Skull Base Osteomyelitis: Historical Perspective, Diagnosis and Management Update.

SBO is a life-threatening disease that requires a high index of suspicion based on these patients complex underlying medical co-morbidities and clinician's acumen. Once a diagnosis is made, is it critical to communicate and work closely with other multidisciplinary teams (neuroradiology for appropriate choice of imaging study and interpretation; infectious disease for appropriate medical treatment and duration; internist to properly manage their underlying medical co-morbidities). Despite advances in imaging, the diagnosis is first made based on clinical judgment, appropriate culture, and tissue biopsy.

Mitigation of a Coronavirus Disease 2019 Outbreak in a Nursing Home Through Serial Testing of Residents and Staff.

Nursing homes and long-term care facilities represent highly vulnerable environments for respiratory disease outbreaks, such as coronavirus disease 2019 (COVID-19). We describe a COVID-19 outbreak in a nursing home that was rapidly contained by using a universal testing strategy of all residents and nursing home staff.

Factors Associated With Central Line-Associated Bloodstream Infections in a Cohort of Adult Home Parenteral Nutrition Patients.

BACKGROUND: Central line-associated bloodstream infection (CLABSI) is a potentially life-threatening complication in home parenteral nutrition (HPN) patients. We investigated potential predictors of CLABSI in a cohort of adult HPN patients METHODS: Patients managed by the HPN service at the Hospital of University of Pennsylvania on January 1, 2018, were included and followed through June 30, 2019, using existing medical records to collect demographic and clinical data. CLABSIs were adjudicated prospectively by infectious disease experts. Variables with P ≤ .2, when comparing patients with CLABSIs and those without, were included in logistic regression models. RESULTS: Among 114 patients, mean age was 54 ± 16 years, 78/114 were female, and BMI was 25 ± 5.6. Median experience with HPN was 516 days (range, 15-10,281), and 30 had prior CLABSI. Catheter types were peripherally inserted central catheters (83/114), tunneled (27), and implanted (4). The incidence of CLABSI was 0.89 per 1000 catheter days. One multivariate model identified ostomy/wound (odds ratio [OR], 22.0; 95% CI, 4.8-101.7), tunneled/implanted catheter (OR, 4.4; 95% CI, 1.4-13.9), and BMI < 18.5 (OR, 5.9; 95% CI, 1.4-24.2) as predictors of CLABSI. A second model identified patients with 2 potential predictors (OR, 22.9; 95% CI, 5.6-93.5) and tunneled/implanted catheter (OR, 6.7; 95% CI, 2.1-21.8) at high risk of CLABSI. Whether CLABSIrates might be reduced by more intense training in wound or catheter care (especially for those with multiple predictors), different types of catheters, or rapid treatment of malnutrition will require further study.

Internal Medicine Residents' Knowledge and Practice of Pulmonary Tuberculosis Diagnosis.

BACKGROUND: Internal medicine physicians are often the first providers to encounter patients with a new diagnosis of tuberculosis. Given the public health risks of missed tuberculosis cases, assessing internal medicine residents' ability to diagnose tuberculosis is important. METHODS: Internal medicine resident knowledge and practice patterns in pulmonary tuberculosis diagnosis at 7 academic hospitals were assessed utilizing (a) a 10-item validated pulmonary tuberculosis diagnosis assessment tool and (b) a retrospective chart review of 343 patients who underwent a pulmonary tuberculosis evaluation while admitted to a resident-staffed internal medicine or infectious disease service. Our primary outcomes were the mean score and percentage of correct responses per assessment tool question, and the percentage of patients who had Centers for Disease Control and Prevention-recommended tuberculosis diagnostic tests obtained. RESULTS: Of the 886 residents who received the assessment, 541 responded, yielding a response rate of 61%. The mean score on the assessment tool (SD) was 4.4 (1.6), and the correct response rate was 57% (311/541) or less on 9 of 10 questions. On chart review, each recommended test was obtained for ≤43% (148/343) of patients, other than chest x-ray (328/343; 96%). A nucleic acid amplification test was obtained for 18% (62/343) of patients, whereas 24% (83/343) had only 1 respiratory sample obtained. Twenty patients were diagnosed with tuberculosis. CONCLUSIONS: Significant knowledge and practice gaps exist in internal medicine residents' abilities to diagnose tuberculosis. As residents represent the future providers who will be evaluating patients with possible tuberculosis, such deficiencies must be addressed.

