Community-Based Testing for SARS-CoV-2 - Chicago, Illinois, May-November 2020.

On May 13, 2020, Chicago established a free community-based testing (CBT) initiative for SARS-CoV-2, the virus that causes COVID-19, using reverse transcription-polymerase chain reaction (RT-PCR). The initiative focused on demographic groups and geographic areas that were underrepresented in testing by clinical providers and had experienced high COVID-19 incidence, including Hispanic persons and those who have been economically marginalized. To assess the CBT initiative, the Chicago Department of Public Health (CDPH) compared demographic characteristics, economic marginalization, and test positivity between persons tested at CBT sites and persons tested in all other testing settings in Chicago. During May 13-November 14, a total of 253,904 SARS-CoV-2 RT-PCR tests were conducted at CBT sites. Compared with those tested in all other testing settings in Chicago, persons tested at CBT sites were more likely to live in areas that are economically marginalized (38.6% versus 32.0%; p<0.001) and to be Hispanic (50.9% versus 20.7%; p<0.001). The cumulative percentage of positive test results at the CBT sites was higher than that at all other testing settings (11.1% versus 7.1%; p<0.001). These results demonstrate the ability of public health departments to establish community-based testing initiatives that reach communities with less access to testing in other settings and that experience disproportionately higher incidences of COVID-19.

Adrenal functional reserve in the full spectrum of chronic kidney disease.

BACKGROUND: Altered cortisol levels have been associated with an increase in mortality and a decrease in health-related quality of life in patients with chronic kidney disease (CKD); however, adrenal response to adrenocorticotropic hormone (ACTH) stimulation test has not been evaluated in patients with stage 3a to 5 CKD with and without renal replacement therapy (RRT). OBJECTIVE: To evaluate adrenal function in patients with CKD. MATERIALS AND METHODS: Adults with CKD underwent a low-dose cosyntropin stimulation test (1 µg synthetic ACTH), with serum cortisol levels being measured at 0, +30 and +60 minutes post-test. RESULTS: Sixty participants with stage 3, 4 and 5 CKD (with and without RRT) were included. None of the patients had adrenal insufficiency (AI). The correlation observed between cortisol concentration at baseline and 30 minutes and 1 hour after stimulation and glomerular filtration rate (GFR) was negative and statistically significant (r: -0.39 [p = 0.002], r: -0.363 [p = 0.004], r: -0.4 [p = 0.002], respectively). CONCLUSION: Since CKD early stages, cortisol levels increase as GFR decreases. Therefore, we conclude that systematic screening for AI is not necessary in CKD patients.

ANTECEDENTES: Niveles alterados de cortisol se han asociado a un incremento en la mortalidad y disminución en la calidad de vida en pacientes con enfermedad renal crónica (ERC), sin embargo, la respuesta adrenal a la prueba de estimulación con adrenocorticotropina (ACTH) no ha sido evaluada en pacientes con ERC etapas 3a a 5 con y sin terapia de reemplazo renal (TRR). OBJETIVO: Evaluar la función adrenal de pacientes con ERC. MATERIALES Y MÉTODOS: Adultos con ERC se sometieron a una prueba de estimulación con cosintropina a dosis baja (1 mg de ACTH sintética) y se midieron los niveles séricos de cortisol a los 0, +30 y +60 minutos postestimulación. RESULTADOS: 60 participantes con ERC en etapas 3, 4 y 5 (con y sin TRR) fueron incluidos. Ninguno de los pacientes presentó insuficiencia adrenal (IA). La correlación observada entre la concentración basal, a los 30 minutos y 1 hora de cortisol postestimulación y la tasa de filtrado glomerular (TFG) fue negativa y estadísticamente significativa (r: ­0.39 [p = 0.002], r: ­0.363 [p = 0.004], r: ­0.4 [p = 0.002], respectivamente). CONCLUSIÓN: Desde etapas tempranas de la ERC los niveles de cortisol se incrementan a medida que la TFG disminuye. Concluimos que no es necesario un tamizaje sistemático para detectar IA en pacientes con ERC.

