Guidelines for Diagnosis and Management of Infective Endocarditis in Adults: A WikiGuidelines Group Consensus Statement.

Importance: Practice guidelines often provide recommendations in which the strength of the recommendation is dissociated from the quality of the evidence. Objective: To create a clinical guideline for the diagnosis and management of adult bacterial infective endocarditis (IE) that addresses the gap between the evidence and recommendation strength. Evidence Review: This consensus statement and systematic review applied an approach previously established by the WikiGuidelines Group to construct collaborative clinical guidelines. In April 2022 a call to new and existing members was released electronically (social media and email) for the next WikiGuidelines topic, and subsequently, topics and questions related to the diagnosis and management of adult bacterial IE were crowdsourced and prioritized by vote. For each topic, PubMed literature searches were conducted including all years and languages. Evidence was reported according to the WikiGuidelines charter: clear recommendations were established only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were crafted discussing the risks and benefits of different approaches. Findings: A total of 51 members from 10 countries reviewed 587 articles and submitted information relevant to 4 sections: establishing the diagnosis of IE (9 questions); multidisciplinary IE teams (1 question); prophylaxis (2 questions); and treatment (5 questions). Of 17 unique questions, a clear recommendation could only be provided for 1 question: 3 randomized clinical trials have established that oral transitional therapy is at least as effective as intravenous (IV)-only therapy for the treatment of IE. Clinical reviews were generated for the remaining questions. Conclusions and Relevance: In this consensus statement that applied the WikiGuideline method for clinical guideline development, oral transitional therapy was at least as effective as IV-only therapy for the treatment of IE. Several randomized clinical trials are underway to inform other areas of practice, and further research is needed.

Use of Baricitinib in Combination With Remdesivir and Steroid in COVID-19 Treatment: A Multicenter Retrospective Study.

Introduction Hospitalized patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can develop severe complications. Baricitinib, a Janus kinase (JAK) JAK1/JAK2 inhibitor used to treat rheumatoid arthritis, has been proposed to prevent intracellular uptake of SARS-CoV-2 by targeting the angiotensin-converting enzyme 2 (ACE2) receptor, suppressing cytokine storm. We evaluated the effects of baricitinib on coronavirus disease 2019 (COVID-19) patient survival. Methods We conducted a retrospective study of 100 COVID-19 patients hospitalized in Southern California, United States, throughout September 2021. Univariate analysis of study variables was conducted with bivariate analysis of their relationships using chi-square and t-test with p-value <0.05 considered significant. Kaplan-Meier survival analysis was performed to compare outcomes of COVID-19 patients treated with baricitinib and those that were not. Results Our study included a patient population with a mean age of 62 years. Twenty-four percent of our patients were admitted to the intensive care unit (ICU), 16% were placed on mechanical ventilation, and 27% were expired. Patients receiving baricitinib were more likely to be admitted to the ICU and receive concomitant remdesivir therapy. Use of baricitinib increased median survival (p = 0.045). Conclusion Baricitinib administered with remdesivir and dexamethasone was shown to increase the survival of hospitalized patients with COVID-19. More studies are required to evaluate the benefits of conjunctive therapy with baricitinib, remdesivir, and dexamethasone. Though our study shows increased survival in patients receiving therapy, our study is limited by small sample size and there was not enough data to confirm whether baricitinib therapy decreased disease progression. Further studies are required.

Discoid Lupus and Human Immunodeficiency Virus: A Retrospective Chart Review to Determine the Prevalence and Progression of Co-occurrence of these Conditions at a Single Academic Center.

