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INTRODUCTION: Pancreatic ductal adenocarcinoma is associated with significant morbidity and mortality as most patients present with advanced disease. The development of ascites has been associated with poor outcomes and further characterization and contemporary management strategies are needed. METHODS: A total of 437 patients enrolled in the Gastrointestinal Biobank at Cedars-Sinai Medical Center who had epithelial pancreatic malignancy were included in the prospective cohort group. Overall, 41.7% of patients included in this study developed ascites. Most patients with ascites (>80%) had high serum-ascites albumin gradient ascites. In both univariate and multivariate analysis, a history of ≥1 form of chemotherapy was significantly associated with ascites. Estimated median overall survival in patients with ascites was significantly lower than in patients without ascites, 473 days vs 573 days, and ascites had a hazard ratio of 1.37. RESULTS: Patients with ascites who received diuretics and indwelling peritoneal catheter had an estimated median survival of 133 days from diagnosis of ascites, and those who received only the indwelling peritoneal catheter without diuretics had an estimated median survival of only 54 days. The estimated median survival from the diagnosis of ascites was 92 days, and the median time to puncture was 7 days. The median time from first tap to death was 45 days. DISCUSSION: The use of diuretics is lower than would be expected for patients with pancreatic ductal adenocarcinoma with elevated serum-ascites albumin gradient. Other therapies such as beta blockers should be investigated in this subset of patients. The etiology of ascites in these patients is poorly understood, and further research is needed to establish treatment guidelines and improve outcomes.

BackgroundChildhood cancers are associated with high mortality and morbidity, and some maternal prescription drug use during pregnancy has been implicated in cancer risk. There are few studies on the effects of hypertension, preeclampsia, and the use of antihypertensives in pregnancy on children's cancer risks.ObjectiveThis population-based cohort study analyzed the relationship between hypertension, preeclampsia, and antihypertensives taken during pregnancy and the risks of childhood cancers in the offspring.MethodsData on all children born in Taiwan between 2004 and 2015 (N = 2,294,292) were obtained from the Maternal and Child Health Database. This registry was linked with the National Health Insurance Database and Cancer Registry to get the records of maternal use of diuretics or other antihypertensives in pregnancy and records of children with cancer diagnosed before 13 years. We used Cox proportional hazard modeling to estimate the influence of maternal health conditions and antihypertensive drug exposure on the risks of developing childhood cancers.ResultsOffspring of mothers with hypertension (chronic or gestational) had a higher risk of acute lymphocytic lymphoma [hazard ratio (HR) = 1.87, 95% Confidence Interval (CI) 1.32 - 2.65] and non-Hodgkin's lymphoma (HR = 1.96, 95% CI 1.34 - 2.86). We estimated only a weak increased cancer risk in children whose mothers used diuretics (HR = 1.16, 95% CI 0.77 - 1.74) or used antihypertensives other than diuretics (HR = 1.15, 95% CI 0.86 - 1.54) before birth.ConclusionsIn this cohort study, children whose mothers had chronic and gestational hypertension had an increased risk of developing childhood cancer.

OBJECTIVE: Bronchopulmonary dysplasia (BPD), defined according to the level of respiratory support and supplemental oxygen administered at 36 weeks postmenstrual age, has multi-factorial causes. Diuretics have been used to prevent or treat established BPD and are the most frequently prescribed medication for the management of severe BPD. There is significant variation in the use of diuretics, and there is limited evidence showing improvement in medium to long term outcomes. We explored whether the use of diuretics in infants with BPD reduced the duration of HoT in a service that uses a unified protocol-driven pathway to monitor and wean HoT. MATERIAL AND METHODS: A retrospective cohort study of 281 infants with BPD discharged home with oxygen therapy between 2001 and 2018. Of the 281 infants, 154 had complete data sets and were included in the study population. RESULTS AND CONCLUSIONS: Forty-nine infants (31.8%) were exposed to at least one diuretic, and 105 infants (68.2%) were not exposed to any. There was no difference in the duration of HoT in infants exposed to diuretics compared to those who were unexposed. Infants exposed to diuretics had a significantly longer length of stay (LoS) in the hospital compared to unexposed infants (P < .001). We conclude that in a setting of a service in which diuretics are actively discontinued post-discharge and in which weaning of HoT is driven by a unified protocol, the use of diuretics pre-discharge does not reduce the duration of HoT. [ABSTRACT FROM AUTHOR]