Safety and efficacy of step-down to oral outpatient treatment versus inpatient antimicrobial treatment in pediatric cancer patients with febrile neutropenia: A noninferiority multicenter randomized clinical trial.

BACKGROUND: It has been suggested that low-risk febrile neutropenia (FN) episodes can be treated in a step-down manner in the outpatient setting. This recommendation has been limited to implementation in middle-income countries due to concerns about infrastructure and lack of trained personnel. We aimed to determine whether early step-down to oral antimicrobial outpatient treatment is not inferior in safety and efficacy to inpatient intravenous treatment in children with low-risk FN. PROCEDURE: A noninferiority randomized controlled clinical trial was conducted in three hospitals in Mexico City. Low-risk FN was identified in children younger than 18 years. After 48 to 72 hours of intravenous treatment, children were randomly allocated to receive outpatient oral treatment (experimental arm, cefixime) or to continue inpatient treatment (standard of care, cefepime). Daily monitoring was performed until neutropenia resolution. The presence of any unfavorable clinical outcome was the endpoint of interest. We performed a noninferiority test for comparison of proportions. RESULTS: We identified 1237 FN episodes; 117 cases were randomized: 60 to the outpatient group and 57 for continued inpatient treatment. Of the FN episodes, 100% in the outpatient group and 93% in the inpatient group had a favorable outcome (P < 0.001). The mean duration of antibiotics was 4.1 days (SD 2.5; 95% CI, 3.4-4.8 days) in the outpatient group and 4.4 days (SD 2.5; 95% CI, 3.7-5.0 days) in the inpatient group (P = 0.70). CONCLUSIONS: In our population, step-down oral outpatient treatment of low-risk FN was as safe and effective as inpatient intravenous treatment. Clinical Trials Identifier: NCT04000711.

Extremely Low-Frequency Magnetic Fields and the Risk of Childhood B-Lineage Acute Lymphoblastic Leukemia in a City With High Incidence of Leukemia and Elevated Exposure to ELF Magnetic Fields.

It is important to study the relationship between extremely low-frequency magnetic fields (ELF-MFs) and childhood leukemia, particularly in locations with a high incidence of this neoplasm in children and an elevated exposure to ELF-MF, such as Mexico City. The aim was to investigate the association between ELF-MF exposure and the risk of B-lineage acute lymphoblastic leukemia (B-ALL). A case-control study was conducted in Mexico City during the period from 2010 to 2011. Residential 24-h ELF-MF measurements were obtained for 290 incident B-ALL patients and 407 controls, aged less than 16 years. Controls were frequency-matched by sex, age (±18 months), and health institution. The adjusted odds ratios (aOR) and 95% confidence intervals (CIs) were calculated. ELF-MF exposure at <0.2 µT was used to define the reference group. ELF-MF exposure at ≥0.3 µT was observed in 11.3% of the controls. Different ELF-MF intensity cutoff values were used to define the highest exposure category; the highest exposure category for each cutoff value was associated with an increased risk of B-ALL compared with the corresponding lower exposure categories. The aORs were as follows: ≥0.2 µT = 1.26 (95% CI: 0.84-1.89); ≥0.3 µT = 1.53 (95% CI: 0.95-2.48); ≥0.4 µT = 1.87 (95% CI: 1.04-3.35); ≥0.5 µT = 1.80 (95% CI 0.95-3.44); ≥0.6 µT = 2.32 (95% CI: 1.10-4.93). ELF-MF exposure as a continuous variable (per 0.2 µT intervals) was associated with B-ALL risk (aOR = 1.06; 95% CI: 1.01-1.12). In the present study, the proportion of children exposed to ≥0.3 µT is among the highest reported worldwide. Additionally, an ELF-MF exposure ≥0.4 µT may be associated with the risk of B-ALL. Bioelectromagnetics. © 2020 Bioelectromagnetics Society.

Ready Access to Molecular Rotors Based on Boron Dipyrromethene Dyes-Coumarin Dyads Featuring Broadband Absorption.

