Immunotherapy: ALLOGENEIC UMBILICAL CORD BLOOD REGULATORY T CELLS DECREASE INFLAMMATION AND PRESERVE ANTI-TUMOR ACTIVITY OF CAR T CELLS

Background & Aim: With larger accessibility and increased number of patients being treated with CART cell therapy, real-world toxicity continues to remain a significant challenge to its widespread adoption. We have previously shown that allogeneic umbilical cord blood derived (UCB) regulatory T cells (Tregs) can resolve uncontrolled inflammation and can treat acute and immune mediated lung injury in a xenogenic model as well as in patients suffering from COVID-19 acute respiratory distress syndrome. The unique properties of UCB Tregs including: i) lack of plasticity when exposed to inflammatory micro-environments;ii) no requirement for HLA matching;iii) long shelf life of cryopreserved Tregs;and iv) immediate product availability for on demand treatment, makes them an attractive source for treating acute inflammatory syndromes. Therefore, we hypothesized that add-on therapy with UCB derived Tregs may resolve uncontrolled inflammation responsible for CART cell therapy associated toxicity. Methods, Results & Conclusion(s): UCB Tregs were added in 1:1 ratio to CART cells, where no interference in their ability to kill CD19+ Raji cells, was detected at different ratios : 8:1 (80.4% vs. 81.5%);4:1 (62.0% vs. 66.2%);2:1 (50.1% vs. 54.7%);1:1 (35.4% vs. 44.1%) (Fig 1A). In a xenogenic B cell lymphoma model, multiple injections of Tregs were administered after CART injection (Fig 1B), which did not impact distribution of CD8+ T effector cells (Fig 1C) or CART cells cells (Fig 1D) in different organs. No decline in the CAR T levels was observed in the Tregs recipients (Fig 1E). Specifically, no difference in tumor burden was detected between the two arms (Fig 2A). No tumor was detected in CART+Tregs in liver (Fig 2B) or bone marrow (Fig 2C). A corresponding decrease in multiple inflammatory cytokines in peripheral blood was observed in CART+Tregs when compared to CART alone (Fig 2D). Here we show "proof of concept" for add-on therapy with Tregs to mitigate hyper-inflammatory state induced by CART cells without interference in their on-target anti-tumor activity. The timing of Tregs administration after CART cells have had sufficient time for forming synapse with tumor cells allows for preservation of their anti-tumor cytotoxicity, such that the infused Tregs home to the areas of tissue damage to bind to the resident antigen presenting cells which in turn collaborate with Tregs to resolve inflammation. Such differential distribution of cells allow for a Treg "cooling blanket" and lays ground for clinical study. [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy

Percutaneous tracheostomy in head and neck oncology surgery: How Covid-19 changed our practice

Enhanced experience in performing percutaneous tracheostomies during the COVID-19 pandemic resulted in changes to airway management protocol for patients undergoing major head and neck reconstructive surgery within our department. Most patients now receive a percutaneous tracheostomy over the previously favoured surgical tracheostomy. The aim of this study was to review our experience in performing percutaneous tracheostomies, whilst comparing complication rates with surgical tracheostomies performed in similar settings. All consecutive patients undergoing free flap reconstructive surgery for head and neck cancer between June 2020 and November 2021 were included, with 56 patients receiving a percutaneous tracheostomy. Data across a range of variables including age, BMI, comorbidities and complications was compared with 56 surgical tracheostomies performed for the same group of patients before the COVID-19 pandemic and resultant protocol changes. In the percutaneous group, a marginally lower complication rate was observed over the surgical tracheostomy group;28.57% and 30.35% respectively. Analysis of the 16 patients who experienced complications in the percutaneous group led to development of selection criteria to identify appropriate patients to receive a percutaneous tracheostomy in future, based on factors such as BMI, bleeding risk and positioning deformities. The COVID-19 pandemic has offered a multitude of learning experiences for healthcare professionals to change our practice. In our unit, this has involved modifying the routine tracheostomy procedure used for airway management intra- and post-operatively in major head and neck reconstruction surgery.Copyright © 2023 The Authors