Developing an Assessment Framework for Essential Internal Medicine Subspecialty Topics.

BACKGROUND: Assessing residents by direct observation is the preferred assessment method for infrequently encountered subspecialty topics, but this is logistically challenging. OBJECTIVE: We developed an assessment framework for internal medicine (IM) residents in subspecialty topics, using tuberculosis diagnosis for proof of concept. METHODS: We used a 4-step process at 8 academic medical centers that entailed (1) creating a 10-item knowledge assessment tool; (2) pilot testing on a sample of 129 IM residents and infectious disease fellow volunteers to evaluate validity evidence; (3) implementing the final tool among 886 resident volunteers; and (4) assessing outcomes via retrospective chart review. Outcomes included tool score, item performance, and rates of obtaining recommended diagnostics. RESULTS: Following tool development, 10 infectious disease experts provided content validity. Pilot testing showed higher mean scores for fellows compared with residents (7 [SD = 1.8] versus 3.8 [SD = 1.7], respectively, P < .001) and a satisfactory Kuder-Richardson Formula 20 (0.72). Implementation of the tool revealed a 14-minute (SD = 2.0) mean completion time, 61% (541 of 886) response rate, 4.4 (SD = 1.6) mean score, and ≤ 57% correct response rate for 9 of 10 items. On chart review (n = 343), the rate of obtaining each recommended test was ≤ 43% (113 of 261), except for chest x-rays (96%, 328 of 343). CONCLUSIONS: Our assessment framework revealed knowledge and practice gaps in tuberculosis diagnosis in IM residents. Adopting this approach may help ensure assessment is not limited to frequently encountered topics.

Strategies to Improve Hepatocellular Carcinoma Surveillance in Veterans With Hepatitis B Infection.

Attitudes of patients as well as infectious disease, gastroenterology, and primary care providers need to be addressed to improve surveillance rates for high-risk patients with chronic hepatitis B infections.

Interferon Stimulated Gene Expression in HIV/HCV Coinfected Patients Treated with Nitazoxanide/Peginterferon-Alfa-2a and Ribavirin.

A combination of nitazoxanide (NTZ), peginterferon (PegIFN), and ribavirin (RBV) may result in higher sustained virologic response (SVR) rates in hepatitis C virus (HCV) monoinfected patients. This study evaluated the effect of NTZ on interferon-stimulated gene (ISG) expression in vitro and in vivo among HIV/HCV genotype-1 (GT-1) treatment-naive patients. The ability of NTZ to enhance host response to interferon (IFN) signaling using the HCV cell culture system was initially evaluated. Second, ISG expression in 53 patients with treatment outcomes [21 SVR and 32 nonresponders (NR)] in the ACTG A5269 trial, a phase-II study (4-week lead in of NTZ 500 mg daily followed by 48 weeks of NTZ, PegIFN, and weight-based RBV), was assessed. The relative expression of 48 ISGs in peripheral blood mononuclear cells (PBMCs) was measured at baseline, week 4, and week 8 of treatment in a blinded manner. In vitro NTZ produced a direct and additive antiviral effect with IFN-alfa, with pretreatment of NTZ resulting in maximal HCV suppression. NTZ augmented IFN-mediated ISG induction in PBMCs from relapsers and SVRs (p < 0.05), but not NR. In ACTG A5269, baseline expression of most ISGs was similar between NR and SVR. NTZ minimally induced 17 genes in NR and 13 genes in SVR after 4 weeks of therapy. However, after initiation of PegIFN and RBV, ISG induction was predominantly observed in the SVR group and not NR group. NTZ treatment facilitates IFN-induced suppression of HCV replication. Inability to achieve SVR with IFN-based therapy in this clinical trial is associated with diminished ISG response to therapy that is refractory to NTZ.

Simplified diagnostic monitoring for hepatitis C, in the new era of direct-acting antiviral treatment.

