Highly sensitive voltammetric determination of hydrochlorothiazide using a glassy carbon electrode modified with Super P carbon black nanoparticles.

Hydrochlorothiazide is an extremely important diuretic that regulates body functions, which can prevent several diseases. However, the abuse of this diuretic is concerning since it does not require a medical prescription, particularly for aesthetic purposes such as weight loss, which can lead to various health problems, including ventricular arrhythmia. The present work aims to use a glassy carbon electrode modified with Super P carbon black (SPCB/GCE) to quantify hydrochlorothiazide through Linear Sweep Adsorptive Stripping Voltammetry (LSAdSV). The modification of the GCE with SPCB significantly improved the response of hydrochlorothiazide. Furthermore, due to the adsorptive nature of charge transport, applying preconcentration time enhanced sensitivity. The optimized system provided a linear range of 0.5 to 30.0 µmol L-1 with a detection limit of 0.083 µmol L-1. Pharmaceutical tablet analyses indicated approximately 25 mg per tablet, which was confirmed by the UV-vis and in agreement with that indicated by the manufacturer. Furthermore, analyses of the tea, synthetic urine, tap water and lake water samples indicated recovery values close to 100%, demonstrating that there was no matrix effect. Therefore, it is possible to infer that the proposed method together with the sensor modified with carbon black nanoparticles presented excellent results, demonstrating that it can be an alternative method of monitoring this drug in different samples.

Acetazolamide therapy in patients with acute heart failure: a systematic review and meta-analysis of randomized controlled trials.

Acute heart failure (AHF) often leads to unfavorable outcomes due to fluid overload. While diuretics are the cornerstone treatment, acetazolamide may enhance diuretic efficiency by reducing sodium reabsorption. We performed a systematic review and meta-analysis on the effects of acetazolamide as an add-on therapy in patients with AHF compared to diuretic therapy. PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCT). A random-effects model was employed to compute mean differences and risk ratios. Statistical analysis was performed using R software. The GRADE approach was used to rate the certainty of the evidence. We included 4 RCTs with 634 patients aged 68 to 81 years. Over a mean follow-up of 3 days to 34 months, acetazolamide significantly increased diuresis (MD 899.2 mL; 95% CI 249.5 to 1549; p < 0.01) and natriuresis (MD 72.44 mmol/L; 95% CI 39.4 to 105.4; p < 0.01) after 48 h of its administration. No association was found between acetazolamide use and WRF (RR 2.4; 95% CI 0.4 to 14.2; p = 0.3) or all-cause mortality (RR 1.2; 95% CI 0.8 to 1.9; p = 0.3). Clinical decongestion was significantly higher in the intervention group (RR 1.35; 95% CI 1.09 to 1.68; p = 0.01). Acetazolamide is an effective add-on therapy in patients with AHF, increasing diuresis, natriuresis, and clinical decongestion, but it was not associated with differences in mortality.

Torsemide versus Furosemide in the Treatment of Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. / Torsemida em Comparação com Furosemida no Tratamento da Insuficiência Cardíaca: Uma Revisão Sistemática e Metanálise de Ensaios Clínicos Randomizados.

Furosemide is the most used diuretic for volume overload symptoms in patients with heart failure (HF). Recent data suggested that torsemide may be superior to furosemide in this setting. However, whether this translates into better clinical outcomes in this population remains unclear. To assess whether torsemide is superior to furosemide in the setting of HF. We performed a systematic review and meta-analysis of RCTs comparing the efficacy of torsemide versus furosemide in patients with HF. PubMed, Embase, and Web of Science were searched for eligible trials. Outcomes of interest were all-cause hospitalizations, hospitalizations for HF (HHF), hospitalizations for all cardiovascular causes, all-cause mortality, and NYHA class improvement. Echocardiographic parameters were also assessed. We applied a random-effects model to calculate risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) and a 0.05 level of significance. 12 RCTs were included, comprising 4,115 patients. Torsemide significantly reduced HHF (RR 0.60; 95% CI, 0.43-0.83; p=0.002; I2=0%), hospitalization for cardiovascular causes (RR 0.72; 95% CI, 0.60-0.88; p=0.0009; I2=0%), and improved LVEF (MD 4.51%; 95% CI, 2.94 to 6.07; p<0.0001; I2=0%) compared with furosemide. There was no significant difference in all-cause hospitalizations (RR 0.93; 95% CI, 0.86-1.00; p=0.04; I2=0%), all-cause mortality (RR 0.98; 95% CI, 0.87-1.10; p=0.73; I2=0%), NYHA class improvement (RR 1.25; 95% CI, 0.92-1.68; p=0.15; I2=0%), or NYHA class change (MD -0.04; 95% CI, -0.24 to 0.16; p=0.70; I2=15%) between groups. Torsemide significantly reduced hospitalizations for HF and cardiovascular causes, also improving LVEF.

