Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Evaluation of the effects of Occlusal Stabilization Appliance on the cervical dystonia symptoms

Background and aims: Cervical dystonia is a contraction of the neck muscles that causes movement problems, pain, and dysfunction in daily functioning. This problem can occur for a variety of reasons, and today it is more common due to computer work or working with mobile phones (any factor that causes prolonged pressure on the neck). Occlusal Stabilization Appliance (OSA) is a dental splint that is said that it is a good method to relax neck and face muscles, reduce symptoms, and even relieve cervical dystonia. In this study, we aimed to investigate the effects of OSA in reducing patient's symptoms. Methods: In this experimental study performed on patients with cervical dystonia referred to Shohada-e-Tajrish Hospital from start to the end of 2019, 7 patients were studied. OSA was created for patients and the patients were followed up 24 hours, 3 months after using OSA. Follow-ups were performed using the Dystonia Assessment Questionnaire (TWSTRS) and dystonia scaling and examination for improvement. Results: Three patients were male and four were female. The mean age was 42 ± 11.66 years. Patients had a mean history of dystonia of 10±8 years. There was no statistically significant difference between total relaxation, pain reduction, increased sleep quality, and tremor disappearance between 24 hours and 3 months after prosthesis, but there was a statistically significant difference in increased comfort 24 hours and 3 months after prosthesis (P-value = 0.053). Using OSA improves Rotation, Duration, and Maintain head max time. Conclusion: The use of OSA in the short term improves pain, increases the quality of sleep, relaxation, and elimination of tremor, but in the long term, has no effect on reducing these parameters

Effects of Levofloxacin on Expression of Apoptosis Genes of Ovarian Follicles in NMRI Mouse in Vitro and in Vivo

Background and Objectives: Levofloxacin is a fluoroquinolone. Long-term use of antibiotics, including fluoroquinolone antibiotics, causes dystrophic changes in the ovaries. In this study, the effects of levofloxacin on the development of ovarian follicles and their apoptosis in the in vitro and in vivo conditions of NMRI Mouse were investigated. Methods: In the vitro study, isolated ovaries of animals were treated with levofloxacin at concentrations of 1, 2, 5, 10 µg/ml for 6 days and in the vivo study were treated with levofloxacin at concentrations of 100, 200, 400 and 800 mg/kg. After 24 days, animals were sacrificed in the in vivo groups and ovary samples were obtained. Hematoxylin and eosin (H&E) stains for histological studies also Real Time PCR techniques for study of expression rate of Bax and Bcl-2 genes were performed in both groups. Results: The results of the in vitro study showed that the dose of 2 μg/ml induced apoptosis in the monolayer primary follicles. Doses of 5 and 10 μg/ml increased the induction of apoptosis in the multilayer primary follicle. The number of secondary follicles at the 5 μg/ml dose had the most decrease. While at the dose of 10 μg/ml, the number of mature follicles had the most increase. As the antibiotic concentration increases, the expression of the Bax gene decreases and Bcl-2  gene increases significantly. The results of the in vitro study showed that the number of primary and secondary follicles decreased dose-dependently. The number of atretic follicles increased significantly with increasing dose. The expression of the Bax and Bcl-2  genes increased with increasing levofloxacin antibiotic concentration. Conclusion: This study demonstrates that levofloxacin induces apoptosis in ovarian follicle

Imaging features of estrogen-negative breast cancers: a correlation study with human epidermal growth factor type II overexpression

Background: Estrogen-negative breast cancers have different clinical course, prognostic features and treatment response in comparison to estrogen receptor-positive (ER-positive) breast cancers. Human epidermal growth factor receptor 2 (HER2) oncoprotein has found to have a pivotal role in natural cell growth and cell division and is suggested to be directly related to tumor invasiveness in breast cancer patients. The purpose of this study was to retrospectively assess the mammography, ultrasound, and magnetic resonance imaging (MRI) features of estrogen negative breast cancers with and without overexpression of HER2/neu receptor. Methods: In this cross-sectional retrospective study, mammographic, ultrasound and MRI features as well as HER2 status were assessed in patients with ER-negative breast cancer that were referred to Cancer Institute of Imam Khomeini Hospital Complex in Tehran from October 2015 to October 2017. Clinicopathologic data and mammography, ultrasound, and MRI features were reviewed and were correlated with HER2 status of estrogen-negative tumors. Results: Of the 172 patients with ER-negative breast cancer, 101 patients were positive for HER2/neu receptor (58.8%). There was a significant correlation between HER2-positivity and tumor type (P=0.004). Among estrogen negative breast cancers, significant association were found between HER2 and tumor histologic grade (P=0.024) and TNM stage (P=0.021). HER2-positive tumors were more likely to present with microcalcification (P=0.007) and have irregular shapes (P=0.034) in mammography than HER2-negative tumors. No association was found between HER-2 status and tumor size, shape, margin, posterior feature, halo or orientation of the tumor in ultrasound. We also found no correlation between HER2 status and MRI features including mass shape or margin, internal enhancement pattern or curve type among estrogen-negative breast cancers. Conclusion: Findings of this study showed that among estrogen-negative breast cancers, HER2/neu positive tumors are more likely to be diagnosed at higher stage and have higher histologic grade at the time of diagnosis. Tumor mass shape and microcalcification in mammography are found to be associated with HER2 status among patients with estrogen-negative breast cancer

