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ObjectiveWe present the final analysis results of the phase 2 JADE study (ClinicalTrials.gov Identifier:NCT03361956).Design232 patients with chronic hepatitis B (CHB) not currently treated at study start (NCT) at study start or virologically suppressed were randomised to receive 75 mg (part 1) or 250 mg (part 2) JNJ-56136379, a hepatitis B virus (HBV)–capsid assembly modulator, one time per day or placebo with nucleos(t)ide analogue (NA) (tenofovir disoproxil fumarate/entecavir) or JNJ-56136379 alone (NCT-only) for ≥24 and ≤48 weeks.ResultsIn patients who are NCT hepatitis B e-antigen (HBeAg) positive, JNJ-56136379 75 mg+NA and 250 mg+NA showed limited mean (SE) hepatitis B surface antigen (HBsAg) declines (0.14 (0.10) and 0.41 (0.15), respectively) from baseline at Week 24 (primary endpoint; placebo+NA: 0.25 (0.11) log10international unit (IU)/mL).In patients who are NCT HBeAg positive, mean (SE) HBV DNA declines at Week 24 were 5.53 (0.23) and 5.88 (0.34) for JNJ-56136379 75 mg+NA and 250 mg+NA, respectively, versus 5.21 (0.42) log10IU/mL for placebo+NA. In NCT patients, mean (SE) HBV RNA declines were 2.96 (0.23) and 3.15 (0.33) versus 1.33 (0.32) log10copies/mL, respectively.Patients with HBsAg declines had HBeAg and hepatitis B core-related antigen (HBcrAg) declines and some early on-treatment isolated alanine aminotransferase flares. Viral breakthrough occurred with JNJ-56136379 monotherapy with the emerging resistant-variant T33N, but not with JNJ-56136379+NA. JNJ-56136379 treatment beyond Week 24 had a generally small additional effect on viral markers.No study treatment-related serious adverse events or clinically significant changes in laboratory parameters occurred.ConclusionsIn patients with non-cirrhotic CHB, JNJ-56136379+NA showed pronounced reductions in HBV DNA and HBV RNA, limited HBsAg or HBeAg declines in patients who are NCT HBeAg positive, and was well tolerated, but no clear benefit with regards to efficacy of JNJ-56136379 over NA was observed.

HBV nucleos(t)ide reverse transcriptase inhibitors (NrtIs) do not completely suppress HBV replication. Previous reports indicate persistent viremia during NrtI treatment despite HBV DNA being undetectable. HBV core inhibitors may enhance viral suppression when combined with NrtIs. This phase II trial (NCT03576066) evaluated the efficacy and safety of the investigational core inhibitor, vebicorvir (VBR), in virologically- suppressed patients on NrtIs.Non-cirrhotic, NrtI-suppressed patients with chronic HBV were randomised to VBR 300 mg once daily or matching placebo (PBO) for 24 weeks. Treatment was stratified by hepatitis B e antigen (HBeAg) status. The primary endpoint was change from Baseline in serum HBeAg or hepatitis B surface antigen (HBsAg) after 24 weeks.Of 73 patients enrolled, 47 were HBeAg positive and 26 were HBeAg negative. In HBeAg-positive and -negative patients, there were no differences in the change from Baseline at Week 24 for HBsAg or HBeAg. Using a novel, high-sensitivity assay to detect HBV DNA, a greater proportion of patients with detectable HBV DNA at Baseline achieved undetectable HBV DNA at Week 24 in the VBR+NrtI vs. PBO+NrtI group. In HBeAg-positive patients, a greater change from Baseline in HBV pregenomic (pg)RNA was observed at Week 24 with VBR+NrtI vs. PBO+NrtI. Treatment-emergent adverse events (TEAEs) in VBR+NrtI patients included upper respiratory tract infection, nausea, and pruritus. No serious adverse events, Grade 4 TEAEs, or deaths were reported.In this 24-week study, VBR+NrtI demonstrated a favourable safety and tolerability profile. While there were no significant changes in viral antigen levels, enhanced viral suppression was demonstrated by greater changes in DNA and pgRNA with the addition of VBR compared to NrtI alone.NCT03576066.Core inhibitors represent a novel approach for the treatment of chronic hepatitis B virus (HBV) infection, with mechanisms of action distinct from existing treatments. In this study, vebicorvir added to existing therapy reduced HBV replication to a greater extent than existing treatment and was generally safe and well tolerated.

