The Infectious Disease Society of America (IDSA) 2010 Clinical Practice Guidelines for the management of cryptococcosis outlined three key populations at risk of disease: (1) HIV-infected, (2) ...transplant recipient, and (3) HIV-negative/non-transplant. However, direct comparisons of management, severity and outcomes of these groups have not been conducted.
Annual changes in frequency of cryptococcosis diagnoses, cryptococcosis-attributable mortality and mortality were captured. Differences examined between severe and non-severe disease within the context of the three groups included: demographics, symptoms, microbiology, clinical management and treatment. An average of nearly 15 patients per year presented at Duke University Medical Center (DUMC) with cryptococcosis. Out of 207 study patients, 86 (42%) were HIV-positive, 42 (20%) were transplant recipients, and 79 (38%) were HIV-negative/non-transplant. HIV-infected individuals had profound CD4 lymphocytopenia and a majority had elevated intracranial pressure. Transplant recipients commonly (38%) had renal dysfunction. Nearly one-quarter (24%) had their immunosuppressive regimens stopped or changed. The HIV-negative/non-transplant population reported longer duration of symptoms than HIV-positive or transplant recipients and 28% (22/79) had liver insufficiency or underlying hematological malignancies. HIV-positive and HIV-negative/non-transplant patients accounted for 89% of severe disease cryptococcosis-attributable deaths and 86% of all-cause mortality.
In this single-center study, the frequency of cryptococcosis did not change in the last two decades, although the underlying case mix shifted (fewer HIV-positive cases, stable transplant cases, more cases with neither). Cryptococcosis had a relatively uniform and informed treatment strategy, but disease-attributable mortality was still common.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Checkpoint inhibitors produce durable responses in numerous metastatic cancers, but immune-related adverse events (irAEs) complicate and limit their benefit. IrAEs can affect organ systems ...idiosyncratically; presentations range from mild and self-limited to fulminant and fatal. The molecular mechanisms underlying irAEs are poorly understood. Here, we report a fatal case of encephalitis arising during anti-programmed cell death receptor 1 therapy in a patient with metastatic melanoma. Histologic analyses revealed robust T cell infiltration and prominent programmed death ligand 1 expression. We identified 209 reported cases in global pharmacovigilance databases (across multiple cancer types) of encephalitis associated with checkpoint inhibitor regimens, with a 19% fatality rate. We performed further analyses from the index case and two additional cases to shed light on this recurrent and fulminant irAE. Spatial and multi-omic analyses pinpointed activated memory CD4
T cells as highly enriched in the inflamed, affected region. We identified a highly oligoclonal T cell receptor repertoire, which we localized to activated memory cytotoxic (CD45RO
GZMB
Ki67
) CD4 cells. We also identified Epstein-Barr virus-specific T cell receptors and EBV
lymphocytes in the affected region, which we speculate contributed to neural inflammation in the index case. Collectively, the three cases studied here identify CD4
and CD8
T cells as culprits of checkpoint inhibitor-associated immune encephalitis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Sustained virologic response (SVR) rates in patients with hepatitis C virus (HCV) monoinfection and human immunodeficiency virus (HIV)/HCV coinfection treated with direct acting antiviral (DAA) ...therapy are similar in clinical trials. The objective of this study was to examine differences in patient characteristics, drug-drug interactions, and treatment pathways between these groups in a real-world clinical setting.
We performed an ambispective review of patients prescribed DAA therapy between September 2015 and April 2018 at a tertiary academic center. The primary endpoint was time from a decision to treat to treatment initiation. Secondary endpoints included patient characteristics; frequency and type of DAA medication interactions; frequency, type, and timing of antiretroviral therapy (ART) changes; and treatment outcomes.
