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.     

Development of a fused imidazo[1,2-a]pyridine based fluorescent probe for Fe3+ and Hg2+ in aqueous media and HeLa cells

A new fluorescent sensor 5 based on a fused imidazopyridine scaffold has been designed and synthesized via cascade cyclization. The reaction features the formation of three different C–N bonds in sequence. Imidazopyridine based fluorescent probe 5 exhibits highly sensitive and selective fluorescent sensing for Fe³⁺(‘turn-on’) and Hg²⁺(‘turn-off’). The excellent selectivity of imidazopyridine for Fe³⁺/Hg²⁺ was not hampered in the presence of any of the competing cations. The limit of detection (LOD) of 5 toward Fe³⁺ and Hg²⁺ has been estimated to be 4.0 ppb and 1.0 ppb, respectively, with a good linear relationship (R² = 0.99). Notably, 5 selectively detects Fe³⁺/Hg²⁺ through fluorescence enhancement signalling both in vitro and in HeLa cells.

A new fluorescent sensor 5 having fused imidazopyridine scaffold has been synthesized via cascade cyclization. It exhibits highly sensitive and selective detection of Fe³⁺ (‘turn-on’) and Hg²⁺ (‘turn-off’) in vitro and in HeLa cells.     

A Survey of Pulmonary Function Abnormalities Following Thoracotomy

Objective

To study the incidence and type of pulmonary function abnormalities after thoracotomy in children.

Methods

Children below 12 y of age who had undergone thoracotomy for any condition and have at least 2 y follow up were included in the study. Detailed assessment of the patients included history and general examination, clinical assessment of pulmonary function, bedside tests to assess pulmonary function and laboratory pulmonary function test using portable spirometer.

Results

Fifty two patients were included in the study. Twenty-seven were cases of esophageal atresia with trachea-esophageal fistula (EATEF), nine pulmonary metastasis from abdominal solid tumors, six mediastinal masses, three hydatid cyst, three eventration of diaphragm, two bronchiectasis, and one each of H-type TEF and congenital esophageal stenosis. The mean age at the time of evaluation was 6.3 y (range 2–18 y). While all the patients were clinically assessed, only 25 (48 %) were eligible for bedside tests and 23 (44 %) for spirometery. The incidences of abnormalities picked were: dyspnea during exercise 8/52 (15.4 %), dyspnea on exercise and on climbing stairs 1/52 (2 %), decreased breath holding time 2/25 (8 %), abnormal incentive spirometry 1/25 (4 %), mild restrictive pattern on pulmonary function test (PFT) 11/23 (47.8 %), moderate restrictive pattern on PFT 2/23 (8.7 %). None had an obstructive pattern on PFT.

Conclusions

Though the incidences of pulmonary function abnormalities were high, these were of mild grade. Close follow up of patients after thoracotomy would be needed for early pick up and appropriate management of these abnormalities to prevent long-term consequences.     

Overview of pyridine nucleotides review series

Pyridine nucleotides are abundant soluble coenzymes and they undergo reversible oxidation and reduction in several biological electron-transfer reactions. They are comprised of two mononucleotides, adenosine monophosphate and nicotinamide mononucleotide, and are present as oxidized and reduced nicotinamide adenine dinucleotides in their unphosphorylated (NAD(+) and NADH) and phosphorylated (NADP(+) and NADPH) forms. In the past, pyridine nucleotides were considered to be primarily electron-shuttling agents involved in supporting the activity of enzymes that catalyze oxidation-reduction reactions. However, it has recently been demonstrated that pyridine nucleotides and the balance between the oxidized and reduced forms play a wide variety of pivotal roles in cellular functions as important interfaces, beyond their coenzymatic activity. These include maintenance of redox status, cell survival and death, ion channel regulation, and cell signaling under normal and pathological conditions. Furthermore, targeting pyridine nucleotides could potentially provide therapeutically useful avenues for treating cardiovascular diseases. This review series will highlight the functional significance of pyridine nucleotides and underscore their physiological role in cardiovascular function and their clinical relevance to cardiovascular medicine.     

Withania somnifera reverses Alzheimer's disease pathology by enhancing low-density lipoprotein receptor-related protein in liver

A 30-d course of oral administration of a semipurified extract of the root of Withania somnifera consisting predominantly of withanolides and withanosides reversed behavioral deficits, plaque pathology, accumulation of β-amyloid peptides (Aβ) and oligomers in the brains of middle-aged and old APP/PS1 Alzheimer's disease transgenic mice. It was similarly effective in reversing behavioral deficits and plaque load in APPSwInd mice (line J20). The temporal sequence involved an increase in plasma Aβ and a decrease in brain Aβ monomer after 7 d, indicating increased transport of Aβ from the brain to the periphery. Enhanced expression of low-density lipoprotein receptor-related protein (LRP) in brain microvessels and the Aβ-degrading protease neprilysin (NEP) occurred 14-21 d after a substantial decrease in brain Aβ levels. However, significant increase in liver LRP and NEP occurred much earlier, at 7 d, and were accompanied by a rise in plasma sLRP, a peripheral sink for brain Aβ. In WT mice, the extract induced liver, but not brain, LRP and NEP and decreased plasma and brain Aβ, indicating that increase in liver LRP and sLRP occurring independent of Aβ concentration could result in clearance of Aβ. Selective down-regulation of liver LRP, but not NEP, abrogated the therapeutic effects of the extract. The remarkable therapeutic effect of W. somnifera mediated through up-regulation of liver LRP indicates that targeting the periphery offers a unique mechanism for Aβ clearance and reverses the behavioral deficits and pathology seen in Alzheimer's disease models.     

Treatment of skeletal class II division 1 malocclusion with mandibular deficiency using myofunctional appliances in growing individuals

Class II division 1 malocclusion is the most common malocclusion seen in day-to-day practice. The majority of the patients with class II division 1 malocclusions have the presence of underlying skeletal discrepancy between maxilla and mandible. The treatment of skeletal class II division 1 depends upon the age of the patient, growth potential, severity of malocclusion, and compliance of patient with treatment. Myofunctional appliance can be successfully used to treat growing patients with class II division 1 malocclusion having retrusive mandible. This article presents a discussion on treatment of class II division 1 due to mandibular deficiency with growth modification approach using myofunctional appliances and a series of three case reports of treatment of skeletal class II division 1 malocclusion using myofunctional appliance followed by fixed mechanotherapy.