Introduction: Comorbidities are common among older people, and during the last decade, a strong association between heart failure (HF) and cognitive impairment has been found. As much as 40–50% of individuals with HF will also have some degree of cognitive impairment. Previous studies report an undertreatment for some cardiovascular diseases in patients with major neurocognitive disorder (NCD). Objective: The aim of this present study was to explore differences in pharmacological treatment of HF in individuals diagnosed with HF with or without comorbidity of major NCD. Methods: This study combined data from three different Swedish national registers: the Swedish National Patient Register, the Swedish registry for cognitive/dementia disorders (SveDem), and the Swedish Prescribed Drug Register. A logistic regression model including variables for age, sex, major NCD, and nursing home residency was used to analyze associations between drug use and major NCD. Results: We found a lower prevalence of filled prescriptions of renin-angiotensin system (RAS) inhibitors, β-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) among patients with major NCD. Living in a nursing home was associated with lower prevalence of RAS inhibitors, BBs, digitalis glycosides, and sodium-glucose cotransporter-2 (SGLT2) inhibitors. Females were found to have higher odds of using BBs, loop diuretics and digitalis glycosides, and lower odds of using RAS inhibitors and SGLT2 inhibitors than males. Conclusion: Our findings indicate that there is possible undertreatment among individuals with HF identified in specialized care with co-occurring major NCD. Major NCD was associated with less filled prescriptions of basal pharmacological treatments such as RAS inhibitors, BBs, and MRAs. Future research needs to not only investigate this relationship further but also focus on reasons for the undertreatment of HF and other comorbidities within this group. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated whether the oral vasopressin V2 receptor antagonist tolvaptan has beneficial effects on mortality in real-world congestive heart failure (CHF) patients with hypoperfusion (i.e. the wet–cold pattern), from the viewpoint of cardiorenal syndrome. Methods: Data on 5511 consecutive CHF patients were extracted from the Tokyo CCU Network data registry. Congestion and hypoperfusion were defined by Nohria–Stevenson clinical profiles at the time of hospitalization. Propensity scores for tolvaptan use were calculated for each patient and used to assemble two matched cohorts of patients receiving tolvaptan or not in the CHF with and without hypoperfusion groups. Results: Of the entire study cohort, 1073 patients (19%) had CHF with hypoperfusion (i.e. the wet–cold pattern). In-hospital mortality was significantly higher for CHF patients with than without hypoperfusion (log-rank, P < 0.001). The rate of tolvaptan use did not differ significantly between CHF patients with and without hypoperfusion (15% vs. 14%, respectively; P = 0.7848). In the propensity-matched CHF with hypoperfusion cohort, there was a significant association between the use of tolvaptan and a reduction in in-hospital mortality (log-rank, P = 0.0052). Conversely, in the matched CHF without hypoperfusion cohort, tolvaptan use was not associated with in-hospital mortality (log-rank, P = 0.4417). Conclusion: There was a significant association between the use of tolvaptan and a reduction in in-hospital mortality in CHF patients with, but not without, hypoperfusion. These findings hint at possible individualized therapies for patients with CHF. [ABSTRACT FROM AUTHOR]

• The ATHENA-HF clinical trial did not find additional decongestive benefit of spironolactone 100 mg/day for 96 hours in acute heart failure. • We performed a post hoc analysis of whether this spironolactone dosage had any pharmacodynamic effects. • We found that increased spironolactone dosing limited potassium losses in acute heart failure treatment and reduced the need for potassium replacement. • However, patients with acute heart failure and lower serum potassium levels did not experience greater decongestion with this intervention. The ATHENA-HF (Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure) clinical trial found no improvements in natriuretic peptide levels or clinical congestion when spironolactone 100 mg/day for 96 hours was used in addition to usual treatment for acute heart failure. We performed a post hoc analysis of ATHENA-HF to determine whether spironolactone treatment induced any detectable pharmacodynamic effects and whether patients with potentially greater aldosterone activity experienced additional decongestion. Trial subjects previously treated with spironolactone were excluded. We first examined for changes in renal potassium handling. Using the baseline serum potassium level as a surrogate marker of spironolactone activity, we then divided each treatment arm into tertiles of baseline serum potassium and explored for differences in laboratory and clinical congestion outcomes. Among spironolactone-naïve patients, the change in serum potassium did not differ after 24 hours or 48 hours but was significantly greater with spironolactone treatment compared to placebo at 72 hours (0.23 ± 0.55 vs 0.03 ± 0.60 mEq/L; P = 0.042) and 96 hours (0.32 ± 0.51 vs 0.13 ± 0.72 mEq/L; P = 0.046). Potassium supplementation was similar at treatment start and at 24 hours, but spironolactone-treated patients required substantially less potassium replacement at 48 hours (24% vs 36%; P = 0.048), 72 hours (21% vs 37%; P = 0.013), and 96 hours (11% vs 38%; P < 0.001). When the treatment arms were divided into tertiles of baseline serum potassium, there were no differences in the 96-hour log N-terminal pro-B-type natriuretic peptide levels, net fluid loss, urine output, or dyspnea relief in any of the potassium groups, with no effect modification by treatment exposure. Spironolactone 100 mg/day for 96 hours in patients receiving intravenous loop diuresis for acute heart failure has no clear added decongestive ability but does meaningfully limit potassium wasting. [ABSTRACT FROM AUTHOR]

