Tova M. Gardin

Bio: Tova M. Gardin is an academic researcher from Yale University. The author has contributed to research in topics: Immigration policy & Antibody. The author has an hindex of 3, co-authored 5 publications receiving 436 citations. Previous affiliations of Tova M. Gardin include Harvard University.

Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019: A Review.

Abstract: Importance Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing human coronavirus disease 2019 (COVID-19), which has now spread into a worldwide pandemic. The pulmonary manifestations of COVID-19 have been well described in the literature. Two similar human coronaviruses that cause Middle East respiratory syndrome (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV-1) are known to cause disease in the central and peripheral nervous systems. Emerging evidence suggests COVID-19 has neurologic consequences as well. Observations This review serves to summarize available information regarding coronaviruses in the nervous system, identify the potential tissue targets and routes of entry of SARS-CoV-2 into the central nervous system, and describe the range of clinical neurological complications that have been reported thus far in COVID-19 and their potential pathogenesis. Viral neuroinvasion may be achieved by several routes, including transsynaptic transfer across infected neurons, entry via the olfactory nerve, infection of vascular endothelium, or leukocyte migration across the blood-brain barrier. The most common neurologic complaints in COVID-19 are anosmia, ageusia, and headache, but other diseases, such as stroke, impairment of consciousness, seizure, and encephalopathy, have also been reported. Conclusions and Relevance Recognition and understanding of the range of neurological disorders associated with COVID-19 may lead to improved clinical outcomes and better treatment algorithms. Further neuropathological studies will be crucial to understanding the pathogenesis of the disease in the central nervous system, and longitudinal neurologic and cognitive assessment of individuals after recovery from COVID-19 will be crucial to understand the natural history of COVID-19 in the central nervous system and monitor for any long-term neurologic sequelae.

A student proposal for ethical guidelines in anatomical education: Ethical and policy considerations

Abstract: The recent publication of a story regarding anatomical dissection in a medical school has revealed the need for increased attention to the ethical and policy aspects of anatomical education. While most of the attention devoted to these questions thus far has been focused on procedures before and after dissection, from the perspective of medical students, there are important considerations during the process of dissection itself. This proposal was developed by two third-year medical students through a review of the relevant published literature, reflection upon their personal experiences in anatomy courses in two separate institutions, and informal discussion of these topics with peers. The proposal is that basic ethical guidelines should be established and monitored by an independent committee tasked with reviewing them. The proposed guidelines include: First, a clear set of expectations about what the student is expected to learn with respect to anatomical knowledge and dissection technique; second, the establishment by schools or national bodies of minimal ethical standards regarding respectful behavior toward the donor bodies, and the communication of these standards to teachers and students involved in educational dissections; third, the use of materials that encourage students to view their donors with respect and ensure proper treatment of them; and fourth, the establishment of an oversight group (at each medical school and at national level) comprising students, faculty, community members, and staff, who will regularly review the anatomical education program and update these ethical guidelines as appropriate. While many of these proposals are already implemented in some anatomy departments, the establishment of clear guidelines at a national as well as a school-by-school level will permit students the freedom to participate fully in their education, knowing they have met the highest ethical standards as they prepare for a career as a humanistic physician.

Distribution of Physicians With H-1B Visas By State and Sponsoring Employer

Abstract: Author Affiliations: Harvard Medical School, Boston, Massachusetts. Corresponding Author: Ishani Ganguli, MD, MPH, Division of General Internal Medicine and Primary Care, Brigham and Women’s Hospital, Harvard Medical School, 1620 Tremont St, Third Floor, Boston, MA 02120 (iganguli@partners.org). Accepted for Publication: March 24, 2017. Published Online: April 19, 2017. doi:10.1001/jama.2017.4342 Author Contributions: Dr Ganguli and Mr Souza had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Ganguli, McWilliams, Mehrotra. Acquisition, analysis, or interpretation of data: Ganguli, Souza, McWilliams. Drafting of the manuscript: Ganguli. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Ganguli, Souza, McWilliams. Administrative, technical, or material support: Mehrotra. Supervision: Mehrotra. Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. Funding/Support: This article was supported by grant P01 AG032952 from the National Institute on Aging of the National Institutes of Health. Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Meeting Presentation: Presented at the Society of General Internal Medicine Annual Meeting; April 19, 2017; Washington, DC. 1. Krogsbøll LT, Jørgensen KJ, Gøtzsche PC. General health checks in adults for reducing morbidity and mortality from disease. JAMA. 2013;309(23):2489-2490. 2. Cuenca AE. Making Medicare annual wellness visits work in practice. Fam Pract Manag. 2012;19(5):11-16. 3. Lazarus D. Obamacare covers free annual physicals, right? wrong. http://www.latimes.com/business/lazarus/la-fi-lazarus-obamacare-physicals -20160802-snap-story.html. Accessed January 7, 2017. 4. Chung S, Lesser LI, Lauderdale DS, Johns NE, Palaniappan LP, Luft HS. Medicare annual preventive care visits: use increased among fee-for-service patients, but many do not participate. Health Aff (Millwood). 2015;34(1):11-20. 5. Hu J, Jensen GA, Nerenz D, Tarraf W. Medicare’s annual wellness visit in a large health care organization: who is using it? Ann Intern Med. 2015;163(7): 567-568. 6. Jensen GA, Salloum RG, Hu J, Ferdows NB, Tarraf W. A slow start: use of preventive services among seniors following the Affordable Care Act’s enhancement of Medicare benefits in the US. Prev Med. 2015;76:37-42.

