Search Results (681)

Heart failure readmissions remain a major challenge for healthcare systems, contributing significantly to morbidity, mortality, and increased healthcare costs. Despite advancements in medical and device-based therapies, rehospitalization rates remain high, particularly within the first 30 days of discharge. This review aims to evaluate the primary factors associated with HF readmissions and discuss evidence-based strategies to reduce these rates. The review examines the efficacy of pharmacological therapies and their impact on readmission rates, highlighting key interventions such as diuretics, beta-blockers, ACE inhibitors, ARBs, ARNIs, SGLT2 inhibitors, and intravenous iron supplementation. Additionally, device-based interventions, including CardioMEMS, LVADs, CRT-P/D, ICDs, Furoscix, and the ReDS vest, are critically evaluated for their role in the early detection and management of decompensation. Non-pharmacological strategies are also underscored, such as dietary modifications, exercise, cardiac rehabilitation, and structured follow-up programs. By synthesizing current evidence, this review provides a comprehensive analysis of heart failure readmission factors and proposes multidisciplinary, patient-centered strategies to improve outcomes and reduce hospitalizations. Full article

Systemic Capillary Leak Syndrome (SCLS) and Cytokine Release Syndrome (CRS) have both been described as rare but severe adverse reactions induced by Programmed cell death protein 1 (PD-1) inhibitors such as pembrolizumab. We report the case of a 40-year-old woman undergoing treatment with pembrolizumab for a stage 4 cervical squamous cell carcinoma who presented with anasarca, hypotension, hemoconcentration and signs of multisystemic inflammation. After elimination of alternative causes such as nephrotic syndrome, cardiac dysfunction and cirrhosis, she was diagnosed with both pembrolizumab-induced SCLS and CRS. She was successfully treated with a multimodal treatment approach including intravenous immunoglobulins, steroids, diuretics and axitinib for SCLS as well as ruxolitinib for CRS. After several months of hospitalization, her symptoms finally improved with this treatment regimen, and she was able to attain euvolemic state and be discharged from the hospital. This case highlights certain rare and severe adverse effects of treatment with PD-1 inhibitors. Furthermore, it proposes a novel therapeutic approach for similar cases based upon probable underlying physiopathological mechanisms in SCLS and CRS. Full article

An 89-year-old male developed a persistent high fever (around 39 °C) approximately two weeks following endoscopic reduction of sigmoid volvulus. He had no history of hypercalcemia but was using diuretics and proton pump inhibitors. Renal and thyroid status were normal. He was largely bedridden and asymptomatic except for fever. Laboratory tests demonstrated elevated C-reactive protein (4.75 mg/dL), but some tumor markers (including CEA, CA19-9, and CA125), anti-nuclear antibodies, MPO-ANCA, PR3-ANCA, β-D-glucan, and interferon-gamma release assay were all negative. Urinalysis was unremarkable. Blood cultures obtained from two sets were negative. Chest–abdomen–pelvis contrast-enhanced computed tomography (CT), and echocardiography did not reveal any evident neoplastic lesions or focal sites of infection. Despite various antibiotic therapies, the patient’s spike fever persisted for nearly one month, leading to a diagnosis of fever of unknown origin (FUO). The patient experienced partial symptomatic relief with corticosteroid therapy, though mild fever continued. Two months after the volvulus onset, diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) was performed, revealing hyperintensities at the right sternoclavicular joint, leading to a diagnosis of sternoclavicular arthritis. Neck CT revealed calcification in this joint. Despite difficulty in joint fluid analysis, low infection risk and the patient’s prolonged bedridden state and advanced age led to suspicion of pseudogout. Nonsteroidal anti-inflammatory drugs relieved fever and normalized inflammatory markers. DWIBS may be a valuable tool for detecting potential focus sites in FUO. Full article

