Publications by authors named "Varun K Phadke"

Standardized examinations measure progress throughout medical education. Successful completion of the American Board of Internal Medicine Certification Examination (ABIM-CE) benchmarks completion of internal medicine (IM) residency training. Recent declines in initial ABIM-CE pass rates may prompt residency programs to examine strategies to improve learner performance.

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Introduction: Maribavir was recently approved by the FDA, expanding treatment options for post-solid-organ transplant refractory/resistant CMV. We sought to describe the post-marketing experience with maribavir at a large academic transplant center.

Methods: This was a retrospective observational study of all renal transplant recipients treated with maribavir for refractory/resistant CMV DNAemia/disease.

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Article Synopsis
  • Rabies remains a high-mortality disease, prompting the exploration of a novel vaccine called ChAd155-RG, which uses a genetically modified chimpanzee adenovirus vector to improve immunization logistics.
  • A phase 1 clinical trial involving healthy adults compared the safety and immune response of ChAd155-RG to the standard vaccine, RabAvert, assessing factors like side effects and antibody levels.
  • Results showed that while ChAd155-RG was generally safe, it demonstrated lower and less lasting antibody responses against rabies compared to RabAvert, possibly influenced by participants' preexisting immunity to the adenovirus vector used in the vaccine.
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Background: Transplant infectious diseases (TID) is a growing area of expertise within infectious diseases (ID), but TID training is not standardized. Previous surveys of fellows identified opportunities to improve TID education resources but did not explore didactic, clinical, and nonclinical experiences comprehensively.

Methods: The American Society of Transplantation ID Community of Practice surveyed adult and pediatric fellows in US-based general ID or dedicated TID training programs to explore their didactic exposure, clinical experiences, and non-direct patient care activities in TID.

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Donor-derived infection is an uncommon but potentially devastating complication of solid organ transplantation (SOT). Accurate and timely identification of unexpected infectious disease transmission events has implications not only for the recipient(s) experiencing infection, but also other recipients of organs or tissues from the same donor who may require additional testing or risk mitigation, as well as the broader organ transplant regulatory framework. This narrative review synthesizes data from published reports of symptomatic unexpected donor-derived infections in SOT recipients to provide clinicians with a systematic approach to the evaluation of undifferentiated illnesses that may be of donor origin.

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Article Synopsis
  • CMV infections pose significant health risks for solid organ transplant recipients, leading to increased morbidity and mortality rates.
  • Traditional prevention methods include prophylactic, preemptive, and hybrid strategies, but new research emphasizes the potential of using CMV-specific immune assays for personalized risk assessment.
  • The effectiveness of these assays can vary based on timing related to the transplant and the type of immunosuppressive treatment, with a focus on measuring CD4+ and CD8+ T-Cell responses for a comprehensive understanding of immune recovery.
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Background: Cytomegalovirus (CMV) infection has broad implications for morbidity and mortality in renal transplant recipients (RTR). Routine surveillance for CMV replication with PCR-based quantitative nucleic acid testing (qNAT) assays is standard practice in most transplant centers, but the impact of assay sensitivity on antiviral decision-making and virologic outcomes has not been studied. We investigated the effects of an ultrasensitive CMV qNAT assay on multiple clinical outcomes, including time to detection and duration of CMV DNAemia.

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Mutations accumulated by novel Severe Acute Respiratory Syndrome Coronavirus 2 Omicron sublineages contribute to evasion of previously effective monoclonal antibodies for treatment or prevention of Coronavirus Disease 2019 (COVID-19). Other authorized or approved antiviral drugs such as nirmatrelvir/ritonavir, remdesivir, and molnupiravir are, however, predicted to maintain activity against these sublineages and are key tools to reduce severe COVID-19 outcomes in vulnerable populations. A stepwise approach may be taken to target the appropriate antiviral drug to the appropriate patient, beginning with identifying whether a patient is at high risk for hospitalization or other complications of COVID-19.

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Immunocompromised patients with prolonged coronavirus disease 2019 symptoms present diagnostic and therapeutic challenges. We measured viral nucleocapsid antigenemia in 3 patients treated with anti-CD20 immunotherapy who acquired severe acute respiratory syndrome coronavirus 2 infection and experienced protracted symptoms. Our results support nucleocapsid antigenemia as a marker of persistent infection and therapeutic response.

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Back Pain and Lower-Extremity WeaknessA 42-year-old man with HIV presented for evaluation of acute-onset back pain and lower-extremity weakness. How do you approach the evaluation, and what is the diagnosis?