PURPOSE OF REVIEW: Approximately 150-175 million people are infected with hepatitis C virus (HCV). Until very recently, the complexity, cost and poor efficacy and tolerability of pegylated interferon and ribavirin (PEG-RBV) treatment have hindered scale up in low-income and middle-income countries (L&MICs). Similarly, the diagnostic and monitoring algorithm associated with PEG-RBV has been expensive and complicated because of the poor efficacy and frequency of adverse drug effects of PEG-RBV therapy. This article provides an overview of the potential changes to the diagnosis and monitoring algorithm and describes key promising tools in the diagnostics pipeline. RECENT FINDINGS: Interferon-free direct-acting antiviral (DAA) therapy sets the stage to significantly simplify laboratory requirements and make the overall diagnostic package much less expensive. Diagnostic simplification and cost-reduction will be key to enable implementation of HCV screening and treatment in L&MICs. SUMMARY: There is the potential to introduce simplified monitoring for hepatitis C. Antigen testing could be used as a replacement for HCV RNA PCR tests, to establish active infection and then to prove cure after stopping DAA treatment. If new DAA treatments can be shown to be pan-genotypic, genotyping may no longer be required.

Prevalence and risk factors for patient-reported joint pain among patients with HIV/hepatitis C coinfection, hepatitis C monoinfection, and HIV monoinfection.

BACKGROUND: To determine the prevalence of patient-reported joint pain among patients with human immunodeficiency virus (HIV)/chronic hepatitis C virus (HCV) coinfection, chronic HCV monoinfection, and HIV monoinfection followed in hepatology and infectious disease outpatient practices. METHODS: Standardized interviews were performed among 79 HIV/HCV-coinfected, 93 HCV-monoinfected, and 30 HIV-monoinfected patients in a cross-sectional study within hepatology and infectious disease clinics at three centers. The Multi-Dimensional Health Assessment Questionnaire was used to ascertain joint pain and associated symptoms. Information on potential risk factors for joint pain was obtained during the interview and by chart review. Logistic regression was used to determine adjusted odds ratios (aORs) with 95% confidence intervals (CIs) of joint pain associated with risk factors of interest among chronic HCV-infected and HIV-infected patients. RESULTS: Joint pain was more commonly reported in HCV-monoinfected than HIV/HCV-coinfected (71% versus 56%; p = 0.038) and HIV-monoinfected (71% versus 50%; p = 0.035) patients. A previous diagnosis of arthritis and current smoking were risk factors for joint pain among HCV-infected patients (arthritis: aOR, 4.25; 95% CI, 1.84-9.81; smoking: aOR, 5.02; 95% CI, 2.15-11.74) and HIV-infected (arthritis: aOR, 5.36; 95% CI, 2.01-14.25; smoking: aOR, 6.07; 95% CI, 2.30-16.00) patients. CONCLUSION: Patient-reported joint pain was prevalent among all three groups, but more common among chronic HCV-monoinfected than either HIV/HCV-coinfected or HIV-monoinfected patients. A prior diagnosis of arthritis and current smoking were risk factors for patient-reported joint pain among both HCV-infected and HIV-infected patients.

Induction of Multiple Immune Regulatory Pathways with Differential Impact in HCV/HIV Coinfection.

Persistent viral infections including HCV, HBV, and HIV are associated with increased immune regulatory pathways including the extrinsic FoxP3+CD4+ regulatory T cells (Tregs) and intrinsic inhibitory pathways such as programed death-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) with potentially reversible suppression of antiviral effector T cells (1-12). Immunological consequences of viral coinfections relative to these immune regulatory pathways and their interplay are not well-defined. In this study, we examined the frequency, phenotype, and effector function of circulating T cell subsets in patients with chronic HCV and/or HIV infection, hypothesizing that HCV/HIV coinfection will result in greater immune dysregulation with pathogenetic consequences (13, 14). We show that multiple T cell inhibitory pathways are induced in HCV/HIV coinfection including FoxP3+ Tregs, PD-1, and CTLA-4 in inverse association with overall CD4 T cell frequency but not with liver function or HCV RNA titers. The inverse association between CD4 T cell frequency and their FoxP3, PD-1, or CTLA-4 expression remained significant in all subjects combined regardless of HCV and/or HIV infection, suggesting a global homeostatic mechanism to maintain immune regulation relative to CD4 T cell frequency. PD-1 blockade rescued T cell responses to HIV but not HCV without significant impact by CTLA-4 blockade in vitro. Collectively, these findings highlight complex immune interactions in viral coinfections and differential regulatory pathways influencing virus-specific T cells that are relevant in immunotherapeutic development.