Background: Adherence to current clinical guidelines is crucial for ensuring optimal therapy in patients with heart failure (HF). This study aims to explore how cardiologists, as specialists in heart failure, approach the clinical scenarios encountered in the management of HF patients, in line with the recommended guidelines. A heart failure-focused meeting was organized, during which participating cardiologists engaged actively. During HF meetings in which cardiologists participated, 108 questionnaires were distributed electronically. In total, 57 men and 51 women expressed their opinions regarding the Delphi analysis. Results: A strong consensus on the benefits of beta-blockers in improving prognoses for, and reducing mortality in, patients with HF and reduced systolic function emerged. The majority of cardiologists continue to prefer intravenous therapy with continuous loop-diuretic administration in combination with thiazide diuretics. The use of metolazone elicits fewer preferences, probably due to concerns about side effects. Certainly, SGLT2i is useful in reducing hospitalizations and reducing congestion; however, there is no full consensus on whether MRAi should be discontinued in favor of SGLT2i alone. The majority of participants would discontinue MRAs in the presence of hyperkalemia and worsening renal function, maintaining sacubitril/valsartan, and indicating a priority for renal safety. There was near-unanimous agreement on the early initiation of sacubitril/valsartan after the stabilization of patients hospitalized for heart failure. Conclusions: A significant majority (97%) of cardiologists expressed a preference for utilizing all of the guideline-recommended drug classes in the management of heart failure, even if this meant not always reaching the maximum tolerated dose for each medication. This approach underscores the importance of comprehensive therapy, targeting multiple pathophysiological mechanisms in heart failure. Cardiologists emphasized that while achieving optimal dosing is ideal, flexibility in treatment regimens is often necessary to accommodate individual patient characteristics, tolerance, and clinical status. The findings highlight the need for personalized treatment strategies that align with current guidelines, while also recognizing the challenges and variability in patient responses to therapy. Full article

Background/Objectives: Antihypertensive treatment is crucial for preventing major adverse cardiovascular events, but suboptimal adherence remains a challenge. Methods: This is a secondary analysis of routine care data from a large pragmatic trial comparing two thiazide diuretics: chlorthalidone (CTD) and hydrochlorothiazide (HCTZ). In the trial, 13,523 older hypertensive patients were randomized from 72 Veterans Affairs medical centers. Medication possession ratio (MPR), reflecting adherence to either study medication (CTD or HCTZ), was used and compared across all randomized patients. Results: The overall median MPR was 95% for all randomized patients and 80% for 6656 individuals who reached 2.4 years for the average follow-up. Lower MPR was observed in Black, separated, urban-living, and comorbid patients. About 30% of the participants (n = 4022) were categorized as non-adherent using a definition of MPR < 80%. Those with baseline systolic blood pressure ≥ 136, recent smoking history, and prior heart failure and Black participants had decreased odds of having an MPR ≥ 80%, while increased odds of reaching that threshold were observed in those who had an eGFR ≥ 60, received ≥3 antihypertensive medications, were married, or resided in rural areas. Conclusions: This analysis provided assessment of real-world medication adherence in a sizable older hypertensive cohort. The proportion of non-adherence found in our analysis was comparable to national trends for US older adults taking blood pressure medications. Identifying sociodemographic characteristics and health conditions associated with non-adherence can help clinicians design targeted interventions for improved adherence to clinically prescribed medications. This is important as hypertension and the older adult population are both expected to grow significantly in the future. Full article

