An open-label phase II trial of sotrovimab (VIR-7831) prophylaxis against COVID-19 infection in immunocompromised individuals with impaired SARS-CoV-2 humoral immunity.

Background: Immunocompromised individuals have a limited humoral immune response to SARS-CoV-2 vaccination and are at higher risk of severe COVID-19. Sotrovimab is a monoclonal antibody (mAb) targeting a conserved SARS-CoV-2 spike protein epitope.

Methods: This phase II open-label study evaluated the safety and tolerability of sotrovimab pre-exposure prophylaxis in immunocompromised adults with impaired vaccine response.

Urine Cell-Free RNA vs Plasma Cell-Free RNA for Monitoring of Kidney Injury and Immune Complications.

Background: There is increasing interest in the use of circulating cell-free RNA (cfRNA) in plasma as an analyte for diagnosing and monitoring disease. While it is known that cfRNA can also be isolated from urine, the diagnostic potential of urine cfRNA, particularly relative to plasma cfRNA, remains underexplored.

Methods: Matched plasma and urine were collected from hematopoietic stem cell transplant (HSCT) recipients (n = 24), immune-checkpoint-inhibitor (ICI) recipients with or without acute kidney injury (AKI) (n = 46), and healthy volunteers (n = 5), yielding 297 samples.

Letermovir Treatment for Refractory or Resistant Cytomegalovirus Infection or Disease or with Concurrent Organ Dysfunction: A Phase 2 Open Label Study.

Introduction: Refractory or resistant cytomegalovirus (CMV) infection and disease pose a significant challenge in immunocompromised patients, including solid organ transplant (SOT) and allogeneic hematopoietic cell transplant (allo-HCT) recipients. This study aimed to evaluate letermovir as a treatment for patients with CMV infection or disease.

Methods: We performed an open-label, phase II non-randomized clinical trial.

Clinical Characteristics and Outcomes in Patients With Cryptococcaemia From a Large Population-Based Cohort.

Background: Cryptococcus bloodstream infections (BSIs) or cryptococcaemia are severe opportunistic infections with high mortality, predominantly affecting immunocompromised individuals or those with end-stage organ disease. Population-based studies examining infection trends and associations between host factors, geography, antifungal resistance, and clinical outcomes are few.

Methods: Blood cultures with growth of Cryptococcus species were retrospectively identified over a 20-year period (January 1, 2000-December 31, 2019) from a state-wide database.

Population-based longitudinal study over two decades of Candida and Candida-like species bloodstream infection reveals gender and species differences in mortality, recurrence and resistance.

Background: The global burden of bloodstream infection (BSI) due to Candida, and species previously classed as Candida (Candida-like species) is substantial. Recent emergence of Candida auris, fluconazole-resistant Candida parapsilosis and echinocandin-resistant Nakaseomyces glabratus emphasise the importance of global and regional surveillance.

Methods: Blood cultures with growth of Candida/Candida-like species in Queensland, Australia (population ≈ 5 million) over a 20-year period (1 January 2000-31 December 2019) were retrospectively identified.

Fabrication of disposable microextraction analytical tool for detection of bacterial pathogen using volatile metabolites emission.

A disposable paper-based thin film solid-phase microextraction (TF-SPME) patch was developed for the detection of bacterial pathogen. The study was based on the extraction of volatile organic compounds from the bacterial culture medium by a nanoparticle blended polymer-coated microextraction patch and then analyzed by gas chromatography-mass spectrometry to identify the volatile metabolic signature associated with the bacterial pathogen during the growth phase of the bacterial species in the culture medium. The TF-SPME patches were fabricated using a divinylbenzene/multiwall carbon nanotube/polydimethylsiloxane coating mixture employing a film applicator for uniform coating on a regular cellular paper substrate.

Development of a Paper-Based Disposal Thin-Film Solid-Phase Microextraction Tool for the Quantification of Environmentally Hazardous 4-Chlorophenol in Water.

The presence of chlorinated compounds in water resources presents various environmental and health risks. Therefore, there is a precise need to develop a potential technique for fast and efficient monitoring of chlorinated contaminants in water due to environmental protection and regulation compliance. Here, we designed a paper-based thin-film solid-phase microextraction (TF-SPME) patch to estimate 4-chlorophenol (4-CRP), a widely known environmentally hazardous pollutant in water samples.