The Percutaneous Tracheostomy in Head and Neck Oncology Surgery

Introduction/Aims: Enhanced experience in performing percutaneous dilatational tracheostomies (PDT) during the COVID-19 pandemic resulted in changes to airway management for patients undergoing head and neck reconstructive surgery at Queen Elizabeth Hospital Birmingham. All patients now receive a percutaneous tracheostomy over the previously favoured surgical tracheostomy (ST), unless contraindicated. This ambispective case series aimed to review experiences in performing percutaneous tracheostomies, whilst comparing complication rates with surgical tracheostomies performed in similar settings. In addition, we propose a selection criteria for identifying patients suitable for PDT. Material(s) and Method(s): All patients undergoing free flap reconstruction for head and neck cancer treatment between June 2020-November 2021 were included, with 56 patients receiving PDT. This was compared with data of 56 ST performed before the COVID-19 pandemic. Results/Statistics: In the percutaneous group, a marginally lower complication rate was observed over the surgical tracheostomy group;28.57% and 30.35% respectively. Although not statistically significant, time to decannulation was slightly lower in PDT group (5.8 days) compared to ST group (7.3 days). An additional observed advantage included quicker tracheostomy wound healing with PDT. Analysis of the 16 patients who experienced complications with PDT aided development of the selection criteria for identifying patients for percutaneous tracheostomy. This selection criteria considers BMI, ASA, bleeding risk and positioning deformities. Conclusions/Clinical Relevance: This study has demonstrated PDT to be an equally safe and successful technique with a similar complication rate to ST in head and neck cancer reconstruction surgery. Moving forward, further studies with larger sample sizes would be recommended to draw conclusions. Copyright © 2022

Randomized, Multi-Center, Double-Blinded, Placebo Controlled Safety and Early Efficacy Trial of Cryopreserved Cord Blood Derived T-Regulatory Cell Infusions (CK0802) in the Treatment of COVID-19 Induced ARDS. (RESOLVE Trial)

Background. COVID19 associated moderate to severe acute respiratory distress syndrome (ARDS) is associated with high rates of morbidity and mortality. Immune dysfunction and hyper-inflammatory responses result in a vicious cycle of tissue inflammation and end organ damage. Based on the suggestion of early efficacy of adoptive therapy with allogeneic T regulatory cells in COVID19 ARDS (Gladstone et al., Ann Int Med 2020), Cellenkos ® initiated a randomized, placebo controlled, multi-center trial of multiple doses of CK0802 (allogeneic, off-the-shelf, cryopreserved, cord blood derived T regulatory cells) for treatment of moderate-to-severe COVID19-related ARDS patients. Study design. Multi-center, randomized, blinded, placebo controlled trial of CK0802 at two different doses (100 million cells and 300 million cells ) were compared to placebo. Each patient was randomized to receive the assigned product on days 0, 3 and 7 (Figure 1), without HLA matching. Enrollment was staggered for the first 6 active treatment patients with 7 days between each patient while monitoring for any safety signals. Subsequent patients were enrolled on a continuous basis. DSMB monitoring occurred after every cohort of 15 patients (5 controls;5 of each active treatment). Results are presented as median (with range) unless otherwise indicated. Primary Outcomes. The two co-primary outcomes were: • Dose Limiting Toxicity (DLT) = Regimen related grade 3, 4, or 5 toxicity within 48 hours of first infusion • S28 = [Alive and not intubated 28 days after the date of first infusion] = 28-day treatment success Secondary Outcomes. Secondary outcomes, recorded from first day of infusion up to 28 days later, included: i) time to extubation, ii) ventilator-free days;iii) organ failure-free days;iii) ICU free days;iv) PaO 2/FiO 2 between days 0 and 11;and v) 28-day all-cause mortality Covariates. Patient covariates recorded at enrollment included: i) age, ii) gender iii) on vasopressors;iii) on hemodialysis;iv) duration of intubation prior to enrollment. Study Conduct. The multicenter study (n=5 centers) was activated in October 2020 and enrollment completed in March 2021. Results. Forty-five patients were enrolled (60% male, median age 60 [range 21-85], 46.7% Caucasian race). At baseline 13% were on hemodialysis;62% on vasopressors;SOFA score=8 (6-13);PaO 2=85 mmHg (45-133);FiO 2=60% (40-100);PEEP=10 cmH 2O (5-18) with a median duration of intubation of 48 hrs (0-120) prior to enrollment. Patient were intubated a median of 72 [0-144] hours prior to infusion. Sixty percent of patients were alive and extubated at day 28. Median time to extubation from first infusion was 10.5 [2-46] days and median ventilator free days at day 28 was 12 [0-26]days. No treatment related SAEs were reported. Time to extubation from first infusion was 10.5 days (2-46) and at day 28 the ventilator free days were 12 (0-26). The estimated day 28 overall survival was 78.6% with the following breakdown according to the co-variates: i) age>60 yrs =77.5% vs. age<60yrs=79.9%;ii) female=85.7% vs male=73.7%;iii) on vasopressor=65.8% vs. 77.8%;iv) on hemodialysis=75% vs. 79%. Duration of intubation to enrollment had no impact on 28d survival. At baseline, 14 pts were positive for both HLA I and HLA II antibodies (Abs);3 pts positive for HLA I Ab only, and 9 positive for HLA II Ab only. In 20 paired samples collected on day 0 and day 28, HLA I Ab and HLA II Ab seroconversion was observed in 4 and 1 pt, respectively. Discussion This is the first clinical trial to examine safety and early efficacy of multiple doses of allogenic, off-the-shelf, cryopreserved, T regulatory cells for the treatment of COVID-19-related ARDS. Full data analysis of treatment groups (placebo;CK0802-100 million;CK0802-300 million) is ongoing and will be presented at the conference. Additional data to be presented will include: 3- and 6- month QOL, mental health, and cognitive index analyses, and paired Biomarker analysis. [Formula presented] Disclosures: Hari: Janssen: Honoraria, Membership on an ntity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau;GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau;Celgene-BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau;Millenium: Membership on an entity's Board of Directors or advisory committees, Research Funding;Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau;Adaptive Biotech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau;Karyopharm: Consultancy;Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Sadeghi: Cellenkos Inc.: Current Employment. Parmar: Cellenkos Inc.: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding. Mukherjee: Vor Biopharma: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: coinventor on issued and pending patent applications licensed to Vor Biopharma. S.M. has equity ownership and is on the Scientific Advisory Board of Vor Biopharma., Research Funding.