Chilean Schinus molle has been used in traditional medicine for effects such as antibacterial, antifungal, anti-inflammatory, analgesic, antiviral, antitumoral, antioxidant, antispasmodic, astringent, antipyretic, cicatrizant, cytotoxic, diuretic, among others. In this study, we evaluated the pharmacological potential of Schinus molle seed essential oil extract (SM_EO) through in vitro and in silico approaches. In vitro, the antioxidant potential was analyzed, and antitumor activity was evaluated in non-tumor and human epithelial tumor cell lines. Caenorhabditis elegans was used as a model for evaluating toxicity, and the chemical composition of the SM_EO was analyzed using gas chromatography–mass spectrometry. The oil contained four major monoterpenes: α-phellandrene (34%), β-myrcene (23%), limonene (13%), and β-phellandrene (7%). Based on quantum mechanical calculations, the reactivity of the molecules present in the SM_EO was estimated. The results indicated that α- phellandrene, β-phellandrene, and β-myrcene showed the highest nucleophilic activity. In addition, the compounds following these as candidates for antioxidant and antiproliferative activities were α-phellandrene, β-phellandrene, ρ-cymene, sabinene, caryophyllene, l-limonene, and α-pinene, highlighting β-myrcene. Based on ADME-Tox properties, it is feasible to use these compounds as new drug candidates. Moreover, the antibacterial activity MIC value obtained for B. cereus was equivalent to 2 μg/mL, and for Y. enterocolitica, S. enteritidis, and S. typhimurium, the MIC value was 32.5 μg/μL. SM_EO could selectively inhibit the proliferation of human epithelial mammary tumor MCF7 cells treated with SM_EOs at 64 and 16 ug/mL—a significant increase in BCL-2 in a dose-dependent manner—and showed low toxicity against Caenorhabditis elegans (from 10 to 0.078 mg·mL⁻¹). These findings suggest that SM_EO may be a potential source of bioactive compounds, encouraging further investigation for applications in veterinary medicine, cosmetics, and sanitation. Full article

Objectives: Lermoyez syndrome (LS) is a rare variant of endolymphatic hydrops with a unique clinical presentation characterized by reversible sensorineural hearing loss preceding vertigo. This review aims to synthesize available literature on LS to clarify its clinical characteristics, diagnostic approach, management strategies, and outcomes, and to highlight the distinguishing features from Menière’s disease (MD). Methods: A systematic literature review according to PRISMA guidelines was conducted from 1919 to 2025. The extracted data included demographics, symptom profiles, audiovestibular testing, imaging findings, treatment approaches, and patient outcomes. Results: A total of 23 studies were identified, reporting 53 individual cases of LS. Patients ranged from 27 to 85 years of age, with a mean age of 50.34 years and a male predominance (64.1%). The hallmark of LS across cases was a reproducible clinical pattern of unilateral low-frequency hearing loss followed by vertigo and subsequent auditory recovery. Audiometry typically confirmed reversible sensorineural hearing loss, while vestibular tests and imaging were often unremarkable, primarily used to exclude alternative diagnoses. Treatment approaches varied and were often based on MD protocols, including dietary modifications, vasodilators, diuretics, and vestibular suppressants. Prognosis was generally favorable, with most patients experiencing both hearing recovery and symptom resolution. Conclusions: LS remains a clinically distinct but underrecognized inner ear disorder. Its defining feature—the paradoxical improvement in hearing after vertigo—distinguishes it from Menière’s disease and should prompt clinicians to consider LS in differential diagnosis. Due to the rarity of LS and the lack of standardized guidelines, diagnosis and treatment rely on careful clinical assessment and individualized management strategies. Full article

Cardiorenal syndrome (CRS) is a term used to describe the combined dysfunction of the heart and kidneys. This complex disorder is widely acknowledged to be challenging in both its diagnosis and management, and this is the case particularly in the elderly population, due to multi-morbidity, polypharmacy, and age-related physiological changes. Given advancements in medicine and more prolonged cumulative exposure to risk factors in the elderly population, it is likely that the prevalence of chronic kidney disease (CKD) and heart failure (HF) will continue to rise going forward. Hence, understanding the mechanisms involved in the development of CRS is paramount. There are five different CRS types—they are categorised depending on the primary organ involved the acuity of disease. The pathophysiological process behind CRS is complex, involving the interplay of many processes including hemodynamic changes, neurohormonal activation, inflammation, oxidative stress, and endothelial dysfunction and vascular stiffness. The numerous diagnostic and management challenges associated with CRS are significantly further exacerbated in an elderly population. Biomarkers used to aid the diagnosis of CRS, such as serum creatinine and brain natriuretic peptide (BNP), can be challenging to interpret in the elderly population due to age-related renal senescence and multiple comorbidities. Polypharmacy can contribute to the development of CRS and therefore, before initiating treatment, coordinating a patient-centred, multi-speciality, holistic review to assess potential risks versus benefits of prescribed treatments is crucial. The overall prognosis of CRS in the elderly remains poor. Treatments are primarily directed at addressing the sequelae of the underlying aetiology, which often involves the removal of fluid through diuretics or ultrafiltration. Careful considerations when managing elderly patients with CRS is essential due to the high prevalence of frailty and functional decline. As such, in these patients, early discussions around advance care planning should be prioritised. Full article

