Hybrid immunity: the immune response of COVID-19 survivors to vaccination

Hybrid immunity can become a turning-point opportunity to defeat the infection in context with the current pandemic scenario. Adopting policies aligned with the data mentioned above may be particularly beneficial for regions like Latin America. While this region shares only ~5% of the world population, it accumulates +16% of the ~200 million COVID-19 total cases, so far reported1. Acknowledging the reduced diagnostic capabilities of these countries, this entire area is probably one of the most affected globally, leading to one of the more numerous populations of convalescent people. From both an economic and pharmacological perspective, applying a one-dose regime of pertinent vaccines to convalescent individuals is sustainable5. As COVID-19 survivors may need just one vaccination to achieve high levels of protective immunity, massive antibody screening for SARS-CoV-2 spike antibodies could help prioritize and free up doses, optimize vaccine supply efficiency, and surpass problems linked to the current vaccine manufacturing bottleneck

RADI-04. Stereotactic radiosurgery in alveolar soft part sarcoma brain metastasis

Background Alveolar soft part sarcoma (ASPS), although rare, has the highest incidence of brain metastasis amongst all sarcomas. Stereotactic radiosurgery (SRS) has been shown to be a well tolerated and effective treatment of intracranial sarcomatous metastasis. However, there is a paucity of published literature that guides radiation therapy in this condition. Methods This is a single centre retrospective review of all ASPS patients with intraparenchymal brain metastasis in our centre treated with stereotactic radiosurgery (SRS). SRS dosing is dichotomised into high and low dose (≥25 Gy and <25 Gy respectively) and outcomes such as local recurrence (LR) and radiation effects are noted. Successful treatment was defined as a lesion that regressed, is stable, or has less than 25% increase in tumour volume. Local recurrence (LR) was defined as increase in tumour volume by more than 25% during follow up. Results There were three patients with 11 ASPS metastatic brain lesions, one of which underwent retreatment. Each lesion was followed up for a mean duration of 12 months (range: 5 – 22 months). Five lesions treated with a high dose regime and six lesions were given low dose. Lesions treated with high dose SRS experienced significantly less LR (20% vs 83.3%, OR 20.0 [95%CI 0.93 – 430), p = 0.036) with no increase in undue symptomatic radiation effects. Retreatment of lesions with LR after initial SRS using a low dose regime was successful, albeit only in the single recurrent lesion. Conclusions We conclude that SRS can be used as a first line treatment for ASPS brain metastasis that are not surgically accessible and that using a high dose for treatment is effective and safe. Multicentre collaborative studies can be performed to validate this claim.

Coronary microcirculation damage in anthracycline cardiotoxicity

Aims The aim of this study was to study changes in coronary microcirculation status during and after several cycles of anthracycline treatment. Methods and Results Large-White male pigs (n = 40) were included in different experimental protocols (ExPr.) according to anthracycline cumulative exposure (0.45 mg/kg intracoronary (IC) doxorubicin per injection) and follow-up: Control (no doxorubicin); Single injection and sacrifice either at 48 hours (ExPr. 1) or 2 weeks (ExPr. 2); Three injections two weeks apart (low cumulative dose) and sacrifice either 2 weeks (ExPr. 3) or 12 weeks (ExPr. 4) after third injection; Five injections two weeks apart (high cumulative dose) and sacrifice 8 weeks after fifth injection (ExPr. 5). All groups were assessed by serial cardiac magnetic resonance (CMR) to quantify perfusion and invasive measurement of coronary flow reserve (CFR). At the end of each protocol, animals were sacrificed for ex vivo analyses. Vascular function was further evaluated by myography in explanted coronary arteries of pigs undergoing ExPr. 3 and controls. A single doxorubicin injection had no impact on microcirculation status, excluding a direct chemical toxicity. A series of five fortnightly doxorubicin injections (high cumulative dose) triggered a progressive decline in microcirculation status, evidenced by reduced CMR-based myocardial perfusion and CFR-measured impaired functional microcirculation. In the high cumulative dose regime (ExPr. 5), microcirculation changes appeared long before any contractile defect became apparent. Low cumulative doxorubicin dose (3 biweekly injections) was not associated with any contractile defect across long-term follow-up, but provoked persistent microcirculation damage, evident soon after third dose injection. Histological and myograph evaluations confirmed structural damage to arteries of all calibers even in animals undergoing low cumulative dose regimes. Conversely, arteriole damage and capillary bed alteration occurred only after high cumulative dose regime. Conclusion Serial in vivo evaluations of microcirculation status using state-of-the-art CMR and invasive CFR show that anthracyclines treatment is associated with progressive and irreversible damage to the microcirculation. This long-persisting damage is present even in low cumulative dose regimes, which are not associated with cardiac contractile deficits. Microcirculation damage might explain some of the increased incidence of cardiovascular events in cancer survivors who received anthracyclines without showing cardiac contractile defects.

What is the uncertainty in efficacy of COVID-19 vaccines? A Bayesian analysis

This short paper reports a Bayesian analysis of the publicly available COVID-19 trial results. The analysis casts some doubts on whether the half+full dose regime of the AstraZeneca COVID-19 vaccine is truly more effective than the 2x full dose regime. The 95% posterior interval for the efficacy of the half+full dose regime is 66.6-96.3%, while for the 2x full dose regime it is 39.0-74.8%. Hence, it is possible that in both dosage regimes the vaccine has similar efficacy, around 70%. The estimated efficacy for the Pfizer vaccine is 89.9-97.4% and for Moderna 86.3-97.5%. These results should be interpreted with care though, since this analysis does not account for differences in for instance trial population, COVID-19 testing, and storage requirements for the various vaccines.