Herein we report on a straightforward access method for boron dipyrromethene dyes (BODIPYs)-coumarin hybrids linked through their respective 8- and 6- positions, with wide functionalization of the coumarin fragment, using salicylaldehyde as a versatile building block. The computationally-assisted photophysical study unveils broadband absorption upon proper functionalization of the coumarin, as well as the key role of the conformational freedom of the coumarin appended at the meso position of the BODIPY. Such free motion almost suppresses the fluorescence signal, but enables us to apply these dyads as molecular rotors to monitor the surrounding microviscosity.

Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial.

BACKGROUND: Dulaglutide and liraglutide, both glucagon-like peptide-1 (GLP-1) receptor agonists, improve glycaemic control and reduce weight in patients with type 2 diabetes. In a head-to-head trial, we compared the safety and efficacy of once-weekly dulaglutide with that of once-daily liraglutide in metformin-treated patients with uncontrolled type 2 diabetes. METHODS: We did a phase 3, randomised, open-label, parallel-group study at 62 sites in nine countries between June 20, 2012, and Nov 25, 2013. Patients with inadequately controlled type 2 diabetes receiving metformin (≥1500 mg/day), aged 18 years or older, with glycated haemoglobin (HbA1c) 7·0% or greater (≥53 mmol/mol) and 10·0% or lower (≤86 mmol/mol), and body-mass index 45 kg/m(2) or lower were randomly assigned to receive once-weekly dulaglutide (1·5 mg) or once-daily liraglutide (1·8 mg). Randomisation was done according to a computer-generated random sequence with an interactive voice response system. Participants and investigators were not masked to treatment allocation. The primary outcome was non-inferiority (margin 0·4%) of dulaglutide compared with liraglutide for change in HbA1c (least-squares mean change from baseline) at 26 weeks. Safety data were collected for a further 4 weeks' follow-up. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01624259. FINDINGS: We randomly assigned 599 patients to receive once-weekly dulaglutide (299 patients) or once-daily liraglutide (300 patients). 269 participants in each group completed treatment at week 26. Least-squares mean reduction in HbA1c was -1·42% (SE 0·05) in the dulaglutide group and -1·36% (0·05) in the liraglutide group. Mean treatment difference in HbA1c was -0·06% (95% CI -0·19 to 0·07, pnon-inferiority<0·0001) between the two groups. The most common gastrointestinal adverse events were nausea (61 [20%] in dulaglutide group vs 54 [18%] in liraglutide group), diarrhoea (36 [12%] vs 36 [12%]), dyspepsia (24 [8%] vs 18 [6%]), and vomiting (21 [7%] vs 25 [8%]), with similar rates of study or study drug discontinuation because of adverse events between the two groups (18 [6%] in each group). The hypoglycaemia rate was 0·34 (SE 1·44) and 0·52 (3·01) events per patient per year, respectively, and no severe hypoglycaemia was reported. INTERPRETATION: Once-weekly dulaglutide is non-inferior to once-daily liraglutide for least-squares mean reduction in HbA1c, with a similar safety and tolerability profile. FUNDING: Eli Lilly and Company.

Genotyping, extracellular compounds, and antifungal susceptibility testing of Trichosporon asahii isolated from Mexican patients.

Trichosporon asahii is considered an opportunistic pathogen responsible for severe infections, mainly in immunocompromised patients. The aims of this study were to investigate the prevalent genotypes among 39 clinical isolates of this microorganism by sequencing the IGS1 region and to determine the in vitro production of DNAse, hemolysin, aspartyl proteinase, phospholipase and esterase, as well as the susceptibilities of the isolates to amphotericin B, anidulafungin, micafungin, caspofungin, voriconazole, posaconazole, fluconazole and 5-flucytosine. Our findings showed that genotype I was the most prevalent comprising 69.23% of the isolates. We confirmed the production of esterase for all our isolates, and report the production of DNAse and aspartyl proteinase in 84.62% and 23% of the isolates, respectively. Only one isolate of T. asahii produced hemolysin. None of the isolates showed phospholipase activity. Fifty-three percent of the T. asahii strains exhibited amphotericin B MICs ≥ 2 µg/ml. The three echinocandins evaluated yielded high MICs (≥2 µg/ml) in all isolates. Thirty-five percent of the isolates had high MICs for 5-flucytosine (≥32 µg/ml), and 97% of the isolates were susceptible to the evaluated triazoles.