After the first release of synthalin B (dodecamethylenbiguanide) in 1928 and its later retraction in the 1940s in Germany, the retraction of phenformin (N-Phenethylbiguanide) and of Buformin in the USA (but not outside) because of the lethal complication of acidosis seemed to have put an end to the era of the biguanides as oral antidiabetics. The strongly hygroscopic metformin (1-1-dimethylbiguanide), first synthesized 1922 and resuscitated as an oral antidiabetic (type 2 of the elderly) compound first released in 1959 in France and in other European countries, was used in the first large multicenter prospective long-term trial in England in the UKPDS (1977–1997). It was then released in the USA after a short-term prospective trial in healthy overweight “young” type 2 diabetics (mean age 53 years) in 1995 for oral treatment of type 2 diabetes. It was, however, prescribed to mostly multimorbid older patients (above 60–65 years of age). Metformin is now the most used oral drug for type 2 diabetes worldwide. While intravenous administration of biguanides does not have any glucose-lowering effect, their oral administration leads to enormous increase in their intestinal concentration (up to 300-fold compared to that measured in the blood), to reduced absorption of glucose from the diet, to increased excretion of glucose through the stool, and to decrease in insulin serum level through increased hepatic uptake and decreased production. Intravenously injected F18-labeled glucose in metformin-treated type 2 diabetics accumulates in the small and even more in the large intestine. The densitometry picture observed in metformin-treated overweight diabetics is like that observed in patients after bowel-cleansing or chronically taking different types of laxatives, where the accumulated radioactivity can even reach values observed in colon cancer. The glucose-lowering mechanism of action of metformin is therefore not only due to inhibition of glucose uptake in the small intestine but also to “attraction” of glucose from the hepatocyte into the intestine, possibly through the insulin-mediated uptake in the hepatocyte and its secretion into the bile. Furthermore, these compounds have also a diuretic effect (loss of sodium and water in the urine) Acute gastrointestinal side effects accompanied by fluid loss often lead to the drugs’ dose reduction and strongly limit adherence to therapy. Main long-term consequences are “chronic” dehydration, deficiency of vitamin B12 and of iron, and, as observed for all the biguanides, to “chronic” increase in fasting and postprandial lactate plasma level as a laboratory marker of a clinical condition characterized by hypotension, oliguria, adynamia, and evident lactic acidosis. Metformin is not different from the other biguanides: synthalin B, buformin, and phenformin. The mechanism of action of the biguanides as antihyperglycemic substances and their side effects are comparable if not even stronger (abdominal pain, nausea, vomiting, diarrhea, fluid loss) to those of laxatives. Full article

Hypomagnesemia is a frequent and often underrecognized electrolyte disturbance with important clinical consequences, especially in hospitalized and critically ill patients. This multifactorial condition arises from impaired intestinal absorption, renal magnesium wasting, and the effects of various medications. Magnesium, the second most abundant intracellular cation, is crucial in enzymatic and physiological processes; its deficiency is associated with neuromuscular, cardiovascular, and metabolic complications. This narrative review focuses on the mechanisms and clinical consequences of drug-induced hypomagnesemia, highlighting the major drug classes involved such as diuretics, antibiotics, antineoplastic agents, and immunosuppressants. Management strategies include magnesium supplementation and adjunctive therapies like amiloride and SGLT2 inhibitors to reduce renal magnesium losses. Recognizing and addressing drug-induced hypomagnesemia is essential to improve patient outcomes and prevent long-term complications. Full article

