Convalescent plasma therapy for severe Covid-19 in patients with hematological malignancies

BackgroundData on convalescent plasma therapy (CPT) in patients of hematological malignancies with severe Covid-19 is scarce.ObjectiveTo study 14-day mortality in patients who received CPT.Patients & methodsRetrospective multicentre observational study conducted in 4 centres treating haematological malignancies across Delhi-national capital region. Total 33 haematological malignancies patients with severe Covid-19 who received CPT were analysed.ResultsThe median age of the study cohort was 62 years (18–80 years). Twenty one percent patients had 1 comorbidity, 18 % had 2 comorbidities and 6% patients had 3 and 5 comorbidities each. Twenty four patients were on active therapy. Sixty nine percent of patients required ICU stay. Twenty five patients received plasma therapy within 7 days (early) of diagnosis of Covid-19 infection. Median day of plasma infusion from date of diagnosis of Covid-19 infection was 4 days (range: 2–25 days). Patient who had early initiation of plasma therapy had shorter duration of hospitalisation (12.7 vs 24.3 days, p = 0.000). Overall mortality in the cohort was 45.5%. There was no effect of disease status, active therapy, presence of comorbidity on mortality. There was no difference in the mortality in patients receiving early vs late initiation of plasma therapy or in patients receiving one versus two plasma therapy.ConclusionsWe provide a large series of patients with hematological malignancies and role of CPT in this group.     

Atrial function in the Fontan circulation: comparison with invasively assessed systemic ventricular filling pressure

The International Journal of Cardiovascular Imaging - Abnormal atrial mechanics in biventricular circulations have been associated with elevated left heart filling pressures. Similar associations...     

Surgical management of pygopagus conjoined twins with spinal bifida

Purpose

Conjoined twins are a rare complication of 9 monozygotic twins and are associated with high perinatal mortality. Pygopagus are one of the rare types of conjoined twins with only a handful of cases reported in the literature.

Case summary

We present the case of one-and-half month-old male pygopagus conjoined twins, who were joined together dorsally in lower lumbar and sacral region and had spina bifida and shared a single thecal sac with combined weight of 6.14 kg. Spinal cord was separated at the level of the conus followed by duraplasty. They had uneventful recovery with normal 15 months follow-up.

Conclusion

Separation of conjoined twins is recommended in where this is feasible with the anticipated survival of both or one infant.

     

Axial T1ρ MRI as a diagnostic imaging modality to quantify proteoglycan concentration in degenerative disc disease

European Spine Journal - The aim of the study was to investigate if axial T1ρ MR images had similar accuracy as established sagittal T1ρ MRI for the assessment of proteoglycan...     

The metabolic syndrome: what to treat, how to treat, what are the goals?

Metabolic syndrome is a cluster of risk factors for cardiovascular disease that include obesity, atherogenic dyslipidemia, raised blood pressure, and insulin resistance. The growing trend of obesity is associated with increased prevalence of metabolic syndrome. Optimizing diet and exercise are still the leading therapy for controlling the metabolic syndrome. Based on the current evidence, further emphasis should be placed on aggressive management of other metabolic risk factors such as high blood pressure and dyslipidemia.     

Pyruvate carboxylase is critical for non–small-cell lung cancer proliferation

Anabolic biosynthesis requires precursors supplied by the Krebs cycle, which in turn requires anaplerosis to replenish precursor intermediates. The major anaplerotic sources are pyruvate and glutamine, which require the activity of pyruvate carboxylase (PC) and glutaminase 1 (GLS1), respectively. Due to their rapid proliferation, cancer cells have increased anabolic and energy demands; however, different cancer cell types exhibit differential requirements for PC- and GLS-mediated pathways for anaplerosis and cell proliferation. Here, we infused patients with early-stage non–small-cell lung cancer (NSCLC) with uniformly ¹³C-labeled glucose before tissue resection and determined that the cancerous tissues in these patients had enhanced PC activity. Freshly resected paired lung tissue slices cultured in ¹³C₆-glucose or ¹³C₅,¹⁵N₂-glutamine tracers confirmed selective activation of PC over GLS in NSCLC. Compared with noncancerous tissues, PC expression was greatly enhanced in cancerous tissues, whereas GLS1 expression showed no trend. Moreover, immunohistochemical analysis of paired lung tissues showed PC overexpression in cancer cells rather than in stromal cells of tumor tissues. PC knockdown induced multinucleation, decreased cell proliferation and colony formation in human NSCLC cells, and reduced tumor growth in a mouse xenograft model. Growth inhibition was accompanied by perturbed Krebs cycle activity, inhibition of lipid and nucleotide biosynthesis, and altered glutathione homeostasis. These findings indicate that PC-mediated anaplerosis in early-stage NSCLC is required for tumor survival and proliferation.     

Deficiency of Fibroblast Growth Factor-Inducible 14 (Fn14) Preserves the Filtration Barrier and Ameliorates Lupus Nephritis

TNF ligand superfamily member 12, also known as TNF-related weak inducer of apoptosis (TWEAK), acts through its receptor, fibroblast growth factor-inducible 14 (Fn14), to mediate several key pathologic processes involved in tissue injury relating to lupus nephritis. To explore the potential for renal protection in lupus nephritis by targeting this pathway, we introduced the Fn14 null allele into the MRL-lpr/lpr lupus mouse strain. At 26–38 weeks of age, female Fn14-knockout MRL-lpr/lpr mice had significantly lower levels of proteinuria compared with female wild-type MRL-lpr/lpr mice. Furthermore, Fn14-knockout mice had significantly improved renal histopathology accompanied by attenuated glomerular and tubulointerstitial inflammation. There was a significant reduction in glomerular Ig deposition in Fn14-knockout mice, despite no detectable differences in either serum levels of antibodies or splenic immune cell subsets. Notably, we found that the Fn14-knockout mice displayed substantial preservation of podocytes in glomeruli and that TWEAK signaling directly damaged barrier function and increased filtration through podocyte and glomerular endothelial cell monolayers. Our results show that deficiency of the Fn14 receptor significantly improves renal disease in a spontaneous lupus nephritis model through prevention of the direct injurious effects of TWEAK on the filtration barrier and/or modulation of cytokine production by resident kidney cells. Thus, blocking the TWEAK/Fn14 axis may be a novel therapeutic intervention in immune-mediated proliferative GN.