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Ionizable amino lipids are a major constituent of the lipid nanoparticles for delivering nucleic acid therapeutics (e.g., DLin-MC3-DMA in ONPATTRO , ALC-0315 in Comirnaty , SM-102 in Spikevax ). Scarcity of lipids that are suitable for cell therapy, vaccination, and gene therapies continue to be a problem in advancing many potential diagnostic/therapeutic/vaccine candidates to the clinic. Herein, we describe the development of novel ionizable lipids to be used as functional excipients for designing vehicles for nucleic acid therapeutics/vaccines in vivo or ex vivo use in cell therapy applications. We first studied the transfection efficiency (TE) of LNP-based mRNA formulations of these ionizable lipid candidates in primary human T cells and established a workflow for engineering of primary immune T cells. We then adapted this workflow towards bioengineering of CAR constructs to T cells towards non-viral CAR T therapy. Lipids were also tested in rodents for vaccine applications using self-amplifying RNA (saRNA) encoding various antigens. We have then evaluated various ionizable lipid candidates and their biodistribution along with the mRNA/DNA translation exploration using various LNP compositions. Further, using ionizable lipids from the library, we have shown gene editing of various targets in rodents. We believe that these studies will pave the path to the advancement in nucleic acid based therapeutics and vaccines, or cell gene therapy agents for early diagnosis and detection of cancer, and for targeted genomic medicines towards cancer treatment and diagnosis.
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Globalisation, industrialisation, and ease of international travel are making a huge impact on urban ecology. It is also influencing the climate, exaggerated by increased pollution, global temperature, and greenhouse gasses. All these factors together play a pivotal role in the increased emergence of infectious human diseases like fungal, bacterial, and viral. Many microorganisms are commensal and coâ€exist as microflora of healthy individuals. However, when the immune system is compromised due to disruption of mucosal barriers or presence of other environmental factors including increased air pollution, these microorganisms get an opportunity to invade and cause infections. In a similar way, the ongoing COVIDâ€19 pandemic, mediated by SARSâ€CoVâ€2, has also led to an increase in a number of nosocomial infections and secondary infections or superinfections like bacterial, fungal, and viral. Several studies have suggested that adaptation to higher temperatures is one of the key contributors to the emergence of many fungus like Candida auris and mucormycetes. Even bacteria like Acinetobacter baumannii, Mycobacterium tuberculosis, etc. or viral infections mediated by Ebola, H1N1, Encephalitis, and SARSâ€CoVâ€2 become more virulent with change in climate and urban ecology. Lifestyle change including uncontrolled intake of animal foods which possibly resulted in the zoonotic transfer of SARSâ€CoVâ€2 to humans, an increase in sexually transmitted diseases including AIDS due to uncontrolled lifestyles in a modern urban society are few other examples. Although these are the results of humans’ need and greed, it is not too late to take actions towards sustainable developments and adopting preventive plans to save the future world. This chapter mainly attempts to understand how such changes in environmental factors, altered climate, and urban ecology can lead to emergence of several infectious diseases, followed by a discussion of preventive measures to keep a steady but sustainable global development of human lives. © 2022 John Wiley & Sons Ltd.
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In the U.S., those who lack broadband internet have limited ability to connect to care providers over a telemedicine video visit (VV). During the coronavirus disease pandemic, VVs have become increasingly common, but are not equitably accessible, which may exacerbate existing health disparities. Widening health disparities are of particular concern in the rural U.S. where broadband is lacking. Because public libraries are trusted sources of health information and typically offer free use of broadband internet to patrons, they can help bridge the digital health divide and assist patrons with VVs. However, no guidelines currently exist for care providers and libraries to implement this potentially complex undertaking. In this paper, we review concepts related to the digital health divide and its impact on telemedicine inequities, and propose a research framework for evaluating public libraries as potential hubs for residents living in broadband-poor communities to connect to a telemedicine VV. There is currently a paucity of research evaluating the use of libraries for telemedicine, although partnerships between libraries and health providers may be increasing. We use an established health implementation science framework to guide a research agenda to examine the reach, efficacy, adoption, implementation, and maintenance of collaborative programs between libraries and health providers intended to leverage public libraries to improve access to telemedicine VVs in broadband-poor communities. The use of public libraries as spaces from which patrons can participate in VVs with providers is promising, but research is urgently needed to guide implementation.
