A Perspective of the Urinary Microbiome in Lower Urinary Tract Infections - A Review.

PURPOSE OF REVIEW: Greater availability of sequencing methods has broadened the knowledge of the urinary microbiome in an environment previously believed to be sterile. This review discusses internal and external influences that promote either a balance or a dysbiosis of the urinary tract and the future perspectives in understanding lower urinary tract infections. RECENT FINDINGS: Efforts have been made to identify a "core" urinary microbiome in which Firmicutes and Bacteroidetes account for most of the bacterial representations. A shift to a Proteobacteria-dominant representation shapes the fingerprint of the infectious urinary microbiome; furthermore, the virome and the mycobiome are important modulators of the urinary microbiome, which have been recently explored to determine their role in the health-disease process of the lower urinary tract. A disturbance of bacterial representation and diversity triggers a transition from health to disease; conversely, a functional cooperative interplay between the host and microbiome allows for basic metabolic and immune functions to take place.

Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials.

OBJECTIVE: To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk. DESIGN: Network meta-analysis. DATA SOURCES: Medline, Embase, and Cochrane CENTRAL up to 11 August 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias. MAIN OUTCOME MEASURES: Frequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review. RESULTS: 764 trials including 421 346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 3 to 40 fewer deaths in 1000 patients over five years; see interactive decision support tool (https://magicevidence.org/match-it/200820dist/#!/) for all outcomes. CONCLUSIONS: In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with some differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019153180.

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.

SERUM MORNING CORTISOL AS A SCREENING TEST FOR ADRENAL INSUFFICIENCY.

Objective: To evaluate the performance of morning serum cortisol (MSC) compared to a 10 mg adrenocortico-tropic hormone (ACTH) stimulation test in the diagnosis of adrenal insufficiency (AI). Methods: A retrospective, cross-sectional analysis of ACTH stimulation tests were conducted. From a total of 312 potentially eligible ACTH stimulation tests, 306 met the inclusion criteria. The population was randomized into 2 groups: test (n = 159) and validation (n = 147). In the test group, the receiver operating characteristics curve test evaluated the diagnostic performance of MSC. Results: A subnormal cortisol response to ACTH was found in 25.8% of the test group. The area under the curve values of MSC to predict AI at +30 minutes, +60 minutes, or at maximal cortisol response were 0.874, 0.897, and 0.925 (95% confidence interval [CI] 0.81 to 0.92, 0.83 to 0.93, and 0.87 to 0.96). The Youden index was 234.2 mmol/L with a sensitivity of 83.3% (95% CI 65.2 to 94.3%), and a specificity of 89.1% (95% CI 82.4 to 93.9%). Positive and negative predictive values were 64.1% (95% CI 47.1 to 78.8%) and 95.8% (95% CI 90.5 to 98.6%). There was no difference in age, gender, AI prevalence, or mean serum cortisol at +30 or +60 minutes in the validation group; however, a lower mean MSC value was found. Lower sensitivity and specificity values (88.3% and 60%, respectively) were found for the 234.2 mmol/L cutoff value. Conclusion: This study supports the role of MSC as a first-step diagnostic test in patients with clinically suspected AI. The short stimulation test could be omitted in almost half of the cases. Prospective and longitudinal studies to reproduce and confirm the cutoff values proposed are warranted. Abbreviations: ACTH = adrenocorticotropic hormone; AI = adrenal insufficiency; AUC = area under the curve; CI = confidence interval; HPA = hypothalamic pituitary adrenal; ITT = insulin tolerance test; MSC = morning serum cortisol.