Deciphering the Role of WWTPs in Cold Environments as Hotspots for the Dissemination of Antibiotic Resistance Genes.

Cold environments are the most widespread extreme habitats in the world. However, the role of wastewater treatment plants (WWTPs) in the cryosphere as hotspots in antibiotic resistance dissemination has not been well established. Hence, a snapshot of the resistomes of WWTPs in cold environments, below 5 °C, was provided to elucidate their role in disseminating antibiotic resistance genes (ARGs) to the receiving waterbodies. The resistomes of two natural environments from the cold biosphere were also determined. Quantitative PCR analysis of the aadA, aadB, ampC, blaSHV, blaTEM, dfrA1, ermB, fosA, mecA, qnrS, and tetA(A) genes indicated strong prevalences of these genetic determinants in the selected environments, except for the mecA gene, which was not found in any of the samples. Notably, high abundances of the aadA, ermB, and tetA(A) genes were found in the influents and activated sludge, highlighting that WWTPs of the cryosphere are critical hotspots for disseminating ARGs, potentially worsening the resistance of bacteria to some of the most commonly prescribed antibiotics. Besides, the samples from non-disturbed cold environments had large quantities of ARGs, although their ARG profiles were highly dissimilar. Hence, the high prevalences of ARGs lend support to the fact that antibiotic resistance is a common issue worldwide, including environmentally fragile cold ecosystems.

Telmisartan for treatment of Covid-19 patients: An open multicenter randomized clinical trial.

Background: Angiotensin receptor blockers (ARBs), such as telmisartan, have been postulated to treat Covid-19-induced lung inflammation. Methods: This is a parallel-group, randomized, two-arm, open-label, adaptive, multicenter superiority trial with 1:1 allocation ratio. Participants included patients from 18 years of age hospitalized with Covid-19 with 4 or fewer days since symptom onset enrolled at a university and a community hospital in Buenos Aires, Argentina. Exclusion criteria included prior intensive care unit (ICU) admission and use of ARBs/angiotensin converting enzyme inhibitors at randomization. Control arm received standard care alone and treatment arm telmisartan 80 mg twice daily for 14 days. Primary outcomes were C-reactive protein (CRP) plasma levels at day 5 and 8 after randomization. Secondary outcomes included time to discharge within 15 days, admission to ICU and death at 15- and 30-days. NCT04355936 (Completed). Findings: A pragmatic decision to end the study before the third interim analysis was made on Oct. 30th due to sharp reduction in recruitment. A total of 162 patients were randomized. 158 patients enrolled between May 14 and October 30 2020, were included in the analysis, 80 in the standard care and 78 in the telmisartan added to standard care group. Baseline absolute CRP serum levels were 5.53 ± 6.19 mg/dL (95% CI 6.91 to 4.15, n = 80) and 9.04 ± 7.69 (95% CI 9.04 to 10.82, n = 74) in the standard care and telmisartan added to standard care groups, respectively. Day 5 control-group CRP levels were 6.06 ± 6.95 mg/dL (95% CI 7.79-4.35, n = 66) while telmisartan group were 3.83 ± 5.08 mg/dL (95% CI 5.08-2.59, n = 66, p = 0.038). Day 8 CRP levels were 6.30 ± 8.19 mg/dL (95% CI 8.79-3.81, n = 44) and 2.37 ± 3.47 mg/dL (95% CI 3.44-1.30, n = 43, p = 0.0098) in the control and telmisartan groups, respectively (all values expressed as mean ± SD). Kaplan-Meier analysis showed that telmisartan-treated patients had a lower median time-to-discharge (control=15 days; telmisartan=9 days). Death by day 30 was reduced in the telmisartan-treated group (control 22.54%, 16/71; telmisartan 4.29%, 3/70 participants; p = 0.0023). Composite ICU, mechanical ventilation or death was reduced by telmisartan treatment at days 15 and 30. No adverse events were reported. Interpretation: Our study suggests that the ARB telmisartan, a widely used antihypertensive drug, is safe and could reduce morbidity and mortality in hospitalized patients infected with SARS -CoV-2 by anti-inflammatory effects. Further studies employing telmisartan are needed for confirmation of our results and to define its true therapeutic value as a tool against Covid-19.