A furosemida é o diurético mais utilizado para o tratamento de sintomas de sobrecarga de volume em pacientes com insuficiência cardíaca. Dados recentes sugerem que a torsemida pode ser superior à furosemida neste contexto. No entanto, ainda não é claro se isso se traduz em melhores resultados clínicos nesta população. Avaliar se a torsemida é superior à furosemida no contexto da insuficiência cardíaca. Realizamos uma revisão sistemática e metanálise de estudos clínicos randomizados (ECRs) comparando a eficácia da torsemida em comparação com a furosemida em pacientes com insuficiência cardíaca. PubMed, Embase e Web of Science foram as bases de dados pesquisadas em busca de estudos elegíveis. Os desfechos de interesse foram internações por todas as causas, internações por insuficiência cardíaca (IIC), internações por todas as causas cardiovasculares, mortalidade por todas as causas, e melhoria de classe da NYHA. Parâmetros ecocardiográficos também foram avaliados. Foi aplicado um modelo de efeitos aleatórios para calcular as razões de risco (RR) e as diferenças médias (DM) com intervalos de confiança (IC) de 95% e nível de significância de 0,05. Foram incluídos 12 ECRs, envolvendo 4.115 pacientes. A torsemida reduziu significativamente a IIC (RR de 0,60; IC de 95%, 0,43-0,83; p=0,002; I2=0%), internação por causas cardiovasculares (RR de 0,72; IC de 95%, 0,60-0,88; p=0,0009; I2=0%), e melhora da fração de ejeção do ventrículo esquerdo (FEVE) (DM de 4,51%; IC de 95%, 2,94 a 6,07; p<0,0001; I2=0%) em comparação com a furosemida. Não houve diferença significativa no número de internações por todas as causas (RR de 0,93; IC de 95%, 0,86-1,00; p=0,04; I2=0%), mortalidade por todas as causas (RR de 0,98; IC de 95%, 0,87-1,10; p=0,73; I2=0%), melhora da classe NYHA (RR de 1,25; IC de 95%, 0,92-1,68; p=0,15; I2=0%), ou mudança de classe NYHA (DM de -0,04; IC de 95%, -0,24 a 0,16; p=0,70; I2=15%) entre os grupos. A torsemida reduziu significativamente as internações por insuficiência cardíaca e causas cardiovasculares, melhorando também a FEVE.

Optimizing management of chronic pulmonary hypertension in preterm infants: strategies for a complex population.

PURPOSE OF REVIEW: Pulmonary hypertension (PH) is commonly observed in premature infants with bronchopulmonary dysplasia (BPD) and is associated with poor outcomes and increased mortality. This review explores the management of this intricate condition of the pulmonary vasculature, which exhibits heterogeneous effects and may involve both arterial and postcapillary components. RECENT FINDINGS: Current management of BPD-PH should focus on optimizing ventilatory support, which involves treatment of underlying lung disease, transitioning to a chronic phase ventilation strategy and evaluation of the airway. Data on management is limited to observational studies. Diuretics are considered a part of the initial management, particularly in infants with right ventricular dilation. In many cases, pulmonary vasodilator therapy is required to induce pulmonary arterial vasodilation, reduce right ventricular strain, and prevent coronary ischemia and heart failure. Echocardiography plays a pivotal role in guiding treatment decisions and monitoring disease progression. SUMMARY: BPD-PH confers a heightened risk of mortality and long-term cardio-respiratory adverse outcomes. Echocardiography has been advocated for screening, while catheterization allows for confirmation in select more complex cases. Successful management of BPD-PH requires a multidisciplinary approach, focusing on optimizing BPD treatment and addressing underlying pathologies.