Chlortalidone (CLT) is a thiazide‐type diuretic with high affinity for the erythrocyte carbonic anhydrase. Therapeutically, it is mostly used to treat edema and hypertension due to liver cirrhosis, heart insufficiency, or renal dysfunction. Although diuretics and masking agents are prohibited by the World Anti‐Doping Agency (WADA) at all times in sports, substances belonging to this category are constantly detected in athlete samples, according to WADA's annual testing figures. Within this group of structurally diverse compounds, a threshold of 20 ng/mL has been introduced for six substances solely due to their presence as contaminants in other permitted drugs because of pharmaceutical production processes. In a recent presumptive doping case with a low urinary CLT concentration, the question of unintentional doping, for example, by contaminated non‐steroidal anti‐inflammatory drug intake, arose. To examine this potential scenario, a co‐elimination of low‐dose CLT and hydrochlorothiazide (HCTA; 20 × 50 μg, 0.2 mg/day each) was conducted on five consecutive days in two volunteers. Urine samples were subjected to liquid chromatography‐tandem mass spectrometry (LC–MS/MS). Moreover, we examined the incorporation of CLT in scalp hair. HCTA is rapidly excreted renally in comparatively high concentrations. In contrast, the elimination of CLT is considerably slower (terminal elimination half‐life extended by a factor of 12) and, consequently, much less concentrated in corresponding urine samples (45 and 53 ng/mL, respectively). Conversely, a higher hair incorporation of chlorthalidone was observed with simultaneous dosing of both. The results suggest that an unintentional intake of sub‐therapeutic CLT doses due to contamination might result in an adverse analytical finding. [ABSTRACT FROM AUTHOR]

Overactivation of mineralocorticoid receptors occurs in cardiorenal diseases. Many patients with type 2 diabetes often progress to chronic kidney disease (CKD) and require dialysis. Finerenone is the first oral non-steroidal mineralocorticoid receptor antagonist used in patients with diabetic kidney disease and heart failure. Finerenone (Kerendia®) is more potent than spironolactone in reducing inflammation and fibrosis in CKD and exerts its effect equally on the heart and kidneys, improving cardiovascular outcomes. Research demonstrates that finerenone improves proteinuria and glomerular filtration rate if taken alone or in combination with sodium-glucose transporter 2 inhibitors. Finerenone has been found to decrease mortality in patients with diabetic renal disease and improve quality of life. Its side effects, unlike those of spironolactone, do not include gynecomastia. However, it can result in hyperkalemia, which needs to be monitored. In this review, we aim to investigate the mechanisms of action of finerenone and its implications in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

A 7‐year‐old male castrated Cavalier King Charles Spaniel was hospitalized for 12 days for treatment of severe congestive heart failure secondary to myxomatous mitral valve disease. During that time, 6 serum samples from different days were analyzed for serum biochemical and renin‐angiotensin‐aldosterone system components. Serum chloride concentrations (ranging from 71.6 to 103.1 mmol/L) were inversely related to angiotensin I concentrations, aldosterone concentrations, a surrogate marker of renin activity, and a surrogate marker of adrenal responsiveness to angiotensin II. In light of recent studies showing that hypochloremia is associated with advanced heart failure in dogs and is associated with poor outcomes in people, the information from the dog in this report supports exploration of RAAS dysregulation as an underlying mechanism. [ABSTRACT FROM AUTHOR]

Background: Cirrhotic refractory ascites (RA) patients have few alternatives for treatment. Empagliflozin is now known to have natriuretic and neurohormonal modulatory effects. This research investigated the safety and efficacy of empagliflozin in the management of RA when added to the standard of care (SoC) compared to SoC alone. Methods: Patients were randomized to receive either a fixed dose of 10 mg of empagliflozin plus standard of care (SoC) or SoC alone. Patients were followed up for 3 months. The primary endpoint was achieving no need for large-volume paracentesis (LVP). Results: Forty-two patients were randomized equally, and intention-to-treat was performed. There was a statistically significant decrease in the need for LVP in the empagliflozin group compared to the SoC group (100% in the SoC vs. 42.9% in the empagliflozin group, p < 0.001). By the end of the study, the total resolution of ascites was reported in approximately 24% of patients. Muscle cramps and newly developed hyponatremia were more common in the empagliflozin group, but they were mild. Acute kidney injury was more common in the SoC group. Conclusions: Empagliflozin may be an effective option for use as an add-on therapy in the management of RA, with an accepted safety profile. Trial registration: The trial was registered at www.clinicaltrials.gov under the identifier NCT05430243. The registration was submitted on 18/06/2022. It is available at https://clinicaltrials.gov/study/NCT05430243. [ABSTRACT FROM AUTHOR]

Background: The venous excess ultrasound score (VExUS) is used to objectify systemic venous congestion. The aim of the paper was to determine the association between VExUS grades and worsening renal function (WRF), reduced natriuretic response, diuretics resistance, and mortality in patients with acute heart failure (AHF). Methods: One hundred patients were included, and Doppler ultrasound of hepatic, portal, and renal veins was performed. Severity of congestion was graded using the VExUS score (grade 0, 1, 2, or 3). Sodium concentration in a spot urine sample was assessed in 2 h after the first loop diuretic administration and was adjusted for the prescribed dose of furosemide (31 mmol/40 mg). Diuretics resistance was defined as the need to double the starting dose of intravenous furosemide in 6 h. Results: Patients with VExUS grade 3 showed a higher incidence of WRF (OR: 11.17; 95% CI: 3.86–32.29; p < 0.001) and a decreased natriuretic response: a spot urine sodium content of <50 mmol/L (OR: 21.53; 95% CI: 5.32–87.06; p < 0.001) and an adjusted spot urine sodium content of <31 mmol/40 mg (OR: 9.05; 95% CI: 3.15–25.96; p < 0.001). The risk of diuretic resistance (OR: 15.31; 95% CI: 5.05–46.43; p < 0.001), as well as the need for inotropic and/or vasopressor support (OR: 11.82; 95% CI: 3.59–38.92; p < 0.001), was higher in patients with severe congestion. The hospital mortality rate increased in patients with VExUS grade 3 compared to in patients with other grades (OR: 26.4; 95% CI: 5.29–131.55; p < 0.001). Conclusions: Patients with AHF and VExUS grade 3 showed a higher risk of developing WRF, a decreased diuretic and natriuretic response, a need for inotropic and/or vasopressor support, and a poor prognosis during their hospital stay. [ABSTRACT FROM AUTHOR]

