Explore the vast range of titles available.

Toll-like receptors (TLR) 4 and its endogenous ligands are highly expressed in aorta. In the present study, we have explored the effect of TLR-4 activation by pro-inflammatory and angiogenic factors in PBMCs of patients with Takayasu Arteritis (TA). In the screening cohort, PBMCs of TA (n = 6) and healthy controls (n = 6) were stimulated with LPS and cultured. mRNA expression of 84 genes were quantitated by RT2 Profiler™ PCR Array kit in PBMCs. Validation set of additional PBMCs from TA (n = 7) and healthy controls [HC) (n = 7) were then stimulated with LPS to study expression of selected genes with delta Ct > 0.1 in the screening cohort. Significant gene expressions were correlated with Indian Takayasu arteritis activity scores (ITAS 2010). Increased expression of CCL2 was observed only in unstimulated PBMCs of patients with TA [median relative difference (RD) of 2.37] as compared to HC (RD 1.37, p < 0.03) in validation cohort, while stimulation with TLR4 ligand led to increased mRNA expression of IL-1β (RD 7.9, p < 0.028) and IL-1R2 (RD 0.08 p < 0.013) genes as compared to that of HC [RD of 5.32 for IL-1β and 0.01 for IL-1R2, respectively] in validation cohort. TLR4 activation also led to significantly higher expression of HPSE, TIMP1 and low expression of VEGFB, S1PR1, SERPINF1, ANGPLT4, ANGPT2, TIE1 and NOS3 genes in the screening cohort. But expression of VEGFB was not significant in validation cohort. The significant gene expressions, however, did not correlate with ITAS [ITAS2010 and ITAS-A (CRP)]. TLR4 activation leads to increased expression of IL-1β and IL-1R2 genes in PBMCs of patients with TA.

Transfusions of red blood cells (RBCs), platelets, and plasma are critical therapies for infants and neonates (particularly preterm neonates) in the neonatal intensive care unit, who are the most frequently transfused subpopulation across all ages. Although traditionally a significant gap has existed between the blood utilization and the evidence base essential to adequately guide transfusion practices in infants and neonates, pediatric transfusion medicine is evolving from infancy and gradually coming of age. It is entering an exciting era with recognition as an independent discipline, a new and evolving high-quality evidence base for transfusion practices, novel technologies and therapeutics, and national/international collaborative research, educational, and clinical efforts. Triggers and thresholds for red cell transfusion are accumulating evidence with current phase III clinical trials. Ongoing trials and studies of platelet and plasma transfusions in neonates are anticipated to provide high-quality evidence in years to come. This article aims to summarize the most current evidence-based practices regarding blood component therapy in neonates. Data on the use of specific components (RBCs, plasma, and platelets) are provided. We attempt to define thresholds for anemia, thrombocytopenia, and abnormal coagulation profile in neonates to highlight the difficulties in having a specific cutoff value in neonates and preterm infants. Indications for transfusion of specific products, transfusion thresholds, and current practices and guidelines are provided, and possible adverse outcomes and complications are discussed. Finally, the critical research knowledge gaps in these practices as well as ongoing and future research areas are discussed. In an era of personalized medicine, neonatal transfusion decisions guided by a strong evidence base must be the overarching goal, and this underlies all of the strategic initiatives in pediatric and neonatal transfusion research highlighted in this article.

Babesia spp. are tickborne parasites that cause the clinical infection babesiosis, which has an increasing incidence in the United States. We performed an analysis of hospitalizations in the United States during 2010-2016 in which babesiosis was listed as a diagnosis. We used the National Inpatient Sample database to characterize the epidemiology of Babesia-associated admissions, reflecting severe Babesia-related disease. Over a 7-year period, a total of 7,818 hospitalizations listed babesiosis as a primary or secondary admitting diagnosis. Hospitalizations were seasonal (71.2% occurred during June-August) and situated overwhelmingly in the Northeast and Midwest. The patients were predominantly male and of advanced age, which is consistent with the expected epidemiology. Despite a higher severity of illness in more than (58.5%), the mortality rate was low (1.6%). Comparison with state reporting data suggests that the number of hospitalized persons with babesiosis increased modestly during the observation period.

The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma. Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician-principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had-or were at risk of progression to-severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (<1%), and the overall crude 30-day mortality rate was 25.2% (95% CI, 25.0% to 25.5%). This registry study was limited by the observational and pragmatic study design that did not include a control or comparator group; thus, the data should not be used to infer definitive treatment effects. These results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease. ClinicalTrials.gov NCT#: NCT04338360.