Candida parapsilosis complex induces local inflammatory cytokines in immunocompetent mice.

Despite the increasing incidence of the Candida parapsilosis complex in the clinical setting and high mortality rates associated with disseminated infection, the host-fungus interactions regarding Candida parapsilosis sensu stricto and the closely related species C. orthopsilosis and C. metapsilosis remains blurred. In this study, we analyzed inflammatory cytokines levels and histopathology as well as fungal burden in spleen, kidney and lung of mice infected with six strains of the "psilosis" group with different enzymatic profiles. Strong interleukin 22 (IL-22) and tumor necrosis factor α (TNF-α) responses were observed in analyzed organs from infected mice (P < .0001) regardless of the species and enzymatic profile. TNF-α and IL-22 levels were related with spleen inflammation and fungal load. Fungal cells were detected only in spleen and kidney of infected mice, especially by day 2 post-challenge. The kidney showed glomerular retraction and partial destruction of renal tubules. Our data suggest that a strong inflammatory response, mainly of IL-22 and TNF-α, could be involved in Candida parapsilosis complex infection control.

Therapeutic efficacy of posaconazole in a murine model of disseminated trichosporonosis.

OBJECTIVES: To study the effect of the initiation time of posaconazole treatment from 1 to 3 days after systemic infection by Trichosporon asahii in mice. METHODS: BALB/c mice, 4-5 weeks old, were intravenously infected with 1 × 10(7) cfu/mouse of T. asahii. The onset of treatment varied from 1 to 3 days after infection. Orally administered posaconazole at 0.5, 1, 2, 5 or 10 mg/kg body weight/day was compared with orally administered fluconazole (at 10 mg/kg/day) and intraperitoneally administered amphotericin B (at 1 mg/kg) on alternating days. Livers, kidneys and spleens of mice that died or survived to day 25 were removed to determine fungal tissue burdens. RESULTS: When therapy began 1 day after challenge, posaconazole at ≥ 1 mg/kg significantly prolonged survival of mice compared with that of the control group and considerably reduced the fungal tissue burden over the control group. On the other hand, when treatment was started 3 days after infection, regimens of 5 and 10 mg/kg posaconazole significantly prolonged mice survival over that of the control group and appreciably diminished the fungal load compared with untreated mice. In this model, as the severity of trichosporonosis increased, higher doses of posaconazole were required to achieve equivalent activity levels. Fluconazole and amphotericin B were ineffective in preventing mice death and in significantly reducing fungal tissue burden. Posaconazole displayed potent in vivo activity against the strain tested. CONCLUSIONS: Posaconazole may be a suitable option in the treatment of disseminated T. asahii infection.

Evaluation of in vivo pathogenicity of Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis with different enzymatic profiles in a murine model of disseminated candidiasis.

Six isolates of the Candida parapsilosis complex with different enzymatic profiles were used to induce systemic infection in immunocompetent BALB/c mice. Fungal tissue burden was determined on days 2, 5, 10, and 15 post challenge. The highest fungal load irrespective of post-infection day was detected in the kidney, followed by the spleen, lung, and liver, with a tendency for the fungal burden to decrease by day 15 in all groups. Significant differences among the strains were not detected, suggesting that the three species of the "psilosis" group possess a similar pathogenic potential in disseminated candidiasis regardless of their enzymatic profiles.

HOMA-IR as a predictor of Health Outcomes in Patients with Metabolic Risk Factors: A Systematic Review and Meta-analysis.