The Role of Immune Checkpoint Therapy in Propagating Neurologic Immune-Related Adverse Events: Inducing or “Unmasking” Autoimmunity?

Abstract: In 2010, a novel agent, ipilimumab, demonstrated improved survival rates in patients with previously untreatable metastatic melanoma.1 Ipilimumab was approved by the Food and Drug Administration in 2011 and launched a class of pharmaceuticals that would come to be known as immune checkpoint inhibitors (ICIs). Normally, the immune system monitors developing malignancies as they acquire progressive mutations and eliminates them through a process of immunoediting or immune surveillance.2 Select tumors learn to coopt self-tolerance mechanisms (immune checkpoints) to evade this immune detection. ICIs inhibit these negative regulators of T-cell activation, unleashing an unchecked immune response. Because this response is not specific to tumor antigens, a host of immune-related adverse events (irAEs) can ensue. Neurologic irAEs are rare3 but provide diagnostic and therapeutic challenges. They also offer important insights into the mechanisms of autoimmunity.

H-1B Visa Applications for Physicians-Reply.

Abstract: vide an expeditious alternative to the BPCIA’s patent dispute resolution process. The 2011 Leahy-Smith American Invents Act established the inter partes review, a procedure that allows third parties to challenge the existence of a patent by submitting additional information bearing on patentability of the claimed invention to the US Patent and Trademark Office. In contrast to ordinary judicial proceedings, which require challengers to prove invalidity by “clear and convincing evidence,” there is no presumption of patent validity in inter partes review proceedings.4 Rather, the petitioner has the burden of proving unpatentability to the Patent and Trademark Office by a “preponderance of the evidence.” Several biosimilar manufacturers, including Amgen, Boehringer Ingelheim, Celltrion Healthcare, Coherus BioSciences, Hospira, and Momenta Pharmaceuticals, have begun to challenge branded biologic patents through this mechanism.5 We emphasize that even with reduced patent litigation, in the absence of interchangeability status, the approval and market launch of multiple biosimilars may not result in substantial cost savings. Patient and physician aversion to nonmedical switching, in conjunction with payer rebate dynamics, may ensure that competition will not reduce or stabilize prices for the consumer. The best way to meet the price reduction goals of the BPCIA will be to effectively implement technical and regulatory procedures to determine the automatic substitution of biosimilars for branded biologics.

Features, Evaluation and Treatment Coronavirus (COVID-19)