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Learning outcomes: This case analysis will make the audience aware of the sudden nature of the crisis, specifically the transboundary crisis. They will be introduced to the concepts of participative leadership and situational leadership. Majorly the audience would learn to remain composed in times of crisis and comprehend how a circumstance can transform a participatory leadership style into a situational leadership style. The case will allow the audience to brainstorm how to take innovative decisions to manage a crisis situation. The primary objectives of the case are as follows: ■ to understand a transboundary crisis and its characteristics to deal with it;■ to visualise the application of participative and situational leadership and evaluate and analyse the most suitable leadership style during an unknown crisis;■ to make the students aware of how to remain composed in times of crisis and, for instance, implementing the change of leadership styles per the situation's requirement;and ■ to make students learn to design innovative decision-making strategies to develop a crisis management plan for managing future crises. Case overview/synopsis: The case highlights the successful management of the crises faced by a multi-specialty hospital named "Shukan-Caring Lives”, established in 2017 in Vadodara city of Gujarat, India. The case revolves around the Chief Operating Officer, his executive management body and the paramedical and medical staff of the hospital, who dealt with the grave Corona crisis. This case shows how the change in leadership style from participative to situational leadership style could manage the situation by taking brilliant initiatives and providing insightful solutions with a lot of dedication, showing how situational leadership can deal with the transboundary crisis. Complexity academic level: The case is an excellent example of a transboundary crisis for any organisation and demonstrates a novel idea of transforming the participative leadership style into a situational leadership style as and when the need arises. The topics of transboundary crisis and management crisis can be taught in strategic management. At the same time, leadership styles and transformation of leadership style can be covered in organisation behaviour. Management development programmes can also include such kinds of cases to give exposure to crisis and its management. The target audience would be PG management students, management executives and senior-level managers in various courses. Supplementary material: Teaching notes are available for educators only. Subject code: CSS 11: Strategy. © 2023, Emerald Publishing Limited.
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Circular economy is gaining popularity across the world, but its implementation in Jaipur District, as in other developing nations, is lacking. The Covid-19 epidemic has resulted in massive volumes of hazardous trash that require specific handling. The goal of this study was to evaluate CE and waste management efforts in Jaipur District, India during the Covid-19 epidemic. Two quarantine healthcare centers in Jaipur District were used as case studies, with data collected using quantitative and qualitative approaches and evaluated to establish the problems of hazardous waste management in Jaipur District. A total of 220 questionnaires were sent to the employees, with 216 (98.18%) of them being returned. There were 118 males (55%) and 98 women (45%) among the respondents, who worked in a variety of fields, including health workers (n = 108;50%), maintenance personnel (n = 62;28.7%), and cleaners/waste handlers (n = 46;21.29%). The majority of the participants (94.44%) said Covid-19 wastes should be separated, whereas 116 people (53.7%) thought managing personal protective equipment during a pandemic was reasonable. According to the findings, training and retraining of personnel on hazardous waste management at the examined healthcare institutions is critical to the implementation and enforcement of national policies for solid waste management. Rajasthan's government must dispose of biological waste in one step, straight out of town, rather than in two steps, first in Jhalana, Jaipur, and then in Jamdoli, Jaipur. © 2023, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.
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The COVID-19 pandemic has caused a huge decline in money usage, with everything turning online these days. It has contributed to an increase in contactless payments that was unimaginable before. A credit card is the most extensively used method of payment, and it is becoming increasingly digital as the number of daily electronic transactions increases, making it more vulnerable to fraud. Credit card firms have suffered losses because of widespread card fraud. The most common worry is the recognition of credit card fraud. As a result, organizations are looking toward advanced device understanding technologies since they can handle a lot of data and spot irregularities that humans would miss. The development of effective To stop these losses, fraud detection algorithms are essential. An increasing number of these algorithms rely on cutting-edge computer methods that can assist fraud investigators. However, the appearance of the full-proof Fraud Detection System demands the use of high performing algorithms that are both exact and sturdy enough to handle massive amounts of data. The algorithm is run using open-source software using R statistical programming. This project tries to provide options by studying several fraud detection systems and highlighting their strengths and limitations. © 2022 IEEE.
