Unilateral leg pain caused by cryptococcal myositis: An unusual presentation of disseminated cryptococcosis in a kidney transplant recipient.

Cryptococcal disease is a rare but often serious infection in solid organ transplant recipients, commonly presenting as meningitis and pneumonia but can rarely cause myositis. We report the case of a 43-year-old female kidney transplant recipient with two previous graft failures requiring re-transplantations who presented with a 1-month duration of worsening unilateral leg pain, swelling, and shortness of breath. Blood cultures isolated Cryptococcus neoformans. A calf biopsy was performed and histopathology revealed myonecrosis with yeast forms consistent with Cryptococcus spp. Liposomal amphotericin B (LamB) was administered. Her course was complicated by hypoxemic respiratory failure with development of ground glass opacities on chest imaging. Work-up revealed bacterial and C neoformans pneumonia and probable Pneumocystis jirovecii pneumonia (PJP) She received trimethoprim-sulfamethoxazole and LamB and was discharged on fluconazole. Shortly thereafter she was re-admitted with confusion, septic shock, and multi-organ failure. Work-up revealed PJP with subsequent development of cryptococcal meningitis. Despite aggressive management, she expired. Disseminated cryptococcal infection may manifest as myositis. Presence of cryptococcal infection is a marker of severe net state of immunosuppression (IS), hence, presence of other opportunistic infections is likely. Early recognition of cryptococcal infection, institution of targeted therapy, and IS reduction are important to improve overall survival.

Bordetella bronchiseptica: a rare cause of meningitis.

BACKGROUND: Bordetella bronchiseptica is a gram-negative, obligate aerobic coccobacillus known to cause disease in domesticated animals and pets. In humans, B. bronchiseptica commonly leads to respiratory infections like pneumonia or bronchitis, and animal contact usually precedes the onset of symptoms. CASE PRESENTATION: We report a case of post-traumatic B. bronchiseptica meningitis without recent surgery in the setting of immunosuppression with a monoclonal antibody. Our case concerns a 77-year-old male with ulcerative colitis on infliximab who sustained a mechanical fall and developed a traumatic cerebrospinal fluid leak complicated by meningitis. He received meropenem then ceftazidime during his hospital course, and temporary neurosurgical drain placement was required. His clinical condition improved, and he was discharged at his baseline neurological status. CONCLUSIONS: B. bronchiseptica is an unusual cause of meningitis that may warrant consideration in immunocompromised hosts with known or suspected animal exposures. To better characterize this rare cause of meningitis, we performed a systematic literature review and summarized all previously reported cases.

SARS-CoV-2 Persistence in Immunocompromised Patients Requiring Treatment With Convalescent Plasma: A Case Report.

Severe acute respiratory syndrome-2 (SARS-CoV-2) infection in immunocompromised patients presents a challenge, as patients with such conditions may have severe courses. Identifying modalities to shorten the course or lessen the severity of infection could be potentially beneficial. A 76-year-old male with follicular lymphoma on rituximab and lenalidomide presented with COVID-19 pneumonia requiring intensive care unit (ICU) level care for persistent hypoxemia. He was treated with an extended course of remdesivir, as recommended by the Infectious Diseases service, but he maintained a persistently high viral load, necessitating a delay of his cancer treatment until he had recovered from his infection. On hospital day 31, he was given one dose of convalescent plasma with improvement in his SARS-CoV-2 viral load. He was able to be discharged and resumed cancer treatment soon thereafter. Convalescent plasma is a potential therapeutic option for immunocompromised patients with SARS-CoV-2 infection and should be considered early in the hospital course. Additionally, cycle threshold monitoring may be beneficial in certain scenarios: for instance to guide consideration of alternative therapies in patients with severe COVID-19 who have persistent symptoms and viremia while on guideline-directed therapy.

Considerations when prescribing opioid agonist therapies for people living with HIV.

INTRODUCTION: Medications for opioid use disorder (MOUD) include opioid agonist therapies (OAT) (buprenorphine and methadone), and opioid antagonists (extended-release naltrexone). All forms of MOUD improve opioid use disorder (OUD) and HIV outcomes. However, the integration of services for HIV and OUD remains inadequate. Persistent barriers to accessing MOUD underscore the immediate necessity of addressing pharmacoequity in the treatment of OUD in persons with HIV (PWH). AREAS COVERED: In this review article, we specifically focus on OAT among PWH, as it is the most commonly utilized form of MOUD. Specifically, we delineate the intersection of HIV and OUD services, emphasizing their integration into the United States Ending the HIV Epidemic (EHE) plan by offering comprehensive screening, testing, and treatment for both HIV and OUD. We identify potential drug interactions of OAT with antiretroviral therapy (ART), address disparities in OAT access, and present the practical benefits of long-acting formulations of buprenorphine, ART, and pre-exposure prophylaxis for improving HIV prevention and treatment and OUD management. EXPERT OPINION: Optimizing OUD outcomes in PWH necessitates careful attention to diagnosing OUD, initiating OUD treatment, and ensuring medication retention. Innovative approaches to healthcare delivery, such as mobile pharmacies, can integrate both OUD and HIV and reach underserved populations.