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Objectives: To determine the incidence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among healthcare personnel (HCP) and to assess occupational risks for SARS-CoV-2 infection.

Design: Prospective cohort of healthcare personnel (HCP) followed for 6 months from May through December 2020.

Setting: Large academic healthcare system including 4 hospitals and affiliated clinics in Atlanta, Georgia.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations may diminish vaccine-induced protective immune responses, particularly as antibody titers wane over time. Here, we assess the effect of SARS-CoV-2 variants B.1.

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Toxoplasma gondii can cause severe opportunistic infection in immunocompromised individuals, but diagnosis is often delayed. We conducted a retrospective review of solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients with toxoplasmosis between 2002 and 2018 at two large US academic transplant centers. Patients were identified by ICD-9 or ICD-10 toxoplasmosis codes, positive Toxoplasma polymerase chain reaction test result, or pathologic diagnosis.

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Purpose Of Review: Coronavirus disease 2019 (COVID-19) is caused by a complex interplay between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics and host immune responses. Hosts with altered immunity, including solid organ transplant recipients, may be at increased risk of complications and death due to COVID-19. A synthesis of the available data on immune responses to SARS-CoV-2 infection is needed to inform therapeutic and preventative strategies in this special population.

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Among 353 healthcare personnel in a longitudinal cohort in 4 hospitals in Atlanta, Georgia (May-June 2020), 23 (6.5%) had severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies. Spending >50% of a typical shift at the bedside (OR, 3.

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Background: Testing of vaccine candidates to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an older population is important, since increased incidences of illness and death from coronavirus disease 2019 (Covid-19) have been associated with an older age.

Methods: We conducted a phase 1, dose-escalation, open-label trial of a messenger RNA vaccine, mRNA-1273, which encodes the stabilized prefusion SARS-CoV-2 spike protein (S-2P) in healthy adults. The trial was expanded to include 40 older adults, who were stratified according to age (56 to 70 years or ≥71 years).

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Adenovirus infection is commonly associated with self-limited respiratory and gastrointestinal illnesses. However, infection in immunocompromised individuals, such as transplant recipients, can cause severe life-threatening illness including pneumonitis, hemorrhagic cystitis, nephritis, hepatitis, and enterocolitis. In orthotopic liver transplant recipients, adenovirus viremia can cause hepatitis leading to marked transaminitis, allograft loss, and death.

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Purpose Of Review: The use of durable ventricular assist devices (VAD) to manage end-stage heart failure is increasing, but infection remains a leading cause of morbidity and mortality among patients with VAD. In this review, we synthesize recent data pertaining to the epidemiology, diagnosis, management, and prevention of VAD infections, discuss transplant considerations in patients with VAD infections, and highlight remaining knowledge gaps. We also present a conceptual framework for treating clinicians to approach these infections that draws on the same principles that guide the treatment of analogous infections that occur in patients without VAD.

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HIV infection can result in vision loss from different causes, including HIV retinopathy and uveitis secondary to other infections, such as toxoplasmosis and viral retinitis. It is imperative to identify any infectious causes of uveitis to successfully treat the condition and prevent further vision loss. Metagenomic deep sequencing (MDS) is an emerging technology that presents an unbiased approach to the evaluation of clinical syndromes, including uveitis, that have not been diagnosed by pathogen-specific testing.

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Article Synopsis
  • RSV is a significant health threat to infants worldwide, highlighting the need for effective surveillance and case definitions for better control and vaccine evaluation.* -
  • This study analyzed clinical data from infants under 6 months at Children's Healthcare of Atlanta, finding that a newly developed case definition (cough, shortness of breath, coryza, wheeze, poor feeding, and chest indrawing) showed high specificity and positive predictive value for RSV infection.* -
  • The current WHO definition for acute respiratory infections demonstrated high sensitivity and could be useful as an initial screening tool, while the new definition may provide more accurate confirmation of RSV cases.*
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Article Synopsis
  • The study focused on infants under 2 months in Guatemala hospitalized with acute respiratory illnesses (ARIs), aiming to identify cases of pertussis (whooping cough).
  • Among 301 infants, 11 cases of pertussis were confirmed, showing significant differences in health metrics compared to non-pertussis cases, including higher white blood cell counts and intensified care requirements.
  • The findings indicate a concerning trend, as pertussis-positive infants had a notably higher admission rate to intensive care and an elevated case fatality rate, emphasizing the need for greater awareness and prevention strategies for this vulnerable age group.
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