CONTEXT: Discoid lupus erythematosus (DLE) and human immunodeficiency virus (HIV) are both disorders of the immune system. The pathophysiology of these diseases varies greatly as DLE is characterized by an overactive immune system that attacks normal host cells, whereas HIV is characterized by an exogenous attack on the immune system that depletes it of key cell types. Although the reason is unknown, co-occurrence of DLE and HIV is rare. AIMS: The goal of this study is to determine the prevalence of co-occurrence of DLE and HIV and to determine whether patients with both DLE and HIV share any clinical feature. SUBJECTS AND METHODS: The medical records of all patients seen within a single academic health center over a 20-year period were reviewed to determine the prevalence of cutaneous lupus, HIV, and co-occurrence of these conditions. The charts of patients diagnosed with both conditions were further reviewed to determine similarities between them. RESULTS: Of the 10,719 patients diagnosed with HIV and 182 patients diagnosed with cutaneous lupus, only 2 patients were diagnosed with both conditions. Both of these patients were diagnosed with DLE several years after being diagnosed with HIV. They had an undetectable HIV viral load, normal CD4 T-cell counts, and were on antiretroviral therapy when diagnosed with DLE. CONCLUSION: These results confirm that co-occurrence of DLE and HIV is rare. Although our study population was small, findings from these patients suggest that in HIV-positive patients, DLE manifestations occur when their HIV disease activity is minimal.

Late-onset bexarotene-induced CD4 lymphopenia in a cutaneous T-cell lymphoma patient.

Various infections, autoimmune diseases, medications, and total-body irradiation are known factors associated with CD4 lymphopenia, defined as a CD4 T-cell count below 300 cells/mL or less than 20% of total lymphocytes. We report a rare case of a patient with cutaneous T-cell lymphoma (CTCL) who developed profound CD4 lymphopenia in the setting of long-term bexarotene therapy. Bexarotene is a third-generation retinoid that inhibits epithelial cell proliferation and is approved for treatment of advanced CTCL (stages IIB-IVB) in adult patients who have failed at least 1 prior systemic therapy. This case illustrates the importance of surveillance for CD4 leukopenia in patients on long-term bexarotene therapy with routine complete blood cell counts (CBC) and T-cell counts as well as consideration of rotating patients off bexarotene therapy even in those who derive continuous benefit.

Histiocytoid giant cellulitis-like Sweet's syndrome: case report and review of the literature.

BACKGROUND: Histiocytoid Sweet syndrome is an uncommon variant in which the dermal infiltrate is composed of mononuclear cells with a histiocytic appearance that represent immature myeloid cells. Giant cellulitis-like Sweet syndrome is a recently described variant characterized by relapsing widespread giant lesions. PURPOSE: We report a unique patient with histiocytoid giant cellulitis-like Sweet syndrome and review the current literature on histiocytoid Sweet syndrome and giant cellulitis-like Sweet syndrome. MATERIAL AND METHODS: We reviewed PubMed for the following terms and have reviewed the literature: histiocytoid, giant cellulitis-like, and Sweet syndrome. RESULTS: Six individuals, including our patient, have been reported with giant cellulitis-like Sweet syndrome; four had obesity, two had a hematologic malignancy, and one had breast cancer. Histiocytoid Sweet syndrome has been reported in association with autoimmune diseases, infection or inflammation, inflammatory bowel disease, malignancies, medications, and other conditions. CONCLUSIONS: Histiocytoid Sweet syndrome is a rare variant of Sweet syndrome, often associated with malignancy. Giant cellulitis-like Sweet syndrome has been reported in six individuals; four of the patients were obese and three of the patients had an associated cancer. Our patient had histiocytoid giant cellulitis-like Sweet syndrome-associated myelodysplastic syndrome/myeloproliferative disorder. The diagnosis of histiocytoid Sweet syndrome or giant cellulitis-like Sweet syndrome should prompt the clinician to consider additional evaluation for a Sweet syndrome-associated malignancy.

Eccrine chromhidrosis secondary to hyperbilirubinemia.