Asthma and cardiovascular disease (CVD) often co-exist. When a patient has both conditions, management requires an approach that addresses the unique challenges of each condition separately, while also considering their potential interactions. However, specific guidance on the management of asthma in patients with CVD and on the management of CVD in patients with asthma is still lacking. Nevertheless, health care providers need to adopt a comprehensive approach that includes both respiratory and CVD health. The management of CVD in patients with asthma requires a delicate balance between controlling respiratory symptoms and minimising potential cardiovascular (CV) risks. In the absence of specific guidelines for the management of patients with both conditions, the most prudent approach would be to follow established guidelines for each condition independently. Careful selection of asthma medications is essential to avoid exacerbation of CV symptoms. In addition, optimal management of CV risk factors is essential. However, close monitoring of these patients is important as there is evidence that some asthma medications may have adverse effects on CVD and, conversely, that some CVD medications may worsen asthma symptoms. On the other hand, there is also increasing evidence of the potential beneficial effects of asthma medications on CVD and, conversely, that some CVD medications may reduce the severity of asthma symptoms. We aim to elucidate the potential risks and benefits associated with the use of asthma medications in patients with CVD, and the potential pulmonary risks and benefits for patients with asthma who are prescribed CVD medications. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusion The TRANSFORM‐HF trial found no difference in clinical outcomes between torsemide versus furosemide after hospitalization for heart failure. This analysis aimed to assess the impact of diuretic dosing on the primary and secondary clinical outcomes.This post‐hoc analysis of TRANSFORM‐HF categorized patients into three groups by discharge diuretic dose: (1) ≤40 mg, (2) >40–80 mg, and (3) >80 mg of furosemide equivalents. The associations between discharge dose and 12‐month clinical events, and change in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ‐CSS), were assessed. Overall, 2379 patients were included, aged 65 years (interquartile range 56–75), 883 (37.1%) women, and 812 (34.2%) Black. Furosemide had adjusted hazard ratios (aHR) for all‐cause mortality of 1.21 (95% confidence interval [CI] 0.91–1.59) for discharge dose group 2 and 1.40 (95% CI 1.04–1.88) for group 3, compared with group 1. For torsemide, aHRs were 1.74 (95% CI 1.32–2.30) for group 2 and 1.58 (95% CI 1.14–2.19) for group 3. No evidence of heterogeneity for the association between increased mortality and higher dose was found by loop diuretic type (pinteraction = 0.17). Higher doses of furosemide and torsemide were associated with increased risk of all‐cause hospitalization and the composite of all‐cause mortality and hospitalization, without evidence of heterogeneity by loop diuretic type (pinteraction > 0.2). Changes in KCCQ‐CSS from baseline at 12 months was similar across dose groups for both drugs.Following hospitalization for heart failure, higher loop diuretic dosing was independently associated with worse clinical and patient‐reported outcomes. The correlation between higher loop diuretic dose and outcomes was consistent, regardless of loop diuretic used. [ABSTRACT FROM AUTHOR]

Aims: Early evaluation of the natriuretic response is recommended to guide diuretic therapy in acute decompensated heart failure (ADHF). However, its implementation in daily practice is hampered by implementation barriers and increased time constraints. The Readily Available Urinary Sodium Analysis in Patients with Acute Decompensated Heart Failure (EASY‐HF) study assessed the feasibility, efficacy and safety of a nurse‐led urinary sodium‐based diuretic titration protocol with the use of a point‐of‐care urinary sodium sensor. Methods and results: The EASY‐HF study was a single‐centre, randomized, open‐label study comparing diuretic management at the treating physician's discretion as standard of care (SOC) with a nurse‐led natriuresis‐guided protocol in patients with ADHF. The LAQUAtwin Sodium Meter (HORIBA) was used as point‐of‐care sensor to measure urine sodium concentration. The primary endpoint was natriuresis after 48 h. Secondary endpoints included safety profile and user‐friendliness of both the protocol and the point‐of‐care sensor. Sixty patients were randomized towards SOC (n = 30) versus protocolized care (n = 30). The mean age was 80 ± 8 years, 25% were women and median N‐terminal pro‐B‐type natriuretic peptide was 4667 (2667–7709) ng/L. Natriuresis after 48 h was significantly higher in the protocolized versus SOC group (820 ± 279 vs. 657 ± 273 mmol; p = 0.027). Pre‐defined safety endpoints were similar among both groups. The sensor‐based protocol was evaluated as easy to use by the nursing staff, and preferred over urinary collections. Conclusion: A nurse‐led diuretic titration protocol via a point‐of‐care urinary sodium sensor was feasible, safe and resulted in an increased natriuresis in ADHF compared to SOC. [ABSTRACT FROM AUTHOR]