School Libraries as Promoters of Open Educational Resources to Galvanize Education: An Exploratory Study

In the COVID pandemic, educational institutions have adopted an online education delivery mode to ensure continuity in the students' learning process. The school teachers started taking online classes, and libraries delivered resources through WhatsApp or developed digital library webpages/portals. In this scenario, the importance of Open Educational Resources (OERs) cannot be overlooked, as they are free from copyright issues and can be reused by anyone without any prerequisite author permissions. The present study made efforts to identify the advocacy of such OERs by CBSE affiliated Indian public schools of Chandigarh, Delhi and Delhi West regions identified from the school directory of CBSE. After identifying Indian public schools providing links of OERs on their websites, the study aimed at listing the OERs supplied by the Indian public school/library to their users to find out the most common and distinctly found national and international OERs © 2021, Library Philosophy and Practice. All Rights Reserved.

A systematic review of international guidelines regarding the role of radiography in the diagnosis of osteoarthritis

Background: A substantial proportion of primary care osteoarthritis (OA) consultations are associated with an X-ray request (1,2). Uncertainty exists regarding the ability of radiography to improve a clinical OA diagnosis, and the over-use of radiography may lead to inappropriate referrals due to severe radiographic features that do not correlate with patients' symptoms. Additionally, there are cost implications of unnecessarily imaging such a prevalent disease. As evidence questions the utility of routine radiography in OA, the extent to which radiography is supported by international guidelines is unknown. Objectives: To undertake a systematic review and narrative synthesis of UK and international guideline recommendations on the role of radiography in the diagnosis of OA. Methods: A systematic search of eleven electronic databases (including EMBASE, MEDLINE CINAHL, Epistemonikos and Guideline Central) and the websites of nine professional organisations (including NICE, Royal College of Radiologists (RCR), EULAR, and the American College of Radiology (ACR)) identified the most recent evidence-based guidelines produced by professional organisations on the role of imaging in OA. Guidelines not addressing the role of radiography in the diagnosis of OA were excluded, as were non-English and spinal OA guidelines. Each title was screened by one reviewer whilst each abstract and full text underwent dual screening. A single reviewer, using a standard proforma, undertook data extraction. Each guideline was independently appraised by two reviewers using the AGREE II tool. A narrative synthesis of the nature and consistency of OA radiographic recommendations was performed. Results: 18 evidence-based OA guidelines published between 1998-2019 were included. These guidelines considered OA at any joint (n=8), or at the knee (n=3), hip (n=2), hand (n=2), wrist (n=1), foot (n=1), and ankle (n=1). Seven guidelines were produced by European organisations;four guidelines were produced by EULAR. Guidelines were targeted at general practitioners (n=11), radiologists (n=7), rheumatologist (n=4) and orthopaedic surgeons (n=3). Using the AGREE II tool, the identified guidelines scored highly on rigour of development (mean score 69%) but poorly on applicability (32%). All 18 guidelines recommended X-rays as the first-line modality, where imaging was indicated. A clinical diagnosis of OA without radiographic confirmation was recommended by all eleven guidelines produced by organisations represented general practitioners, with seven guidelines justifying this due to a poor correlation between radiographic features and clinical symptoms. Only three guidelines explicitly discouraged the routine use of radiography for the diagnosis of OA and only two guidelines reassured practitioners of a low probability of missing serious pathology when not routinely requesting radiographs. Guidelines produced by organisations representing radiologists were more supportive of radiography. The ACR recommended radiographic confirmation in patients suspected to have OA at the hand, wrist, hip, knee, ankle, and foot. Conversely, the RCR recommended radiographic confirmation in patients suspected to have OA at the hand, feet, and hip, but not the knee. Conclusion: Differences in guideline recommendations on the utility of radiography in OA appear related to country/region, professional organisation, and joint. The use and utility of radiography in OA may need to be reviewed in light of a shift towards remote consultations, a change that has been accelerated by COVID-19 in many countries.

