on DR-TB treatment between January 2012 and March 2019 at Médecins Sans Frontières independent clinic in Mumbai, India.MethodsThis is a retrospective study using routinely collected clinical data. DR-TB care included individualised treatment, psychosocial support, and integrated psychiatric care.ResultsDuring the study period, 341 DR-TB patients were enrolled, with a median age of 25 years (IQR:20.0-36.5 years), 185 (54.2%) females, 143 (41.9%) with PreXDR-TB, and 140 (41.0%) with XDR-TB. All 341 patients were screened by a counsellor, 119 (34.9%) were referred for psychiatric evaluation, and 102 (29.9% of 341) were diagnosed with a psychiatric comorbidity. Among 102 diagnosed with a psychiatric comorbidity, 48 (47.0%) were diagnosed at baseline, and 86 (84.3%), or 25.2% of all 341 patients enrolled, were treated with psychotropic drugs. Depressive disorders were diagnosed in 49 (48.0%), mixed anxiety and depression in 24 (23.5%), neurocognitive disorders and anxiety in five (4.9%), and medication induced psychosis in two (2.0%). No anti-TB drugs were significantly associated with psychiatric comorbidities developed during treatment. Of 102 DR-TB patients with a psychiatric comorbidity, 75.5% (77) had successful DR-TB treatment outcomes, compared to 61.1% (146/239) not diagnosed with a psychiatric comorbidity (p = 0.014).ConclusionIn our setting, among people started on DR-TB treatment, and with a complex TB resistance profile, about one in three patients experienced a psychiatric comorbidity, of which half developed this comorbidity during treatment. With comprehensive psychiatric care integrated into DR-TB care delivery, treatment outcomes were at least as good among those with psychiatric comorbidities compared to those without such comorbidities.

Background: Toric Intraocular lenses (IOLs) are supposed to be aligned at a particular axis for spectacle-free vision for distance. The evolution of topographers and optical biometers has made it quite achievable for us to aim the target. However, the result sometimes remains unpredictable. A big aspect of this depends on the preop axis marking for toric IOL alignment. Errors in axis marking have been reduced recently with the array of different toric markers in the market, but still we see postoperative refractive surprises due to faulty marking. Purpose: In this video, we present a novel slit lamp–based toric marker innovation, STORM, which gives us a hands-free approach to a reliable and accurate axis marking on the cornea. The axis marker is a simple modification to our age-old marker, with the advantage of no touch and slit-lamp assistance, which will make it error free and easy to use. Synopsis: The present innovation answers the problem statement of stable, economical, and accurate marking solution. Many a times, hand-holding devices create inaccurate and stressed condition while marking the cornea before corneal surgery. Highlights: The invention can be used for marking of accurate and easy astigmatic axis of a toric IOL preoperatively, that is, before the surgery. If the appropriate device is used to mark the cornea, it would impact the outcome of surgery. This device also makes the patient and the surgeon comfortable to mark the cornea with accuracy and without hesitation.Video link: https://youtu.be/4MVM7HRwz70

BACKGROUND: In addition to HLA genetic incompatibility, non-HLA difference between donor and recipients of transplantation leading to allograft rejection are now becoming evident. We aimed to create a unique genome-wide platform to facilitate genomic research studies in transplant-related studies. We designed a genome-wide genotyping tool based on the most recent human genomic reference datasets, and included customization for known and potentially relevant metabolic and pharmacological loci relevant to transplantation. METHODS: We describe here the design and implementation of a customized genome-wide genotyping array, the TxArray, comprising approximately 782,000 markers with tailored content for deeper capture of variants across HLA, KIR, pharmacogenomic, and metabolic loci important in transplantation. To test concordance and genotyping quality, we genotyped 85 HapMap samples on the array, including eight trios. RESULTS: We show low Mendelian error rates and high concordance rates for HapMap samples (average parent-parent-child heritability of 0.997, and concordance of 0.996). We performed genotype imputation across autosomal regions, masking directly genotyped SNPs to assess imputation accuracy and report an accuracy of >0.962 for directly genotyped SNPs. We demonstrate much higher capture of the natural killer cell immunoglobulin-like receptor (KIR) region versus comparable platforms. Overall, we show that the genotyping quality and coverage of the TxArray is very high when compared to reference samples and to other genome-wide genotyping platforms. CONCLUSIONS: We have designed a comprehensive genome-wide genotyping tool which enables accurate association testing and imputation of ungenotyped SNPs, facilitating powerful and cost-effective large-scale genotyping of transplant-related studies.