Clinical factors related to severe enterocolitis after adjuvant CAPOX for colorectal cancer: a retrospective analysis.

BACKGROUND: CAPOX regimen is a standard option in stage III adjuvant colon cancer. Gastrointestinal toxicity is well described with fluoropyrimidine regimens and can be life-threatening. Identification of risk factors associated with severe gastrointestinal toxicity may help clinicians when choosing the adjuvant regimen. MATERIALS AND METHODS: We retrospectively analysed 61 patients treated with adjuvant CAPOX. Our primary objective was to estimate the incidence of severe chemotherapy-induced enterocolitis among patients treated with CAPOX. A secondary objective was to describe the main demographic and clinical characteristics of these patients. A univariate logistic regression was performed to estimate the odds ratio (OR) with a 95% CI to identify a predictor for severe enterocolitis. RESULTS: Grade 3 diarrhoea was reported in 10 patients (16.3%). Admissions to hospital due to toxicity occurred in nine cases. Reasons for hospitalisation were severe enterocolitis in eight cases (13.1%) and rectal bleeding plus thrombocytopenia in one case. Age > 70 years (OR 9.6; 95% CI 1.81-50.6; p = 0.008), primary surgery involving right/transverse colon (OR 16.8; 95% CI 2.88-98.8; p = 0.002) and Angiotensin II Receptor Blocker (ARB) use (OR 8.14; 95% CI 1.64-40.3; p = 0.010) were associated with severe enterocolitis. CONCLUSION: Our data showed that adjuvant CAPOX induced severe enterocolitis in 13.1% of patients. In addition, we found that advanced age, right colectomy and concurrent use of ARB were statistically associated with these events. Awareness of these factors could be easily incorporated into the treatment decision and patient orientation.

Removal of microorganisms and antibiotic resistance genes from treated urban wastewater: A comparison between aluminium sulphate and tannin coagulants.

The presence of antibiotic resistant-bacteria (ARB) and antibiotic resistance genes (ARG) in treated effluents of urban wastewater treatment plants (WWTP) may represent a threat to the environment and public health. Therefore, cost-effective technologies contributing to minimize loads of these contaminants in the final effluents of WWTP are required. This study aimed at assessing the capacity of coagulation to reduce the ARB&ARG load in secondary treated urban wastewater (STWW), as well as the impact of the process on the structure and diversity of the bacterial community. Coagulation performance using aluminium sulphate, a synthetic substance, and tannins, a biowaste, was compared. Samples were analysed immediately before (STWW) and after the coagulation treatment (Alu, Tan), as well as after 3-days storage in the dark at room temperature (RSTWW, RAlu, RTan), to assess possible reactivation events. Both coagulants decreased the turbidity and colour and reduced the bacterial load (16S rRNA gene copy number, total heterotrophs (HET), and ARB (faecal coliforms resistant to amoxicillin (FC/AMX) or ciprofloxacin (FC/CIP) up to 1-2 log immediately after the treatment. Both coagulants reduced the load of intl1, but in average, aluminium sulphate was able to decrease the content of the analysed ARGs (blaTEM and qnrS) to lower levels than tannin. Reactivation after storage was observed mainly in RTan. In these samples the load of the culturable populations and qnrS gene prevalence increased, sometimes to values higher than those found in the initial wastewater. Reactivation was also characterized by an increment in Gammaproteobacteria relative abundance in the bacterial community, although with distinct patterns for RTan and RAlu. Curvibacter, Undibacterium and Aquaspirillum were among the most abundant genera in RAlu and Aeromonas, Pseudomonas and Stenotrophomonas in RTan. These bacterial community shifts were in agreement with the variations in the culturable bacterial counts of HET for RTan and FC/CIP for RAlu. In summary, the overall performance of aluminium sulphate was better than that of tannins in the treatment of treated urban wastewater.