Kidney Replacement Therapies and Ultrafiltration in Cardiorenal Syndrome.

BACKGROUND: Some patients with cardiorenal syndrome 1 and congestion exhibit resistance to diuretics. This scenario complicates management and is associated with a worse prognosis. In some cases, rescue treatment may be considered by starting kidney replacement therapies or ultrafiltration. This decision is complex and necessitates a profound understanding of these techniques and the pathophysiology of this syndrome. These modalities are classified into continuous, intermittent, and ultrafiltration therapies, each with its own advantages and disadvantages that are pertinent in selecting the optimal treatment. SUMMARY: In patients with diuretic-resistant cardiorenal syndrome, extracorporeal ultrafiltration and kidney replacement therapies have the potential to relieve congestion, restore the neurohormonal system, and improve quality of life. KEY MESSAGES: (i) In cardiorenal syndrome, the resistance to diuretics is common. (ii) Extracorporeal ultrafiltration and renal replacement therapies are rescue options that may improve the management of these patients. (iii) Better understanding of these modalities will help the development of new devices which are friendlier, safer, and more affordable for patients in these clinical settings.

Effect of antihypertensive agents on sleep apnea and ambulatory blood pressure in patients with hypertension: A randomized controlled trial.

BACKGROUND: Obstructive sleep apnea (OSA) and hypertension are common conditions that may be linked through sympathetic activation and water retention. We hypothesized that diuretics, which reduce the body water content, may be more effective than amlodipine, a blood pressure (BP)-lowering agent implicated with edema, in controlling OSA in patients with hypertension. We also aimed to compare the effects of these treatments on ambulatory blood pressure monitoring (ABPM). METHODS: In a randomized, double-blind clinical trial, we compared the effects of chlorthalidone/amiloride 25/5 mg with amlodipine 10 mg on OSA measured by portable sleep monitor and BP measured by ABPM. The study included participants older than 40 who had moderate OSA (10-40 apneas/hour of sleep) and BP within the systolic range of 140-159 mmHg or diastolic range of 90-99 mmHg. RESULTS: The individuals in the experimental groups were comparable in age, gender, and other relevant characteristics. Neither the combination of diuretics nor amlodipine alone reduced the AHI after 8 weeks of treatment (AHI 26.3 with diuretics and 25.0 with amlodipine. P = 0.713). Both treatments significantly lowered office, 24-h, and nighttime ABP, but the two groups had no significant difference. CONCLUSION: Chlorthalidone associated with amiloride and amlodipine are ineffective in decreasing the frequency of sleep apnea episodes in patients with moderate OSA and hypertension. Both treatments have comparable effects in lowering both office and ambulatory blood pressure. The notion that treatments could offer benefits for both OSA and hypertension remains to be demonstrated. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER: NCT01896661.

Evaluation and estimation of diuretic activity of the linalyl acetate in the rats.

This study aimed to explore the diuretic activity of linalyl acetate (LA). LA is an essential oil, it is an integral phyto-constituent of various plants. In this study, acute and chronic diuretic activities were explored by measuring the levels of different electrolytes and pH in the urine of experimental rats. Rats were divided into five groups. The control group was given 10 mg/kg normal saline, the treated group was given 10 mg/kg furosemide, and the remaining 3 groups received different doses of LA including 25, 50, and 75 mg/kg through intraperitoneal route, to determine its diuretic potential. Urine volume for acute diuretic activity was measured for 6 hours however for chronic diuretic activity was measured for 6 days. For a comparative study of LA with a control group and treated group with reference drug, diuretic index was used. Moreover, the underlying mechanism of the diuretic activity was also explored by comparing atropine, L-NAME, and indomethacin. The results of each group with 6 rats in each group were obtained by ± standard error of the mean of every group. Analysis of Variance (ANOVA) was used for statistical analysis. Results revealed that the LA 75 mg/kg dose showed comparable results as of furosemide. Moreover, this study revealed the involvement of muscarinic receptors to produce diuresis in comparison with atropine with very little involvement of prostanoids and no effect on NO pathway induced by indomethacin and L-NAME respectively. It is concluded that LA possess anti-diuretic potential. Muscarinic receptors might be involved in producing diuretic effects.