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When we hear the word Covid, there is fear and uncertainty and with the chances of third wave, the only ray of hope is Covid Vaccination and strict Covid Protocols issued by Government of India (GoI). For every citizen it is crucial to understand that the mechanism of Procuring Covid Vaccination. The entire drive of vaccination in India can be divided into three phases. On 16th January, 2021 Phase-I was launched targeting to protect those sections of society who were more vulnerable to Covid, i.e., Health Care Workers and Front Line Workers. Phase-II was initiated from 1st March, 2021 and 1st April, 2021 which focused on protecting the next vulnerable, Phase-III launched on 1st May, 2021with the aim to reach larger mass, the policy was liberalized and was opened to private players to purchase the vaccination.The most difficult task in this entire pandemic must have been procurement of Covid Vaccination for each and every State. Since in India, there is no centralized Procurement Legislation, the process of procuring vaccination has been facing several challenges, viz-a-viz modus operandi, fair treatment to each State, chances of black marketing, and unavailability of sufficient human resources. In this research paper, the key highlights are methods and tools used by GoI and various States to procure Covid Vaccinations to its citizen and its comparison with the developed nations. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.
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INTRODUCTION: The Mayo Clinic, Mankato Intensive Care Unit (ICU) has seen a steady increase in central line utilization, known to increase risk for central line-associated bloodstream infections (CLABSI). The "central line" or "device utilization rate" (DUR) for quarter 4 (Q4) 2021 was at 63%, increased from a pre-covid baseline of 45% in 2019. The CLABSI rate in Q4 of 2021 rose to 5.67, the highest in the past 5 years. The aim of this project was to decrease the ICU DUR by 36.5% from a baseline of 63% to 40% by 09/2022 without adversely impacting staff satisfaction. This effort was anticipated to positively impact patient outcomes, patient safety and the patient experience. METHOD(S): A multidisciplinary team conducted a review of current practices and potential contributors to the increased DUR were identified. The root causes of increased central line usage were determined to be lack of awareness on appropriate central line indication and gaps in communication. Interventions were implemented to address the key barriers: (a) Process: A vascular access algorithm was created to suggest the type of access needed based on duration of line and medication infusions. A rounding checklist included indications for central line placement and alternatives for vascular access. (b) Communication: Enhancement of daily interdisciplinary rounds and implementation of evening rounds to discuss central line indication and barriers to removal (c) Education: Central line education was provided during daily nurse huddles and weekly newsletters. An educational poster was created and displayed in the ICU, and (d) Closed Loop Feedback: The result of the post-intervention numeric improvement measure and sample size were monitored. Quarterly data will be reviewed for discussion. Key project milestones were recorded throughout the project. RESULT(S): The pandemic saw a surge in ICU patients, and it caused an uptick in central line placement. The project brought awareness of our DUR. Discussions of appropriate placement and early removal of central lines helped decrease our DUR. By June 2022, our DUR rate has decreased to less than 40%. CONCLUSION(S): Through a defined process we have been able to decrease central line utilization in our ICU. We will continue to monitor to ensure that our improvements are sustained.
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INTRODUCTION: During the COVID-19 pandemic, the burden on the healthcare system makes it critical to examine readmission patterns. In this study, we evaluated the readmission rates and risk factors associated with COVID-19 from the large SCCM Discovery VIRUS: COVID-19 Registry. METHOD(S): This was a retrospective, cohort study including hospitalized adult patients from 181 hospitals in 24 countries within the VIRUS: COVID-19 Registry. Demographic, clinical, and outcome data were extracted and divided into two groups: Patients with readmission with COVID-19 in 30 days from discharge and those who were not. A univariate analysis is done using chi-square and t-test as appropriate. Multivariable logistic regression was used to measure risk factor associations with 30-day readmission. RESULT(S): Among 20,283 patients, 1,195 (5.9%) were readmitted within 30 days from discharge. The median (IQR) age of readmitted patients was 66 (55-78) years and 45.2% were female, 60.2% were white, and 78.9% non-Hispanic. Higher odds of readmission were observed in patients aged >60 vs 18-40 years (OR 2.76;95% CI, 2.23-3.41), moderate COVID-19 disease (WHO Ordinal scale 4-5) vs Severe COVID-19 (WHO Ordinal scale 6-9) (OR 1.23;95% CI, 1.10-1.39), no ICU admission at index hospitalization (OR 1.70;95% CI, 1.32-1.80), and Hospital length of stay <=14 vs >14 days (OR 1.53;95% CI, 1.32-1.80) vs those not readmitted (p= < 0.001). Comorbidities including coronary artery disease (OR 2.14;95% CI 1.84-2.48), hypertension (OR 1.58;95% CI 1.40-1.78), congestive Heart Failure (OR 2.54;95% CI 2.16-2.98), chronic pulmonary disease (OR 2.26;95% CI 1.94-2.63), diabetes (OR 1.32;95% CI 1.17-1.49) or chronic kidney disease (CKD) (OR 2.41;95% CI 1.2.09-2.78) were associated with higher odds of readmission. In multivariate logistic regression adjusted for age group, hospital length of stay <=14 days and, highest WHO COVID-19 ordinal scale and index ICU admission coronary artery disease, congestive heart failure, chronic pulmonary disease, chronic kidney disease, hospital length of stay <=14 days and age >60 years remained independent risk factors for readmission within 30 days. CONCLUSION(S): Among hospitalized patients with COVID-19, those readmitted had a higher burden of comorbidities compared to those non-readmitted.
