Impact of fluvoxamine on outpatient treatment of COVID-19 in Honduras in a prospective observational real-world study.

Background: The COVID-19 pandemic has impacted millions of lives globally. While COVID-19 did not discriminate against developed or developing nations, it has been a significant challenge for third world countries like Honduras to have widespread availability of advanced therapies. The concept of early treatment was almost unheard of when early outpatient treatments utilizing repurposed drugs in Latin American countries began showing promising results. One such drug is fluvoxamine, which has shown tremendous potential in two major studies. As a direct result, fluvoxamine was added to the standard of care in a major medical center outpatient COVID-19 clinic. Methods: This is a prospective observational study performed at the Hospital Centro Médico Sampedrano (CEMESA) in San Pedro Sula, Cortes, Honduras in the COVID-19 outpatient clinic. All patients were at least 15 years of age who had presented with mild or moderate signs and symptoms of COVID-19, and who also had a documented positive SARS-CoV-2 antigen or Reverse Transcription Polymerase Chain Reaction (RT-PCR) were included in the study. These patients then were all prescribed fluvoxamine. The cohort of patients who decided to take fluvoxamine were compared for primary endpoints of mortality and hospitalization risk to the cohort who did not take fluvoxamine. Patients were then monitored for 30 days with the first follow up at 7 days and the second follow up at 10-14 days of symptom onset. Categorical variables were compared by Pearson Chi-square test. The Relative risk was calculated using regression models. Continuous variables were compared by t-test and Wilcoxon rank-sum tests. Results: Out of total 657 COVID-19 cases, 594 patients took fluvoxamine and 63 did not take fluvoxamine. A total of five patients (0.76 percent) died, with only one death occurring in the fluvoxamine group. Patients who received fluvoxamine had a significantly lower relative risk of mortality (RR 0.06, p 0.011, 95% CI 0.007-0.516). There was a lower relative risk of hospitalization in the patients who in the fluvoxamine group. (-10 vs. 30 hospitalizations, RR 0.49, p = 0.035, 95% CI 0.26-0.95). There was 73 percent reduction in relative risk of requiring oxygen in the fluvoxamine group (RR 0.27, p < 0.001, 95% CI 0.14-0.54 Mean lymphocytes count on the first follow-up visit was significantly higher in the fluvoxamine group (1.72 vs. 1.38, Δ 0.33, p 0.007, CI 0.09-0.58). Conclusion: The results of our study suggest that fluvoxamine lowers the relative risk of death, hospitalization, and oxygen requirement in COVID 19 patients.

A New Potential Strategy for Acute Non-Alcoholic Steatohepatitis (NASH).

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States, and 25% of patients with NAFLD progress to non-alcoholic steatohepatitis (NASH). NAFLD is predicted to be the most common indication for liver transplantation by 2030. Despite associated high morbidity and mortality, there is currently no approved therapy for NASH. PCSK9 inhibitors are approved for reducing LDL in patients who are statin-intolerant or need further LDL reduction. Increased LDL levels are independently associated with an elevated risk of NAFLD. CASE REPORT We present a case of a 39-year-old woman with acute NASH with familial hypercholesterolemia that was refractory to lifestyle modifications and HMG-CoA reductase inhibitors. An episode of rhabdomyolysis warranted a search for alternatives to statin therapy. Results of a liver biopsy showed microvesicular and macrovesicular steatosis with ballooning degeneration, indicating acute NASH. She was started on PCSK9 inhibitors as salvage therapy. Three monthly doses resulted in a more than an 80% reduction in ALT and AST and a 48% reduction in LDL levels. A liver biopsy done 8 months after the first biopsy showed normalization of liver histology. CONCLUSIONS The use of PCSK9 inhibitors showed a dramatic response in this patient who failed conventional therapies, and the encouraging results seen in this case merit further research into the use of PCSK9 inhibitors as first-line therapy for the acute phase of NASH.

Upper extremity Histoplasma capsulatum treatment with isavuconazole.

Extrapulmonary Histoplasma capsulatum infections in the immunocompetent population are rare and pose a diagnostic challenge. Upper extremity histoplasmosis without a primary lung infection is uncommon. It is possible to acquire it by inadvertent trauma with direct inoculation. Our case describes an immunocompetent patient with progressive swelling with minimal pain in the wrist associated with a small puncture wound on the left dorsal forearm. The initial workup failed to identify a specific etiology. For the following six weeks, the patient experienced progressive worsening of symptoms, warranting a referral to an orthopedic hand surgeon. Left lower extremity magnetic resonance imaging (MRI) findings were non-specific. The surgeon performed a surgical exploration and debridement with the excision of hypertrophic tissue. Initial stains showed a granulomatous tissue but did not reveal an organism; however, a month later, mold was identified on the growth medium. The patient was initiated in isavuconazole empiric therapy. Four weeks later, a matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) confirmed the diagnosis as Histoplasma capsulatum. The patient had clinical remission with isavuconazole used as the United States Food and Drug Administration (FDA) off label use.