Comparison of Different Uses of Cyclophosphamide in Lupus Nephritis: A Meta-Analysis of Randomized Controlled Trials

Background: The present study aims to compare the relative efficacy and safety of different uses of cyclophosphamide (CYC) in lupus nephritis (LN). Methods: We searched the Cochrane Library, EMBASE, Global Health, MEDLINE and PubMed for articles from the database till June 2018. Results: 12 randomized controlled trials with 994 participants were included. The meta-analysis indicated that the short-interval lower-dose intravenous CYC regime remarkably reduced 24-hour proteinuria [mean difference (MD) -0.45; 95% confidence interval (CI) -0.62 to -0.27; I2 0%], incidence of major infections [odds ratio (OR) 0.62, 95% CI 0.40 to 0.95; I2 42%], gonadal toxicity (OR 0.41, 95% CI 0.27 to 0.62; I2 0%), and leukopenia (OR 0.55, 95% CI 0.33 to 0.94, I2 0%), while high-dose regime had an obvious lower probability of doubling of serum creatinine (Scr) level (OR 2.43; 95% CI 1.19 to 4.95; I2 0%). However, the difference in the complete and total remission rates between the two regimens was not observed. Conclusion: The result suggested that the short-interval lower-dose CYC regime remarkably reduced 24-hour proteinuria and the incidence of adverse events, while the long-course high-dose regime played a significant role in reducing the rate of doubling Scr level.

Efficacy of low dose magnesium sulphate regime and Pritchard’s regime in controlling of eclamptic convulsion and prevention of recurrence

Background: Eclampsia is defined as the onset of convulsions or coma during pregnancy or in post-partum period in a patient who has signs and symptoms of pre-eclampsia. It is life threatening emergency that continues to be a major cause of serious maternal morbidity and mortality also along with high perinatal mortality and morbidity. The present study undertaken to determine the efficacy of low dose magnesium sulphate regime and Pritchard’s regime in controlling eclamptic convulsion and prevention of recurrence of convulsion.Methods: Out of total 60 patients enrolled in the study; 30 were given low dose magnesium sulphate regime and remaining 30 with Pritchard’s regime. Selection of patients was done with simple random sampling. Relevant history was obtained from the patient, if conscious, or from the relatives. Through clinical examination was done and blood samples were collected for investigations after securing IV line.Results: There was insignificant difference regarding type of eclampsia in both groups. Recurrence of convulsion in Pritchard’s regime group was 6.67% and in Low dose regime group found to be 10% but this was statistically insignificant. Total dose of magnesium sulphate required in Low dose regime group was less than that required for Pritchard’s regime.Conclusions: Low dose magnesium sulphate Regime proved equally effective as that of Pritchard’s regime in control of convulsion in spite of less amount of drug and comparatively low serum magnesium levels and hence there is hardly any fear of intoxicator.

Role of low dose Magnesium sulphate in eclampsia

Background: Eclampsia is one of the challenging medical complications seen during pregnancy. With the use of magnesium sulphate for control of convulsion in eclampsia, it can be managed effectively.Methods: This is a prospective study done in a tertiary care hospital. Considering low body mass index of patients of developing area, authors had used low dose regime of magnesium sulphate. 100 patients had been enrolled for low dose magnesium sulphate regime after categorizing patients as per inclusion and exclusion criteria. The primary outcome to be measured was recurrence of fits in any patients who received low dose magnesium sulphate. The secondary outcome measured were development of any toxicity, level of serum magnesium level, maternal and perinatal outcome.Results: It was observed that 93% of the patients responded to low dose regime. 7% developed recurrence of fits for that additional dose of 2 gram of 20% magnesium sulphate was given to the patients. Not even a single patient developed signs of toxicity. 94% and 95% of the patients acquired therapeutic level of serum magnesium at 4 hours and 10 hours of magnesium sulphate administration, respectively. Maternal mortality was 5% and perinatal mortality was 24.4%.Conclusions: Low dose of magnesium sulphate can prevent and treat eclampsia. Low dose regimen also reduces incidence of toxicity with improved maternal and perinatal outcome.

Comparative evaluation of simultaneous administration of mifepristone and misoprostol; and misoprostol alone for induction of second trimester abortion

Background: The present study was conducted with the aim to assess the safety and efficacy of misoprostol alone and misoprostol with simultaneous mifepristone for second trimester termination of pregnancy.Methods: The study was conducted on 160 cases, divided in two groups of 80 cases each. In the study group 200 mg mifepristone and 200 μgm misoprostol given together on admission followed by miso every 3 hrs upto a maximum of 8 doses or until the abortion occurs, whichever occurs early. In the control group only miso was given in the same dose regime. If abortion did not occur within this duration it was considered failure of method. The results were analysed.Results: The success rate in first regimen was 98%. Mean induction abortion interval was significantly shorter in the study group, 8.62±1.96 h as compared to 14.5±3.01 h in the control group. The mean dose of the misoprostol required was significantly less in study group. The side effects like nausea, vomiting, fever, abdominal cramps, diarrhoea were observed more in control group (30%) in comparison to study group (12.1%).Conclusions: Mifepristone with simultaneous misoprostol is better than misoprostol alone and there is no need to wait for 24 hr after mifepristone for administration of misoprostol.