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BACKGROUND: Throughout the COVID-19 pandemic, concerns have emerged regarding missed cases of child maltreatment. Evidence suggests an increased incidence of child maltreatment despite a documented decline in reports to child protective services. In Ottawa, reports dropped by 30-40% at the start of the pandemic in 2020. Pediatricians play an important role in the detection of child maltreatment and many have shifted from in person to virtual care. However, there is a paucity of published literature on this topic. We hypothesize that the shift to virtual visits is a barrier to identifying cases of child maltreatment and may contribute to missed cases. OBJECTIVE(S): Our survey assesses if and how Canadian pediatricians are identifying child maltreatment over virtual medical appointments, as well as the barriers and enabling factors to doing so. DESIGN/METHODS: The Canadian Paediatric Surveillance Program (CPSP) is a joint effort with the Canadian Paediatric Society and Public Health Agency of Canada towards national pediatric surveillance through monthly surveys to 95% of Canadian pediatricians. Using their infrastructure, a one-time survey was sent to 2770 pediatricians between November 2021 and January 2022 with data analyzed for qualitative themes and descriptive statistics. RESULT(S): There was a 34% response rate (n= 928) and 704 valid responses. Exclusions were for no provision of virtual care, incomplete surveys or no reported cases of child maltreatment in their career (n=93, 10%). The average number of years in independent practice was 17.5 years, and 69% had not provided virtual care prior to the pandemic. Based on a virtual visit, at least one case of child maltreatment was reported by 16% of physicians prior to the pandemic, and by 11% following March 2020. Nearly one-third (30%) of these cases required a subsequent in-person visit prior to making the report. Social stressors and clear disclosures from patients and caregivers were the main factors leading to reports. The virtual physical exam was not a factor that triggered concerns of maltreatment in any case. Respondents reported at a rate of 68% that it was slightly or much more difficult to detect child maltreatment over virtual visits. Concerns that a case had been missed or identified late in association with virtual care were reported by 29% of physicians (n=206) with some commenting that clear harm resulted. CONCLUSION(S): This survey shows that virtual medical care presents barriers to identifying child maltreatment and may be an important factor in missed cases of child maltreatment.
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Background: COVID-19 disease, a pandemic for more than two years, has major morbidity and mortality related to pulmonary involvement. Chest radiography is the main imaging tool for critically ill patients. As the availability of arterial blood gas analysis is limited in the Level I and II healthcare centres, which are major partners in providing healthcare in resource-limited times, we planned the present study. Objectives: To assess the role of chest radiography in predicting the need for oxygen/ventilator support in critically ill COVID-19 patients. Methods: This hospital-based, retrospective study included 135 patients who needed oxygen/ventilator support and had optimal-quality chest radiographs at admission. All the chest X-rays were evaluated and a severity score was calculated on a predesigned pro forma. Statistical evaluation of the data obtained was done using appropriate tools and methods. Results: Males outnumbered females, with a mean age of 54.35 ± 14.49 years. More than 72% of patients included in our study needed ventilator support while the rest needed oxygen support. There was a significant statistical correlation between the chest radiograph severity score and SPO2 /PaO2 levels in our study. Using a cut-off value >8 for the chest radiograph severity score in predicting the need for ventilator support in a Covid-19 patient, the sensitivity, specificity and accuracy was 85.7%, 92.5% and 89.5%, respectively. Conclusion: Chest radiography remains the mainstay of imaging in critically ill COVID-19 patients when they are on multiple life-support systems. Though arterial blood gas analysis is the gold standard tool for assessing the need for oxygen/ventilator support in these patients, the severity score obtained from the initial chest radiograph at the time of admission may also be used as a screening tool. Chest radiography may predict the need for oxygen/ventilator support, allowing time for patients to be moved to an appropriate-level healthcare centre, thus limiting morbidity and mortality.
