Background
There is scarcity of data on outcome of COVID-19 in patients with hematological malignancies. Primary objective of study was to analyse the 14-day and 28-day mortality. Secondary objectives were to correlate age, comorbidities and remission status with outcome.
Methods
Retrospective multicentre observational study conducted in 11 centres across India. Total 130 patients with hematological malignancies and COVID-19 were enrolled.
Results
Fever and cough were commonest presentation. Eleven % patients were incidentally detected. Median age of our cohort was 49.5 years. Most of our patients had a lymphoid malignancy (
n
= 91). One-half patients (52%) had mild infection, while moderate and severe infections contributed to one-fourth each. Sixty seven patients (52%) needed oxygen For treatment of COVID-19 infection, half(
n
= 66) received antivirals. Median time to RT-PCR COVID-19 negativity was 17 days (7–49 days). Nearly three-fourth (
n
= 95) of our patients were on anticancer treatment at time of infection, of which nearly two-third (
n
= 59;64%) had a delay in chemotherapy. Overall, 20% (
n
= 26) patients succumbed. 14-day survival and 28-day survival for whole cohort was 85.4% and 80%, respectively. One patient succumbed outside the study period on day 39. Importantly, death rate at 1 month was 50% and 60% in relapse/refractory and severe disease cohorts, respectively. Elderly patients(age ≥ 60)(
p
= 0.009), and severe COVID-19 infection (
p
= 0.000) had a poor 14-day survival. The 28-day survival was significantly better for patients in remission (
p
= 0.04), non-severe infection (p = 0.00), and age < 60 years (
p
= 0.05).
Conclusions
Elderly patients with hematological malignancy and severe covid-19 have worst outcomes specially when disease is not in remission.
Substrate-cell interactions for a bioimplant are driven by substrate's surface characteristics. In addition, the performance of an implant and resistance to degradation are primarily governed by its surface properties. A bioimplant typically degrades by wear and corrosion in the physiological environment, resulting in metallosis. Surface engineering strategies for limiting degradation of implants and enhancing their performance may reduce or eliminate the need for implant removal surgeries and the associated cost. In the current study, we tailored the surface properties of stainless steel using submerged friction stir processing (FSP), a severe plastic deformation technique. FSP resulted in significant microstructural refinement from 22 μm grain size for the as-received alloy to 0.8 μm grain size for the processed sample with increase in hardness by nearly 1.5 times. The wear and corrosion behavior of the processed alloy was evaluated in simulated body fluid. The processed sample demonstrated remarkable improvement in both wear and corrosion resistance, which is explained by surface strengthening and formation of a highly stable passive layer. The methylthiazol tetrazolium assay demonstrated that the processed sample is better in supporting cell attachment, proliferation with minimal toxicity, and hemolysis. The athrombogenic characteristic of the as-received and processed samples was evaluated by fibrinogen adsorption and platelet adhesion via the enzyme-linked immunosorbent assay and lactate dehydrogenase assay, respectively. The processed sample showed less platelet and fibrinogen adhesion compared with the as-received alloy, signifying its high thromboresistance. The current study suggests friction stir processing to be a versatile toolbox for enhancing the performance and reliability of currently used bioimplant materials.
We asked if transfer
RNA (tRNA) ever got an opportunity of translating
its own sequence during evolution, what would have been the function
of such
tR
NA-encoded
p
eptides (tREPs)? If not, could one artificially synthesize tREPs
to study the corresponding functional outcomes? Here, we report a
novel, first-in-the-class, chemically synthesized tREP-18 molecule
originating from the
Escherichia coli
tRNA sequence showing potent antileishmanial property. As a first
step,
E. coli
tRNAs were computationally
translated into peptide sequence equivalents and a database of full-length
hypothetical tREPs was created. The tREP sequences were sent into
sequence, structure, and energy filters to narrow down potential peptides
for experimental validation. Based on the functional predictions,
tREPs were screened against antiparasitic targets, leading to the
identification of tREP-18 as a potential antiparasitic peptide. The
in vitro assay of chemically synthesized tREP-18 on the
Ag83
strain of
Leishmania donovani
showed
its potent antileishmanial property (IC50 value of 22.13 nM). The
atomic force microscopy and scanning electron microscopy images indicated
significant alteration in the cytoskeletal architecture of tREP-18-treated
parasites. Also, tREP-18 seems to destabilize the mitochondrial membrane
potential of parasites, disrupting their cellular integrity and leading
to parasitic death. The cellular assays of the tREP-18 peptide on
the BS12 strain, a clinical isolate of post-kala azar dermal leishmaniasis,
demonstrated its significant efficacy at an IC50 value of 15 nM. The
tREP-18 peptide showed a toxic effect on the amastigote stage of the
parasite, showing macrophage pathogen clearance at a concentration
of 22.5 nM. This study provides the proof of the concept of making
a new class of functional peptides from tRNA sequences. It also opens
a huge untapped tRNA-peptide space toward novel discoveries and applications.
In the future, it would be interesting to perform tREP edits and redesign
tREPs toward specific applications.
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