3-Demethyl-2-geranyl-4-prenylbellidifoline, a natural xanthone with diuretic and kidney protective properties.

OBJECTIVES: The diuretic and kidney protective effect of the 3-demethyl-2-geranyl-4-prenylbellidifoline (DGP) were evaluated in rats. METHODS: The normotensive (NTR) and spontaneously hypertensive rats (SHR) received, once a day for 7 days, oral treatment with DGP (0.1 mg/kg), hydrochlorothiazide (10 mg/kg), or vehicle (10 ml/kg). Urine, blood, and kidney samples were collected for further analysis. KEY FINDINGS: The urine and Na+ elimination content were significantly higher in the groups that received DGP. Furthermore, a Ca2+-sparing action was detected in the urine of DGP-treated groups, which was consistent with the reduction in calcium oxalate crystal formation. Relevantly, the treatment did not change the parameters examined in the blood. Concerning the renal analyses, DGP treatment recovered the morphological damages of the kidney corpuscle area of SHR. In addition to the differences observed between the NTR and SHR vehicle groups, DGP augmented the amount of reduced glutathione and the activity of glutathione S-transferase GST while reducing the catalase and N-acetyl-ß-D-glucosaminidase activity and nitrite levels. CONCLUSION: Together, this study displayed the prolonged diuretic action of DGP and its natriuretic, Ca2+-sparing, and antiurolytic effects. The antioxidative and anti-inflammatory effects of DGP were evidenced in SHR kidneys, opening perspectives for further studies regarding the benefits of this xanthone.

Osmotic demyelination as a complication of hyponatremia correction: a systematic review.

BACKGROUND: Rapid correction of hyponatremia, especially when severe and chronic, can result in osmotic demyelination. The latest guideline for diagnosis and treatment of hyponatremia (2014) recommends a correction limit of 10 mEq/L/day. Our aim was to summarize published cases of osmotic demyelination to assess the adequacy of this recommendation. METHOD: Systematic review of case reports of osmotic demyelination. We included cases confirmed by imaging or pathology exam, in people over 18 years of age, published between 1997 and 2019, in English or Portuguese. RESULTS: We evaluated 96 cases of osmotic demyelination, 58.3% female, with a mean age of 48.2 ± 12.9 years. Median admission serum sodium was 105 mEq/L and > 90% of patients had severe hyponatremia (<120 mEq/L). Reports of gastrointestinal tract disorders (38.5%), alcoholism (31.3%) and use of diuretics (27%) were common. Correction of hyponatremia was performed mainly with isotonic (46.9%) or hypertonic (33.7%) saline solution. Correction of associated hypokalemia occurred in 18.8%. In 66.6% of cases there was correction of natremia above 10 mEq/L on the first day of hospitalization; the rate was not reported in 22.9% and in only 10.4% was it less than 10 mEq/L/day. CONCLUSION: The development of osmotic demyelination was predominant in women under 50 years of age, with severe hyponatremia and rapid correction. In 10.4% of cases, there was demyelination even with correction <10 mEq/L/day. These data reinforce the need for conservative targets for high-risk patients, such as 4-6 mEq/L/day, not exceeding the limit of 8 mEq/L/day.

Diuretic Tolerance to Repeated-Dose Furosemide in Infants Born Very Preterm with Bronchopulmonary Dysplasia.