Modeling Invasive Aspergillosis Risk for the Application of Prophylaxis Strategies.

The epidemiology of invasive aspergillosis (IA) is evolving. To define the patient groups who will most likely benefit from primary or secondary prophylaxis, particularly those whose medical conditions and IA risk change over time, it is helpful to depict patient populations and their risk periods in a temporal visual model. The Sankey approach provides a dynamic figure to understand the risk of IA for various patient populations.

Oral Antibiotics for Treatment of Gram-Negative Bacteremia in Solid Organ Transplant Recipients: A Propensity Score Weighted Retrospective Observational Study.

Background: We assessed the safety and efficacy of oral antibiotic step-down therapy for uncomplicated gram-negative blood stream infections in solid-organ transplant recipients.

Methods: We identified all solid-organ transplant recipients within the Massachusetts General and Brigham and Women's Hospital systems from 2016 to 2021 with uncomplicated gram-negative bacteremia involving an organism susceptible to an acceptably bioavailable oral antibiotic agent. Using inverse probability of treatment-weighted models based on propensity scores adjusting for potential clinical confounders, we compared outcomes of those transitioned to oral antibiotics with those who continued intravenous (IV) therapy for the duration of treatment.

Safety and tolerability study of sotrovimab (VIR-7831) prophylaxis against COVID-19 infection in immunocompromised individuals with impaired SARS-CoV-2 humoral immunity.

Background: Multiple vaccines have been approved since August 2021 to prevent infection with SARS-CoV-2; however, 20-40% of immunocompromised people fail to develop SARS-CoV-2 spike antibodies after COVID-19 vaccination and remain at high risk of infection and more severe illness than non-immunocompromised hosts. Sotrovimab (VIR-7831) is a monoclonal neutralizing antibody that binds a conserved epitope on the SARS-CoV-2 spike protein. It is neither renally excreted nor metabolized by P450 enzymes and therefore unlikely to interact with concomitant medications (e.

Blastomycosis in New England: 5 Cases and a Review.

The geographic range of blastomycosis is thought to include New England, but documentation is sparse. We report 5 cases of infection with that were likely acquired in New England between 2011 and 2021. Our experience suggests that chart coding for the diagnosis of blastomycosis is imprecise and that mandatory reporting might help resolve uncertainties about the prevalence and extent of blastomycosis.

Modulation of Tumor-Treating Fields by Cerebral Edema from Brain Tumors.

Purpose: Cerebral edema is an important component of brain metastasis, and its presence may alter the distribution of tumor-treating fields (TTFields). We therefore performed a computational study to model the extent of this alteration according to various edema conditions associated with the metastasis.

Methods And Materials: Postacquisition magnetic resonance imaging data sets were obtained from 2 patients with solitary brain metastases from non-small cell lung cancer.

A consensus conference to define the utility of advanced infectious disease diagnostics in solid organ transplant recipients.

The last decade has seen an explosion of advanced assays for the diagnosis of infectious diseases, yet evidence-based recommendations to inform their optimal use in the care of transplant recipients are lacking. A consensus conference sponsored by the American Society of Transplantation (AST) was convened on December 7, 2021, to define the utility of novel infectious disease diagnostics in organ transplant recipients. The conference represented a collaborative effort by experts in transplant infectious diseases, diagnostic stewardship, and clinical microbiology from centers across North America to evaluate current uses, unmet needs, and future directions for assays in 5 categories including (1) multiplex molecular assays, (2) rapid antimicrobial resistance detection methods, (3) pathogen-specific T-cell reactivity assays, (4) next-generation sequencing assays, and (5) mass spectrometry-based assays.

Low incidence of invasive fungal disease following CD19 chimeric antigen receptor T-cell therapy for non-Hodgkin lymphoma.

CAR T-cell therapy has revolutionized the treatment of hematologic malignancies, although its use may be complicated by toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and infections. Invasive fungal disease (IFD) has been reported after CAR T-cell therapy, but the incidence in the absence of antifungal prophylaxis is unknown. Optimal prophylaxis strategies are widely debated.

Safety evaluation of Fy Protein™ (Nutritional Fungi Protein), a macroingredient for human consumption.