INTRODUCTION: There exists clinical interest in the following question: Is there an association between HOMA-IR and the risk of developing metabolic diseases? AIMS: Assessing the association between high values of HOMA-IR with the incidence of T2DM, MACE, essential hypertension, dyslipidemia, NASH, and cancer in healthy participants and participants with a component of metabolic syndrome. METHODS: Databases were searched by an experienced librarian to find eligible studies. Observational cohort studies enrolling healthy adults and adults with metabolic syndrome components that evaluated HOMA as a marker of IR were considered for inclusion. Eligibility assessment, data extraction and risk of bias assessment were performed independently and in duplicate. Baseline characteristics of patients, cutoff values of HOMA-IR to predict metabolic events were extracted independently and in duplicate. RESULTS: 38 studies (215,878 participants) proved eligible. A higher HOMA-IR value had a significant effect on the risk of developing T2DM (HR 1.87; CI 1.40-2.49), presenting non-fatal MACE (HR 1.46; CI 1.08-1.97) and hypertension (HR 1.35; CI 1.15-1.59). No association was found regarding cancer mortality and fatal MACE with higher HOMA-IR values, there was not enough information to carry out a meta-analysis to establish an association between higher values of HOMA with cancer incidence, dyslipidemia, and NASH. CONCLUSIONS: High values of HOMA were associated with an increased risk of diabetes, hypertension, and non-fatal MACE; yet, not for cardiovascular or cancer mortality. More research is needed to determine the value of the HOMA index in metabolic and cardiovascular outcomes. PROSPERO REGISTRATION NUMBER: CRD42020187645.

Intensive vs. conventional blood pressure goals in older patients with type 2 diabetes: a systematic review and meta-analysis.

PURPOSE: Assess the effect of intensive vs conventional blood pressure goals on patient-important outcomes in older adults with type 2 diabetes. METHODS: A comprehensive search was performed using electronic databases. Randomized controlled trials comparing intensive vs conventional blood pressure goals in adults over 60 years of age with type 2 diabetes were included. Events were evaluated using a modified Mantel-Haenszel meta-analysis with Peto's method. Study selection and data extraction were performed independently and in duplicate. RESULTS: Seven trials were included. A 19% risk reduction (OR 0.81; 95% CI 0.69-0.95; I2 = 8%; p = 0.35) in the occurrence of major adverse cardiovascular events (MACE) and 37% risk reduction (OR 0.63; 95% CI 0.51-0.79; I2 = 0%; p = 0.56) in the occurrence of fatal or non-fatal stroke was documented in the intensive treatment group. There were no differences in the occurrence of all-cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and peripheral vascular disease. Data regarding treatment adverse effects and microvascular outcomes was scarce. CONCLUSIONS: Intensive blood pressure goals in older patients with diabetes were associated with a lower risk of stroke and MACE, but not with all-cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and peripheral vascular disease.

A Versatile ES Cell-Based Melanoma Mouse Modeling Platform.

The cumbersome and time-consuming process of generating new mouse strains and multiallelic experimental animals often hinders the use of genetically engineered mouse models (GEMM) in cancer research. Here, we describe the development and validation of an embryonic stem cell (ESC)-GEMM platform for rapid modeling of melanoma in mice. The platform incorporates 12 clinically relevant genotypes composed of combinations of four driver alleles (LSL-BrafV600E, LSL-NrasQ61R, PtenFlox, and Cdkn2aFlox) and regulatory alleles to spatiotemporally control the perturbation of genes of interest. The ESCs produce high-contribution chimeras, which recapitulate the melanoma phenotypes of conventionally bred mice. Using the ESC-GEMM platform to modulate Pten expression in melanocytes in vivo, we highlighted the utility and advantages of gene depletion by CRISPR-Cas9, RNAi, or conditional knockout for melanoma modeling. Moreover, complementary genetic methods demonstrated the impact of Pten restoration on the prevention and maintenance of Pten-deficient melanomas. Finally, we showed that chimera-derived melanoma cell lines retain regulatory allele competency and are a powerful resource to complement ESC-GEMM chimera experiments in vitro and in syngeneic grafts in vivo Thus, when combined with sophisticated genetic tools, the ESC-GEMM platform enables rapid, high-throughput, and versatile studies aimed at addressing outstanding questions in melanoma biology.Significance: This study presents a high-throughput and versatile ES cell-based mouse modeling platform that can be combined with state-of-the-art genetic tools to address unanswered questions in melanoma in vivo See related commentary by Thorkelsson et al., p. 655.