Background Granulomatosis with polyangiitis (GPA) is small vessel vasculitis with heterogeneous clinical presentation. In the present population-based cohort study, we classified patients with GPA based on clinical features at presentation using an unsupervised clustering approach and compared their mortality, infections and frequency of comorbidities. Methods In this open cohort study, de-identified primary care data of patients with GPA included in the IQVIA Medical Research Data database between 1 January 1995 and 25 September 2019 was analysed retrospectively. Latent class analysis was performed to create symptom clusters of patients based on 16 categories of symptoms representing various organ involvement. All-cause mortality of resultant clusters was compared after adjusting for age, sex, Townsend deprivation quintile and smoking status at index date using extended Cox proportional hazards models. Prescription of antibiotics, considered as an indirect indicator of recurrent bacterial infection, was compared using a recurrent event model, after adjusting for quarterly use of steroid as a time-dependent covariate. Cumulative frequencies of common comorbidities were compared among the clusters at index visit, 1-year and 3-year follow-up. Results Altogether, 649 patients with GPA [median age 60.0 (IQR: 49.6–70.1)] were included. Three clusters were identified: patients with limited disease mainly with involvement of ENT and cough were classified into cluster 1 ( n  = 426); cluster 2 had generalised non-renal disease ( n  = 176); while patients in cluster 3 had renal-predominant disease ( n  = 47). Many patients in cluster 1 developed generalised disease at the end of 1 year. Mortality in clusters 2 and 3 was higher compared with cluster 1. Mortality in cluster 1 itself was 68% higher than the general population without GPA. The duration of antibiotics prescription and frequency of coexisting medical illnesses was also higher in clusters 2 and 3. Conclusions In a primary care setting, patients with GPA can be classified into three distinct clusters with different prognosis, susceptibility to recurrent infections and presence of comorbidities. The tendency of cluster 1 to evolve into a more generalised disease raises questions about current immunosuppressive treatment approaches in these patients.

We performed genetic association study for genes encoding angiogenic and angiostatic proteins in patients with Takayasu arteritis (TAK). A total of 96 SNPs involving 60 genes were studied. Genotyping was performed in Fluidigm 96.96 Dynamic Array chip. All statistical analysis for SNP evaluation was performed using PLINK software. Initial analyses revealed five SNPs from three genes [IL-18 (encodes Interleukin-18), FGF2 (encodes Fibroblast Growth Factor-2), and ANGPT1 (encodes Angiopoietin-1)] as significantly different between controls and cases (uncorrected p < 0.05). After permutation-based analysis, two tag SNPs on the promoter region of IL-18 (rs187238 and rs1946518) and one 3'UTR tag SNP (rs1476217) of FGF2 were significantly associated with susceptibility to TAK, with p and OR (95% CI) of 0.0006 and 1.64 (1.25-2.17), 0.03 and 1.28 (1.02-1.64) & 0.016 and 1.33 (1.05-1.67), respectively; while, the two tag SNPs of ANGPT1 gene (rs6469101 and rs16875900) showed a trend (p = 0.055 & p = 0.051, respectively after permutation based correction). There is robust linkage disequilibrium between the two tag SNPs of IL-18 gene as validated by 1000 genome data of South Asian population; the eQTL effects of these tag SNPs of IL-18 and FGF2 genes on adjacent genes further suggest that these tag SNPs act as genetic risks for development of TAK in South Asians, with possible functional implications towards future biomarker development. Genotype phenotype study by genetic model-based analysis also revealed associations between genotype subsets and clinical features like fever, visual loss, left subclavian and coronary artery involvement in our TAK patients.

When Coronavirus Disease-19 (COVID-19) struck the world in December 2019, initiatives started to investigate the efficacy of convalescent plasma, a readily available source of passive antibodies, collected from recovered patients as a therapeutic option. This was based on historical observational data from previous virus outbreaks. A scoping review was conducted on the efficacy and safety of convalescent plasma and hyperimmune immunoglobulins for COVID-19 treatment. This review included the latest Cochrane systematic review update on 30-day mortality and safety. We also covered use in pediatric and immunocompromised patients, as well as the logistic challenges faced in donor recruitment and plasma collection in general. Challenges for low resource countries were specifically highlighted. A major challenge is the high donation frequency required from first-time donors to ensure a safe product, which minimizes the risk of transfusion-transmitted infectious. This is particularly difficult in low- and middle- income countries due to inadequate infrastructure and insufficient blood product supplies. High-certainty evidence indicates that convalescent plasma does not reduce mortality or significantly improve clinical outcomes in patients with moderate to severe COVID-19 infection. However, CCP may provide a viable treatment for patients unable to mount an endogenous immune response to SARS-CoV-2, based on mostly observational studies and subgroup data of published and ongoing randomized trials. Convalescent plasma has been shown to be safe in adults and children with COVID-19 infection. However, the efficacy in pediatric patients remains unclear. Data on efficacy and safety of CCP are still underway in ongoing (randomized) studies and by reporting the challenges, limitations and successes encountered to-date, research gaps were identified to be addressed for the future. This experience serves as a valuable example for future pandemic preparedness, particularly when therapeutic options are limited, and vaccines are either being developed or ineffective due to underlying immunosuppression.

Most theories indicated the development and differentiation of either ectopic adrenal or hematopoietic stem cell receiving triggering stimulus (obesity, hypertension, chronic inflammation, endocrine disorders), another theory was evolution of myelolipoma from metaplastic change of embryonic primitive mesenchymal cells or embolism of bone marrow cells through the blood stream. The fourth hypotheses was based on the chromosomal translocation (3; 21) which related to development of acute myeloid leukemia and myelodysplastic syndrome. [...]in such case myelolipoma might be a neoplastic phenomenon as a result of chromosomal mutation. The histopathology confirmed a diagnosis of myelolipoma and excluded liposarcoma. [...]a close correlation between the radiological findings and histopathological findings helped reach the right diagnosis.