BACKGROUND: Eccrine chromhidrosis, or colored eccrine sweating, may be caused by contamination of sweat by dyes, pigmentation from microorganisms, or more rarely, hyperbilirubinemia. Pigment usually affects the palms and soles, where abundant sweat glands are found.Purpose, Material and Methods: We report a unique case of eccrine chromhidrosis in the setting of hyperbilirubinemia and review the current literature available on PubMed of previously reported cases. RESULTS: Six patients with chromhidrosis have been previously reported in the setting of significant hyperbilirubinemia, in association with fever and thickened stratum corneum. CONCLUSIONS: Eccrine chromhidrosis secondary to hyperbilirubinemia is very rare, but can be diagnosed on the basis of classic clinical findings, dermoscopic examination, and negative tissue cultures.

Hypoxia potentiates microRNA-mediated gene silencing through posttranslational modification of Argonaute2.

Hypoxia contributes to the pathogenesis of various human diseases, including pulmonary artery hypertension (PAH), stroke, myocardial or cerebral infarction, and cancer. For example, acute hypoxia causes selective pulmonary artery (PA) constriction and elevation of pulmonary artery pressure. Chronic hypoxia induces structural and functional changes to the pulmonary vasculature, which resembles the phenotype of human PAH and is commonly used as an animal model of this disease. The mechanisms that lead to hypoxia-induced phenotypic changes have not been fully elucidated. Here, we show that hypoxia increases type I collagen prolyl-4-hydroxylase [C-P4H(I)], which leads to prolyl-hydroxylation and accumulation of Argonaute2 (Ago2), a critical component of the RNA-induced silencing complex (RISC). Hydroxylation of Ago2 is required for the association of Ago2 with heat shock protein 90 (Hsp90), which is necessary for the loading of microRNAs (miRNAs) into the RISC, and translocation to stress granules (SGs). We demonstrate that hydroxylation of Ago2 increases the level of miRNAs and increases the endonuclease activity of Ago2. In summary, this study identifies hypoxia as a mediator of the miRNA-dependent gene silencing pathway through posttranslational modification of Ago2, which might be responsible for cell survival or pathological responses under low oxygen stress.

Functional adult myocardium in the absence of Na+-Ca2+ exchange: cardiac-specific knockout of NCX1.

The excitation-contraction coupling cycle in cardiac muscle is initiated by an influx of Ca2+ through voltage-dependent Ca2+ channels. Ca2+ influx induces a release of Ca2+ from the sarcoplasmic reticulum and myocyte contraction. To maintain Ca2+ homeostasis, Ca2+ entry is balanced by efflux mediated by the sarcolemmal Na+-Ca2+ exchanger. In the absence of Na+-Ca2+ exchange, it would be expected that cardiac myocytes would overload with Ca2+. Using Cre/loxP technology, we generated mice with a cardiac-specific knockout of the Na+-Ca2+ exchanger, NCX1. The exchanger is completely ablated in 80% to 90% of the cardiomyocytes as determined by immunoblot, immunofluorescence, and exchange function. Surprisingly, the NCX1 knockout mice live to adulthood with only modestly reduced cardiac function as assessed by echocardiography. At 7.5 weeks of age, measures of contractility are decreased by 20% to 30%. We detect no adaptation of the myocardium to the absence of the Na+-Ca2+ exchanger as measured by both immunoblots and microarray analysis. Ca2+ transients of isolated myocytes from knockout mice display normal magnitudes and relaxation kinetics and normal responses to isoproterenol. Under voltage clamp conditions, the current through L-type Ca2+ channels is reduced by 50%, although the number of channels is unchanged. An abbreviated action potential may further reduce Ca2+ influx. Rather than upregulate other Ca2+ efflux mechanisms, the myocardium appears to functionally adapt to the absence of the Na+-Ca2+ exchanger by limiting Ca2+ influx. The magnitude of Ca2+ transients appears to be maintained by an increased gain of sarcoplasmic reticular Ca2+ release. The myocardium of the NCX1 knockout mice undergoes a remarkable adaptation to maintain near normal cardiac function.