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Health is the basic human right and an important indicator of the nations' commitment towards the health of its citizen and hence every country strives to increase the health standard and provide basic medical facility to all. This right to health is an outcome of various legal sanctions, both internationally and of countries specific. The right to health is enshrined as a basic human right internationally. The right to health is an inclusive right, extending not only to timely and appropriate health care, but also to the underlying determinants of health as per (Report of Committee on Economic, Social and Cultural Rights). Though the Constitution of India does not expressly recognize the Right to Health as a fundamental right under Part III of the Constitution (Fundamental Rights), it is considered as an inseparable part of the Right to Life. Article 23. As a result, the child labour and human trafficking are prohibited in India. This article aims to analyse the impact of fast-changing lifestyle, habits, stress, COVID-19 pandemic and other factors on public health in India. It is more sensitized since last two years. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.
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The Internet of Things consists of physical things with sensors, computing power, and software that link to other devices or systems through the Internet or another communication network. Currently, IoT is being employed in health care research. Using a healthcare dataset, a trained network was used in this research to make judgments. The study uses the LSTM model for prediction in the present IoT system to produce a reliable and adaptable solution for healthcare. Connecting everything to the internet so people may live in a secure and comfy environment is the goal of the Internet of Things. Connecting everything in our environment is the main goal of the IoT. The internet might have an impact on computers that aren't directly connected to it. With the aid of the Internet of Things, patients who live distant from a healthcare centre are being helped. Researching the present IoT system's problems is essential in order to develop an effective, practical, and scalable solution for improving healthcare. There must be a strong basis for health-care apps to succeed. It has been anticipated that mankind would face increased health care issues in the future with the introduction of COVID 19. Healthcare solutions that are more trustworthy and precise will be needed, along with the capacity to treat health concerns remotely in a highly effective manner. Existing IoT-based studies are being analyzed for their effectiveness and accuracy by researchers doing in-depth analyses. The integration of LSTM-based intelligent approach to IoT system is being proposed as a method to increase the accuracy of the medical prescription and prescribing system. Research is focusing on improving accuracy and performance. Copyright © 2022, Anka Publishers. All rights reserved.
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Till today, we are using conventional technologies for memory-related applications. However, as the size of the electronic devices are shrinking day by day, such conventional memory devices will not be compatible with emerging applications like artificial intelligence, cloud storage, data mining, Internet of Things, etc. After the coronavirus outburst, these technologies are more needed as now all work is online. Henceforth, high data storage and fast information processing is one of the vital requirements which is to be researched. So, the researchers are now approaching the new memory technologies such as resistive random access memory (RRAM) which is superior than conventional memory devices in terms of scalability, speed, power consumption, design structure and many more other advantages. With all the pros, RRAM also has some cons like higher level of variability and reliability issues. So, to discuss all these issues, we present the basics of RRAM, their advantages, applications and technological trends in this manuscript. © 2023, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.
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We highlight the benefits of a formal preseason in professional football in terms of there being a lower injury rate at the start of the season following a formal preseason. Data Background The 'preseason' is an established period of the professional football season for players to gain fitness and has been demonstrated to subsequently improve player performance following the start of the season. Although players are at greater risk of injury in the preseason period, it is questioned whether a preseason subsequently decreases the risk of injury in the start of the formal season itself. Due to the established nature of the preseason no studies have previously reviewed the effect of the preseason on injury rates in the subsequent season. Our aim was to report the injury rate from post-lockdown professional football games (no preseason programme -NPP) and compare to the start of the season (following a preseason programme -FPP). This would then provide a comparison between the two groups and a determination of the potential beneficial effect of a formal preseason on the injury rates at the start of the formal season. Methods We compared the injuries sustained across 4 European Professional Football Leagues (Premier League, Serie A, Bundesliga, La Liga) from the first 2 games for each team at the start of the 2019-20 season (FPP group) and from the first 2 games for each team after the re-start of football following lockdown (NPP group). We recorded the frequency, injuries per game, contact and soft tissue injuries. An injury was recorded if the player was deemed unable to continue play. Results In total 156 games were reviewed, 78 in the FPP group and 78 in the NPP group. A total of 10 injuries were observed in the FPP group games, 0.13 per game, compared to 30 injuries in the NPP group games, 0.39 per game (p=0.001). The ratio of contact to soft tissue injuries was the same for both groups (1:4). There was no significant difference in the length of downtime between the leagues stopping and restarting (92-103 days) and no correlation between injury rate and length of downtime. Conclusions Injuries in elite professional football were more common in the first 2 games following the restart after lockdown than in the first 2 games of the 2019/20 season. We believe this is due to the beneficial effect of a normal preseason being absent for the restart. We highlight the importance of preseason in reducing injury rates amongst professional footballers.