Background Bamlanivimab and casirivimab/imdevimab are monoclonal antibody (mAb) treatments used for mild to moderate coronavirus disease 2019 (COVID-19) in high-risk patients. To date, there are few data summarizing real-world evidence comparing the 2 mAbs. Additionally, there are insufficient data to guide administration timing relative to symptom onset. The purpose of this study was to evaluate 30-day failure rates for each agent and to identify the relationship between symptom onset and efficacy. Methods We performed a retrospective cohort study of a 6-month period at a large community medical center. Consecutive outpatients diagnosed with COVID-19 disease by nasopharyngeal (NP) polymerase chain reaction (PCR) testing received either bamlanivimab 700 mg or casirivimab/imdevimab 1200 mg/1200 mg. Each patient was followed for a total of 30 days. Three independent, blinded physicians performed adjudication for revisit reasons. The primary outcome was therapy-related failure, defined as COVID-19-related hospital admission within 30 days of infusion. Multivariable logistic regression was performed to adjust for confounders that may have influenced hospital admission in either group. Results During the period from November 2020 to May 2021, 183 patients were treated with bamlanivimab and 270 with casirivimab/imdevimab. The mean age was ~67 years and body mass index 30 kg/m2. Thirty-day admission for therapy-related failure rates were 4.8% and 13.7% for casirivimab/imdevimab and bamlanivimab, respectively (P = .001). No significant differences were found between early ( Conclusions There was a higher failure rate with bamlanivimab vs casirivimab/imdevimab. No difference in efficacy was found between early vs late administration of either mAb.

Nucleos(t)ide reverse transcriptase inhibitors do not completely suppress HBV DNA in chronic HBV infection (cHBV). Vebicorvir (VBR) is an investigational core inhibitor that interferes with multiple aspects of HBV replication. This phase II trial evaluated the safety and efficacy of VBR in combination with entecavir (ETV) in treatment-naïve patients with cHBV.HBeAg-positive, treatment-naïve patients without cirrhosis were randomised 1:1 in a double-blind manner to once-daily VBR 300 mg+ETV 0.5 mg or placebo (PBO)+ETV 0.5 mg for 24 weeks. The primary endpoint was change in mean logAll patients in both treatment groups (PBO+ETV: 12/12; VBR+ETV: 13/13) completed the study. At Week 12, VBR+ETV led to a greater mean (SD) reduction from Baseline in logIn this 24-week study, VBR+ETV provided additive antiviral activity over PBO+ETV in treatment-naïve patients with cHBV, with a favourable safety and tolerability profile.NCT03577171 LAY SUMMARY: Hepatitis B is a long-lasting viral infection of the liver. Current treatments can suppress hepatitis B virus but do not offer the opportunity of cure, hence, new treatment approaches are required. Herein, we show that the combination of the novel core inhibitor vebicorvir with an existing antiviral (entecavir) in treatment-naïve patients chronically infected with hepatitis B virus demonstrated greater antiviral activity than entecavir alone. Additionally, vebicorvir was safe and well tolerated. Thus, further studies evaluating its potential role in the treatment of chronic hepatitis B are warranted.

With the deployment of COVID19 vaccine many are wondering when do we get back to normal and what does that even look like...

We describe the first case of multisystem inflammatory syndrome in an adult patient after coronavirus disease-19 (COVID-19) A 34-year-old Hispanic man, who tested positive for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) 1 month before presentation, was admitted for fever, abdominal pain, headache, and myalgia The patient deteriorated, developing multisystem organ failure He required intensive care unit admission, mechanical ventilation, vasopressors, and continuous renal replacement therapy Laboratory workup showed depletion of serum complement levels After immunosuppressive therapy with intravenous immunoglobulin and corticosteroids, complement levels improved, and the patient made a full recovery © Wolters Kluwer Health, Inc All rights reserved

Introduction: Histoplasma Capsulatum (HC) is one of the most common endemic mycoses in the United States of America, and has also been reported in large numbers in various regions of Central and South America. It can cause disease ranging in severity from an upper respiratory tract-like infection, to deep single organ disease and most concerning, widely disseminated disease resulting in harmful sequelae. Presumed Ocular Histoplasmosis Syndrome (POHS) is the most common ocular manifestation of histoplasmosis and usually results in permanent disability. Discussion and Conclusion: In this study, we describe a rarely reported case of histoplasmosis endophthalmitis that was treated with itraconazole and resulted in almost complete resolution of all retinal findings and symptoms.