Congestion is a common cause of clinical deterioration and the most common clinical presentation at admission in acute heart failure (HF). Therefore, finding effective and sustainable ways to alleviate congestion has become a crucial goal for treating HF patients. Congestion is a result of complex underlying pathophysiology; therefore, it is not a direct cause of the disease but its consequence. Any therapy that directly promotes sodium/water removal only, thus targeting only clinical symptoms, neither modifies the natural course of the disease nor improves prognosis. This review aims to provide a comprehensive evaluation of the current decongestive therapies and propose a new (not diuretic‐centred) paradigm of long‐term congestion management in HF that attempts to correct the underlying pathophysiology, thus improving congestion, preventing its development, and favourably altering the natural course of the disease rather than merely treating its symptoms. [ABSTRACT FROM AUTHOR]

Background: Heart failure is a major health problem especially with the changing lifestyle. It is one of the most common causes for hospital admission especially among the elderly population. Acute decompensated heart failure results in recurrent hospitalisation increasing the morbidity. It also causes poor quality of life and economic burden. Identifying the precipitating factor and studying the prognostic factors can guide the therapeutic management. Objective. To estimate admission serum chloride levels in acute decompensated heart failure and to study correlation of admission serum chloride levels with the duration of stay in these patients. Methods: This study was carried out in the Department of General Medicine, Karnataka Institute of Medical Sciences, Hubballi. Cases were selected among patients who had presented to KIMS hospital, IPD section with the signs and symptoms of acute decompensated heart failure considering the inclusion and exclusion criteria and were studied between December 2020 to December 2022 (2years). Result: Mean age of 106 patients studied is 52.46 years. 59 (57%) of the patients were males. Coronary artery disease was the most common risk factor (66%) for ADHF in the population studied. Mean serum chloride level during admission is 98.56meq/L. Duration of hospital stay in tertile I, II and III were 9, 7.7 and 6.7 days respectively. A low serum chloride level, hypotension and use of inotropes correlated with longer duration of stay in hospital. Serum chloride level during admission was inversely correlated with the duration stay (p=<0.001). Conclusion: Serum chloride level is a significant prognostic factor in acute decompensated heart failure. It plays a key role in neurohormonal regulation of the disease. Hypochloraemia also contributes to development of diuretic resistance. Having serum chloride within normal range helps diuretic therapy in ADHF. [ABSTRACT FROM AUTHOR]

Background: The use of continuous infusion or IV boluses to treat acute decompensated heart failure (ADHF) with loop diuretics is still debatable. Aim and Objective: To evaluate differences between the two administration routes on the thoracic fluid content (TFC) and the renal functions. Methods: Sixty patients with ADHF admitted to the critical care medicine department, Saifee Hospital, Mumbai, were initially enrolled in the study. Twenty patients were excluded due to EF > 40%, myocardial infarction within 30 days, and baseline serum creatinine level > 4.0 mg/dL. Furosemide (120 mg/day) was given to the remaining 50 pts who continued the study after 1:1 randomization to either continuous infusion (group-I, 25 pts) or three equal intermittent daily doses (group-II, 25 pts). Subsequent dose titration was allowed after 24 h, but not earlier, according to patient's response. No other diuretic medications were allowed. All patients were daily evaluated for NYHA class, urine output, TFC, body weight, serum K+, and renal chemistry. Results: The mean and SD age (Q1-Q3) was 55.95±5.27years old with 28 (56%) males. Apart from TFC which was significantly higher in group-I, the admission demographic, clinical, laboratory and comorbid conditions were similar in both groups. There was statistically insignificant tendency for increased urine output during the 1st and 2nd days in group-I compared to group-II (p = .08). The mean and SD values of TFC on admission were high for all patients 66.52±6.84 kΩ-1 compared to normal range of 25-35 kΩ-1 [20] reflecting pulmonary congestion. In both groups, the TFC was significantly reduced after 24 h of furosemide therapy compared to baseline. It decreased from 1 to 66.52±6.84 kΩ-1 in group I (P = <0.001) and from 51±7.65kΩ-1 to 50.5 (41-60.8) in group II (P = .001). The admission TFC values were significantly higher in group I compared to group II (P = .0001). Conclusions: Continuous furosemide infusion in ADHF patients may result in increased diuresis and decreased TFC, but at the expense of a higher risk of renal function degradation and a lack of symptom relief or shorter ICU stays. [ABSTRACT FROM AUTHOR]

Hyponatraemia is the most common electrolyte disorder in hospital patients associated with increased morbidity, mortality, hospital stay and financial burden. The speed of a correction with 3% sodium chloride as a 100- to 150-ml intravenous bolus or continuous infusion depends on the severity and persistence of the symptoms and needs frequent biochemical monitoring. The rapid intermittent administration of hypertonic saline is preferred for treatment of symptomatic hyponatraemia. In asymptomatic mild hyponatraemia, an adequate solute intake with an initial fluid restriction (FR) of 500 ml/day adjusted according to the serum sodium (sNa) levels is preferred. Almost half of the syndrome of inappropriate antidiuretic hormone (SIADH) patients do not respond to FR as first-line therapy. At present, urea and tolvaptan are considered the most effective second-line therapies in SIADH. However, the evidence for guidance on the choice of second-line therapy of hypotonic hyponatraemia is lacking. Oral urea is considered to be a very effective and safe treatment. Mild and asymptomatic hyponatraemia is treated with adequate solute intake (salt and protein) and initial FR with adjustments based on sNa levels. Specific treatment with vaptans may be considered in either euvolaemic or hypervolaemic patients with high ADH activity. In order to ensure optimal patient outcome, close monitoring and readiness for administration of either hypotonic fluids or desmopressin may be crucial in the decision-making process for specific treatment and eventual overcorrection consequences. According to the guidelines, gradual correction and clinical evaluation is preferable over rapid normalization of sNa towards the laboratory reference ranges. [ABSTRACT FROM AUTHOR]

