US201 Study: A Phase 2, Randomized Proof-of-Concept Trial of Favipiravir for the Treatment of COVID-19.

BACKGROUND: Favipiravir is used to treat influenza, and studies demonstrate that it has antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We performed a randomized, open-label, multicenter, phase 2 proof-of-concept trial of favipiravir in hospitalized adult patients with polymerase chain reaction (PCR)-positive coronavirus disease 2019 (COVID-19). Patients were randomized to standard of care (SOC) or favipiravir treatment (1800mg per os twice a day [b.i.d.] on day 1, followed by 1000mg b.i.d. for 13 days). The primary end point was time to viral clearance on day 29. RESULTS: Fifty patients were enrolled and stratified by disease severity (critical disease, severe disease, or mild to moderate disease). Nineteen patients were censored from the event of viral clearance based on being SARS-CoV-2 PCR-negative at the study outset, being PCR-positive at day 29, or because of loss to follow-up. Data from the 31 remaining patients who achieved viral clearance show enhanced viral clearance in the favipiravir group compared with the SOC group by day 29, with 72% of the favipiravir group and 52% of the SOC group being evaluable for viral clearance through day 29. The median time to viral clearance was 16.0 days (90% CI, 12.0 to 29.0) in the favipiravir group and 30.0 days (90% CI, 12.0 to 31.0) in the SOC group. A post hoc analysis revealed an effect in the subgroup of patients who were neutralizing antibody-negative at randomization. Treatment-emergent adverse events were equally distributed between the groups. CONCLUSIONS: We demonstrate that favipiravir can be safely administered to hospitalized adults with COVID-19 and believe that further studies are warranted. CLINICALTRIALSGOV REGISTRATION: NCT04358549.

An Innovation of Postsurgical Nasal Retainer in a Unilateral Cleft Lip and Palate Patient.

ABSTRACT: Postoperative nasal asymmetry is a notable problem following primary cleft lip repair and cleft rhinoplasty in patients with unilateral cleft lip and palate. Postsurgical nasal retainer could play an essential role in maintaining the corrected position of the nose during the healing process. However, the manufactured retainers are usually not affordable, nor individualized. The authors report the efficacy of our custom-made postoperative nasal retainer, made from an oxygen nasal cannula, acrylic resin, and orthodontic wire made of stainless steel, in a patient with complete unilateral cleft lip and palate.

Colitis as a Sole Presentation of SARS-CoV-2 Infection: Case Report.

On March 11, 2020, COVID-19 was declared as a pandemic by World Health Organization. Criteria for identifying persons under investigation for SARS-CoV-2 infection by Centers for Disease Control and Prevention remain focusing on fever and respiratory symptoms. We report a case of COVID-19 patient who presented with colitis alone.

The clinical significance of neutrophilic pleocytosis in cerebrospinal fluid in patients with viral central nervous system infections.

BACKGROUND: Viral central nervous system (CNS) infections are typically characterized by a cerebrospinal fluid (CSF) lymphocytic pleocytosis. A CSF neutrophilic pleocytosis presentation has been described, but its prognostic and clinical significance is unknown. The objectives of this study were to (1) compare the clinical and laboratory characteristics of viral CNS infections with a CSF neutrophilic pleocytosis to those with a lymphocytic pleocytosis, and (2) evaluate factors associated with an adverse clinical outcome. METHODS: A retrospective study of patients with confirmed viral CNS infections was conducted. The patients were divided into those with CSF neutrophilic pleocytosis and those with CSF lymphocytic pleocytosis. Clinical findings and outcomes were compared between the two groups. RESULTS: Of the 182 patients included in the study, 45 (24.7%) had CSF neutrophilic pleocytosis. Enterovirus infections were the cause of 64% of neutrophil-predominant CSF and 33% of lymphocyte-predominant CSF (p<0.001), while herpes infections were the cause of 46% of lymphocytic pleocytosis and 20% of neutrophilic pleocytosis (p=0.003). Moreover, neutrophilic pleocytosis was seen more commonly in younger patients (p=0.001), patients with respiratory symptoms (p=0.04), and patients with higher CSF white cell counts (p=0.004). Twenty-nine patients had an adverse clinical outcome (15.9%); the only predictor independently associated with an adverse clinical outcome on multivariable logistic regression analysis was an encephalitis presentation (p=0.01). CONCLUSIONS: The results of a study exploring the association between CSF neutrophilic pleocytosis and clinical and prognostic significance are presented here. This study suggests that CSF neutrophilic pleocytosis is not associated with higher adverse clinical outcomes.