Background: Cardiovascular diseases, particularly hypertension, and gastrointestinal disorders represent major public health concerns in Mexico. Although a range of pharmacological treatments exists, their use is associated with adverse effects, highlighting the need for safer therapeutic alternatives. Species of the Ipomoea genus are widely employed in Mexican traditional medicine (MTM) for their purgative, anti-inflammatory, analgesic, and sedative properties. Particularly, Ipomoea purpurea is traditionally used as a diuretic and purgative; its leaves and stems are applied topically for their anti-inflammatory and soothing effects. This study aimed to determine their phytochemical composition and to evaluate the associated vasodilatory activity, modulatory effects on intestinal smooth-muscle motility, and toxicological effects of the methanolic (ME-Ip) and dichloromethane (DE-Ip) extracts obtained from the aerial parts of I. purpurea. Methods: The phytochemical composition of the ME-Ip and DE-Ip extracts of I. purpurea was assessed using UPLC-QTOF-MS and GC-MS, respectively. For both extracts, the vasodilatory activity and effects on intestinal smooth muscle were investigated using ex vivo models incorporating isolated rat aorta and ileum, respectively, whereas acute toxicity was evaluated in vivo. Results: Phytochemical analysis revealed, for the first time, the presence of two glycosylated flavonoids within the Ipomoea genus; likewise, constituents with potential anti-inflammatory activity were detected. The identified compounds in I. purpurea extracts may contribute to the vasodilatory, biphasic, and purgative effects observed in this species. The EC₅₀ values for the vasodilatory effects of the methanolic (ME-Ip) and dichloromethane (DE-Ip) extracts were 0.80 and 0.72 mg/mL, respectively. In the initial phase of the experiments on isolated ileal tissues, both extracts induced a spasmodic (contractile) effect on basal motility, with ME-Ip exhibiting higher potency (EC₅₀ = 27.11 μg/mL) compared to DE-Ip (EC₅₀ = 1765 μg/mL). In contrast, during the final phase of the experiments, both extracts demonstrated a spasmolytic effect, with EC₅₀ values of 0.43 mg/mL for ME-Ip and 0.34 mg/mL for DE-Ip. In addition, both extracts exhibited low levels of acute toxicity. Conclusions: The phytochemical profile and the vasodilatory and biphasic effects of the I. purpurea extracts explain, in part, the use of I. purpurea in MTM. The absence of acute toxic effects constitutes a preliminary step in the toxicological safety assessment of I. purpurea extracts and demonstrates their potential for the development of phytopharmaceutic agents as adjuvants for the treatment of cardiovascular and gastrointestinal disorders. Full article

Objectives: Patients with acute heart failure (AHF) often receive initial non-invasive ventilation (NIV). This study aimed to evaluate the prognostic role of NIV in patients hospitalized for AHF. Methods: This was a retrospective cohort study. We enrolled patients admitted to our cardiac intensive care unit with a diagnosis of AHF. Anthropometric, clinical, pharmacological, and instrumental assessments were collected. Both in-hospital and 180-day post-discharge mortality were evaluated. Results: Among 200 patients (mean age 81 ± 9 years; 52% male), NIV was applied in 80 cases (40%). These patients had more severe NYHA functional class, a higher prevalence of de novo AHF, required higher diuretic doses, and had longer hospital stays. In multivariate analysis, NIV remained significantly associated with length of stay (LOS) (r = 0.26; p = 0.0004). In-hospital mortality was 5% overall and significantly higher in the NIV group compared to non-NIV patients (10% vs. 1.6%, p < 0.001). At 180 days, mortality was also significantly higher in the NIV group [hazard ratio (HR) 1.84; 95% confidence interval (CI): 1.18–2.85; p = 0.006]. After adjusting for age, BNP, CRP, arterial blood gas parameters, renal function, and LVEF, NIV remained an independent predictor of 180-day mortality (HR 1.61; 95% CI: 1.01–2.54; p = 0.04). Conclusions: Patients with AHF who required NIV exhibited more severe disease and longer hospital stays. NIV use was independently associated with both in-hospital and post-discharge mortality, suggesting its potential role as a prognostic marker in AHF. Full article