Objectives Area under the concentration–time curve (AUC)–guided dosing of vancomycin was introduced in a clinical setting; however, the target range of non–steady-state AUCs, such as Day 1 AUC and Day 2 AUC, remains controversial. Therefore, we sought to determine pharmacokinetic parameter thresholds and identify independent risk factors associated with acute kidney injury (AKI) to establish a safe initial dosing design for vancomycin administration. Methods A single-centre, retrospective, cohort study of hospitalized patients treated with vancomycin was conducted to determine the threshold of both non–steady-state AUCs (Day 1 and 2 AUCs) and trough levels at the first blood sampling point (therapeutic drug monitoring, TDM). In addition, independent risk factors associated with AKI were evaluated using univariate and multivariate logistic regression analyses. Results The thresholds for predicting AKI were estimated as 456.6 mg·h/L for AUC0-24h, 554.8 mg·h/L for AUC24-48h, 1080.8 mg·h/L for AUC0-48h and 14.0 μg/mL for measured trough levels, respectively. In a multivariate analysis, Day 2 AUC ≥ 554.8 mg·h/L [adjusted odds ratio (OR), 57.16; 95% confidence interval (CI), 11.95–504.05], piperacillin/tazobactam (adjusted OR, 15.84; 95% CI, 2.73–127.70) and diuretics (adjusted OR, 4.72; 95% CI, 1.13–21.01) were identified as risk factors for AKI. Conclusions We identified thresholds for both AUCs in the non–steady-state and trough levels at the first TDM. Our results highlight the importance of monitoring not only the AUC but also trough levels during vancomycin treatment to reduce the likelihood of AKI. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the utility of Pulse index Contour Continuous Cardiac Output (PiCCO) monitoring in critically ill patients. Study Design: Cross-sectional study. Setting: Intensive Care Unti of Sindh Institute of Urology and Transplant, Karachi, Pakistan. Period: October 2022 to March 2023. Methods: Patients presenting with various types of shock, requiring high-dose vasopressors or inotropes, and not responding to initial fluid therapy were analyzed. Demographic details, SOFA score, APACHE score, and invasive hemodynamic parameters using the PiCCO system were documented. Results: Out of 142 ICU admissions, 38 patients were included in the study. Most patients were males (73%) with a median age of 39 years. Significant changes were observed in the cardiac index, cardiac performance index, global ejection fraction, and systemic vascular resistance index (SVRI), all with p-values less than 0.05. The interventions included the initiation of inotropes in 22 patients (57.8%), diuretics in 4 patients (10.5%), and intravenous fluids in 19 patients (50%). Additionally, vasopressor doses were adjusted in 18 patients (47.3%). Initially, patients were presumed to have pure septic shock based on CO2 gap, mixed venous saturation, and echocardiographic assessment. However, after applying PiCCO monitoring, the diagnosis was revised to mixed shock in 21 patients (55.2%). Conclusion: PiCCO monitoring appears to be a valuable tool in the ICU for managing patients with complex hemodynamic profiles, facilitating targeted interventions that lead to significant improvements in hemodynamic stability. [ABSTRACT FROM AUTHOR]

Purpose: To study the association between the use of drugs for hypertension or heart failure, particularly diuretics, and risk of death in COVID-19. Methods: We conducted a cohort study, based on record linked individual-based data from national registers, of all Swedish inhabitants 50 years and older (n = 3,909,321) at the start of the first SARS-CoV-2 wave in Sweden. The association between use of angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), thiazides, loop diuretics, aldosterone antagonists, beta blocking agents and calcium channel blockers at the index date 6 March 2020, and death in COVID-19 during 7 March to 31 July 2020, was analysed using Cox-proportional hazards regression, adjusted for a wide range of possible confounders. Results: Use of loop diuretics was associated with higher risk [adjusted hazard ratio (HR) 1.26; 95% confidence interval (95% CI) 1.17–1.35] and thiazides with reduced risk (0.78; 0.69–0.88) of death in COVID-19. In addition, lower risk was observed for ACEI and higher risk for beta-blocking agents, although both associations were weak. For ARB, aldosterone antagonists and calcium channel blockers no significant associations were found. Conclusion: In this nationwide cohort of nearly 4 million persons 50 years and older, the use of loop diuretics was associated with increased risk of death in COVID-19 during the first SARS-CoV-2 wave in Sweden. This contrasted to the decreased risk observed for thiazides. As treatment with loop diuretics is common, particularly in the elderly, the group most affected by severe COVID-19, this finding merit further investigation. [ABSTRACT FROM AUTHOR]