Three hundred and twelve patients were included. Almost half (43%) were HIV/HCV coinfected. Patients with HIV/HCV coinfection were more likely to be African American (p<0.001), have a diagnosed psychiatric disorder (p<0.001) and have a higher pill burden (p = 0.014). Patients with HIV/HCV coinfection were more likely to report an alcohol abuse history (p<0.001), injection drug use history (p<0.024), or active use of illicit substances (p = 0.019). In a multivariable regression model assessing the primary endpoint, time to treatment initiation was increased in patients requiring a change in ART therapy (OR = 9.2, p < 0.001) or a non-ART medication adjustment (OR = 2.4, p = 0.003), and in patients with Medicaid (OR = 6.7, p < 0.001). After controlling for all these factors, HIV/HCV coinfection still significantly impacted time to treatment initiation (OR = 1.7, p = 0.020). The groups had similar rates of drug interaction frequency, treatment completion, observed SVR, and side effects.
Patients with HIV/HCV coinfection are more likely to have a variety of factors that add complexities to HCV treatment. In addition to these challenges, patients with HIV/HCV coinfection experience a longer time to treatment initiation while patients with HCV monoinfection were more frequently lost to care. Care delivery models may incorporate this data to improve patient engagement, access, and outcomes.
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A Clinical Review of Diabetic Foot Infections Chastain, Cody A; Klopfenstein, Nathan; Serezani, Carlos H ...
Clinics in podiatric medicine and surgery,
07/2019, Volume:
36, Issue:
3
Journal Article
Peer reviewed
"Diabetic foot infections (DFIs) are a common cause of morbidity and mortality. This article summarizes current knowledge regarding DFI epidemiology, disease pathogenesis, and the impact of ...antimicrobial resistance among DFI. An evidence-based approach to clinical assessment, diagnosing osteomyelitis, as well as medical and surgical treatment is discussed, including a review of empiric and directed antibiotic treatment recommendations. The current state and needs of the clinical literature are identified throughout, with a discussion of the supporting role of infectious diseases specialists as well as future directions of the field."
Hospitalizations for drug-use associated infective endocarditis (DUA-IE) have led to increasing surgical consultation for valve replacement. Cardiothoracic surgeons’ perspectives about the process of ...decision making around operation for people with DUA-IE are largely unknown.
This multisite semiqualitative study sought to gather the perspectives of cardiothoracic surgeons on initial and repeat valve surgery for people with DUA-IE through purposeful sampling of surgeons at 7 hospitals: University of Alabama, Tufts Medical Center, Boston Medical Center, Massachusetts General Hospital, University of North Carolina-Chapel Hill, Vanderbilt University Medical Center, and Rhode Island Hospital-Brown University.
Nineteen cardiothoracic surgeons (53% acceptance) were interviewed. Perceptions of the drivers of addiction varied as well as approaches to repeat valve operations. There were mixed views on multidisciplinary meetings, although many surgeons expressed an interest in more efficient meetings and more intensive postoperative and posthospitalization multidisciplinary care.
Cardiothoracic surgeons are emotionally and professionally impacted by making decisions about whether to perform valve operation for people with DUA-IE. The use of efficient, agenda-based multidisciplinary care teams is an actionable solution to improve cross-disciplinary partnerships and outcomes for people with DUA-IE.