Chloride, long considered a passive extracellular anion, has emerged as a key determinant in the pathophysiology and management of heart failure (HF) and cardiorenal syndrome. In contrast to sodium, which primarily reflects water balance and vasopressin activity, chloride exerts broader effects on neurohormonal activation, acid–base regulation, renal tubular function, and diuretic responsiveness. Its interaction with With-no-Lysine (WNK) kinases and chloride-sensitive transporters underscores its pivotal role in electrolyte and volume homeostasis. Hypochloremia, frequently observed in HF patients treated with loop diuretics, is independently associated with adverse outcomes, diuretic resistance, and arrhythmic risk. Conversely, hyperchloremia—often iatrogenic—may contribute to renal vasoconstriction and hyperchloremic metabolic acidosis. Experimental data also implicate chloride dysregulation in myocardial electrical disturbances and an increased risk of sudden cardiac death. Despite mounting evidence of its clinical importance, serum chloride remains underappreciated in contemporary risk assessment models and treatment algorithms. This review synthesizes emerging evidence on chloride’s role in HF, explores its diagnostic and therapeutic implications, and advocates for its integration into individualized care strategies. Future studies should aim to prospectively validate these associations, evaluate chloride-guided therapeutic interventions, and assess whether incorporating chloride into prognostic models can improve risk stratification and outcomes in patients with heart failure and cardiorenal syndrome. Full article

The assessment of systemic congestion in acute heart failure (AHF) remains clinically challenging, particularly across different left ventricular ejection fraction (LVEF) phenotypes. This study aimed to evaluate whether differences exist in the degree of congestion, assessed through a multimodal approach including physical examination, biomarkers (NT-proBNP, CA125), and point-of-care ultrasound using the Venous Excess Ultrasound (VExUS) protocol, between patients with preserved (HFpEF) and reduced ejection fraction (HFrEF). We conducted a prospective observational study involving 90 hospitalized AHF patients, 80 of whom underwent a complete VExUS assessment. Although patients with HFrEF exhibited higher levels of NT-proBNP and CA125, and more frequent signs of third-space fluid accumulation such as pleural effusion and ascites, no statistically significant differences were found in VExUS grades between the two groups. These findings suggest that the VExUS protocol provides consistent and reproducible information on systemic venous congestion, regardless of LVEF phenotype. Its integration into clinical practice may help refine congestion assessment and optimize diuretic therapy. Further multicenter studies with larger populations are warranted to validate its diagnostic and prognostic utility and to determine its potential role in guiding individualized treatment strategies in AHF. Full article

Background/Objectives: Acetazolamide is widely used for acute mountain sickness (AMS) prophylaxis. Whilst generally safe, acute kidney injury (AKI) is a rare but serious adverse event. We present a case of anuric AKI following minimal exposure to acetazolamide, contributing to the limited literature on its nephrotoxicity at prophylactic doses. Methods: A 54-year-old previously healthy male ingested 250 mg/day of oral acetazolamide for two days. He developed acute anuria and lumbar pain. Diagnostic evaluation included laboratory tests, imaging, microbiological cultures, autoimmune panels, and diuretic response. No signs of infection, urinary tract obstruction, or systemic disease were found. Results: The patient met KDIGO 2012 criteria for stage 3 AKI, with peak serum creatinine of 10.6 mg/dL and metabolic acidosis. Imaging confirmed non-obstructive nephrolithiasis. Conservative treatment failed; intermittent hemodialysis was initiated. Renal function recovered rapidly, with the normalization of serum creatinine and urinary output by day 4. Conclusions: This case represents the lowest cumulative dose of acetazolamide reported to cause stage 3 AKI. The findings support a pathophysiological mechanism involving sulfonamide-induced crystalluria and intratubular obstruction. Physicians should consider acetazolamide in the differential diagnosis of AKI, even with short-term prophylactic use. Full article