Adoptive Therapy with Cord Blood T Regulatory Cells Enhances Anti-Myeloma Efficacy of T Cell Based Immunotherapies

Background. Inflammatory tumor microenvironment leads to T cell exhaustion in multiple myeloma leading to treatment failure and relapse. Specifically, T cell based therapies including bispecific antibodies and chimeric antigen receptor (CAR) T cell are associated with the additional side effects of non-specific T cell activation and cytokine release syndrome. Adoptive therapy with allogeneic cord blood (CB) T regulatory (Treg) cell therapy has been shown to be safe with clinical efficacy in a wide range of diseases including graft vs. host disease (GvHD), inflammatory bone marrow failures and COVID-19 induced acute respiratory distress syndrome. Furthermore, combination of Tregs with donor lymphocyte infusion (DLI) has led to resolution of leukemia relapse without GvHD flare up. We hypothesize that co-administration of Tregs with adoptive T cell based therapy will improve myeloma outcomes. Methods. 3x106 GFP-labeled MM.1S cells were injected into NSG mice followed by 5x106 CD3+ T conventional (Tcon) cells on day 14. In a subset of the Tcon treated mice, 1x107 CB Treg cells were injected on day 47, 54 and 61. Mice were followed every other day for weight and GvHD score. Non-invasive bioluminescent imaging (BLI) was performed serially. Weekly blood draw was performed for cell analysis and cytokine assays. At the time of euthanasia, blood, spleen and bone marrow were harvested for histopathology and flow analysis. In a subsequent experiment, intra-peritoneal injection of the bi-specific antibody against CD3 and BCMA (BCMA-BiTE) was administered in the xenogenic myeloma model in the presence or absence of CB Treg cells. Pan T cells were injected into all mice to facilitate the anti-tumor action of BiTE. Results. Both Tcon and Tcon+Treg recipients maintained their body weight compared to myeloma alone or myeloma + Treg arm (Figure A). All mice showed evidence of tumor growth by day 20 (Figure A). Widespread MM.1S cell growth in the myeloma only mice at day 27 was demonstrated by BLI whereas no measurable tumor growth was evident in Tcon recipients or Tcon+Treg recipients. By day 69, Tcon only mice were significantly increased tumor growth compared to Tcon+Treg recipients (Figure B). While circulating multiple myeloma cells were detected in myeloma alone and myeloma+Treg arm, no such evidence was detectable in the Tcon or Tcon+Treg recipients. However, upon euthanasia, extramedullary relapse of myeloma as retroperitoneal mass was detected in Tcon recipient (Figure C). Addition of Treg + BiTE led to a similar degree of tumor control compared to BiTE alone treated mice, however, a significant weight loss was observed in this arm (Figure D) with a corresponding high GvHD score (Figure E). Furthermore, addition of CB Treg cells led to decrease of T cell exhaustion phenotypic markers (data not shown). Conclusion. We are the first to show that CB Treg cells can be administered in combination with the T-cell based immunotherapies directed against myeloma. Such a strategy should be examined in the clinical setting. [Formula presented] Disclosures: Nishimoto: Bayer Yakuhin, Ltd:: Research Funding;Janssen Pharmaceutical K.K.:: Research Funding. Sadeghi: Cellenkos Inc.: Current Employment. Shah: GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy;BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding. Patel: Nektar: Consultancy, Research Funding;Celgene: Consultancy, Research Funding;Cellectis: Research Funding;Takeda: Consultancy, Research Funding;Janssen: Consultancy, Research Funding;Oncopeptides: Consultancy;Poseida: Research Funding;Precision Biosciences: Research Funding;Bristol Myers Squibb: Consultancy, Research Funding. Parmar: Cellenkos Inc.: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.