OBJECTIVES: To assess the presence and timing of furosemide diuretic tolerance in infants with bronchopulmonary dysplasia (BPD), and to determine if tolerance is modified by thiazide co-administration. STUDY DESIGN: We performed a retrospective cohort study among infants born very preterm with BPD exposed to repeated-dose furosemide for 72 hours, measuring net fluid balance (total intake minus total output) as a surrogate of diuresis in the 3 days before and after exposure. The primary comparison was the difference in fluid balance between the first and third 24 hours of furosemide exposure. We fit a general linear model for within-subject repeated measures of fluid balance over time, with thiazide co-administration as an interaction variable. Secondary analyses included an evaluation of weight trajectories over time. RESULTS: In 83 infants, median fluid balance ranged between + 43.6 and + 52.7 ml/kg/d in the 3 days prior to furosemide exposure. Fluid balance decreased to a median of + 29.1 ml/kg/d in the first 24 hours after furosemide, but then increased to +47.5 ml/kg/d by the third 24-hour interval, consistent with tolerance (P < .001). Thiazides did not modify the change in fluid balance during furosemide exposure for any time-period. Weight decreased significantly in the first 24 hours after furosemide and increased thereafter (P < .001). CONCLUSIONS: The net fluid balance response to furosemide decreases rapidly during repeated-dose exposures in infants with BPD, consistent with diuretic tolerance. Clinicians should consider this finding in the context of an infant's therapeutic goals. Further research efforts to identify safe and effective furosemide dosage strategies are needed.

From Fish Physiology to Human Disease: The Discovery of the NCC, NKCC2, and the Cation-Coupled Chloride Cotransporters.

The renal Na-K-2Cl and Na-Cl cotransporters are the major salt reabsorption pathways in the thick ascending limb of Henle loop and the distal convoluted tubule, respectively. These transporters are the target of the loop and thiazide type diuretics extensively used in the world for the treatment of edematous states and arterial hypertension. The diuretics appeared in the market many years before the salt transport systems were discovered. The evolving of the knowledge and the cloning of the genes encoding the Na-K-2Cl and Na-Cl cotransporters were possible thanks to the study of marine species. This work presents the history of how we came to know the mechanisms for the loop and thiazide type diuretics actions, the use of marine species in the cloning process of these cotransporters and therefore in the whole solute carrier cotransproters 12 (SLC12) family of electroneutral cation chloride cotransporters, and the disease associated with each member of the family.

Effect on Kidney Function Recovery Guiding Decongestion with VExUS in Patients with Cardiorenal Syndrome 1: A Randomized Control Trial.

INTRODUCTION: In cardiorenal syndrome type 1 (CRS1), vascular congestion is central to the pathophysiology of heart failure and thus a key target for management. The venous evaluation by ultrasound (VExUS) system could guide decongestion effectively and thereby improve outcomes. METHODS: In this randomized clinical trial, patients with CRS1 (i.e., increase in creatinine ≥0.3 mg/dL) were randomized to guide decongestion with VExUS compared to usual clinical evaluation. The primary endpoint was to assess kidney function recovery (KFR), and the key secondary endpoint was decongestion evaluated by physical examination and changes in brain natriuretic peptide (BNP) and CA-125. Exploratory endpoints included days of hospitalization and mortality. RESULTS: From March 2022 to February 2023, a total of 140 patients were randomized 1:1 (70 in the VExUS and 70 in the control group). KFR was not statistically different between groups. However, VExUS improved more than twice the odds to achieve decongestion (odds ratio [OR]: 2.6, 95% CI: 1.9-3.0, p = 0.01) and the odds to reach a decrease of BNP >30% (OR: 2.4, 95% CI: 1.3-4.1, p = 0.01). The survival at 90 days, recongestion, and CA-125 were similar between groups. CONCLUSION: In patients with CRS1, we observed that VExUS-guided decongestion did not improve the probability of KFR but improved the odds to achieve decongestion.

The presence of doping agents in dietary supplements: A glimpse into the Brazilian situation.

Dietary supplements (DS) are intended for healthy people to maintain or improve their overall health. Its consumption is widespread in large part of the general population and at all levels of athletes. Nevertheless, DS use can also pose health risks to individuals and, in the case of athletes, may lead to adverse analytical findings (AAFs) due to the possibility of DS contamination or adulteration with doping agents banned by the World Anti-Doping Agency. Although educational initiatives are being performed in Brazil to warn the sports community about inadvertent doping cases, AAFs connected to the DS administration have been increasingly growing. The findings of DS analyzed by the Brazilian Doping Control Laboratory (LBCD), between 2017 and 2022, after Testing Authorities (TAs) analysis requests, showed an alarming number of tainted samples. Diuretics were the most common adulterants found in all supplement types. However, the profile of prohibited substances in manufactured and compounded dietary supplements (MDS and CDS, respectively) were distinct, with stimulants being most prevalent in MDS and anabolic agents in CDS products. Additionally, MDS samples generally presented higher estimated concentrations of banned substances (mg/g) than CDS samples (µg/g). The common practice of DS intake by athletes continues to be of great concern for a doping-free sport, given the high prevalence of prohibited substances detected in the analyzed samples by the LBCD. The current Brazilian scenario reinforces the importance of raising awareness in the sports community of the possible consequences of an unintentional doping case linked to DS use.

