COVID-19 in vaccinated versus unvaccinated hematologic malignancy patients.

The effect of vaccination on severity of subsequent COVID-19 in patients with hematologic malignancies (HMs) is unknown. In this single-center retrospective cohort study, we found no difference in severity of COVID-19 disease in vaccinated (n = 16) versus unvaccinated (n = 54) HM patients using an adjusted multiple logistic regression model. Recent anti-B-cell therapy was associated with more severe illness.

COVID-19 in Immunocompromised Hosts: What We Know So Far.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused significant morbidity and mortality for patients and stressed healthcare systems worldwide. The clinical features and outcomes of COVID-19 among immunosuppressed patients, who are at presumed risk of more severe disease but who may also have decreased detrimental inflammatory responses, are not well characterized. We review the existing literature on COVID-19 among immunocompromised populations ranging from patients with cancer and solid-organ transplant recipients to patients with HIV and those receiving immunomodulatory therapy for autoimmune disease. Patients with malignancy and solid-organ transplant recipients may be at increased risk of severe COVID-19 disease and death, whereas for those with other types of immunocompromise, current evidence is less clear. Overall, further prospective controlled studies are needed to determine the attributable risk of immunocompromising conditions and therapies on COVID-19 disease prognosis.

Disseminated Legionella micdadei infection in a liver transplant patient presenting as pulmonary nodules and a laryngeal lesion.

We report a liver transplant patient with disseminated Legionella micdadei infection with pulmonary, laryngeal, and suspected muscle involvement. This organism, which stains weakly acid-fast, primarily affects immunocompromised patients. The diagnosis is difficult to make; in this case, the organism was identified via molecular diagnostics on laryngeal and pulmonary biopsy tissue.

Treatment of immunocompromised COVID-19 patients with convalescent plasma.

Immunosuppressed patients such as solid organ transplant and hematologic malignancy patients appear to be at increased risk for morbidity and mortality due to coronavirus disease 2019 (COVID-19) caused by SARS coronavirus 2 (SARS-CoV-2). Convalescent plasma, a method of passive immunization that has been applied to prior viral pandemics, holds promise as a potential treatment for COVID-19. Immunocompromised patients may experience more benefit from convalescent plasma given underlying deficits in B and T cell immunity as well as contraindications to antiviral and immunomodulatory therapy. We describe our institutional experience with four immunosuppressed patients (two kidney transplant recipients, one lung transplant recipient, and one chronic myelogenous leukemia patient) treated with COVID-19 convalescent plasma through the Expanded Access Program (NCT04338360). All patients clinically improved after administration (two fully recovered and two discharged to skilled nursing facilities) and none experienced a transfusion reaction. We also report the characteristics of convalescent plasma product from a local blood center including positive SARS-CoV-2 IgG and negative SARS-CoV-2 PCR in all samples tested. This preliminary evidence suggest that convalescent plasma may be safe among immunosuppressed patients with COVID-19 and emphasizes the need for further data on the efficacy of convalescent plasma as either primary or adjunctive therapy for COVID-19.

Evaluating an Oncology Video Curriculum Designed to Promote Asynchronous Subspecialty Learning for Internal Medicine Residents.

Internal medicine (IM) residents frequently see patients in subspecialty clinics. However, there are few published core subspecialty curricula targeted to residents' learning and practical needs, and little guidance exists regarding delivery of core subspecialty content to residents rotating across multiple clinical sites. Our study objective was to evaluate a novel oncology video curriculum for IM residents as a model for asynchronous subspecialty resident learning. Using the cognitive theory of multimedia learning, we developed a five-part oncology video curriculum targeted specifically to the needs of IM residents. All second- and third-year residents rotating in oncology clinics from October 2018 to March 2019 at a single training program were invited to participate. We evaluated curricular demand, efficacy, and acceptability, using completion rates, knowledge tests, and a survey. Twenty-eight of 31 (90.3%) residents utilized the curriculum. Resident knowledge improved after utilizing the modules, by 36.9% from pre- to posttests (95% CI [31.3-42.5]; P<0.001) and 13.7% from pre- to delayed posttests (95% CI [7.5-20.0]; P<0.001). Twenty-four of 31 (77.4%) answered the survey. Most residents agreed or strongly agreed that the curriculum contributed to their knowledge (95.2%) and added educational value beyond the clinical rotation (93.1%). Our curriculum evaluation supports the asynchronous delivery of oncology education targeted to the learning needs of IM residents using a novel core video curriculum. These curricular methods provide a model for delivering subspecialty education to IM residents with complex and busy schedules.

Clinical Utility of Universal Broad-Range Polymerase Chain Reaction Amplicon Sequencing for Pathogen Identification: A Retrospective Cohort Study.

We assessed the real-world utility of universal broad-range polymerase chain reaction sequencing for pathogen detection. Among 1062 clinical samples, 107/1062 (10.1%) had a clinically significant, positive result, with substantial variation by specimen type. Clinical management was changed in 44/1062 (4.1%). These data can help maximize utility of this emerging diagnostic.