Safety and antiviral activity of the HCV entry inhibitor ITX5061 in treatment-naive HCV-infected adults: a randomized, double-blind, phase 1b study.

BACKGROUND: Hepatitis C virus (HCV) entry involves scavenger receptor B1 (SRB1). In vitro, SRB1 inhibition by ITX5061 impedes HCV replication. METHODS: Multicenter study to assess safety/activity of ITX5061 in previously untreated, noncirrhotic, HCV genotype 1 infected adults. Design included sequential cohorts of 10 subjects with ITX5061 (n = 8) or placebo (n = 2) to escalate duration (3 to 14 to 28 days) or deescalate dose (150 to 75 to 25 mg) based on predefined criteria for safety and activity (≥ 4 of 8 subjects with HCV RNA decline ≥ 1 log10 IU/mL). RESULTS: Thirty subjects enrolled in 3 cohorts: ITX5061 150 mg/day by mouth for 3 (A150), 14 (B150), and 28 (C150) days. Six subjects had grade ≥ 3 adverse events (one in placebo); none were treatment related. One of the 7 C150 subjects (14.3%, 95% confidence interval [CI], .7%-55.4%) had ≥ 1 log10 IU/mL decline in HCV RNA (1.49 log10 IU/mL), whereas none of the 6 placebo, 8 A150 or 8 B150 subjects showed such decline. CONCLUSIONS: Oral ITX5061 150 mg/day for up to 28 days was safe and well tolerated. In the 28-day cohort, 1 of 7 subjects showed antiviral activity; however, predefined criteria for antiviral activity were not met at the doses and durations studied.

Addition of nitazoxanide to PEG-IFN and ribavirin to improve HCV treatment response in HIV-1 and HCV genotype 1 coinfected persons naïve to HCV therapy: results of the ACTG A5269 trial.

BACKGROUND: We hypothesized that nitazoxanide (NTZ) added to pegylated interferon alfa-2a (PEG-IFN) and weight-based ribavirin (WBR) would improve hepatitis C virus (HCV) virologic responses in HCV treatment-naïve HIV-1/HCV genotype 1 coinfected persons. METHODS: Prospective, single-arm study in which subjects received 4-week lead-in (NTZ 500 mg twice daily) followed by 48 weeks of NTZ, PEG-IFN, and WBR. We compared the HCV virologic responses of these subjects to historical controls from the completed ACTG study A5178 who received PEG-IFN and WBR and had similar subject characteristics. Primary endpoints were early virologic response and complete early virologic response (EVR and cEVR). RESULTS: Among 67 subjects (78% male; 48% Black; median age, 50 years), EVR was achieved in 65.7% (90% CI, 55.0%-75.3%), cEVR in 38.8% (28.8%-49.6%). and SVR in 32.8% (23.4%-43.5%). EVR was higher with NTZ (51.4% in A5178; P = .03), but the sustained virologic response (SVR) proportion was similar (27.3% in A5178; P = .24). In contrast to A5178, SVR was similar across IL28B genotypes. Overall, NTZ was safe and well-tolerated. CONCLUSION: Whereas EVR proportion improved significantly in this pilot study, the addition of NTZ to PEG-IFN/WBR did not significantly improve SVR compared to historical controls. NTZ may be associated with an attenuation of the effect of IL28B on HCV treatment response.

Willingness to undergo a repeat liver biopsy among HIV/hepatitis C virus-coinfected and hepatitis C virus-monoinfected patients.