Early triglyceride and glucose index as a risk marker for gestational diabetes mellitus.

OBJECTIVE: To assess the risk of gestational diabetes mellitus (GDM) according to the triglyceride and glucose (TyG) index values during the first trimester of pregnancy in Latin American women. METHODS: Pregnant women were enrolled at their first prenatal visit at the Obstetric Division in the University Hospital "Dr. José E. González". Triglycerides and fasting plasma glucose (FPG) were collected to determine the TyG index. GDM diagnosis was performed by a single-step 2-hour 75-g oral glucose tolerance test. Generalized linear models were used to determine risk ratios; pregnancy outcomes at delivery were collected from the hospital medical records. RESULTS: A total of 164 pregnant women were included. GDM was present in 29 (17.7%) women. No significant differences in age, first-trimester body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters), family history of diabetes, and TyG index were observed between GDM cases and the reference group without GDM. The adjusted analysis showed no association between TyG and GDM (risk ratio [RR] 1.03, 95% confidence interval [CI] 0.57-1.88]). Higher TyG index values between women with and without a diagnosis of GDM in the second trimester were observed. No significant differences were identified in pregnancy outcomes, although a trend was observed for hyperbilirubinemia in women with first-trimester TyG index values greater than 8.7. CONCLUSIONS: Our findings do not support the use of the TyG index for GDM prediction in Latin American women.

A deeper analysis in thyroid research: A meta-epidemiological study of the American Thyroid Association clinical guidelines.

BACKGROUND: The American Thyroid Association (ATA) uses the GRADE or the American College of Physicians (ACP) system to develop recommendations. Recommendations based on low-quality evidence should spur for the conduction of clinical studies, if feasible. The extent to which recommendations by the ATA based on low-quality of evidence are being actively researched remains unknown. METHODS: Clinical guidelines produced by the ATA using the GRADE or the ACP system to classify evidence were deemed eligible. Reviewers, in duplicate and independently, extracted therapeutic recommendations based on low-quality evidence, whereas recommendations with higher quality of evidence, aimed at diagnosis, or best practice statements were excluded. Eligible recommendations based on low-quality evidence were deconstructed to their components using the PICO format. We then searched on clinicaltrials.gov to identify ongoing research. Trials were deemed eligible if they addressed the PICO question with at least one of the intended outcomes. RESULTS: A total of 543 recommendations were retrieved, of which 305 (56%) were based on low-quality of evidence and only 90 were deemed eligible. Of these, we found that 33 (37%) recommendations were actively being researched in 53 clinical trials. Most of the trials were randomized and funded by non-profit organizations. Many clinical trials studied thyroid nodules and differentiated thyroid cancer (26/53; 49%), whereas few studied were aimed at anaplastic thyroid cancer (2/53; 4%). CONCLUSION: One out of three of gaps in evidence, identified as low quality during the development of ATA guidelines, are currently actively researched. This finding calls for the need to develop a better research infrastructure and funding to support thyroid research.

Gut microbiome populations are associated with structure-specific changes in white matter architecture.

Altered gut microbiome populations are associated with a broad range of neurodevelopmental disorders including autism spectrum disorder and mood disorders. In animal models, modulation of gut microbiome populations via dietary manipulation influences brain function and behavior and has been shown to ameliorate behavioral symptoms. With striking differences in microbiome-driven behavior, we explored whether these behavioral changes are also accompanied by corresponding changes in neural tissue microstructure. Utilizing diffusion tensor imaging, we identified global changes in white matter structural integrity occurring in a diet-dependent manner. Analysis of 16S ribosomal RNA sequencing of gut bacteria also showed changes in bacterial populations as a function of diet. Changes in brain structure were found to be associated with diet-dependent changes in gut microbiome populations using a machine learning classifier for quantitative assessment of the strength of microbiome-brain region associations. These associations allow us to further test our understanding of the gut-brain-microbiota axis by revealing possible links between altered and dysbiotic gut microbiome populations and changes in brain structure, highlighting the potential impact of diet and metagenomic effects in neuroimaging.