Severe Influenza A(H1N1) Virus Infection Complicated by Myositis, Refractory Rhabdomyolysis, and Compartment Syndrome

Myositis is a rare and morbid complication of influenza infection that can rapidly progress to rhabdomyolysis with acute renal failure. Here, we describe a 35-year-old obese woman with severe influenza A(H1N1) virus infection complicated by myositis, refractory rhabdomyolysis, and compartment syndrome

Risk Factors for Disseminated Coccidioidomycosis, United States

Of 150,000 new coccidioidomycosis infections that occur annually in the United States, ≈1% disseminate; one third of those cases are fatal. Immunocompromised hosts have higher rates of dissemination. We identified 8 patients with disseminated coccidioidomycosis who had defects in the interleukin-12/interferon-γ and STAT3 axes, indicating that these are critical host defense pathways

Evaluating concurrent validity of criminal justice and clinical assessments among women on probation

Abstract Background Women in the criminal justice (CJ) system experience complex and comorbid medical, psychiatric, and substance use disorders, which often contribute to CJ involvement. To identify intersections between CJ and health needs, we calculated Spearman r correlations between concurrent CJ and clinical assessments from women on probation in Connecticut who were enrolled in a clinical trial. We examined longitudinal trends in CJ risk scores over 9 years of observation (2005–2014), modeling time to probation recidivism with shared gamma frailty models and comparing contiguous time points by Wilcoxon matched-pairs signed rank tests. Results Women (N = 31) were predominantly white (67.7%) with at least some high school education (58.1%) and mostly unemployed (77.4%) and unstably housed (83.9%). Most met clinical criteria for severe substance use and/or psychiatric disorders. Concurrent measures of substance use, mental health, social support, partnerships, and risk by the Level of Service Inventory-Revised (LSI-R) and clinical assessments were not significantly correlated. The LSI-R personal/emotional sub-score, however, positively correlated with the Addiction Severity Index psychiatric composite score (r = 0.40, 95% CI 0.03–0.68, p = 0.03). After adjusting for age, race and number of previous events, having some high school education versus none marginally decreased the hazard for probation recidivism and having > 5 inpatient psychiatric admissions versus none increased the hazard of probation recidivism 7-fold (HR 7.49, 95% CI 1.33–42.12, p = 0.022). Women with 0–1 recurrent probation terms (n = 16) had a significantly lower mean LSI-R score than those with 2–4 recurrent probation terms (35.9 [SD 6.4] versus 39.2 [SD 3.0], p = 0.019), but repeated LSI-R scores did not change over time, nor vary significantly beyond the group mean. Conclusions In this small, quantitative study of women on probation, widely used CJ assessment tools poorly reflected women’s comorbid medical, psychiatric, and substance use needs and varied minimally over time. Findings illustrate the limitations of contemporary CJ assessment tools for women with complex needs. The field requires more comprehensive assessments of women’s social and health needs to develop individualized targeted case plans that simultaneously improve health and CJ outcomes

Complex prosthetic joint infections due to carbapenemase-producing Klebsiella pneumoniae: a unique challenge in the era of untreatable infections

SummaryObjectivesLimited clinical experience exists regarding the management of prosthetic joint infection (PJI) due to multidrug-resistant (MDR) Gram-negative organisms. We review three cases of carbapenem-resistant Klebsiella pneumoniae (CRKP) complicating PJI.MethodsThis was a retrospective study of all patients at a tertiary care institution with CRKP complicating PJI between January 2007 and December 2010. Demographic data, procedures, organisms involved, length of stay, antibiotic treatments, and outcomes were collected. Antimicrobial susceptibility testing was performed on CRKP isolates, and the mechanism of resistance was ascertained by PCR.ResultsThis analysis demonstrated that: (1) the CRKP possessed blaKPC and were difficult to eradicate (persistent) in PJI; (2) multiple surgeries and antibiotic courses were undertaken and patients required a prolonged length of stay; (3) resistance to colistin and amikacin emerged on therapy; (4) the same strain of CRKP may be responsible for relapse of infection; (5) significant morbidity and mortality resulted.ConclusionsThese cases highlight the opportunistic and chronic nature of CRKP in PJIs and the need for aggressive medical and surgical treatment. Further investigations of the management of CRKP PJI and new drug therapies for infections due to MDR Gram-negative organisms are urgently needed

Phase 1 trial to model primary, secondary, and tertiary dengue using a monovalent vaccine.