Improved economic and clinical outcomes with oritavancin versus a comparator group for treatment of acute bacterial skin and skin structure infections in a community hospital.

BACKGROUND: Oritavancin is a lipoglycopeptide antibiotic with in vitro bactericidal activity against gram-positive pathogens indicated for use in adults with acute bacterial skin and skin structure infections (ABSSSI). Its concentration-dependent activity and prolonged half-life provide a convenient single-dose alternative to multi-dose daily therapies for ABSSSI. This retrospective cohort study was conducted to quantify the clinical and economic advantages of using oritavancin compared to other antibiotic agents that have been historically effective for ABSSSI. METHODS: Seventy-nine patients received oritavancin who had failed previous outpatient antibiotic therapy (OPAT) for cellulitis or abscess and were subsequently readmitted to the hospital as an inpatient between 2016 and 2018. These patients were compared to a cohort of 28 patients receiving other antibiotics following OPAT failure and subsequent hospitalization for these two infection types. The primary clinical end point was average length of stay (aLOS) and secondary endpoints included readmission rates for the same indication at 30 and 90 days after discharge and the average hospital cost (aHC). RESULTS: A total of 107 patients were hospitalized for treatment of cellulitis or abscess. Demographic characteristics of both the oritavancin and comparator groups were similar except for the presence of diabetes. The primary clinical endpoint showed a non-significant decrease in aLOS between the oritavancin group versus comparator (2.12 days versus 2.59 days; p = 0.097). The secondary endpoints revealed lower readmission rates associated with oritavancin treatment at 30 and 90 days; the average hospital cost was 5.9% lower for patients that received oritavancin. CONCLUSION: The results of this study demonstrate that oritavancin provides not only a single-dose alternative to multi-day therapies for skin and skin structure infections, but also a clinical and economic advantage compared to other antibiotic agents.

A multi-mechanism approach reduces length of stay in the ICU for severe COVID-19 patients.

PURPOSE: COVID-19 pandemic has multifaceted presentations with rising evidence of immune-mediated mechanisms underplay. We sought to explore the outcomes of severe COVID-19 patients treated with a multi-mechanism approach (MMA) in addition to standard-of-care (SC) versus patients who only received SC treatment. MATERIALS AND METHODS: Data were collected retrospectively for patients admitted to the intensive care unit (ICU). This observational cohort study was performed at five institutions, 3 in the United States and 2 in Honduras. Patients were stratified for MMA vs. SC treatment during ICU stay. MMA treatment consists of widely available medications started immediately upon hospitalization. These interventions target immunomodulation, anticoagulation, viral suppression, and oxygenation. Primary outcomes included in-hospital mortality and length of stay (LOS) for the index hospitalization and were measured using logistic regression. RESULTS: Of 86 patients admitted, 65 (76%) who had severe COVID-19 were included in the study; 30 (46%) patients were in SC group, compared with 35 (54%) patients treated with MMA group. Twelve (40%) patients in the SC group died, compared with 5 (14%) in the MMA group (p-value = 0.01, Chi squared test). After adjustment for gender, age, treatment group, Q-SOFA score, the MMA group had a mean length of stay 8.15 days, when compared with SC group with 13.55 days. ICU length of stay was reduced by a mean of 5.4 days (adjusted for a mean age of 54 years, p-value 0.03) and up to 9 days (unadjusted for mean age), with no significant reduction in overall adjusted mortality rate, where the strongest predictor of mortality was the use of mechanical ventilation. CONCLUSION: The finding that MMA decreases the average ICU length of stay by 5.4 days and up to 9 days in older patients suggests that implementation of this treatment protocol could allow a healthcare system to manage 60% more COVID-19 patients with the same number of ICU beds.

Successful treatment of a prosthetic hip infection due to Enterococcus faecalis with sequential dosing of oritavancin and prosthesis preservation without prosthetic joint surgical manipulation.

A patient with a prosthetic joint infection (PJI) complicated with deep surgical site infection due to vancomycin-susceptible Enterococcus faecalis. The initial treatment consisted of 10 days with daptomycin plus ampicillin. The hip prosthesis was retained and salvaged with six outpatient sequential doses of oritavancin 1200 mg every seven days without intra-articular irrigation or other surgical interventions. The patient was ambulating independently without symptoms after ten months of the last treatment of oritavancin.