UnlabelledThe current system granting liver transplant candidates with hepatocellular carcinoma (HCC) additional Model for End-Stage Liver Disease (MELD) points is controversial due to geographic disparity and uncertainty regarding optimal prioritization of candidates. The current national policy assigns a MELD exception score of 22 immediately upon listing of eligible patients with HCC. The aim of this study was to evaluate the potential effects of delays in granting these exception points on transplant rates for HCC and non-HCC patients. We used Scientific Registry of Transplant Recipients data and liver simulated allocation modeling software and modeled (1) a 3-month delay before granting a MELD exception score of 25, (2) a 6-month delay before granting a score of 28, and (3) a 9-month delay before granting a score of 29. Of all candidates waitlisted between January 1 and December 31, 2010 (n = 28,053), 2773 (9.9%) had an HCC MELD exception. For HCC candidates, transplant rates would be 108.7, 65.0, 44.2, and 33.6 per 100 person-years for the current policy and for 3-, 6-, and 9-month delays, respectively. Corresponding rates would be 30.1, 32.5, 33.9, and 34.8 for non-HCC candidates.ConclusionA delay of 6-9 months would eliminate the geographic variability in the discrepancy between HCC and non-HCC transplant rates under current policy and may allow for more equal access to transplant for all candidates.

We performed RNA sequencing (RNAseq) on peripheral blood mononuclear cells (PBMCs) to identify differentially expressed gene transcripts (DEGs) after kidney transplantation and after the start of immunosuppressive drugs. RNAseq is superior to microarray to determine DEGs because its not limited to available probes, has increased sensitivity, and detects alternative and previously unknown transcripts. DEGs were determined in 32 adult kidney recipients, without clinical acute rejection (AR), treated with antibody induction, calcineurin inhibitor, mycophenolate, with and without steroids. Blood was obtained pre-transplant (baseline), week 1, months 3 and 6 post-transplant. PBMCs were isolated, RNA extracted and gene expression measured using RNAseq. Principal components (PCs) were computed using a surrogate variable approach. DEGs post-transplant were identified by controlling false discovery rate (FDR) at < 0.01 with at least a 2 fold change in expression from pre-transplant. The top 5 DEGs with higher levels of transcripts in blood at week 1 were TOMM40L, TMEM205, OLFM4, MMP8, and OSBPL9 compared to baseline. The top 5 DEGs with lower levels at week 1 post-transplant were IL7R, KLRC3, CD3E, CD3D, and KLRC2 (Striking Image) compared to baseline. The top pathways from genes with lower levels at 1 week post-transplant compared to baseline, were T cell receptor signaling and iCOS-iCOSL signaling while the top pathways from genes with higher levels than baseline were axonal guidance signaling and LXR/RXR activation. Gene expression signatures at month 3 were similar to week 1. DEGs at 6 months post-transplant create a different gene signature than week 1 or month 3 post-transplant. RNAseq analysis identified more DEGs with lower than higher levels in blood compared to baseline at week 1 and month 3. The number of DEGs decreased with time post-transplant. Further investigations to determine the specific lymphocyte(s) responsible for differential gene expression may be important in selecting and personalizing immune suppressant drugs and may lead to targeted therapies.

Emerging evidence suggests that donor/recipient matching in non-HLA (human leukocyte antigen) regions of the genome may impact transplant outcomes and recognizing these matching effects may increase the power of transplant genetics studies. Most available matching scores account for either single-nucleotide polymorphism (SNP) matching only or sum these SNP matching scores across multiple gene-coding regions, which makes it challenging to interpret the association findings. We propose a multi-marker Joint Score Test (JST) to jointly test for association between recipient genotype SNP effects and a gene-based matching score with transplant outcomes. This method utilizes Eigen decomposition as a dimension reduction technique to potentially increase statistical power by decreasing the degrees of freedom for the test. In addition, JST allows for the matching effect and the recipient genotype effect to follow different biological mechanisms, which is not the case for other multi-marker methods. Extensive simulation studies show that JST is competitive when compared with existing methods, such as the sequence kernel association test (SKAT), especially under scenarios where associated SNPs are in low linkage disequilibrium with non-associated SNPs or in gene regions containing a large number of SNPs. Applying the method to paired donor/recipient genetic data from kidney transplant studies yields various gene regions that are potentially associated with incidence of acute rejection after transplant.

Cruciferous plants in the order Brassicales defend themselves from herbivory using glucosinolates: sulfur-containing pro-toxic metabolites that are activated by hydrolysis to form compounds, such as isothiocyanates, which are toxic to insects and other organisms. Some herbivores are known to circumvent glucosinolate activation with glucosinolate sulfatases (GSSs), enzymes that convert glucosinolates into inactive desulfoglucosinolates. This strategy is a major glucosinolate detoxification pathway in a phloem-feeding insect, the silverleaf whitefly Bemisia tabaci, a serious agricultural pest of cruciferous vegetables. In this study, we identified and characterized an enzyme responsible for glucosinolate desulfation in the globally distributed B. tabaci species MEAM1. In in vitro assays, this sulfatase showed a clear preference for indolic glucosinolates compared with aliphatic glucosinolates, consistent with the greater representation of desulfated indolic glucosinolates in honeydew. B. tabaci might use this detoxification strategy specifically against indolic glucosinolates since plants may preferentially deploy indolic glucosinolates against phloem-feeding insects. In vivo silencing of the expression of the B. tabaci GSS gene via RNA interference led to lower levels of desulfoglucosinolates in honeydew. Our findings expand the knowledge on the biochemistry of glucosinolate detoxification in phloem-feeding insects and suggest how detoxification pathways might facilitate plant colonization in a generalist herbivore.