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Oral budesonide is commonly used for the management of Crohn's disease given its high affinity for glucocorticoid receptors and low systemic activity due to extensive first‐pass metabolism through ...hepatic cytochrome P450 (CYP) 3A4. Voriconazole, a second‐generation triazole antifungal agent, is both a substrate and potent inhibitor of CYP isoenzymes, specifically CYP2C19, CYP2C9, and CYP3A4; thus, the potential for drug‐drug interactions with voriconazole is high. To our knowledge, drug‐drug interactions between voriconazole and corticosteroids have not been specifically reported in the literature. We describe a 48‐year‐old woman who was receiving oral budesonide 9 mg/day for the management of Crohn's disease and was diagnosed with fluconazole‐resistant Candida albicans esophagitis; oral voriconazole 200 mg every 12 hours for 3 weeks was prescribed for treatment. Because the patient experienced recurrent symptoms of dysphagia, a second 3‐week course of voriconazole therapy was taken. Seven weeks after originally being prescribed voriconazole, she came to her primary care clinic with elevated blood pressure, lower extremity edema, and weight gain; she was prescribed a diuretic and evaluated for renal dysfunction. At a follow‐up visit 6 weeks later with her specialty clinic, the patient's blood pressure was elevated, and her physical examination was notable for moon facies, posterior cervical fat pad prominence, and lower extremity pitting edema. Iatrogenic Cushing syndrome due to a drug‐drug interaction between voriconazole and budesonide was suspected, and voriconazole was discontinued. Budesonide was continued as previously prescribed for her Crohn's disease. On reevaluation 2 months later, the patient's Cushingoid features had markedly regressed. To our knowledge, this is the first published case report of iatrogenic Cushing syndrome due to a probable interaction between voriconazole and oral budesonide. In patients presenting with Cushingoid features who have received these drugs concomitantly, clinicians should consider the potential drug interaction between these agents, and the risks and benefits of continued therapy must be considered.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Early prediction of outcomes after traumatic brain injury (TBI) is often difficult. To improve prognostic accuracy soon after trauma, we compared different radiological modalities and anatomical ...injury distribution in a group of adult TBI patients. The four methods studied were computed tomography (CT), magnetic resonance imaging (MRI) with T2-weighted imaging (T2WI), fluid-attenuated inversion recovery (FLAIR) imaging, and susceptibility weighted imaging (SWI). The objective of this study was to identify which modality and anatomic model best predict outcome. The patient population consisted of 38 adults admitted between February 2001 and May 2003. Early CT, T2WI, FLAIR, and SWI were obtained for each patient as well as a Glasgow Outcome Score (GOS) between 0.1 and 22 months (mean 9.2 months) after injury. Using a semi-automated computer method, intraparenchymal lesions were traced, measured, and converted to lesion volumes based on slice thickness and pixel size. Lesions were assigned to zones and regions. Outcomes were dichotomized into good (GOS 4-5) and poor (GOS 1-3) outcome groups. Brain injury detected by imaging was analyzed by median total lesion volume, median volume per lesion, and median number of lesions per outcome group. T2WI and FLAIR imaging most consistently discriminated between good and poor outcomes by median total lesion volume, median volume per lesion, and median number of lesions. In addition, T2WI and FLAIR imaging most consistently discriminated between good and poor outcomes by zonal distribution. While SWI rarely discriminated by outcome, it was very sensitive to intraparenchymal injury and its optimal use in evaluating TBI is unclear. SWI and other new imaging modalities should be further studied to fully evaluate their prognostic utility in TBI evaluation.
Purpose of review
An increasing number of specialists and non-specialists are developing clinical programs to treat and cure hepatitis C virus (HCV). The goal of this paper is to evaluate and ...describe optimal strategies to improve outcomes related to HCV care delivery.
Recent findings
Screening and diagnosis of HCV should be guided by established recommendations. Given the recognized disparity in HCV diagnosis and linkage to care, a multi-modal approach involving care coordination and technology resources should be used to improve patient engagement. Access to HCV treatment may be optimized through systematic documentation, prior authorization, and appeal processes. Treatment monitoring should emphasize medication adherence, side effect and drug interaction management, as well as elimination of practical barriers. Finally, post-treatment engagement to promote liver health and reduce the risk of complications or reinfection maximizes the benefit of HCV treatment.
Summary
The landscape of HCV treatment has evolved from a specialist-driven model with few patients qualifying for treatment to an opportunity for non-specialists and other providers to provide curative therapies in most patients. Innovative practice models that employ a multidisciplinary approach will likely improve screening, diagnosis, engagement, and treatment outcomes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We report a case of noninfectious vacuolar interface dermatitis associated with colonic and perianal ulceration in a patient with acquired immunodeficiency syndrome (AIDS), which responded to ...immunosuppressive treatment. Our findings suggest that interface dermatitis in the setting of AIDS may warrant further gastrointestinal evaluation and may respond to immunosuppression.
We report a case of noninfectious vacuolar interface dermatitis associated with colonic and perianal ulceration in a patient with acquired immunodeficiency syndrome (AIDS), which responded to immunosuppressive treatment. Our findings suggest that interface dermatitis in the setting of AIDS may warrant further gastrointestinal evaluation and may respond to immunosuppression.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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