BACKGROUNDRBC transfusion effectiveness varies due to donor, component, and recipient factors. Prior studies identified characteristics associated with variation in hemoglobin increments following transfusion. We extended these observations, examining donor genetic and nongenetic factors affecting transfusion effectiveness.METHODSThis is a multicenter retrospective study of 46,705 patients and 102,043 evaluable RBC transfusions from 2013 to 2016 across 12 hospitals. Transfusion effectiveness was defined as hemoglobin, bilirubin, or creatinine increments following single RBC unit transfusion. Models incorporated a subset of donors with data on single nucleotide polymorphisms associated with osmotic and oxidative hemolysis in vitro. Mixed modeling accounting for repeated transfusion episodes identified predictors of transfusion effectiveness.RESULTSBlood donor (sex, Rh status, fingerstick hemoglobin, smoking), component (storage duration, γ irradiation, leukoreduction, apheresis collection, storage solution), and recipient (sex, BMI, race and ethnicity, age) characteristics were associated with hemoglobin and bilirubin, but not creatinine, increments following RBC transfusions. Increased storage duration was associated with increased bilirubin and decreased hemoglobin increments, suggestive of in vivo hemolysis following transfusion. Donor G6PD deficiency and polymorphisms in SEC14L4, HBA2, and MYO9B genes were associated with decreased hemoglobin increments. Donor G6PD deficiency and polymorphisms in SEC14L4 were associated with increased transfusion requirements in the subsequent 48 hours.CONCLUSIONDonor genetic and other factors, such as RBC storage duration, affect transfusion effectiveness as defined by decreased hemoglobin or increased bilirubin increments. Addressing these factors will provide a precision medicine approach to improve patient outcomes, particularly for chronically transfused RBC recipients, who would most benefit from more effective transfusion products.FUNDINGFunding was provided by HHSN 75N92019D00032, HHSN 75N92019D00034, 75N92019D00035, HHSN 75N92019D00036, and HHSN 75N92019D00037; R01HL126130; and the National Institute of Child Health and Human Development (NICHD).

BackgroundConsensus on treatment of idiopathic inflammatory myositis (IIM), particularly with regard to flares and interstitial lung disease (ILD), does not exist. We studied the long-term outcome and treatment response in our large, retrospective cohort of adult South-Asian patients exclusively with IIM.MethodologyElectronic records of IIM patients satisfying inclusion and exclusion criteria were studied longitudinally at presentation, at 3, 6, 12, 18 and 24 months and thereafter yearly till their last follow up (F/u) visit. Depending on clinical, imaging, and muscle enzyme profile during the F/u period, patients were categorised as complete (CR) and partial responders (PRs). Parameters favouring CR were assessed using multivariate logistic regression analysis. Outcome parameters and flares on immunosuppressants (IS) were then assessed in patients with/without ILD.ResultsTwo hundred thirty-two patients with median F/u duration of 44.5 months (25–80.25) were included. ILD was seen in 40.1%. Patients with non-Jo1 anti-synthetase antibodies (n=26) were numerically more than those with Jo-1 antibody (n=24). CR status was attained by 50.9% patients. Absence of pericardial effusion (p=0.042, OR 4.223, 95% CI: 1.05–16.9) and presence of Gottron’s rash (p=0.044, OR 1.78, 95% CI 1.017–3.121) at baseline predicted CR by multivariate regression. Majority received mycophenolate during the entire F/u period. Discontinuation of steroids was feasible in 51.7% after a median duration of 24 months (18–42). After excluding patients with ILD, flares were numerically lesser in patients only on mycophenolate compared with those only on methotrexate (p=0.06). Further flares were curtailed when switched from other agents to mycophenolate.ConclusionMycophenolate is an effective treatment option in IIM patients with and without co-existing ILD. Presence of Gottron’s rash and absence of pericardial effusion were found to be predictors of favourable clinical outcome in this largest single-centre study.Key points• This largest single-centre study of South Asian adult patients with idiopathic inflammatory myositis showed good clinical outcome and survival with combination treatment regimen consisting of upfront immunosuppressant especially mycophenolate mofetil or sodium (MMF/MMS) along with tapering doses of steroids.• Absence of pericardial involvement and presence of Gottron’s rash were predictors of complete responders in our overall patient cohort.• Testing anti-Jo-1 antibody alone during evaluation of myositis will overlook important prognostic biomarkers such as the presence of non-Jo 1 antisynthetase autoantibodies (PL-7, PL-12, EJ and OJ) as well as Ro52; our cohort had more patients with non-Jo 1 antibodies than Jo-1 antibody; hence, there is a strong case for testing the entire spectrum of myositis autoantibodies in IIM.• Patients on MMF/MMS therapy from onset or even those switched to mycophenolate later had a better outcome, irrespective of their interstitial lung disease status.