Calidad de cuidado médico en una clínica de enfermedad renal avanzada con estrategia multi-causal / Medical care quality in an advanced kidney disease clinic

En enfermedad renal crónica etapa IV (ERC-IV) es alta la mortalidad y progresión a insuficiencia renal extrema (IRE). Objetivo: Valorar la calidad asistencial en una Clínica de Enfermedad Renal Crónica Avanzada (CERCA). Métodos: Estudio prospectivo de pacientes ERC- IV asistidos con un equipo multidisciplinario formal mediante estrategia de educación, asesoramiento nutricional, seguimiento clínico mensual, y tratamiento según metas de presión arterial (<130/80) reducción de proteinuria, uso de inhibidores de enzima de conversión (IECA) y/o Bloqueantes de receptores de angiotensina (BRA), tratamiento de dislipemia, y preparación para diálisis. Resultados: Se analizaron 150 pacientes, 50% masculino, 62,0 ± 14,4 años, Nefropatías vascular 20,4%, diabética 34,2% y 62,5% proteinúricos, con Indice de Charlson 3,67±1,57. En seguimiento de 1,4 años (IQ: 0,6-2,4) disminuyó la PA (147±35 a 132 ± 28mm), colesterol (210±55 a 179±50 mg/dL) y LDL (129±52 a 108±37 mg/dL) con aumento del uso de IECA/BRA (55,9 a 60,6 %) y estatinas (32,2 a 63,3%). La tasa de Mortalidad fue 5,3 e IRE 14,5/100 Pt- año. El Riesgo pérdida de FG mayor a la mediana o IRE aumentó con HTA, Pru >1 g/d y glomerulopatias y se redujo 90% con IEC/BRA (p<0.001). Al ingreso a diálisis la Hemoglobina ≥10g%, vacunación hepatitis B y acceso permanente fueron más frecuentes que en la población general. Conclusiones: En una Clínica multidisciplinaria con estrategia de control de riesgos se alcanzó mejor las metas de tratamiento, disminuyendo los factores de riesgo de progresión y mejorando el cuidado médico al ingreso a diálisis.(AU)

In stage IV chronic kidney disease (stage-IV CKD), mortality and progression to extreme renal failure (ERF) are high. Objective: Assessing the quality of health care in an Advanced Kidney Disease Clinic (AKDC). Methods: Prospective study of patients with stage-IV CKD treated by a multidisciplinary formal team through an educational strategy, nutritional advice, clinical nephrology follow-up, aimed at achieving blood pressure goals (<130/80), proteinuria reduction, use of angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB), dyslipidemia treatment and preparation for dialysis. Results: 150 patients were analyzed, 50% were males, of 62.0 ± 14.4 years of age, 20.4% had vascular kidney diseases, 34.2% had diabetes and 62.5% had proteinuria with a Charlson index of 3.67 ± 1.57. In the 1.4-year follow-up (IQ: 0.6- 2.4), there were decreases in the BP (147±35 to 132±28 mm), cholesterol (210±55 to 179±50 mg/ dl) and LDL (129±52 to 108±37 mg/dl), and there was an increase in the use of ACEI/ARB (55.9to 60.6%) and statins (32.2 to 63.3%). The mortality rate was 5.3 and the ERF rate was 14.5/100 patient-years. The glomerular function loss risk, which was higher than the median or ERF, increased with HTN, Pru >1 g/d and glomerular diseases, and had a 90% decrease with ACEI/ARB(p<0.001). At dialysis entry, hemoglobin levels of≥10g%, hepatitis B vaccination and permanent access were more frequent than in the general population. Conclusions: Treatment goals were best achieved in a multidisciplinary clinic with a riskcontrol strategy, reducing progression risk factors and improving medical care upon dialysis entry.(AU)