Toscana meningoencephalitis: a comparison to other viral central nervous system infections.

BACKGROUND: Toscana virus (TOSV) is an emerging pathogen causing central nervous system (CNS) infection in Mediterranean countries, mostly during summer season. OBJECTIVES: To compare the clinical and laboratory characteristics of Toscana CNS infections to the most common viral pathogens seen in the United States. STUDY DESIGN: We performed a case series of patients with 41 TOSV infection and compared the clinical characteristics, laboratory findings, imaging results and clinical outcomes to the most commonly recognized viral causes of meningoencephalitis in the US [enterovirus (n=60), herpes simplex virus (n=48), and West Nile virus (n=30)] from our multi-center study of patients with aseptic meningoencephalitis syndromes in the Greater Houston area. RESULTS: TOSV infection occurs in different age groups compared to enterovirus, HSV, and WNV. All infections most frequently occur during summer-fall except HSV which distributes throughout the year. All patients with TOSV had history of travel to endemic areas. There are differences in clinical presentation and CSF findings comparing TOSV and enterovirus, HSV, and WNV infection. There are no significant differences in outcomes of each infection except WNV meningoencephalitis which had a poorer outcome compared to TOSV infection. CONCLUSIONS: TOSV is an emerging pathogen that should be considered in the differential diagnosis of patients with CNS infections and a recent travel history to endemic areas.

(1,3)-ß-D-glucan as a prognostic marker of treatment response in invasive candidiasis.

BACKGROUND: (1,3)-ß-D-glucan (BG) is a biomarker for invasive candidiasis (IC). The usefulness of BG level as a prognostic marker of treatment outcome is not well characterized. METHODS: Two hundred fifty-seven patients with proven IC were enrolled in an anidulafungin study. Clinical and microbiological responses at the end of therapy were evaluated. Serial serum BG was measured. Correlation of initial and final BG levels with overall outcome was assessed in each patient. RESULTS: Two hundred three patients had at least 2 BG levels and outcomes assessed. The majority of IC was caused by non-Candida albicans (53%) and found in the blood (84%). Overall, treatment success was 85%. In successfully treated patients, the mean ± SD initial and final BG were 573 ± 681 pg/mL and 499 ± 635 pg/mL (P = .03), respectively; while in treatment-failure patients, the levels were 1224 ± 1585 pg/mL and 1293 ± 1283 pg/mL (P = .29), respectively. A negative slope in BG levels correlated with a successful treatment outcome with a positive predictive value (PPV) of 90%, and a positive slope in BG levels correlated with treatment failure with a negative predictive value (NPV) of 90%. The cutoff value for initial BG <416 pg/mL has potential to predict treatment success with a PPV of 89%. CONCLUSIONS: A decrease in BG levels during therapy is associated with treatment success. An initial BG of <416 pg/mL has potential to predict successful treatment outcomes. Baseline and consecutive serum BG measurements may be useful as prognostic markers of treatment outcome in patients with IC receiving primarily echinocandin therapy.

Correlation of clinical outcomes with ß-glucan levels in patients with invasive candidiasis.

The correlation of ß-glucan (BG) levels with clinical outcomes in invasive candidiasis (IC) remains unknown. Patients with proven IC were followed prospectively from diagnosis to outcome with twice-weekly serum BG sampling. Correlation of BG with clinical outcome was assessed in each patient. BG levels tend to decrease in successfully treated patients and increase in treatment failures. BG levels may be useful as surrogates for outcome evaluation of IC.