Granulocyte-colony stimulating factor may improve pregnancy outcome in patients with history of unexplained recurrent implantation failure: An RCT

Background: Family of colony-stimulating factors (CSF) have an essential role on early cross talk between embryo and uterine endometrium. Objective: The aim of this study was to evaluate the effects of the single dose of Granulocyte-CSF (G-CSF) injection on clinical outcome of assisted reproductive technology cycle in patients with repeated implantation failures. Materials and Methods: This randomized control trial study was performed on 52 infertile women who referred to the clinic with the history of more than three previous In vitro fertilization/Intracytoplasmic sperm injection-embryo transfer failures. All patients were stimulated with standard long protocol. All embryos were transferred on day five in blastocyst stage in both groups. The treated group received 300 μg (0.5 ml) recombinant human G-CSF subcutaneously which was injected 30 min before blastocyst embryo transfer. Results: There was not statistically significant differences in abortion rate in G-CSF and control group (p=0.09). G-CSF treated group showed higher clinical pregnancy rate in comparison with control group (56.2% vs. 40.0%) but it was not statistically significant (p=0.09). Although live birth rate in G-CSF group was higher than control group (53.1% vs. 35.0%) but there wasn’t statistically significant difference in the overall live birth rate between the two groups (p=0.10). G-CSF group had a twin pregnancies while in control group there was no twin pregnancy. Conclusion: Our result demonstrates the possibility that pregnancy outcome is better in women with repeated unexplained In vitro fertilization failure who are treated with G-CSF

The effect of pregabalin and duloxetine treatment on quality of life of breast cancer patients with taxane-induced sensory neuropathy: A randomized clinical trial

Background: The primary side effect of adjuvant chemotherapy with taxanes is the taxane-induced peripheral neuropathy (TIPN), which may have substantial negative impacts on patients' quality of life (QOL). We investigated the effect of pregabalin and duloxetine on QOL of breast cancer patients who experienced TIPN. Materials and Methods: This was a randomized, double-blind clinical trial conducted at a chemotherapy center of Mazandaran University of Medical Sciences, Sari, Iran. Breast cancer patients 18 or more years old were included if they received paclitaxel or docetaxel and experienced neuropathy grade one or higher; and neuropathic pain score of four or more. Patients were treated with pregabalin or duloxetine until 6 weeks. Assessment of sensory neuropathy and QOL was performed at baseline, and 6 weeks after the initiation of the treatment. Results: At baseline, the mean score of global health status/QOL scale for pregabalin and duloxetine groups were 61 (standard deviation [SD]; 5.11) and 60.28 (SD; 5.44), respectively (P = 0.54). After 6 weeks, both interventions were associated with improvement of global QOL compared to baseline. The global health status/QOL score was not different between two groups after 6 weeks. While the emotional functioning was improved more favorably with duloxetine (P < 0.001); pregabalin was associated with more improvement in insomnia and pain scores (P = 0.05 and P < 0.001, respectively). Conclusion: Pregabalin as well as duloxetine improve the global QOL of breast cancer patients with TIPN. Different effects of treatments on subscale of QLQ-C30 could help clinicians to select the appropriate agent individually

Epigenetic quantification of circulating immune cells in peripheral blood of triple-negative breast cancer patients

Background!#!A shift in the proportions of blood immune cells is a hallmark of cancer development. Here, we investigated whether methylation-derived immune cell type ratios and methylation-derived neutrophil-to-lymphocyte ratios (mdNLRs) are associated with triple-negative breast cancer (TNBC).!##!Methods!#!Leukocyte subtype-specific unmethylated/methylated CpG sites were selected, and methylation levels at these sites were used as proxies for immune cell type proportions and mdNLR estimation in 231 TNBC cases and 231 age-matched controls. Data were validated using the Houseman deconvolution method. Additionally, the natural killer (NK) cell ratio was measured in a prospective sample set of 146 TNBC cases and 146 age-matched controls.!##!Results!#!The mdNLRs were higher in TNBC cases compared with controls and associated with TNBC (odds ratio (OR) range (2.66-4.29), all P!##!Conclusion!#!This immunomethylomic study shows that a shift in the ratios/proportions of leukocyte subtypes is associated with TNBC, with decreased NK cell showing the strongest association. These findings improve our knowledge of the role of the immune system in TNBC and point to the possibility of using NK cell level as a non-invasive molecular marker for TNBC risk assessment, early detection, and prevention