Acknowledgements: not applicable.Funder: National Institutes of Health (NIH)BACKGROUND: The four co-circulating and immunologically interactive dengue virus serotypes (DENV1-4) pose a unique challenge to vaccine design because sub-protective immunity can increase the risk of severe dengue disease. Existing dengue vaccines have lower efficacy in DENV seronegative individuals but higher efficacy in DENV exposed individuals. There is an urgent need to identify immunological measures that are strongly associated with protection against viral replication and disease following sequential exposure to distinct serotypes. METHODS/DESIGN: This is a phase 1 trial wherein healthy adults with neutralizing antibodies to zero (seronegative), one non-DENV3 (heterotypic), or more than one (polytypic) DENV serotype will be vaccinated with the live attenuated DENV3 monovalent vaccine rDEN3Δ30/31-7164. We will examine how pre-vaccine host immunity influences the safety and immunogenicity of DENV3 vaccination in a non-endemic population. We hypothesize that the vaccine will be safe and well tolerated, and all groups will have a significant increase in the DENV1-4 neutralizing antibody geometric mean titer between days 0 and 28. Compared to the seronegative group, the polytypic group will have lower mean peak vaccine viremia, due to protection conferred by prior DENV exposure, while the heterotypic group will have higher mean peak viremia, due to mild enhancement. Secondary and exploratory endpoints include characterizing serological, innate, and adaptive cell responses; evaluating proviral or antiviral contributions of DENV-infected cells; and immunologically profiling the transcriptome, surface proteins, and B and T cell receptor sequences and affinities of single cells in both peripheral blood and draining lymph nodes sampled via serial image-guided fine needle aspiration. DISCUSSION: This trial will compare the immune responses after primary, secondary, and tertiary DENV exposure in naturally infected humans living in non-endemic areas. By evaluating dengue vaccines in a new population and modeling the induction of cross-serotypic immunity, this work may inform vaccine evaluation and broaden potential target populations. TRIAL REGISTRATION: NCT05691530 registered on January 20, 2023

Phase 1 trial to model primary, secondary, and tertiary dengue using a monovalent vaccine

Abstract Background The four co-circulating and immunologically interactive dengue virus serotypes (DENV1-4) pose a unique challenge to vaccine design because sub-protective immunity can increase the risk of severe dengue disease. Existing dengue vaccines have lower efficacy in DENV seronegative individuals but higher efficacy in DENV exposed individuals. There is an urgent need to identify immunological measures that are strongly associated with protection against viral replication and disease following sequential exposure to distinct serotypes. Methods/Design This is a phase 1 trial wherein healthy adults with neutralizing antibodies to zero (seronegative), one non-DENV3 (heterotypic), or more than one (polytypic) DENV serotype will be vaccinated with the live attenuated DENV3 monovalent vaccine rDEN3Δ30/31-7164. We will examine how pre-vaccine host immunity influences the safety and immunogenicity of DENV3 vaccination in a non-endemic population. We hypothesize that the vaccine will be safe and well tolerated, and all groups will have a significant increase in the DENV1-4 neutralizing antibody geometric mean titer between days 0 and 28. Compared to the seronegative group, the polytypic group will have lower mean peak vaccine viremia, due to protection conferred by prior DENV exposure, while the heterotypic group will have higher mean peak viremia, due to mild enhancement. Secondary and exploratory endpoints include characterizing serological, innate, and adaptive cell responses; evaluating proviral or antiviral contributions of DENV-infected cells; and immunologically profiling the transcriptome, surface proteins, and B and T cell receptor sequences and affinities of single cells in both peripheral blood and draining lymph nodes sampled via serial image-guided fine needle aspiration. Discussion This trial will compare the immune responses after primary, secondary, and tertiary DENV exposure in naturally infected humans living in non-endemic areas. By evaluating dengue vaccines in a new population and modeling the induction of cross-serotypic immunity, this work may inform vaccine evaluation and broaden potential target populations. Trial Registration NCT05691530 registered on January 20, 2023

Acute encephalopathy with elevated CSF inflammatory markers as the initial presentation of COVID-19

BACKGROUND: COVID-19 is caused by the severe acute respiratory syndrome virus SARS-CoV-2. It is widely recognized as a respiratory pathogen, but neurologic complications can be the presenting manifestation in a subset of infected patients. CASE PRESENTATION: We describe a 78-year old immunocompromised woman who presented with altered mental status after witnessed seizure-like activity at home. She was found to have SARS-CoV-2 infection and associated neuroinflammation. In this case, we undertake the first detailed analysis of cerebrospinal fluid (CSF) cytokines during COVID-19 infection and find a unique pattern of inflammation in CSF, but no evidence of viral neuroinvasion. CONCLUSION: Our findings suggest that neurologic symptoms such as encephalopathy and seizures may be the initial presentation of COVID-19. Central nervous system inflammation may associate with neurologic manifestations of disease