Clinical outcomes and serologic response in solid organ transplant recipients with COVID-19: A case series from the United States.

The coronavirus disease 2019 (COVID-19) pandemic caused by SARS coronavirus 2 (SARS-CoV-2) has caused significant morbidity and mortality for patients and stressed healthcare systems worldwide. The clinical features, disease course, and serologic response of COVID-19 among immunosuppressed patients such as solid organ transplant (SOT) recipients, who are at presumed risk for more severe disease, are not well characterized. We describe our institutional experience with COVID-19 among 10 SOT patients, including the clinical presentation, treatment modalities, and outcomes of 7 renal transplant recipients, 1 liver transplant recipient, 1 heart transplant recipient, and 1 lung transplant recipient. In addition, we report the serologic response in SOT recipients, documenting a positive IgG response in all 7 hospitalized patients. We also review the existing literature on COVID-19 in SOT recipients to consolidate the current knowledge on COVID-19 in the SOT population for the transplant community.

Disseminated Acanthamoeba infection in a heart transplant recipient treated successfully with a miltefosine-containing regimen: Case report and review of the literature.

Disseminated acanthamoebiasis is a rare, often fatal, infection most commonly affecting immunocompromised patients. We report a case involving sinuses, skin, and bone in a 60-year-old woman 5 months after heart transplantation. She improved with a combination of flucytosine, fluconazole, miltefosine, and decreased immunosuppression. To our knowledge, this is the first case of successfully treated disseminated acanthamoebiasis in a heart transplant recipient and only the second successful use of miltefosine for this infection among solid organ transplant recipients. Acanthamoeba infection should be considered in transplant recipients with evidence of skin, central nervous system, and sinus infections that are unresponsive to antibiotics. Miltefosine may represent an effective component of a multidrug therapeutic regimen for the treatment of this amoebic infection.

Baylisascaris procyonis-Associated Meningoencephalitis in a Previously Healthy Adult, California, USA.

After severe neurocognitive decline developed in an otherwise healthy 63-year-old man, brain magnetic resonance imaging showed eosinophilic meningoencephalitis and enhancing lesions. The patient tested positive for antibodies to Baylisascaris spp. roundworms, was treated with albendazole and dexamethasone, and showed improvement after 3 months. Baylisascariasis should be considered for all patients with eosinophilic meningitis.

Raccoon Roundworm Infection Associated with Central Nervous System Disease and Ocular Disease - Six States, 2013-2015.

Baylisascaris procyonis, predominantly found in raccoons, is a ubiquitous roundworm found throughout North America. Although raccoons are typically asymptomatic when infected with the parasite, the larval form of Baylisascaris procyonis can result in fatal human disease or severe neurologic outcomes if not treated rapidly. In the United States, Baylisascaris procyonis is more commonly enzootic in raccoons in the midwestern and northeastern regions and along the West Coast (1). However, since 2002, infections have been documented in other states (Florida and Georgia) and regions (2). Baylisascariasis is not a nationally notifiable disease in the United States, and little is known about how commonly it occurs or the range of clinical disease in humans. Case reports of seven human baylisascariasis cases in the United States diagnosed by Baylisascaris procyonis immunoblot testing at CDC are described, including review of clinical history and laboratory data. Although all seven patients survived, approximately half were left with severe neurologic deficits. Prevention through close monitoring of children at play, frequent handwashing, and clearing of raccoon latrines (communal sites where raccoons defecate) are critical interventions in curbing Baylisascaris infections. Early treatment of suspected cases is critical to prevent permanent sequelae.

Changes in Gender and Racial/Ethnic Diversity in US Residency Program Applications From 2018 to 2022.

Background Residency application patterns by gender and race/ethnicity offer important insights about diversity in residency recruitment. It is unknown how the COVID-19 pandemic and virtual interviewing affected these patterns. Objective We hypothesized that the introduction of virtual interviews caused an increase in applications submitted per applicant and that there may be differences by gender and race/ethnicity. Methods We extracted publicly reported Electronic Residency Application Service application data from 2018 to 2022 for 14 residency specialties with 1000 or more applicants in 2022 by self-reported gender and underrepresented in medicine (UIM) status. We compared patterns before and after virtual interviews were introduced in 2021. Results Among 401 480 residency applicants, the average number of applications submitted per applicant increased for all specialties between 2018 and 2022 across gender and race/ethnicity. Across all years, women applied to more programs than men in 5 specialties (dermatology, neurology, obstetrics/gynecology, pediatrics, and surgery), whereas men applied to more programs than women in 3 (anesthesia, family medicine, and physical medicine and rehabilitation). Across all years, non-UIM applicants applied to more programs than UIM applicants in all 14 specialties. There were no clear changes in application patterns by gender and race/ethnicity during in-person versus virtual interview years. Conclusions The average number of applications submitted per applicant increased over time across gender and race/ethnicity. In some specialties, women applied to more programs than men, and in others vice-versa, whereas non-UIM applicants applied to more programs than UIM applicants in all specialties. Virtual interviews did not change these patterns.