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SESSION TITLE: Management of COVID-19-Induced Complications SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Evans syndrome (ES) is a rare autoimmune disorder characterized by the combination of two or more cytopenias with an incidence of 0.8-3.7%.Here we present a case of COVID-19 pneumonia complicated by the development of ES. CASE PRESENTATION: A 75-year-old female with the past medical history of 50 pack-year smoking, recent asymptomatic COVID-19 Pneumonia 2 week ago came to the emergency room (ER) with shortness of breath. Her vitals and physical exam were unremarkable. Labs were significant for leukocytosis of 11.66 and D-dimer of 3.32. CT pulmonary angiogram showed bilateral pulmonary embolism along with a COVID-19 pattern of pneumonia. She was started on heparin drip and was eventually discharged on Warfarin with Prednisone taper. After 3 weeks, she presented to the ER with worsening shortness of breath. She was found to have platelet count of 4k and Hb of 6.6 gm%(compared to 370k and 13.1 gm% on last discharge) and was started on transfusions which could not be completed due to development of mid-transfusion fever. She received Dexamethasone and IVIG. All forms of active bleeding were ruled out by bronchoscopy, CT scans and EGD. Flow cytometry was negative for ADAMTS13 ruling out thrombotic thrombocytopenic purpura. Bone marrow biopsy was unremarkable. She was positive for IgG warm agglutinin hemolytic anemia. She was discharged on long-term Prednisone taper. In the clinic she was given intermittent IVIG and Romiplostim to improve her counts. Due to multiple failed attempts to wean her off steroids, she was started on Rituximab with an excellent response of platelets increment to 450k and Hb to 8.5 gm%. Rituximab will be given for a total of 8 weeks. DISCUSSION: ES is considered to be caused by immune system dysregulation. ES in COVID-19 is a diagnostic dilemma as the thrombocytopenia is usually misdiagnosed as COVID-19 sequelae and leads to delay in diagnosis. The treatment of ES is usually with steroids 1 mg/kg/day but they only provide short term improvement. Rituximab, plasma exchange, IVIG, and splenectomy are second-line treatments for relapsing/refractory ES. Our patient had an acceptable response to steroids but it was transient,demonstrating the limited role of steroids in the long term and was eventually treated successfully with Rituximab. A review of limited published cases of ES caused by COVID-19 suggests that diagnosis, treatments, and prognosis are usually individualized according to patient characteristics, presenting symptoms, physician preference, and disease complications. CONCLUSIONS: ES is a very rare syndrome although it requires prompt treatment. It is important to be mindful about immunological causes when a COVID-19 patient presents with cytopenia, as delay in treatment can cause poor outcomes. Reference #1: Turgutkaya A, Bolaman AZ, Yavaşoğlu Í. COVID-19-associated Evans syndrome: A case report and review of the literature. Transfus Apher Sci. 2021 Dec 7:103339. doi: 10.1016/j.transci.2021.103339. Epub ahead of print. PMID: 34896007;PMCID: PMC8655821. DISCLOSURES: No relevant relationships by Nitesh Jain No relevant relationships by Kashyap Kela No relevant relationships by Princy Shah No relevant relationships by namita sharma No relevant relationships by AMIT SHARMA
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Background: The Bruton's tyrosine kinase (BTK) inhibitor acalabrutinib is approved for treatment of chronic lymphocytic leukemia(CLL). Acalabrutinib induces durable remissions in most CLL patients, which mostly are partial remissions (PR), and therefore treatment typically is given as long-term monotherapy. As a potential alternative we developed a time-limited regimen, combining acalabrutinib with obinutuzumab. Aims: Here, we report early results from 14 treatment-naïve patients with CLL who enrolled in this ongoing phase 2 trial (NCT04505254) since September, 2020 at MD Anderson Cancer Center. Methods: Patients and Study Design: Treatment-naïve CLL patients requiring therapy as per iwCLL criteria receive acalabrutinib 