Abstract: According to the World Health Organization (WHO), viral diseases continue to emerge and represent a serious issue to public health In the last twenty years, several viral epidemics such as the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 to 2003, and H1N1 influenza in 2009, have been recorded Most recently, the Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia in 2012 In a timeline that reaches the present day, an epidemic of cases with unexplained low respiratory infections detected in Wuhan, the largest metropolitan area in China's Hubei province, was first reported to the WHO Country Office in China, on December 31, 2019 Published literature can trace the beginning of symptomatic individuals back to the beginning of December 2019 As they were unable to identify the causative agent, these first cases were classified as "pneumonia of unknown etiology " The Chinese Center for Disease Control and Prevention (CDC) and local CDCs organized an intensive outbreak investigation program The etiology of this illness is now attributed to a novel virus belonging to the coronavirus (CoV) family, COVID-19 On February 11, 2020, the WHO Director-General, Dr Tedros Adhanom Ghebreyesus, announced that the disease caused by this new CoV was a "COVID-19," which is the acronym of "coronavirus disease 2019" In the past twenty years, two additional coronavirus epidemics have occurred SARS-CoV provoked a large-scale epidemic beginning in China and involving two dozen countries with approximately 8000 cases and 800 deaths, and the MERS-CoV that began in Saudi Arabia and has approximately 2,500 cases and 800 deaths and still causes as sporadic cases This new virus seems to be very contagious and has quickly spread globally In a meeting on January 30, 2020, per the International Health Regulations (IHR, 2005), the outbreak was declared by the WHO a Public Health Emergency of International Concern (PHEIC) as it had spread to 18 countries with four countries reporting human-to-human transmission An additional landmark occurred on February 26, 2020, as the first case of the disease, not imported from China, was recorded in the United States Initially, the new virus was called 2019-nCoV Subsequently, the task of experts of the International Committee on Taxonomy of Viruses (ICTV) termed it the SARS-CoV-2 virus as it is very similar to the one that caused the SARS outbreak (SARS-CoVs) The CoVs have become the major pathogens of emerging respiratory disease outbreaks They are a large family of single-stranded RNA viruses (+ssRNA) that can be isolated in different animal species For reasons yet to be explained, these viruses can cross species barriers and can cause, in humans, illness ranging from the common cold to more severe diseases such as MERS and SARS Interestingly, these latter viruses have probably originated from bats and then moving into other mammalian hosts — the Himalayan palm civet for SARS-CoV, and the dromedary camel for MERS-CoV — before jumping to humans The dynamics of SARS-Cov-2 are currently unknown, but there is speculation that it also has an animal origin The potential for these viruses to grow to become a pandemic worldwide seems to be a serious public health risk Concerning COVID-19, the WHO raised the threat to the CoV epidemic to the "very high" level, on February 28, 2020 Probably, the effects of the epidemic caused by the new CoV has yet to emerge as the situation is quickly evolving World governments are at work to establish countermeasures to stem possible devastating effects Health organizations coordinate information flows and issues directives and guidelines to best mitigate the impact of the threat At the same time, scientists around the world work tirelessly, and information about the transmission mechanisms, the clinical spectrum of disease, new diagnostics, and prevention and therapeutic strategies are rapidly developing Many uncertainties remain with regard to both the virus-host interac ion and the evolution of the epidemic, with specific reference to the times when the epidemic will reach its peak At the moment, the therapeutic strategies to deal with the infection are only supportive, and prevention aimed at reducing transmission in the community is our best weapon Aggressive isolation measures in China have led to a progressive reduction of cases in the last few days In Italy, in geographic regions of the north of the peninsula, political and health authorities are making incredible efforts to contain a shock wave that is severely testing the health system In the midst of the crisis, the authors have chosen to use the "Statpearls" platform because, within the PubMed scenario, it represents a unique tool that may allow them to make updates in real-time The aim, therefore, is to collect information and scientific evidence and to provide an overview of the topic that will be continuously updated

Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19.

Abstract: The newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic respiratory disease. Moreover, thromboembolic events throughout the body, including in the CNS, have been described. Given the neurological symptoms observed in a large majority of individuals with COVID-19, SARS-CoV-2 penetrance of the CNS is likely. By various means, we demonstrate the presence of SARS-CoV-2 RNA and protein in anatomically distinct regions of the nasopharynx and brain. Furthermore, we describe the morphological changes associated with infection such as thromboembolic ischemic infarction of the CNS and present evidence of SARS-CoV-2 neurotropism. SARS-CoV-2 can enter the nervous system by crossing the neural-mucosal interface in olfactory mucosa, exploiting the close vicinity of olfactory mucosal, endothelial and nervous tissue, including delicate olfactory and sensory nerve endings. Subsequently, SARS-CoV-2 appears to follow neuroanatomical structures, penetrating defined neuroanatomical areas including the primary respiratory and cardiovascular control center in the medulla oblongata.

The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings.

Abstract: Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barre syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms that will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.

Symptoms, complications and management of long COVID: a review.

Abstract: Globally, there are now over 160 million confirmed cases of COVID-19 and more than 3 million deaths. While the majority of infected individuals recover, a significant proportion continue to experience symptoms and complications after their acute illness. Patients with 'long COVID' experience a wide range of physical and mental/psychological symptoms. Pooled prevalence data showed the 10 most prevalent reported symptoms were fatigue, shortness of breath, muscle pain, joint pain, headache, cough, chest pain, altered smell, altered taste and diarrhoea. Other common symptoms were cognitive impairment, memory loss, anxiety and sleep disorders. Beyond symptoms and complications, people with long COVID often reported impaired quality of life, mental health and employment issues. These individuals may require multidisciplinary care involving the long-term monitoring of symptoms, to identify potential complications, physical rehabilitation, mental health and social services support. Resilient healthcare systems are needed to ensure efficient and effective responses to future health challenges.