Risk of systemic fungal infections after exposure to wildfires: a population-based, retrospective study in California.

BACKGROUND: Large-scale wildfires in California, USA, are increasing in both size and frequency, with substantial health consequences. The capacity for wildfire smoke to displace microbes and cause clinically significant fungal infections is poorly understood. We aimed to determine whether exposure to wildfire smoke was associated with an increased risk of hospital admissions for systemic fungal infections. METHODS: In this population-based, retrospective study, we used hospital administrative data from 22 hospitals in California, USA, to analyse the association between wildfire smoke exposure and monthly hospital admissions for aspergillosis and coccidioidomycosis. We included hospitals that were members of the Vizient Clinical Data Base or Resource Manager during the study and excluded those that did not have complete reporting into Vizient during the study period. Smoke exposure was estimated using satellite-imaged smoke plumes in the hospital county. Incident rate ratios were calculated for all infection types 1 month and 3 months after smoke exposure. FINDINGS: Between Oct 1, 2014, and May 31, 2018, there were a median of 1638 annual admissions per hospital in the study sample. Individual patient demographics were not collected. We did not observe an association between smoke exposure and rate of hospital admission for aspergillosis. However, hospital admission for coccidioidomycosis increased by 20% (95% CI 5-38) in the month following any smoke exposure. Hospital admission increased by 2% (0-4) for every day that there had been smoke exposure in the previous month, after adjustment for temperature and temporal trend. Similar results were obtained with smoke exposure data from the 3 months before admission. INTERPRETATION: In the months following wildfire smoke exposure, California hospitals saw increased coccidioidomycosis infections. Given the projected increase in California wildfires and their expansion in endemic territories of soil-dwelling fungi, the ability for wildfire smoke to carry microbes and cause human disease warrants further research. FUNDING: None.

Diagnosis, Prognosticators, and Management of Acute Invasive Fungal Rhinosinusitis: Multidisciplinary Consensus Statement and Evidence-Based Review with Recommendations.

BACKGROUND: Acute invasive fungal sinusitis (AIFS) is an aggressive disease that requires prompt diagnosis and multidisciplinary treatment given its rapid progression. However, there is currently no consensus on diagnosis, prognosis, and management strategies for AIFS, with multiple modalities routinely employed. The purpose of this multi-institutional and multidisciplinary evidence-based review with recommendations (EBRR) is to thoroughly review the literature on AIFS, summarize the existing evidence, and provide recommendations on the management of AIFS. METHODS: The PubMed, EMBASE, and Cochrane databases were systematically reviewed from inception through January 2022. Studies evaluating management for orbital, non-sinonasal head and neck, and intracranial manifestations of AIFS were included. An iterative review process was utilized in accordance with EBRR guidelines. Levels of evidence and recommendations on management principles for AIFS were generated. RESULTS: A review and evaluation of published literature was performed on 12 topics surrounding AIFS (signs and symptoms, laboratory and microbiology diagnostics, endoscopy, imaging, pathology, surgery, medical therapy, management of extrasinus extension, reversing immunosuppression, and outcomes and survival). The aggregate quality of evidence was varied across reviewed domains. CONCLUSION: Based on the currently available evidence, judicious utilization of a combination of history and physical examination, laboratory and histopathologic techniques, and endoscopy provide the cornerstone for accurate diagnosis of AIFS. In addition, AIFS is optimally managed by a multidisciplinary team via a combination of surgery (including resection whenever possible), antifungal therapy, and correcting sources of immunosuppression. Higher quality (i.e., prospective) studies are needed to better define the roles of each modality and determine diagnosis and treatment algorithms.

The human fetal immune response to hepatitis C virus exposure in utero.

BACKGROUND: Although the rate of mother-to-child transmission of hepatitis C virus (HCV) is low, the effect of HCV exposure in utero on the fetal immune system is unknown. METHODS: Umbilical cord blood was obtained from 7 neonates born to HCV-seropositive, HCV RNA-positive women and 8 neonates born to HCV-seronegative women. Cord blood mononuclear cells were analyzed by immunophenotyping and by intracellular cytokine staining after HCV-specific and polyclonal stimulation. Plasma was analyzed for anti-HCV immunoglobulin M (IgM), cytokine/granzyme concentrations, and indoleamine 2,3-dioxygenase (IDO) activity. RESULTS: HCV-exposed neonates had significantly lower levels of regulatory T cells expressing HLA-DR, lower CD4(+) and CD8(+) T cell activation, and lower plasma levels of pro-inflammatory markers than did controls. However, CD4(+) and CD8(+) T cells from HCV-exposed neonates had higher IFN-γ production in response to polyclonal stimulation than did T cells from controls. IDO activity was similar between groups. No HCV-specific T cell responses or anti-HCV IgM were detected in any neonates. CONCLUSIONS: HCV-exposed neonates showed a relative suppression of immune activation and pro-inflammatory markers, which was counterbalanced by an increased production capacity for IFN-γ. These results suggest that HCV encounters the fetal immune system in utero, and alters the balance between suppressive and pro-inflammatory responses.