Adoptive Cord Blood T Regulatory Cell Therapy Leads to Resolution of Inflammation and Decreased Proteinuria in Lupus Nephritis

Background. Systemic lupus erythematosus (SLE) is associated with widespread inflammation with multi-organ involvement where renal failure is the most dreaded and fatal complication. Adoptive therapy with cord blood (CB) derived T regulatory cells has been shown to improve outcomes in disease driven by inflammation including graft versus host disease (GvHD), inflammatory bone marrow disorder, COVID-19 induced acute respiratory distress syndrome. We hypothesize that CB Treg therapy can treat lupus nephritis. Methods. The suppressive abilities of CB Tregs expressing CD4+CD25highCD127lowFoxP3+ were assayed by human cytokines assay kits (IL-10, IFN-γ, IP-10, TNF-α, IL-6, and IL-17A) in the cell culture supernatants. For examining the efficacy of CB Tregs in vivo, SLE xenograft model was created with female Rag2-/-γc-/- mice transplanted with 3x106 human SLE-peripheral blood mononuclear cells (PBMCs) by intravenous injection on day 0. The mice were allowed to develop disease and on day 30 post-transplant, they were divided into 2 groups: i) control and ii) treatment. 1x107 ex vivo-expanded, cryopreserved, allogeneic, non-HLA matchedCB Tregs were injected into SLE xenografts intravenously once per week for 4 weeks through the tail vein. Serial blood draws were performed for the phenotypic analysis, cytokine assay and anti-double stranded (ds)DNA IgG antibody analysis. Serial examination of the urine samples was performed for creatinine and albumin quantification. Histopathologic examination of the harvested organs was performed at the time of planned euthanasia at 13 weeks. Results. Co-culture of CB Tregs with the pathogenic SLE-PBMCs decreased the secretion of inflammatory cytokines including IFN-γ, IP-10, TNF-α, IL-6, and IL-17A (Figure A) with a reciprocal increase in the secretion of the anti-inflammatory IL-10 cytokine (Figure B). Adoptive therapy with CB Treg cells led to a significant decrease in circulating CD8+ effector T cells and an increase in CD4+ helper T cells (Figure C). CB Treg recipients showed preserved weight gain (Figure D), lower GvHD score (Figure E) and improved overall survival (Figure F). A significant decrease in proteinuria at 9 weeks post-transplant (Figure G) correlated with a decrease in anti-dsDNA IgG Ab levels (Figure H) and soluble CD40 ligand levels (Figure I). Histopathological results from two index cases from each arm (Figure J) demonstrated that CB Treg recipients show reduced T-cells (CD3+) (Figure K) and B-cells (CD20+) (Figure L) in the kidneys, as well as a decrease in the lymphoid infiltration into glomeruli and renal parenchyma as compared to the control arm (Figure M). Conclusion. We are the first to demonstrate the benefit of allogeneic CB Treg cell therapy for treatment of lupus nephritis. We propose to examine such a strategy in the clinical setting. [Formula presented] Disclosures: Nishimoto: Janssen Pharmaceutical K.K.:: Research Funding;Bayer Yakuhin, Ltd:: Research Funding. Sadeghi: Cellenkos Inc.: Current Employment. Parmar: Cellenkos Inc.: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.