BACKGROUND: Guidelines for chronic hepatitis C virus (HCV) management have recommended that a liver biopsy be repeated at 3-year intervals for HIV/HCV-coinfected patients and 5-year intervals for those with HCV monoinfection to assess fibrosis progression. However, it is unclear if patients are willing to repeat this procedure. OBJECTIVE: To determine the prevalence and factors, particularly HIV coinfection, associated with willingness to repeat a liver biopsy. METHODS: A questionnaire was administered to 235 HCV-infected patients (113 with HIV coinfection) between January 2008 and June 2011 who previously underwent liver biopsy. The main outcome was self-reported willingness to repeat the biopsy. The questionnaire collected data on other hypothesized determinants of willingness to repeat the biopsy. These were evaluated by logistic regression. RESULTS: Among 235 subjects who completed the questionnaire, 32 (14%) reported unwillingness to repeat the biopsy, most commonly because of a perception that it was unimportant for care [13(41%)], concerns regarding pain [12(38%)], and a poor experience with the prior biopsy [7(21%)]. Considering biopsy to be safe [odds ratio (OR), 4.45; 95% CI, 1.50-13.27], important (OR, 4.87; 95% CI, 1.83-12.95), and knowing a person who underwent liver biopsy (OR, 3.45; 95% CI, 1.16-10.23) were associated with willingness to repeat the biopsy. HIV was not associated with willingness to repeat the biopsy (OR, 1.42; 95% CI, 0.67-3.03). CONCLUSIONS: Eighty-six percent of chronic HCV-infected patients were willing to repeat a liver biopsy. HIV was not associated with unwillingness. In patients in whom a repeat liver biopsy is indicated, education on the utility and safety of the biopsy is important to its acceptance.

Adherence to hepatitis C virus therapy in HIV/hepatitis C-coinfected patients.

Adherence to hepatitis C virus (HCV) therapy has been incompletely examined among HIV-infected patients. We assessed changes in interferon and ribavirin adherence and evaluated the relationship between adherence and early (EVR) and sustained virologic response (SVR). We performed a cohort study among 333 HIV/HCV-coinfected patients who received pegylated interferon and ribavirin between 2001 and 2006 and had HCV RNA before and after treatment. Adherence was calculated over 12-week intervals using pharmacy refills. Mean interferon and ribavirin adherence declined 2.5 and 4.1 percentage points per 12-week interval, respectively. Among genotype 1/4 patients, EVR increased with higher ribavirin adherence, but this association was less strong for interferon. SVR among these patients was higher with increasing interferon and ribavirin adherence over the first, second, and third, but not fourth, 12-week intervals. Among HIV/HCV patients, EVR and SVR increased with higher interferon and ribavirin adherence. Adherence to both antivirals declined over time, but more so for ribavirin.

Low prevalence of necrolytic acral erythema in patients with chronic hepatitis C virus infection.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is associated with necrolytic acral erythema (NAE). However, the prevalence of NAE among patients with HCV is unknown, and the clinical and histologic features have not been well defined. OBJECTIVE: We sought to determine the prevalence, overall clinical features, and cutaneous histopathological characteristics of patients with NAE. METHODS: A cross-sectional study was performed among patients with chronic HCV infection cared for at 3 Philadelphia hospitals. Patients completed a questionnaire and underwent a dermatologic examination. All undiagnosed skin lesions with clinical features of NAE as described in the literature underwent skin biopsy. RESULTS: Among 300 patients with chronic HCV infection (median age 55 years; 73% male; 70% HCV genotype 1), 5 of them (prevalence 1.7%; 95% confidence interval 0.5%-3.8%) had skin lesions consistent with NAE clinically, which were analyzed and confirmed with skin biopsy specimen. All 5 skin biopsy specimens demonstrated variable psoriasiform hyperplasia, mild papillomatosis, parakeratosis, and necrotic keratinocytes in the superficial epidermis. All 5 patients were older than 40 years, were African American men, were infected with HCV genotype 1, and had a high viral load (>200,000 IU/mL). LIMITATIONS: Previous descriptions of NAE were used to guide the evaluation and need for a biopsy; however, other unknown clinical characteristics of the disease may exist. The senior author was the sole interpreter of the biopsy specimens. Only 300 of the 2500 eligible patients enrolled in the study. CONCLUSION: The prevalence of NAE among patients with chronic HCV in this sample was very low. Further research is needed to determine the origin and appropriate therapies of NAE.