Aims: The use of loop diuretics in pulmonary arterial hypertension (PAH) is less frequent compared with heart failure. The clinical and prognostic characteristics of PAH patients according to loop diuretic use remain unexplored. In this study, we retrospectively analysed the characteristics and survival of PAH patients requiring different doses of loop diuretics. Methods and results: Patients diagnosed with PAH between 2001 and 2022 at seven European centres for the management of PAH. According to the median equivalent dose of furosemide in the overall cohort, patients were divided into two subgroups: no/low‐dose loop diuretic and high‐dose loop diuretic. Primary outcome was 5 year all‐cause mortality. Among the 397 patients included, 227 (57%) were treated with loop diuretics. Median daily furosemide equivalent dose was 25 mg, and accordingly patients were divided in no/low dose (i.e. ≤25 mg, n = 257, 65%) vs. high dose (i.e. >25 mg, n = 140, 35%). Patients in the high‐dose group were older, more likely to have comorbidities, and had a more severe disease according to the ESC/ERS risk category. Crude 5 year survival was significantly shorter in patients in the high‐dose group, but after adjustment for age, sex, and risk category, high loop diuretic dose was not significantly associated with the primary outcome. Conclusions: Use of high dose of loop diuretics in PAH is associated with a higher burden of comorbidities, more severe disease, and worse survival. However, in PAH, the need of high loop diuretic dose is a marker of disease severity and not an independent prognostic factor. [ABSTRACT FROM AUTHOR]

Background and Aims Many patients are prescribed loop diuretics without a diagnostic record of heart failure. Little is known about their characteristics and prognosis. Methods Glasgow regional health records (2009–16) were obtained for adults with cardiovascular disease or taking loop diuretics. Outcomes were investigated using Cox models with hazard ratios adjusted for age, sex, socioeconomic deprivation, and comorbid disease (adjHR). Results Of 198 898 patients (median age 65 years; 55% women), 161 935 (81%) neither took loop diuretics nor had a diagnostic record of heart failure (reference group), 23 963 (12%) were taking loop diuretics but had no heart failure recorded, 7844 (4%) had heart failure recorded and took loop diuretics, and 5156 (3%) had heart failure recorded but were not receiving loop diuretics. Compared to the reference group, five-year mortality was only slightly higher for heart failure in the absence of loop diuretics [22%; adjHR 1.2 (95% CI 1.1–1.3)], substantially higher for those taking loop diuretics with no record of heart failure [40%; adjHR 1.8 (95% CI 1.7–1.8)], and highest for heart failure treated with loop diuretics [52%; adjHR 2.2 (95% CI 2.0–2.2)]. Conclusions For patients with cardiovascular disease, many are prescribed loop diuretics without a recorded diagnosis of heart failure. Mortality is more strongly associated with loop diuretic use than with a record of heart failure. The diagnosis of heart failure may be often missed, or loop diuretic use is associated with other conditions with a prognosis similar to heart failure, or inappropriate loop diuretic use increases mortality; all might be true. [ABSTRACT FROM AUTHOR]

The escalating threat of antibiotic resistance has led to an increased interest in plant-based antimicrobials as alternative therapeutic agents. Boerhavia diffusa L., commonly known as Punarnava is a medicinal plant extensively utilized in conventional Ayurvedic medication because of its broad spectrum of biological activities, like anti-inflammatory, hepatoprotective and diuretic activities. Despite its widespread use, there is a need for scientific validation of its antibacterial properties, particularly its root extract. This study undertakes a comprehensive phytochemical analysis of Boerhavia diffusa root and evaluates its in-vitro antibacterial activity against a selection of pathogenic bacteria. The results reveal that Boerhavia diffusa root contains multiple bioactive compounds with significant antibacterial activity, thereby supporting its traditional use and suggesting its capacity to provide new antibacterial drugs. [ABSTRACT FROM AUTHOR]

Background: We examined whether denosumab-induced hypocalcaemia is evident in osteoporosis when given loop diuretics that promote urinary calcium excretion. Methods: Japanese Spontaneous Adverse Drug Event Reports was analyzed to examine signals for denosumab-induced hypocalcaemia co-administered loop diuretics. We retrospectively included osteoporotic patients to detect predictors for denosumab-induced hypocalcaemia (corrected calcium level < 8.5 mg/dL) using multivariate logistic regression analysis. We compared differences in corrected calcium levels (ΔCa = nadir-baseline). Results: A significant signal for hypocalcaemia was detected (Reporting odds ratio = 865.8, 95% confidence interval [95% CI]: 596.8 to 1255.9, p < 0.0001). Among 164 patients (hypocalcaemia, 12%), loop diuretics have a significant association with hypocalcaemia (odds ratio [OR] = 6.410, 95% CI: 1.005 to 40.90, p = 0.0494). However, hypocalcaemia was found to be lower in high corrected calcium levels at baseline (OR = 0.032, 95% CI: 0.005 to 0.209, p < 0.0001) and calcium and vitamin D supplementation (OR = 0.285, 95% CI: 0.094 to 0.868, p = 0.0270). In the non-hypocalcaemia, ΔCa decreased significantly in the denosumab plus loop diuretics than in the denosumab alone (-0.9 [-1.3 to -0.7] mg/dL vs. -0.5 [-0.8 to -0.3] mg/dL, p = 0.0156). However, ΔCa remained comparable in the hypocalcaemia despite loop diuretics co-administration (-1.0 [-1.2 to -0.8] mg/dL vs. -0.8 [-1.5 to -0.7] mg/dL, p = 0.7904). Conclusions: Loop diuretics may predispose to developing denosumab-induced hypocalcaemia. [ABSTRACT FROM AUTHOR]