Reporte de caso: síndrome de absorción intravascular en histeroscopia, intoxicación por glicina / Case report: Intravascular absorption syndrome in hysteroscopy, glycine intoxication

El síndrome de absorción intravascular en histeroscopia se origina por la rápida absorción vascular de soluciones isotónicas e hipotónicas utilizadas en irrigación intrauterina, ocasionando hipervolemia y dilución de electrolitos, especialmente hiponatremia. Cuando este síndrome es debido a intoxicación por glicina al 1,5% causa acidosis severa y neurotoxicidad. La incidencia de este síndrome es baja pero puede aumentar por factores como: falta de control de altura de bolsas de irrigación, ausencia de equilibrio de fluidos de soluciones de irrigación, tejidos altamente vascularizados como miomas uterinos y uso de sistema de electrocirugía monopolar. Se reporta el caso de una paciente con miomas uterinos, programada para resección mediante histeroscopia que cursa con síndrome de absorción intravascular por glicina, el temprano diagnóstico y rápido tratamiento intraoperatorio y postoperatorio permitió una evolución favorable. El manejo se basó en el uso de diuréticos, restricción de fluidos y soluciones hipertónicas de sodio.

Intravascular absorption syndrome in hysteroscopy is caused by rapid vascular absorption of isotonic and hypotonic solutions used in intrauterine irrigation, causing hypervolemia and electrolyte dilution, especially hyponatremia. When this syndrome is due to 1.5% glycine toxicity, it causes severe acidosis and neurotoxicity. The incidence of this syndrome is low but may increase due to factors such as: lack of control of the height of irrigation bags, lack of fluid balance in irrigation solutions, highly vascularized tissues such as uterine myomas and use of a monopolar electrosurgery system. The case of a patient with uterine myomas, scheduled for resection by hysteroscopy, who presents with intravascular glycine absorption syndrome, is reported. Early diagnosis and rapid intraoperative and postoperative treatment allowed a favorable evolution. Management was based on the use of diuretics, fluid restriction, and hypertonic sodium solutions.

Diuretic, Natriuretic, And Ca2+-Sparing Effect Of The Alkaloid Boldine In Rats.

BACKGROUND: Previous studies indicate the renal vasodilating effects of boldine, an alkaloid found in Peumus boldus. However, its potential to induce diuresis still needs to be studied. METHODS: Wistar rats were used and the urine volume was noted for 8 h and further studied. RESULTS: The acute treatment at 0.1 and 0.3 mg/kg of boldine showed a diuretic, natriuretic, and Ca2+-sparing effect in rats without changing the urinary elimination of K+and Cl-. When boldine was given in combination with hydrochlorothiazide, there was an increase in urinary volume compared to the vehicle group. However, this was not different from the treatments in its isolated form. Urine Ca2+values ​​remained low but were not enhanced by this association. The excretion of Na+and Cl- was significantly increased compared to the group that received only vehicle or boldine. On the other hand, although the association of amiloride plus boldine did not result in a diuretic effect, the increase in Na+and the reduction in K+excretion were significantly potentiated. Furthermore, in the presence of the non-selective muscarinic receptor antagonist atropine, boldine showed reduced capacity to increase urinary volume, maintaining the natriuretic and Ca2+-sparing effect, besides a very evident K+-sparing action. Similar results were obtained in the presence of the non-selective cyclooxygenase inhibitor indomethacin. Furthermore, boldine showed an ex vivo antiurolithiasis activity, reducing calcium oxalate's precipitation and crystallization. CONCLUSIONS: This study reveals the diuretic, natriuretic, Ca2+-sparing, and antiurolithiatic effects of boldine, an action possibly related to muscarinic receptor activation and prostanoid generation.