Rickettsia typhi central nervous system infection.

A 39 year-old male was residing along the south coast of Texas, the USA, presented with fever, myalgias, headaches, and weight loss for ten days. Symptoms and manifestations progressed to include nuchal rigidity, photophobia, hyponatremia, thrombocytopenia, and transaminitis despite the intravenous administration of ceftriaxone and azithromycin. A lumbar puncture performed in the Emergency Department yielded pleocytosis and glucose cerebrospinal fluid/serum ratio of 0.35, suggestive of meningoencephalitis. Conglomerate data raised the suspicion of meningitis secondary to a zoonotic acquired infection, which was later confirmed to be Rickettsia typhi. Doxycycline is the drug of choice for the suspected Rickettsia disease. After doxycycline administration, the patient improved and was discharged home asymptomatic.

Thymoma Causing Bilateral Upper Extremity Deep Vein Thrombosis.

A 38-year-old African American male presented with progressive pain, swelling, numbness, and warmth of the left upper extremity ten days before admission. A chest computerized tomography scan showed a large 8.3 cm × 6.1 cm x 9.9 cm anterior mediastinal mass with compression of the left brachiocephalic vein and superior vena cava. A venous doppler showed multiple occlusive venous thrombi in bilateral upper extremities, including the bilateral internal jugular and subclavian veins, as well as the left subclavian, axillary, cephalic, brachial and median cubital veins. Further laboratory workup came positive for acetylcholine receptor binding antibody suggesting myasthenia gravis, but the patient was asymptomatic for myasthenia gravis. A percutaneous core CT guided biopsy pathology resulted in a predominant T-cell population CD5 positive with few B cells; the immunophenotypic features suggested Type B2 thymoma. To the best of our knowledge, this case is the only reported thymoma presenting with bilateral deep vein thrombosis of the upper extremities. The deep vein thrombosis therapy was enoxaparin 1mg/kg subcutaneously every 12 hours and dexamethasone 4mg intravenously every 4 hours as an anti-inflammatory drug for thymoma related compression of the mediastinum. The patient was referred to a tertiary oncological medical center for a total thymectomy, chemotherapy, and adjuvant radiotherapy.

Rickettsia typhi infection presenting as severe ARDS.

Murine typhus, also known as endemic typhus, is a disease resulting from an infection caused by the gram-negative bacillus Rickettsia typhi. Murine typhus is identified worldwide, predominantly in tropical and subtropical geographic locations. Transmission occurs through direct inoculation by an arthropod vector, most commonly the rat flea, Xenopsylla cheopis. rickettsial infections are notorious for disseminated infections throughout the endothelial cells. The increase in permeability is an immediate consequence and has the potential of leading to non-cardiogenic pulmonary edema, otherwise known as acute respiratory distress syndrome (ARDS). Clinical manifestations are non-specific and initially mimic typical viral etiologies, obscuring early diagnosis. As a result, clinicians often do not include rickettsial infections in their differential diagnoses. Definitive diagnosis is based on clinical recognition, epidemiologic awareness, and serological testing. Here we present a confirmed case of murine typhus in a young non-immunocompromised patient who developed ARDS one week from the initial onset of symptoms.

Multi-aperture digital coherent combining for free-space optical communication receivers.

Space-to-ground optical communication systems can benefit from reducing the size, weight, and power profiles of space terminals. One way of reducing the required power-aperture product on a space platform is to implement effective, but costly, single-aperture ground terminals with large collection areas. In contrast, we present a ground terminal receiver architecture in which many small less-expensive apertures are efficiently combined to create a large effective aperture while maintaining excellent receiver sensitivity. This is accomplished via coherent detection behind each aperture followed by digitization. The digitized signals are then combined in a digital signal processing chain. Experimental results demonstrate lossless coherent combining of four lasercom signals, at power levels below 0.1 photons/bit/aperture.

781 Mbit/s photon-counting optical communications using a superconducting nanowire detector.

We demonstrate 1550 nm photon-counting optical communications with a NbN-nanowire superconducting single-photon detector. Source data are encoded with a rate-1/2 forward-error correcting code and transmitted by use of 32-ary pulse-position modulation at 5 and 10 GHz slot rates. Error-free performance is obtained with -0.5 detected photon per source bit at a source data rate of 781 Mbits/s. To the best of our knowledge, this is the highest reported data rate for a photon-counting receiver.