Background Casirivimab/imdevimab is a monoclonal antibody (mAb) cocktail with emergency use authorization for mild-to-moderate coronavirus disease 2019 (Covid-19) in patients at high risk for severe disease progression and/or hospitalization. Little is known about the importance of early administration of this product. The objective of this study was to determine if early administration (within 3 days of symptom onset) of casirivimab/imdevimab is associated with better outcomes. Methods Single-center, retrospective cohort study including all consecutive patients who received casirivimab/imdevimab at our institution through May 2021. The primary outcome was 30-day post-infusion hospital admission rate in patients who received mAb ≥ 3 days (later) or < 3 days (early) in relation to patient reported symptom onset. Secondary outcomes included any hospital revisit within 30-days. Adverse events were also captured. Chi-square and independent samples t-test were used to compare categorical and continuous data, respectively. Multivariable logistic regression was used to adjust for confounders. Results 270 patients met the inclusion criteria and were included in the analysis. There were 80 patients with early administration and 190 with later administration. Baseline characteristics for both groups were similar. Mean age was approximately 64 years and BMI 31 mg/m2. Table 1 provides a summary of patient characteristics. Late and early administration of casirivimab/imdevimab were similar in terms of hospital admission for any therapy related failure within 30 days of mAb administration after adjusting for age and Charlson comorbidity index (3.7% vs. 7.5%; adjusted odds ratio 0.69, 95% confidence interval, 0.20 – 2.39; p=0.561). Similarly, there were no significant differences in any hospital revisit. Conclusion We did not find any difference in outcomes between early and late administration of casirivimab/imdevimab. Disclosures Ronald G. Nahass, MD, Abbvie (Grant/Research Support, Speaker’s Bureau)Alkermes (Grant/Research Support)Gilead (Grant/Research Support, Speaker's Bureau)Merck (Grant/Research Support, Speaker's Bureau)

Background Successful treatment of HCV in persons who inject drugs (PWIDS), has been reported for patients who were older or who had used drugs more than 6 months prior. The young, < 35 year of age (yoa), active user has not been well studied or reported. We performed a pilot treatment study in a young cohort of PWIDS to evaluate cure rates of HCV in this population. Methods Young, active PWIDS using < 6months earlier, < 35 yoa were identified. Treatment for HCV with glecaprevir/pibrentasvir (G/P) and concurrent treatment for opiate use disorder with XR Naletrexone (XR-NTX) was provided. Two patients chose methadone. Patients were followed up to 12 months after enrollment. Patients were evaluated for adherence, side effects, alanine aminotransferase (ALT) levels, urine drug screens (UDS) and opioid craving scores using a visual analog scale (VAS) while on XR-NTX to assess management of their addiction. Rates of treatment completion, SVR 4 & 12 were determined. Results 30 patients were recruited: 18 were women. Average age was 28 with a range of 23-35. Recent injection drug use was common with 22 (73%) having injected within the 30 days and all having injected within 3 months of recruitment. The average ALT on enrollment was 106. Genotypes were 1 (15), 3a (11), and unknown (4). Of the 30 patients, 15 failed to come for the required 2 visits prior to starting G/P. Lost to follow up occurred due to relapse of addiction (9), overdose death (1), lost communication and suspected relapse (4). 15 began and completed G/P. 15 were cured of their HCV infection. 17 patients receive one or more doses of XR-NTX. On average patients were on XR-NTX for 4.8 months. Sobriety was measured for patients on XR-NTX using Opiate Craving Scores using the Visual Analogue Scale (VAS) and UDS (Figure 1) demonstrating excellent control of craving and significant declines positive UDS. Toxicities were uncommon with no treatment limiting adverse events. Adverse effects of XR-NTX included mild injection site irritation. No ALT abnormalities were noted. Conclusion Young active PWIDS can successfully be cured of HCV. Their addiction can be concurrently managed with XR-NXT. Our findings suggest it is safe to treatment active users with active HCV with XR-NXT improving elimination goals. Disclosures Ronald G. Nahass, MD, Abbvie (Grant/Research Support, Speaker’s Bureau)Alkermes (Grant/Research Support)Gilead (Grant/Research Support, Speaker’s Bureau)Merck (Grant/Research Support, Speaker’s Bureau) Kathleen H. Seneca, MSN, Abbvie (Research Grant or Support)Alkermes (Research Grant or Support)Gilead (Speaker’s Bureau) Ruth A. Homer, MSW, Abbvie (Grant/Research Support)Alkermes (Grant/Research Support)