Prognostic Evaluation of Microvolt T-Wave Alternans in Hypertrophic Cardiomyopathy: 9-year Clinical Follow-up. / Avaliação Prognóstica da Microalternância da onda T na Cardiomiopatia Hipertrófica em um Seguimento Clínico de 9 anos.

BACKGROUND: Sudden cardiac death (SCD) resulting from ventricular arrhythmia is the main complication of hypertrophic cardiomyopathy (HCM). Microvolt T-wave alternans (MTWA) is associated with the occurrence of ventricular arrhythmias in several heart diseases, but its role in HCM remains uncertain. OBJECTIVE: To evaluate the association of MTWA with the occurrence of SCD or potentially fatal ventricular arrhythmias in HCM patients in a long-term follow-up. METHODS: Patients diagnosed with HCM and NYHA functional class I-II were consecutively selected. At the beginning of the follow-up, the participants performed the MTWA evaluation using the modified moving average during the stress test. The results were classified as altered or normal. The composite endpoint of SCD, ventricular fibrillation, sustained ventricular tachycardia (SVT) or appropriate implantable cardiac defibrillation (ICD) therapy was assessed. The level of significance was set at 5%. RESULTS: A total of 132 patients (mean age of 39.5 ± 12.6 years) were recruited and followed for a mean of 9.5 years. The MTWA test was altered in 74 (56%) participants and normal in 58 (44%). Nine events (6.8%) occurred during the follow-up, with a prevalence of 1.0%/year - six SCDs, two appropriate ICD shocks and one episode of (SVT). Altered MTWA was associated with non-sustained ventricular tachycardia on Holter (p = 0.016), septal thickness ≥30 mm (p < 0.001) and inadequate blood pressure response to effort (p = 0.046). Five patients with altered MTWA (7%) and four patients with normal MTWA (7%) had the primary outcome [OR = 0.85 (95% CI: 0.21 - 3.35, p=0.83)]. Kaplan-Meir event curves showed no differences between normal and altered MTWA. CONCLUSION: Altered MTWA was not associated with the occurrence of SCD or potentially fatal ventricular arrhythmias in HCM patients, and the low rate of these events during long-term follow-up suggests the good prognosis of this heart disease.

FUNDAMENTO: A morte súbita cardíaca (MSC), decorrente de arritmias ventriculares, é a principal complicação da cardiomiopatia hipertrófica (CMH). A microalternância da onda T (MAOT) está associada à ocorrência de arritmias ventriculares em diversas cardiopatias, mas seu papel na CMH permanece incerto. OBJETIVO: Avaliar associação da MAOT com a ocorrência de MSC ou arritmias ventriculares malignas em pacientes com CMH. MÉTODO: Pacientes com diagnóstico de CMH e classe funcional I-II (NYHA) foram selecionados de forma consecutiva. No início do seguimento os participantes realizaram a avaliação da MAOT pela metodologia da média móvel modificada no teste de esforço. Os resultados foram classificados em alterado ou normal. O desfecho foi composto por MSC, fibrilação ventricular, taquicardia ventricular sustentada (TVS) e terapia apropriada do cardioversor desfibrilador implantável (CDI). O nível de significância estatística foi de 5%. RESULTADOS: Um total de 132 pacientes (idade média de 39,5±12,6 anos) foram incluídos, com tempo de seguimento médio de 9,5 anos. A MAOT foi alterada em 74 (56%) participantes e normal em 58 (44%). Durante o seguimento, nove (6,8%) desfechos ocorreram, com prevalência de 1,0%/ano, sendo seis casos de MSC, dois choques apropriados do CDI e um episódio de TVS. MAOT alterada foi associada à taquicardia ventricular não sustentada no Holter (p=0,016), espessura septal≥30 mm (p<0,001) e resposta inadequada da pressão arterial ao esforço (p=0,046). Cinco pacientes (7%) e quatro pacientes (7%) com MAOT alterada e normal, respectivamente, apresentaram desfecho primário [OR=0,85(IC95%: 0,21­3,35, p=0,83)]. Curvas de eventos de Kaplan-Meir não apresentaram diferenças entre MAOT normal e alterada. CONCLUSÃO: A MAOT alterada não foi associada à ocorrência de MSC ou arritmias ventriculares potencialmente fatais em pacientes com CMH, e a baixa taxa desses eventos em um seguimento em longo prazo sugere o bom prognóstico dessa cardiopatia.

