Abstract
Background
The diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–associated multisystem inflammatory syndrome in adults (MIS-A) requires distinguishing it from acute ...coronavirus disease 2019 (COVID-19) and may affect clinical management.
Methods
In this retrospective cohort study, we applied the US Centers for Disease Control and Prevention case definition to identify adults hospitalized with MIS-A at 6 academic medical centers from 1 March 2020 to 31 December 2021. Patients MIS-A were matched by age group, sex, site, and admission date at a 1:2 ratio to patients hospitalized with acute symptomatic COVID-19. Conditional logistic regression was used to compare demographic characteristics, presenting symptoms, laboratory and imaging results, treatments administered, and outcomes between cohorts.
Results
Through medical record review of 10 223 patients hospitalized with SARS-CoV-2–associated illness, we identified 53 MIS-A cases. Compared with 106 matched patients with COVID-19, those with MIS-A were more likely to be non-Hispanic black and less likely to be non-Hispanic white. They more likely had laboratory-confirmed COVID-19 ≥14 days before hospitalization, more likely had positive in-hospital SARS-CoV-2 serologic testing, and more often presented with gastrointestinal symptoms and chest pain. They were less likely to have underlying medical conditions and to present with cough and dyspnea. On admission, patients with MIS-A had higher neutrophil-to-lymphocyte ratio and higher levels of C-reactive protein, ferritin, procalcitonin, and D-dimer than patients with COVID-19. They also had longer hospitalization and more likely required intensive care admission, invasive mechanical ventilation, and vasopressors. The mortality rate was 6% in both cohorts.
Conclusions
Compared with patients with acute symptomatic COVID-19, adults with MIS-A more often manifest certain symptoms and laboratory findings early during hospitalization. These features may facilitate diagnosis and management.
Compared with 106 matched patients with coronavirus disease 2019, 53 adult patients with multisystem inflammatory syndrome were more likely to have preceding severe acute respiratory syndrome coronavirus 2 infection, less likely to have underlying conditions, and had more severe illness.
Graphical Abstract
Graphical Abstract
https://tidbitapp.io/tidbits/a-multicenter-retrospective-cohort-study-to-characterize-patients-hospitalized-with-mis-a-and-covid-19-in-the-united-states-2020-2021
This document discusses preprocedural planning for transcatheter aortic valve replacement, evaluating the imaging modalities used in initial imaging for preprocedure planning under two variants 1) ...Preintervention planning for transcatheter aortic valve replacement: assessment of aortic root; and 2) Preintervention planning for transcatheter aortic valve replacement: assessment of supravalvular aorta and vascular access. US echocardiography transesophageal, MRI heart function and morphology without and with IV contrast, MRI heart function and morphology without IV contrast and CT heart function and morphology with IV contrast are usually appropriate for assessment of aortic root. CTA chest with IV contrast, CTA abdomen and pelvis with IV contrast, CTA chest abdomen pelvis with IV contrast are usually appropriate for assessment of supravalvular aorta and vascular access. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.
Objectives: To compare the efficacy and safety of lumiracoxib with placebo and celecoxib for osteoarthritis OA in a 13 week, multicentre, randomised, double blind study. Methods: After a 37 day ...washout period for nonsteroidal antiinflammatory drugs, 1702 patients with knee OA were randomised to lumiracoxib 200 or 400mg once daily od, celecoxib 200mg od, or placebo 2221. A visual analogue scale VAS pain intensity 40mm was required. Primary efficacy variables were OA pain intensity VAS mm in the target knee, patients global assessment of disease activity VAS mm, and WOMAC pain subscale and total scores at 13weeks. OA pain intensity, patients and physicians global assessment of disease activity, and WOMAC total and all subscale scores were analysed by visit as secondary variables. Results: Lumiracoxib showed significant improvements in all primary and secondary variables compared with placebo. Lumiracoxib 200mg od and celecoxib 200mg od achieved similar improvements in OA pain intensity and functional status. Lumiracoxib 400mg od demonstrated better efficacy for OA pain intensity and patients global assessment of disease activity at weeks 2, 4, and 8 and similar efficacy at week 13 compared with celecoxib 200mg od. The incidence of adverse events AEs, serious AEs, and discontinuations due to AEs was similar in each group. Conclusion: Lumiracoxib demonstrated significant improvement in OA pain intensity, patients global assessment of disease activity, and the WOMAC pain subscale and total scores compared with placebo. Lumiracoxib was well tolerated in this study, with overall tolerability similar to that of placebo and celecoxib.
Tumors may escape immune recognition and destruction through the induction of apoptosis in activated T lymphocytes. Results
from several laboratories suggest that FasL (L/CD95L) expression in tumors ...may be responsible for this process. In this study
of patients with renal cell carcinoma (RCC), we provide evidence for two mechanisms of T-cell apoptosis. One mechanism involves
the induction of apoptosis via FasL expression in tumor cells. This is supported by several observations, including the fact
that tumor cells in situ as well as cultured cell lines expressed FasL mRNA and protein by a variety of techniques. The FasL in RCC is functional
because in coculture experiments, FasL + tumors induced apoptosis in Fas-sensitive Jurkat T cells and in activated peripheral blood T cells but not in resting peripheral
blood T cells. Most importantly, antibody to FasL partially blocked apoptosis of the activated T cells. Moreover, Fas was
expressed by T cells derived from the peripheral blood (53% median) and tumor (44.3% median) of RCC patients. Finally, in situ staining for DNA breaks demonstrated apoptosis in a subset of T cells infiltrating renal tumors. These studies also identified
a second mechanism of apoptosis in RCC patient peripheral T cells. Whereas these cells did not display DNA breaks when freshly
isolated or after culture for 24 h in medium, peripheral blood T cells from RCC patients underwent activation-induced cell
death after stimulation with either phorbol 12-myristate 13-acetate/ionomycin or anti-CD3/CD28 antibodies. Apoptosis mediated
by exposure to FasL in tumor cells or through T-cell activation may contribute to the failure of RCC patients to develop an
effective T-cell-mediated antitumor response.