Native valve endocarditis caused by Corynebacterium striatum with heterogeneous high-level daptomycin resistance: collateral damage from daptomycin therapy?

We describe a patient who developed Corynebacterium striatum native valve endocarditis after receiving two 6-week courses of daptomycin for the treatment of methicillin-resistant Staphylococcus aureus bacteremia and osteomyelitis. The organism exhibited in vitro heteroresistance to daptomycin, with two subpopulations showing daptomycin susceptibility (MIC of ≤ 0.094 µg/ml) and high-level resistance to daptomycin (MIC of ≥ 256 µg/ml). The selection of daptomycin-resistant Gram-positive skin flora with the potential of causing invasive disease may be a concern during prolonged courses of daptomycin.

Multicentric hepatic EBV-associated smooth muscle tumors in an AIDS patient: a case report, investigation of mTOR activation and review of the literature.

Epstein-Barr virus (EBV) - associated smooth muscle tumors (EBV-SMT) are a rare, recently recognized distinct group of mesenchymal tumors that develop exclusively in patients with immunosuppression. It is believed that tumorigenesis is, at least in part, through the activation of the Akt/mammalian target of rapamycin (mTOR) signal pathway. We describe the clinicopathologic and immunohistochemical features of a multifocal hepatic EBV-SMT in a 34-year-old acquired immunodeficiency syndrome (AIDS) patient and investigate the activation status of the mTOR signal pathway in this tumor. In addition, we provide a review of the literature on the clinicopathologic findings of hepatic EBV-SMT in adult AIDS patients, and discuss their biologies and possible therapeutic strategies.

FlindersTechnology Associates (FTA) filter paper-based DNA extraction with polymerase chain reaction (PCR) for detection of Pneumocystis jirovecii from respiratory specimens of immunocompromised patients.

We evaluated the diagnostic value of Flinders Technology Associates (FTA) filter paper together with polymerase chain reaction (PCR) for detection of Pneumocystis jirovecii (carinii) from induced sputum (IS) and bronchoalveolar lavage fluid (BALF) samples. The study involved 162 patients with clinical diagnosis of pneumocystis pneumonia (PcP) of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) patients and other immunocompromised patients. P. jirovecii cysts or trophozoites were detected in IS and BALF by cytological method. The mitochondrial 5S ribosomal ribonucleic acid (rRNA) gene of P. jirovecii was amplified from these samples by using FTA filters together with a one-step PCR method (FTA-PCR). With the FTA-PCR method, the sensitivity and specificity of the test compared to microscopic examination were 67% and 90% for IS, while they were 67% and 91% for BALF, respectively. The sensitivity and specificity of the FTA-PCR test was also comparable to PCR with the conventional deoxyribonucleic acid (DNA) extraction method. We concluded that FTA-PCR is useful to detect P. jirovecii in noninvasive IS.

Pneumocystis jiroveci in HIV/AIDS patients: detection by FTA filter paper together with PCR in noninvasive induced sputum specimens.

OBJECTIVES: To detect P. jiroveci (previously named P. carinii) by PCR using FTA filter paper to extract the DNA, from noninvasive induced sputum samples of HIV/AIDS patients. MATERIAL AND METHOD: Fifty two HIV/AIDS patients suspected of Pneumocystis jiroveci pneumonia (PJP) in King Chulalongkorn Memorial Hospital were recruited. Both cytological method and PCR with FTA filter paper technique were performed to detect P jiroveci from each specimen. RESULTS: The detectability rate of P. jiroveci infection was 21%. The PCR with FTA filter paper method was 4 folds much more sensitive than Giemsa staining technique. P. jiroveci was detected in 18% of the HIV/AIDS patients in spite of receiving standard PJP prophylaxis. CONCLUSION: Detection of P. jiroveci by using FTA filter paper together with PCR in induced sputum samples could detect more cases of P. jiroveci infection than by using cytological method. DNA extraction using the FTA filter paper was more rapid and convenient than other extraction methods. The causes of failure of PJP prophylaxis should be evaluated.