Comprehensive review of SGLT2 inhibitors' efficacy through their diuretic mode of action in diabetic patients.

SGLT2 inhibitors (SGLT2i) are now the mainstay therapy for both diabetes and heart failure. Post-hoc publications, meta-analysis, and conference presentations of the eight SGLT2i Cardiovascular Outcomes trials (CVOTS) done in diabetic patients constantly echo that this class of drug decreases mortality, reduces cardiovascular events, and prevents heart failure and kidney disease. This review of medical agencies' SGLT2i analysis (FDA and EMA) helps to understand the reality of SGLT2i results in those trials, avoiding to consider observational and statistically undemonstrated endpoints as validated. They also confirmed the unique diuretic mode of action of SGLT2i, promoting osmotic diuresis, and its potential adverse events secondary to hypovolemia and hematocrit increase. They also support the understanding that the beliefs in SGLT2i morbi-mortality benefits are largely overstated mostly based on undemonstrated endpoints. Finally, it is clear that SGLT2i's antidiabetic action, secondary to its renal mode of action, plateaued after a few months and decreased strongly over time, questioning its long-term goal of maintaining diabetic patients' HbA1c below 7%. Also, this effect in patients with renal impairment is quasi null. We think that this review would be very helpful to every physician treating diabetic patients to better balance belief and reality of SGLT2i prescription effects.

Ocorrência de carcinoma espinocelular labial não melanocítico em usuários crônicos de hidroclorotiazida / Occurrence of non-melanoma labial squamous cell carcinoma in chronic users of hydrochlorothiazide

Diversos autores desenvolveram estudos acerca da potencial associação entre a etiocarcinogênese do carcinoma espinocelular não melanocítico (CECNM) labial e o uso crônico da hidroclorotiazida (HCTZ). Objetivo: A atual revisão objetivou investigar a relação do diurético HCTZ e o risco de CECNM labial. Métodos: Realizou-se uma revisão de literatura nas bases de dados LILACS, PUBMED/MEDLINE e Periódico CAPES, em que foram incluídos artigos em inglês, português e francês, publicados no período de 2017 a 2022. Foram propostos 60 documentos e, dentre esses, 30 foram selecionados para compor a amostra no estudo. Resultados: Foi evidenciada uma relação entre o uso da HCTZ e a ocorrência de CENM com relação dose cumulativa devido às alterações provocadas pelo fármaco, no entanto, em virtude da heterogeneidade de desenhos metodológicos e concentração dos estudos em populações semelhantes, existem limitações quanto à confiabilidade dessas informações. Conclusão: Identificou-se uma desproporção entre a ocorrência e relevância do CENM e a produção científica vigente, demonstrando a necessidade de estudos com metodologias padronizadas que abranjam diferentes especificidades socioeconômicas e demográficas.(AU)

Several authors have developed studies about a potential association between the etiocarcinogenesis of non-melanocytic lip squamous cell carcinoma (NMSCC) and the chronic use of hydrochlorothiazide (HCTZ). Objective: The current study aimed to investigate the relation between the diuretic HCTZ and the risk of lip NMSCC. Methods: A literature review was carried out in the LILACS, PUBMED/MEDLINE and CAPES Periodical databases, which included articles in English, Portuguese and French, published between 2017 and 2022. Sixty documents were collected and, among these, 30 were selected to compose the sample in the study. Results: There was evidence of a relationship between the use of HCTZ and the occurrence of MSCC with a cumulative dose relationship due to changes caused by the drug, however, because of the heterogeneity of methodological designs and concentration of studies in similar populations, there are limitations regarding the reliability of this information. Conclusion: A disproportion between the occurrence and relevance of the NMSCC and the current scientific production was identified, demonstrating the need for studies with standardized methodologies that cover different demographic socioeconomic specificities.(AU)