Relationship between adherence to hepatitis C virus therapy and virologic outcomes: a cohort study.

BACKGROUND: Adherence to therapy with pegylated interferon and ribavirin for hepatitis C virus (HCV) infection has been incompletely examined. OBJECTIVE: To evaluate the relationship between adherence to HCV therapy and early and sustained virologic response, assess changes in adherence over time, and examine risk factors for nonadherence. DESIGN: Retrospective cohort study. SETTING: National Veterans Affairs Hepatitis C Clinical Case Registry. PATIENTS: 5706 HCV-infected patients (genotypes 1, 2, 3, or 4) with at least 1 prescription for both pegylated interferon and ribavirin between 2003 and 2006 and HCV RNA results before and after treatment initiation. MEASUREMENTS: Adherence was calculated over 12-week intervals by using pharmacy refill data. End points included early virologic response (decrease of ≥2 log(10) HCV RNA at 12 weeks) and sustained virologic response (undetectable HCV RNA 24 weeks after the end of treatment). RESULTS: Early virologic response increased with higher levels of adherence to ribavirin therapy over the initial 12 weeks (patients with HCV genotype 1 or 4, 25 of 68 [37%] with ≤40% adherence vs. 1367 of 2187 [63%] with 91% to 100% adherence [P < 0.001]; patients with HCV genotype 2 or 3, 12 of 18 [67%] with ≤40% adherence vs. 651 of 713 [91%] with 91% to 100% adherence [P < 0.001]). Among patients with HCV genotype 1 or 4, sustained response increased with higher adherence to ribavirin therapy over the second, third, and fourth 12-week intervals. Results were similar for adherence to interferon therapy. Mean adherence to therapy with interferon and ribavirin decreased by 3.4 and 6.6 percentage points per 12-week interval, respectively (P for trend < 0.001 for each drug). Patients who received growth factors or thyroid medications during treatment had higher mean adherence to antiviral therapy. LIMITATION: This was an observational study without standardized timing for outcome measurements. CONCLUSION: Early and sustained virologic responses increased with higher levels of adherence to interferon and ribavirin therapy. Adherence to therapy with both antivirals decreased over time, but more so for ribavirin.

Decreased post-transplant survival among heart transplant recipients with pre-transplant hepatitis C virus positivity.

BACKGROUND: Transplant centers are reluctant to perform heart transplantation in patients with hepatitis C virus (HCV) infection because augmented immunosuppression could potentially increase mortality. However, there have been few studies examining whether HCV infection reduces survival after heart transplantation. METHODS: We used data from the the U.S. Scientific Registry of Transplant Recipients to perform a multicenter cohort study evaluating the association between recipient pre-transplant HCV status and survival after heart transplantation. Adults undergoing heart transplantation between January 1, 1993 and December 31, 2007 were eligible to participate. RESULTS: Among 20,687 heart transplant recipients (443 HCV-positive and 20,244 HCV-negative) at 103 institutions followed for a mean of 5.6 years, mortality was higher among HCV-positive than HCV-negative recipients (177 [40%] vs 6,367 [31.5%]; p = 0.0001). After matching on propensity score, hospital and gender, the hazard ratio (HR) of death for HCV-positive heart transplant recipients was 1.32 (95% confidence interval [CI] 1.08 to 1.61). Mortality rates were higher among HCV-positive heart transplant recipients at 1 year (9.4% vs 8.2%), 5 years (26.3% vs 22.9%), 10 years (53.1% vs 43.4%) and 15 years (74.8% vs 62.3%) post-transplantation. HRs did not vary by gender or overall number of heart transplantations performed at the center. CONCLUSIONS: Pre-transplant HCV positivity is associated with decreased survival after heart transplantation.

Imported Lassa fever, Pennsylvania, USA, 2010.

We report a case of Lassa fever in a US traveler who visited rural Liberia, became ill while in country, sought medical care upon return to the United States, and subsequently had his illness laboratory confirmed. The patient recovered with supportive therapy. No secondary cases occurred.