Fy Protein™ (Nutritional Fungi Protein) is a macro-ingredient produced from the fermentation of the fungal microorganism Fusarium strain flavolapis, isolated from springs in Yellowstone National Park. Fy Protein contains all of the essential amino acids plus fiber, fat, carbohydrates, vitamins, and minerals and is developed as an alternative to animal-based protein foods such as meat and dairy. Fy Protein's nutritional, digestibility, genotoxicity, allergenicity, toxicity, secondary metabolites, and pathogenicity were evaluated.

Clarithromycin-Rifampin-Based Treatment for Nontuberculous Mycobacteria Infections in Immunocompromised Patients who Require Concomitant CYP-Metabolized Medications.

Clarithromycin (CYP inhibitor) can be used instead of azithromycin for nontuberculous mycobacteria therapy in patients requiring CYP substrates to mitigate rifampin's CYP induction. We found no differences in adverse events (10/13 vs 14/17;  = .73), drug intolerability (1/5 vs 4/11;  = 1), or 90-day mortality (0/13 vs 1/17;  = 1) in patients receiving clarithromycin vs azithromycin.

A eulogy for Dr Francisco Miguel Marty Forero.

As some of those who were lucky enough to have been mentored by Dr Francisco Marty in transplant infectious diseases, we stand with the larger medical community in mourning his untimely death and in commemorating him as a uniquely exceptional and talented physician, investigator, teacher, mentor, friend, artist, and human being.

Breath-Based Diagnosis of Infectious Diseases: A Review of the Current Landscape.

Various analytical methods can be applied to concentrate, separate, and examine trace volatile organic metabolites in the breath, with the potential for noninvasive, rapid, real-time identification of various disease processes, including an array of microbial infections. Although biomarker discovery and validation in microbial infections can be technically challenging, it is an approach that has shown great promise, especially for infections that are particularly difficult to identify with standard culture and molecular amplification-based approaches. This article discusses the current state of breath analysis for the diagnosis of infectious diseases.

The Evolving Landscape of Fungal Diagnostics, Current and Emerging Microbiological Approaches.

Invasive fungal infections are increasingly recognized in immunocompromised hosts. Current diagnostic techniques are limited by low sensitivity and prolonged turnaround times. We review emerging diagnostic technologies and platforms for diagnosing the clinically invasive disease caused by , , and Mucorales.

Somatic GATA2 mutations define a subgroup of myeloid malignancy patients at high risk for invasive fungal disease.

Invasive fungal disease (IFD) can be a severe treatment complication in patients with myeloid malignancies, but current risk models do not incorporate disease-specific factors, such as somatic gene mutations. Germline GATA2 deficiency is associated with a susceptibility to IFD. To determine whether myeloid gene mutations were associated with IFD risk, we identified 2 complementary cohorts of patients with myeloid malignancy, based on (1) the diagnosis of invasive aspergillosis (IA), or (2) the presence of GATA2 mutations identified during standard clinical sequencing.

Neuroimaging Markers for Studying Gulf-War Illness: Single-Subject Level Analytical Method Based on Machine Learning.

Gulf War illness (GWI) refers to the multitude of chronic health symptoms, spanning from fatigue, musculoskeletal pain, and neurological complaints to respiratory, gastrointestinal, and dermatologic symptoms experienced by about 250,000 GW veterans who served in the 1991 Gulf War (GW). Longitudinal studies showed that the severity of these symptoms often remain unchanged even years after the GW, and these veterans with GWI continue to have poorer general health and increased chronic medical conditions than their non-deployed counterparts. For better management and treatment of this condition, there is an urgent need for developing objective biomarkers that can help with simple and accurate diagnosis of GWI.

Molecular Testing for Acute Respiratory Tract Infections: Clinical and Diagnostic Recommendations From the IDSA's Diagnostics Committee.

The clinical signs and symptoms of acute respiratory tract infections (RTIs) are not pathogen specific. Highly sensitive and specific nucleic acid amplification tests have become the diagnostic reference standard for viruses, and translation of bacterial assays from basic research to routine clinical practice represents an exciting advance in respiratory medicine. Most recently, molecular diagnostics have played an essential role in the global health response to the novel coronavirus pandemic.

Correction to: Clinical experience with a novel assay measuring cytomegalovirus (CMV)-specific CD4+ and CD8+ T-cell immunity by flow cytometry and intracellular cytokine staining to predict clinically significant CMV events.

After publication of the original article [1], we were notified that an author's family name has been erroneously spelled. Aditya Chandrokar should be replaced with Aditya Chandorkar.