In a study of 34 human immunodeficiency virus (HIV)-seropositive and 12 HIV-seronegative intravenous drug users with 40 and 14 episodes, respectively, of infective endocarditis (IE), there were no differences between groups in the presentation of IE. Staphylococcus aureus was the infecting microorganism in 75% of the HIV-positive patients and 86% of the HIV-negative patients. Overall survival for the HIV-positive patients was 85% compared with 93% for the HIV-negative patients. Ninety percent of patients with asymptomatic HIV infection survived, whereas 60% of patients in CDC group IV survived (P = .052). In contrast to New Jersey seroprevalence surveys showing HIV antibody in 10%-50% of intravenous drug users, HIV antibody seroprevalence rate in this selected population was 75%. IE in the HIV-seropositive intravenous drug user is essentially the same as in the seronegative user. However, patients with symptomatic HIV infection may be more likely to die from their IE. Intravenous drug users with IE have a greater-than-expected seroprevalence of HIV; the reason remains to be determined.

During a 5-month period, we evaluated the sensitivity, specificity, and predictive value of qualitative cultures of intravenous catheters submitted to a university hospital microbiology laboratory. Of 36 catheters submitted for culture from nonseptic patients, 10 (28%) grew one or more microorganisms on qualitative culture. Of 44 catheters cultured from septic patients, 20 (45%) grew one or more microorganisms, but only 5 grew microorganisms that also were isolated from blood cultures. The sensitivity, specificity, and positive predictive values for catheter-related bacteremia were 71%, 96%, and 17%, values similar to those reported for quantitative methods. Although acceptable in terms of sensitivity and specificity, the very low positive predictive value suggests that catheter-related bacteremia cannot be predicted reliably by this test. We conclude, therefore, that nonstandardized qualitative IV catheter cultures have minimal value as predictors of bacteremia and recommend that they not be performed in clinical microbiology laboratories.

We report what we believe is the first case of vertebral osteomyelitis caused by Roseomonas species. The diagnosis of vertebral osteomyelitis can be difficult. The case illustrates the importance of the establishment of an etiologic diagnosis in vertebral osteomyelitis. The features of Roseomonas species and the evaluation of cases of vertebral osteomyelitis are reviewed.

The special article by Sigal 1 entitled "The Lyme Disease [LD] Controversy" crystallizes the issues associated with the problem of LD in New Jersey. As a group of private practice physicians specializing in infectious diseases in an area in New Jersey where LD is hyperendemic, we have similar concerns. We would like to emphasize several of his points and make some suggestions. As Sigal suggests, more physician education is needed. However, in our community some physicians are reluctant to accept the facts reported by Sigal despite repeated personal contacts and exposure to educational programs. The misconceptions described by Sigal are strongly held by these physicians, who view them as necessary to accommodate patient needs and concerns. This is similar to the common practice of prescribing antibiotics for viral upper respiratory tract infections. Patients have developed certain expectations, and the physicians wish to accommodate their customers for fear of losing business.

Toxic shock syndrome has been noted to occur with nasal surgery, both with and without packing. A new synthetic sponge, described as a nasal tampon, has become available for use as packing after surgery. Herein is reported the first case of toxic shock syndrome associated with the use of this nasal tampon.

• Actinomycosis is typically a chronic infection of the cervicofascial, thoracic, or abdominal region. Involvement of the heart occurs but is unusual. We present a case of chronic constrictive pericarditis caused by actinomycetes. The actinomycosis infection was present for 20 years, thereby representing the longest duration reported in the literature, to our knowledge. ( Arch Intern Med . 1989;149:1202-1203)