Depression, anxiety, and stress among private health care practitioners in delhi ncr region during covid-19 pandemic: A cross-sectional study

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a globally prevalent public health pandemic due to a viral COVID-19 infection. This cross-sectional observational study aimed at evaluating the depression, anxiety, and stress levels among private health care practitioners in the Delhi NCR region during the COVID-19 pandemic. The questionnaire included sociodemographic characteristics and Depression, Anxiety, and Stress Scale (DASS)-21. Dentists exhibited the highest level of depression (83.89%), anxiety (89.3%), and stress (89.95%), followed by medical personnel and AYUSH workers. Most of the study cohort showed moderate levels of DASS scale. Fear of contracting the infection and fear of infection transmission to family/friends were the most common causes of mental distress. COVID-19 pandemic has imparted adverse effects on the mental health status of health professionals. The risk factors should be acknowledged, and necessary interventions should be implemented to maintain psychological well-being.

To study the hematological parameters in covid-19 positive cases in different clinical categories

Aims & Objectives: Since it's origin in December 2019 Novel Corona virus infection has behaved in an unprecedented manner. A number of studies had been done so far to find out peculiar characteristics about this disease. However, few studies have shown varied hematological manifestations of this which have been found to have prognostic implications. In this study we aim to assess the hematological parameters of COVID-19 positive cases and in their different clinical categories (mild, moderate and severe). Patients/Materials & Methods: It is an observational study done in Himalayan Institute of medical sciences, Dehradun. (1) Number of cases included were 118 over 3 months duration (July, August, September-2020). (2) The relevant clinical details of all the COVID-19 positive patients such as name, age, UHID were recorded. (3) EDTA sample was run on DXH800 (Beckmencoulter automated analyzer) and all parameters were recorded including the VCS. Inclusion criterion: Patients diagnosed with COVID-19 on Rapid antigentestor RTPCR of all age groups. Exclusioncriterion:Patients with missing hematological parameters. Results: In our study, total number of cases included were 118, out of which 84 (71.18%) were males and 34 (28.81%) were females. Patients above 60 years were 35 (29.6%). The patients were categorized into mild, moderate and severe on the basis of clinical findings and those findings were co-related with the VCS parameters. The significant findings include decreased absolutely mphocytecount in 43.2% cases and absolute eosinopenia in 83.05% of cases, absolute neutrophil count was increased in 44.9% cases and platelet count was reduced in 30.5% of the cases. Discussion & Conclusion: In major number of cases absolute lymphocyte count, absolute eosinophil count and neutrophil to lymphocyte ratio was found significant;so it is advised to categorize patients on the basis of clinical findings and related VCS parameters for early COVID-19 testing.

GLOBAL RESEARCH OUTPUT ON ‘CORONAVIRUS DISEASE-2019' (COVID-19)

Purpose: The present study reflects the trend and growth of publications on COVID-19 viral disease spreading around the world. With the emergence of COVID-19 in Wuhan, China in December 2019, scholars started publishing their researches in form of different kind of publications. Methodology: The data has been extracted from the Scopus database using key TERMS Covid-19 and corona virus 2019. Findings: During six month period around ten thousand publications are contributed by scientists around the globe. The literature produced in different fields but highest output is made in the field of Medicine. BMJ and Journal of Medical Virology journals produced highest amount of research on COVID. Highest numbers of publications have been contributed by China based two institutions viz. Huazhong University of Science and Technology and Tongji Medical College, China. Mahase, E. of UK contributed maximum papers followed by Wiwanitkit, V. of China. © 2020. All Rights Reserved.

Recent and upcoming regulatory changes in the European region: Opportunities for medical writers

The European regulatory landscape for clinical trials and medical devices is in the midst of major transformation. Older policies are giving way to new regulations that emphasise more harmonised and streamlined processes for document submittal, greater public transparency of documents, and the creation of plain language summaries of clinical trials for easier understanding by the general public. This article provides an overview of impor tant new regulations and policies, including some new guidances regarding research related to the COVID-19 pandemic. This article also discusses opportunities for medical writers working in the context of a new regulatory environment that requires balancing increased public disclosure of information and greater privacy protections for individuals. © 2020, European Medical Writers Association. All rights reserved.