Ascites remains a significant challenge in patients with cirrhosis, posing difficulties in management and affecting prognosis. This review examines the current understanding of ascites, including its underlying mechanisms, symptoms, and treatment options, with a specific focus on the innovative Alfa Pump device. The review begins by discussing traditional approaches to managing ascites while also addressing their limitations and potential complications. It then explores the emergence of the Alfa Pump system, a novel implantable device designed to tackle refractory ascites by continuously draining fluid from the abdomen while minimizing circulatory issues. Through a synthesis of current literature and clinical evidence, this narrative review underscores the importance of a multidisciplinary approach in the management of ascites, with a particular emphasis on the evolving role of the Alfa Pump in improving outcomes and quality of life for patients with refractory ascites. [ABSTRACT FROM AUTHOR]

Background: The main cause of hospitalization in patients with heart failure is hypervolemia. Therefore, the primary treatment strategy involves diuretic therapy using intravenous loop diuretics to achieve decongestion and euvolemia. Some patients with acutely decompensated heart failure (ADHF) do not respond well to diuretic treatment, which may be due to diuretic resistance (DR). Such cases require high doses of diuretic medications and combination therapy with diuretics of different mechanisms of action. Although certain predisposing factors for diuretic resistance have been identified (such as hypotension, type 2 diabetes, impaired renal function, and hyponatremia), further research is needed to identify other pathophysiological markers of DR. Objective: This study aims to identify admission markers that can predict a high requirement for intravenous diuretics in hospitalized patients with decompensated heart failure. Methods: This study included 102 adult patients hospitalized for ADHF. At admission, patients underwent clinical assessment, laboratory parameter evaluation (including the N-terminal prohormone of brain natriuretic peptide [NT-proBNP] levels), and hemodynamic assessment using impedance cardiography (ICG). Hemodynamic profiles were based on the use of parameters such as heart rate (HR), blood pressure (BP), and thoracic fluid content (TFC) as markers of volume status. The analysis included 97 patients with documented doses of intravenous diuretic use. Patients were stratified into two groups based on median diuretic consumption (equivalent to 540 mg of intravenous furosemide): the high-loop diuretic utilization (LDU) group (n = 49) and the low-LDU group (n = 48). Results: Compared to low-LDU patients, high-LDU patients had greater thoracic fluid content at admission, both quantitatively (37.4 ± 8.1 vs. 34.1 ± 6.9 kOhm-1; p = 0.024) and qualitatively (TFC ≥ 35 kOhm-1: 59.2% vs. 33.3%; p = 0.011). Anemia was more common in the high-LDU group (67.4% vs. 43.8%; p = 0.019), as was elevated NT-proBNP (≥median of 3952 pg/mL: 60.4% vs. 37.5%; p = 0.024). High LDU was associated with a significantly longer hospitalization duration (12.9 ± 6.4 vs. 7.0 ± 2.6 days; p < 0.001). Logistic regression analysis identified anemia, elevated NT-proBNP, and high TFC as predictors of high LDU (HR: 2.65, 2.54, and 2.90, respectively). In a multifactorial model, only high TFC remained an independent predictor (HR: 2.60, 95% CI 1.04–6.49; p = 0.038). Conclusions: TFC was the sole independent admission marker of a high requirement for intravenous diuretics in patients hospitalized for decompensated heart failure. An objective assessment of volume status by impedance cardiography may support intensive personalized decongestion therapy. [ABSTRACT FROM AUTHOR]

Background The Swiss Society of General Internal Medicine (SGAIM) has chosen the topic "Recognising drug interactions and preventing side effects" as a quality indicator in the primary care setting. Methodology Retrospectively, in a group practice of 6 general practitioners (GPs), all patients aged 65 and over who were prescribed ≥ 5 long-term medications were identified in the year 2022. These medications were systematically checked for interaction reports using the Compendium® software. Results The 226 patients were on average 77 years old and took an average of 7 different medications. In 188 (83.2%) individuals with drug interaction signals, the severity of the drug interaction was classified as mild in 164 (87.3%), moderate in 21 (11.1%) and severe in 3 (1.6%). Diuretics, antidiabetics and ACE-inhibitors/sartans were most frequently involved. In case of severe drug interaction reports, antidepressant agents and amiodarone were most frequently involved. In the multivariate analysis, no statistically significant associations were identified between the number of drug interaction reports and age, gender or type of residence. Conclusion In over 65-year-olds with polypharmacy (≥ 5 medications) in a GP setting, a software-supported systematic drug interaction check identified drug interactions of the prescribed medication in nine out of ten patients. The vast majority of drug interaction reports were minor and not clinically relevant. The number of drug interactions as an indicator of quality of care is limited, as patient-specific information other than their medication regimens is not taken into account. GPs' classification in the clinical context and the context and the assessment of the benefits and risks of (poly-)medication is indispensable. [ABSTRACT FROM AUTHOR]