HIV and Substance Use Disorders.

Over 1.2 million Americans aged 13 years and older have been diagnosed with human immunodeficiency virus (HIV). While HIV incidence has been declining since 2017, the risk of HIV acquisition and transmission persists among persons who use drugs via injection drug use and unprotected sexual intercourse associated with substance use. Untreated substance use disorder (SUD) is associated with poor adherence to HIV antiretroviral therapy, poor HIV outcomes, and increased risk for HIV acquisition. Herein, we describe the intertwined syndemic of HIV and SUD, as well as treatment strategies and evidence-based public health efforts to engage and retain persons who use drugs into care.

Association between high-risk disease loci and response to anti-vascular endothelial growth factor treatment for wet age-related macular degeneration.

PURPOSE: To investigate whether there is an association between known age-related macular degeneration genetic risk variants in the CFH, ARMS2, and HTRA1 genes and response to anti-vascular endothelial growth factor (VEGF) (ranibizumab or bevacizumab) treatment for wet age-related macular degeneration. METHODS: A retrospective review of 150 patients with documented wet age-related macular degeneration based on clinical examination and fluorescein angiogram was performed. Patients received anti-VEGF therapy with ranibizumab and/or bevacizumab. Patients were genotyped for the single-nucleotide polymorphism rs1061170, rs10490924, rs3750848, rs3793917, rs11200638, and rs932275 and for the indel del443ins54 spanning the CFH, ARMS2, and HTRA1 genes. RESULTS: There were 57 patients who were characterized as negative responders to anti-VEGF therapy, and 93 patients who were characterized as positive responders. There was no significant difference in mean baseline visual acuity between the groups. Negative responders were followed for a mean duration of 24.0 months, while positive responders were followed for a mean duration of 22.0 months. Although the frequency of the at-risk alleles was higher in the positive responders when compared with the negative responder, this did not reach statistical significance. Additionally, there was no significant association between genotype and the number of injections or absolute change in visual acuity in both groups of responders. CONCLUSION: In our patient cohort, there was no statistically significant association between response to anti-VEGF therapy and the genotype in both positive-responder and negative-responder groups. Larger studies with more power are necessary to further determine whether a pharmacogenetic association exists between wet age-related macular degeneration and anti-VEGF therapy.

Maintenance on extended-release naltrexone is associated with reduced injection opioid use among justice-involved persons with opioid use disorder.

INTRODUCTION: Opioid use disorder (OUD) and injection drug use (IDU) place justice-involved individuals at increased risk for acquiring or transmitting HIV or hepatitis C virus (HCV). Methadone and buprenorphine have been associated with reduced opioid IDU; however, the effect of extended-release naltrexone (XR-NTX) on this behavior is incompletely studied. METHODS: This study examined injection opioid use and shared injection equipment behavior from a completed double-blind placebo-controlled trial of XR-NTX among 88 justice-involved participants with HIV and OUD. Changes in participants' self-reported daily injection opioid use and shared injection equipment was evaluated pre-incarceration, during incarceration, and monthly post-release for 6 months. The study also assessed differences in time to first opioid injection post-release. The research team performed intention to treat and "as treated" (high treatment versus low treatment) analyses. RESULTS: Fifty-eight of 88 participants (69.5 %) endorsed IDU and 26 (29.5 %) reported sharing injection equipment in the 30 days pre-incarceration; 2 participants (2.2 %) reported IDU during incarceration; 19 (21.6 %) reported IDU one month post-release from prison or jail. Fifty-four (61.4 %) participants had an HIV RNA below 200 copies/mL and 62 (70.5 %) were baseline HCV antibody positive. The 6-month follow-up rate was 49.5 % and 50.5 % for those who received XR-NTX and placebo, respectively, which was not significantly different (p = 0.822). Participants in the XR-NTX and placebo groups had similar low mean opioid injection use post-release and time to first injection opioid use in the Intention-to-treat analysis. In the as-treated analysis, participants in the high treatment group had significantly lower mean proportion of days injecting opioids (13.8 % high treatment versus 22.8 % low treatment, p = 0.02) by month 1, which persisted up to 5 months post-release (0 % high treatment vs 24.3 % low treatment, p < 0.001) and experienced a longer time to first opioid injection post-release (143.8 days high treatment vs 67.4 days low treatment, p < 0.001). CONCLUSIONS: Injection opioid use was low during incarceration and remained low post-release in this justice-involved population. Retention on XR-NTX was associated with reduced intravenous opioid use, which has important implications for reducing transmission of HIV and HCV.

Evaluation of the Impact of HIV Serostatus on the Hepatitis C Virus Care Cascade and Injection Drug Use Among Persons Initiating Medication Treatment for Opioid Use Disorder.