Calidad de cuidado médico en una clínica de enfermedad renal avanzada con estrategia multi-causal / Medical care quality in an advanced kidney disease clinic

En enfermedad renal crónica etapa IV (ERC-IV) es alta la mortalidad y progresión a insuficiencia renal extrema (IRE). Objetivo: Valorar la calidad asistencial en una Clínica de Enfermedad Renal Crónica Avanzada (CERCA). Métodos: Estudio prospectivo de pacientes ERC- IV asistidos con un equipo multidisciplinario formal mediante estrategia de educación, asesoramiento nutricional, seguimiento clínico mensual, y tratamiento según metas de presión arterial (<130/80) reducción de proteinuria, uso de inhibidores de enzima de conversión (IECA) y/o Bloqueantes de receptores de angiotensina (BRA), tratamiento de dislipemia, y preparación para diálisis. Resultados: Se analizaron 150 pacientes, 50% masculino, 62,0 ± 14,4 años, Nefropatías vascular 20,4%, diabética 34,2% y 62,5% proteinúricos, con Índice de Charlson 3,67±1,57. En seguimiento de 1,4 años (IQ: 0,6-2,4) disminuyó la PA (147±35 a 132 ± 28mm), colesterol (210±55 a 179±50 mg/dL) y LDL (129±52 a 108±37 mg/dL) con aumento del uso de IECA/BRA (55,9 a 60,6 %) y estatinas (32,2 a 63,3%). La tasa de Mortalidad fue 5,3 e IRE 14,5/100 Pt- año. El Riesgo pérdida de FG mayor a la mediana o IRE aumentó con HTA, Pru >1 g/d y glomerulopatias y se redujo 90% con IEC/BRA (p<0.001). Al ingreso a diálisis la Hemoglobina ≥10g%, vacunación hepatitis B y acceso permanente fueron más frecuentes que en la población general. Conclusiones: En una Clínica multidisciplinaria con estrategia de control de riesgos se alcanzó mejor las metas de tratamiento, disminuyendo los factores de riesgo de progresión y mejorando el cuidado médico al ingreso a diálisis.

In stage IV chronic kidney disease (stage-IV CKD), mortality and progression to extreme renal failure (ERF) are high. Objective: Assessing the quality of health care in an Advanced Kidney Disease Clinic (AKDC). Methods: Prospective study of patients with stage-IV CKD treated by a multidisciplinary formal team through an educational strategy, nutritional advice, clinical nephrology follow-up, aimed at achieving blood pressure goals (<130/80), proteinuria reduction, use of angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB), dyslipidemia treatment and preparation for dialysis. Results: 150 patients were analyzed, 50% were males, of 62.0 ± 14.4 years of age, 20.4% had vascular kidney diseases, 34.2% had diabetes and 62.5% had proteinuria with a Charlson index of 3.67 ± 1.57. In the 1.4-year follow-up (IQ: 0.6- 2.4), there were decreases in the BP (147±35 to 132±28 mm), cholesterol (210±55 to 179±50 mg/ dl) and LDL (129±52 to 108±37 mg/dl), and there was an increase in the use of ACEI/ARB (55.9to 60.6%) and statins (32.2 to 63.3%). The mortality rate was 5.3 and the ERF rate was 14.5/100 patient-years. The glomerular function loss risk, which was higher than the median or ERF, increased with HTN, Pru >1 g/d and glomerular diseases, and had a 90% decrease with ACEI/ARB(p<0.001). At dialysis entry, hemoglobin levels of≥10g%, hepatitis B vaccination and permanent access were more frequent than in the general population. Conclusions: Treatment goals were best achieved in a multidisciplinary clinic with a riskcontrol strategy, reducing progression risk factors and improving medical care upon dialysis entry.