Introduction Cryopyrin-associated periodic syndrome (CAPS) represents a spectrum of three auto-inflammatory syndromes, familial cold auto-inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), ...and neonatal-onset multisystem inflammatory disease/chronic infantile neurological cutaneous and articular syndrome (NOMID/CINCA) with etiology linked to mutations in the NLRP3 gene resulting in elevated interleukin-1beta (IL-1beta) release. CAPS is a rare hereditary auto-inflammatory disease, which may start early in childhood and requires a life-long treatment. Canakinumab, a fully human anti-IL-1beta antibody, produces sustained selective inhibition of IL-1beta. This study was conducted to assess the efficacy, safety, and pharmacokinetics of canakinumab in the treatment of pediatric CAPS patients. Methods Seven pediatric patients (five children and two adolescents) with CAPS were enrolled in a phase II, open-label study of canakinumab in patients with CAPS. Canakinumab was administered at a dose of 2 mg/kg subcutaneously (s.c.) (for patients with body weight less than or equal to 40 kg) or 150 mg s.c. (for patients with body weight > 40 kg) with re-dosing upon each relapse. The primary efficacy variable was time to relapse following achievement of a complete response (defined as a global assessment of no or minimal disease activity and no or minimal rash and values for serum C-reactive protein (CRP) and/or serum amyloid A (SAA) within the normal range, less than 10 mg/L). Results All patients achieved a complete response within seven days after the first dose of canakinumab and responses were reinduced on retreatment following relapse. Improvements in symptoms were evident within 24 hours after the first dose, according to physician assessments. The estimated median time to relapse was 49 days (95% CI 29 to 68) in children who received a dose of 2 mg/kg. Canakinumab was well tolerated. One serious adverse event, vertigo, was reported, but resolved during treatment. Conclusions Canakinumab, 2 mg/kg or 150 mg s.c., induced rapid and sustained clinical and biochemical responses in pediatric patients with CAPS. Trial registration number ClinicalTrials.gov: NCT00487708
Interleukin 12 (IL-12) is known to play an important role in the development of an antitumor response. Its activity has been shown to be dependent upon the intermediate production of IFN-gamma and ...the influx into the tumor of CD8 lymphocytes. In a murine model, tumor regression induced by IL-12 treatment correlated with IFN-gamma, IP-10, and Mig expression in the tumor bed and was abrogated by antibodies to both chemokines. Here we examined the effects of rHuIL-12 on IFN-gamma and CXC chemokine gene expression in patients with renal cell carcinoma (RCC) in an attempt to determine whether a similar series of molecular events leading to IL-12-mediated tumor regression in mice is also detectable in humans. As in the murine RENCA model, cultured RCC cells themselves could be induced by IFN-gamma to synthesize IP-10 and Mig mRNA. Explanted RCC produced IFN-gamma and IP-10 mRNA in response to IL-12 treatment, which was consistent with the finding that biopsied RCC tumors from IL-12-treated patients also variably expressed augmented levels of those molecules after therapy. Although Mig mRNA was present in the majority of biopsied tumors prior to treatment, both the Mig and IP-10 chemokines as well as IFN-gamma were induced in the peripheral blood mononuclear cells of IL-12-treated patients. Skin biopsies of IL-12-treated patients also all synthesized IP-10 mRNA. This study demonstrates that recombinant human IL-12 therapy of patients with RCC has the potential to induce the expression of gene products within the tumor bed that may contribute to the development of a successful antitumor response.
Therapy to eradicate pharyngeally carried group A streptococci (GAS) has increasingly been used in the management of institutional outbreaks and is now recommended for household contacts of patients ...with streptococcal toxic shock syndrome. In this randomized, controlled trial, contacts of patients with GAS infections were screened for pharyngeal GAS colonization. Those whose cultures were positive were randomized to receive either cefixime (8 mg/kg · d; maximum 400 mg) or rifampin (20 mg/kg; maximum, 600 mg) once a day for 4 days. Two to five days following completion of therapy, repeated cultures were negative for 13 (38%) of 34 rifampin recipients and 71 (77%; 95% CI, 69%–85%) of 97 cefixime recipients. At 10–14 days after treatment, only 53% of cefixime recipients remained culture-negative. Rates of successful clearance improved with increasing age (P < .01); among 17 adults who received cefixime, the success rate was 94%. Four days of therapy with rifampin is not effective for eradication of pharyngeally carried GAS. Four days of therapy with cefixime may be effective for adults, but further studies are needed.
Open Science Grid (OSG) is a consortium that enables many scientific breakthroughs by providing researchers with access to shared High Throughput Computing (HTC) compute clusters in support of ...large-scale collaborative research. To meet the demand on campus, Georgia Institute of Technology (GT)’s Partnership for an Advanced Computing Environment (PACE) team launched a centralized OSG support project, powered by Buzzard, an NSF-funded OSG cluster. We describe Buzzard’s unique multi-tenant architecture, which supports multiple projects on a single CPU/GPU pool, for the benefit of other institutions considering a similar approach to support OSG on their campuses.
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