100 mg orally twice a day for 24 cycles, combined with monthly obinotuzumab for 6 doses, starting in cycle 3. The first dose of obinutuzumab is divided into 100 mg on day 1 and 900 mg on day 2 of cycle 3;1000 mg are given during subsequent cycles (cycles 4-8). Patients who do not achieve a complete remission (CR) after cycle 8 can receive an additional 6 monthly doses of obinotuzumab during cycles 9 -14. Treatment is discontinued after 24 cycles, and patients will be monitored. The primary objective is to determine the durability of remissions after treatment discontinuation, secondary objectives are to determine clinical and laboratory characteristics that predict for early versus late relapse after time-limited therapy. Results: The median age of the patients is 70 yrs (range, 40 -83 yrs), 14% had del17p or TP53 mutation, 43% had an unmutated IgHV and 71% advance stage disease (RAI stage III and IV). The median baseline absolute lymphocyte count (ALC) and b2 microglobulin at start of therapy were 39.2x109/L (range: 7.1 - 188.4 x 109/L) and 4.2 mg/L (range: 2.2 - 7.9 mg/L), respectively. After a median follow-up of 7 months (2 - 16 months), 13 (93%) of patients remain on study;one patient died (7%) due from complications from a presumed bacterial (COVID19-negative) pneumonia after 2 months on therapy. The estimated one-year PFS and OS for the cohort is 92.8 %. Seven patients were evaluable for response assessment after 8 months of therapy. No patient has yet discontinued therapy. All patients achieved a PR (one patient with undetectable minimal residual disease/U-MRD in the bone marrow), accounting for an overall responsonse rate of 100%. The median levels of bone marrow infiltration by CLL cells, quantified by flow cytometry, declined from 83.6% (range: 54.3 - 94.0 %) at baseline to 4.1% (range, 0.0 - 63.3%, n=7, p<0.05, see figure) after 6 cycles of combination treatment. Sixty-four percent of patients completed all doses of obinotuzumab, 50% requiered a dose reduction of acalabrutinib to 100 mg per day due to adverse events (AE). Grade 33 AE were observed in 4 patients (29%), which included decreased neutrophil counts (n=2), syncope (n=1), and grade 5 lung infection (COVID19 not detected, n=1). The most frequently reported non-serious related AE (3 2 patients) were anemia (n=5 [36%]), decreased platelets counts (n=3 [21%]), bruising (n=3 [21%]), limbs edema (n=2 [15%]) and headache (n=2 [15%]). All these events were grade 1. Importantly, no bleeding or atrial fibrillation events were observed. 3285 (Figure Presented ) Summary/Conclusion: Our preliminary data indicate that combination therapy of acalabrutinib plus obinotuzumab induces remissions with a major reduction in bone marrow disease after 6 months of combination therapy. Longer treatment and follow-up is warranted to determine the durability of responses after therapy discontinuation.
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Wastewater-based surveillance (WBS) has been an effective tool for monitoring and understanding potential SARS-CoV-2 transmission across small and large-scale communities. In this study at the University of Saskatchewan, the assessment of SARS-CoV-2 was done over eight months during the 2021-2022 academic year. Wastewater samples were collected using passive samplers that were deployed in domestic sewer lines near adjacent campus residences and extracted for viral RNA, followed by Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR). The results showed similar trends for SARS-CoV-2 detection frequencies and viral loads across university residences, the whole campus, and from related WBS at Saskatoon Wastewater Treatment Plant. The maximum daily detection frequency for seven dormitories considered was about 75 %, while maximum daily case numbers for the residences and campus-wide were about 11 and 75 people, respectively. In addition, self-reported rates of infection on campus peaked during similar time frames as increases in viral load were detected at the Saskatoon wastewater treatment plant. These similarities indicate the usefulness and cost-effectiveness of monitoring the spread of COVID-19 in small-scale communities using WBS.