Background: Persons who inject drugs are at increased risk for acquiring hepatitis C virus (HCV). Medications for opioid use disorder (MOUD) are associated with reduced injection drug use (IDU) frequency among persons with opioid use disorder (OUD). However, whether HCV treatment uptake or changes in IDU frequency differ by HIV serostatus among persons receiving MOUD is incompletely understood. Methods: A secondary analysis was performed of data collected from 2 prospective cohort studies of participants with (PWH) or without HIV with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-diagnosed OUD who were initiated on methadone, buprenorphine, or naltrexone. Results: Of 129 participants, 78 (60.5%) were HCV antibody positive. PWH underwent increased HCV viral load testing (76.7% vs 43.3%; P = .028), but HCV treatment rates did not differ (17.6% vs 10.0%; P = .45) by HIV status. Participants without HIV reported a greater reduction in mean opioid IDU at 90 days (10.7 vs 2.0 fewer days out of 30; P < .001), but there were no group differences at 90 days. Stimulant use did not differ between groups. Urine opioid positivity declined from baseline to 90 days among the entire cohort (61.4% to 38.0%; P < .001) but did not differ by HIV serostatus. Conclusions: PWH who received MOUD underwent higher rates of follow-up HCV testing, but HCV treatment rates did not significantly differ by HIV serostatus. Participants without HIV on MOUD reported a greater reduction in opioid IDU. Improved integration of concomitant OUD with HCV and HIV screening, linkage to care, and treatment are needed for persons without HIV.

Case Report: Disseminated Strongyloidiasis in a Patient with COVID-19.

The SARS-CoV-2 virus has emerged and rapidly evolved into a current global pandemic. Although bacterial and fungal coinfections have been associated with COVID-19, little is known about parasitic infection. We report a case of a COVID-19 patient who developed disseminated strongyloidiasis following treatment with high-dose corticosteroids and tocilizumab. Screening for Strongyloides infection should be pursued in individuals with COVID-19 who originate from endemic regions before initiating immunosuppressive therapy.

Risk Factors Associated with Linkage to Care among Suburban Hepatitis C-Positive Baby Boomers and Injection Drug Users.

INTRODUCTION: Suffolk County, located in Eastern Long Island, has been an epicenter for the opioid epidemic in New York State, yet no studies have examined hepatitis C virus (HCV) prevalence in this population. Additionally, few studies have assessed barriers for linkage to care (LTC) to HCV treatment in people who inject drugs (PWID), a high-risk HCV cohort. We aimed to determine prevalence of HCV infection in a suburban medical center and to assess risk factors associated with LTC in HCV-positive baby boomers and young PWID. METHODS: A retrospective chart review was carried out on adult patients with ICD-9/10 diagnostic codes for HCV from January 2016 to December 2018 at Stony Brook Medicine. Data collected included sociodemographics, RNA serostatus, LTC, health insurance, employment, past medical or psychiatric history, and substance or injection drug use. RESULTS: Overall, 27,049 individuals were screened for HCV and 1017 were HCV seropositive (3.8%), 437 (42.9%) were HCV RNA-positive and 153 (40.6%) achieved LTC. In multivariate analysis, living with cirrhosis was associated with a positive LTC. Medicaid or Medicare insurance was associated with a negative LTC. Intravenous drug users were more likely to be young and have concomitant polysubstance use and psychiatric disease. A bimodal distribution of HCV-positives is present in our population. CONCLUSION: Those with liver cirrhosis are more likely to achieve LTC, as are those with private insurance. Public health efforts to promote awareness of HCV and to facilitate access to treatment among PWID are needed.

Human Myo19 is a novel myosin that associates with mitochondria.

Mitochondria are pleomorphic organelles that have central roles in cell physiology. Defects in their localization and dynamics lead to human disease. Myosins are actin-based motors that power processes such as muscle contraction, cytokinesis, and organelle transport. Here we report the initial characterization of myosin-XIX (Myo19), the founding member of a novel class of myosin that associates with mitochondria. The 970 aa heavy chain consists of a motor domain, three IQ motifs, and a short tail. Myo19 mRNA is expressed in multiple tissues, and antibodies to human Myo19 detect an approximately 109 kDa band in multiple cell lines. Both endogenous Myo19 and GFP-Myo19 exhibit striking localization to mitochondria. Deletion analysis reveals that the Myo19 tail is necessary and sufficient for mitochondrial localization. Expressing full-length GFP-Myo19 in A549 cells reveals a remarkable gain of function where the majority of the mitochondria move continuously. Moving mitochondria travel for many micrometers with an obvious leading end and distorted shape. The motility and shape change are sensitive to latrunculin B, indicating that both are actin dependent. Expressing the GFP-Myo19 tail in CAD cells resulted in decreased mitochondrial run lengths in neurites. These results suggest that this novel myosin functions as an actin-based motor for mitochondrial movement in vertebrate cells.