1.Quality of care among patients with acute heart failure at the emergency room and adherence of physicians at the University of the Philippines – Philippine General Hospital to the division of cardiovascular medicine – heart failure pathway:A retrospective cohort study.
Mark John D. Sabando ; Felix Eduardo R. Punzalan ; Frances Dominique V. Ho ; Tam Adrian P. Aya-ay ; Kevin Paul Da. Enriquez ; Marie Kirk A. Maramara ; Ronald Allan B. Roderos ; Lauren Kay M. Evangelista
Acta Medica Philippina 2026;60(2):22-32
OBJECTIVES
Clinical pathways (CPs) ensure adherence to heart failure (HF) management guidelines. To optimize quality care in a low resource setting, an evidence-based care pathway for the management of acute HF was implemented at the emergency department (ED) of the Philippine General Hospital (PGH), the designated national tertiary hospital and referral center. This study aimed to describe the characteristics of adults with acute HF admitted at the ED and evaluate the quality of care they received, measured using physician adherence to the hospital’s acute heart failure CP.
METHODSThis was a retrospective, descriptive cohort study. We reviewed the inpatient charts of all adult patients with acute HF admitted to the ED of the PGH and referred to the Division of Cardiovascular Medicine between December 1, 2022 and May 31, 2023. Quality of care was assessed based on adherence to quality indicators adapted from routine and conditional order sets detailed in the pathway. Descriptive statistics was utilized to describe patient characteristics, quality of care, and outcomes.
RESULTSTwo hundred thirty-six (236) patients were included, with a mean age of 51.8 years. Majority were male (53.4%); hypertension (61.4%) and ischemic heart disease (53.8%) were the most common comorbidities, and infection the most common precipitant of decompensation (60.6%). There were optimal adherence rates to routine orders, which included referrals to Internal Medicine and Cardiology, baseline vital signs monitoring, fluid intake and output monitoring, chest radiograph, complete blood count, blood urea nitrogen, sodium, potassium, prothrombin time, partial thromboplastin time, arterial blood gas, urinalysis, and N-terminal pro b-type natriuretic peptide. Conditional orders, such as oxygen support, focused echocardiography, thyroid - stimulating hormone, and the use of vasopressors, diuretics, and venous thromboembolism prophylactic agents, were optimally performed when warranted. However, we noted suboptimal adherence to certain resource-intensive conditional orders, such as hourly monitoring of urine output (61.4%), hooking to cardiac monitor (53.8%), and performance of 12-lead ECG within 10 minutes (56.8%). Further, only 43.9% of patients were referred to the intensive care unit. Troponin I, calcium, magnesium, and albumin were ordered in excess.
CONCLUSIONOverall adherence rate of physicians to the hospital’s Acute Heart Failure Pathway was satisfactory. Work is needed to improve adherence to hourly urine output monitoring, consistent hooking to cardiac monitor, and timely performance of 12-lead ECG – an effort that begins with expanding in-hospital diagnostic equipment and human resource supply. We recommend continuous pathway implementation with periodic evaluation and stakeholder feedback to further improve quality of care.
Human ; Male ; Female ; Middle Aged: 45-64 Yrs Old ; Adult ; Albumins ; Blood ; Blood Urea Nitrogen ; Calcium ; Cardiology ; Chart ; Charts ; Cohort Studies ; Critical Care ; Critical Pathways ; Diagnostic Equipment ; Disease ; Diuretics ; Echocardiography ; Electrocardiography ; Emergencies ; Emergency Service, Hospital ; Equipment And Supplies ; Evaluation Studies As Topic ; Feedback ; Heart ; Heart Diseases ; Heart Failure ; Hormones ; Hospitals ; Hospitals, General ; Humans ; Hypertension ; Indicators And Reagents ; Infection ; Infections ; Inpatients ; Intensive Care Units ; Internal Medicine ; Lead ; Magnesium ; Male ; Medicine ; Myocardial Ischemia ; Natriuretic Peptide, Brain ; Natriuretic Peptides ; Nitrogen ; Overall ; Oxygen ; Partial Thromboplastin Time ; Patients ; Peptides ; Philippines ; Physicians ; Potassium ; Prothrombin ; Prothrombin Time ; Quality Of Health Care ; Referral And Consultation ; Sodium ; Statistics ; Tertiary Care Centers ; Thorax ; Thromboembolism ; Thromboplastin ; Thyroid Gland ; Time ; Troponin ; Troponin I ; Universities ; Urea ; Urinalysis ; Urine ; Venous Thromboembolism ; Vital Signs ; Work ; Workforce
2.Efficacy and Safety of SGLT2 Inhibitors in Elderly (≥75 Years) With Type 2 Diabetes: A Real-World Study
Siew Wai Shuit ; Shamharini Nagaratnam ; Fei Bing Yong ; Norisha Nandini Passkaren ; Keen Tien Boey ; Nur Syahirah Asarapoo ; Sathya Rajagopal ; Vikganesa Mahalingam ; Zanariah Hussein
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):36-
Introduction:
Sodium-glucose-linked-transporter inhibitors (SGLT2-i)
have demonstrated cardiovascular and renal benefits in
type 2 diabetes mellitus (T2DM), but patients aged ≥75
years remain underrepresented in major trials, creating
uncertainty regarding their risk–benefit profile. Real-world
data show mixed safety signals. In Malaysia, local evidence
is limited despite a growing elderly diabetic population.
This study evaluates the glycemic efficacy and safety of
SGLT2-i in advanced elderly patients in a real-world public
hospital setting.
Methodology:
We conducted a retrospective observational cohort study
of patients aged ≥75 years with T2DM initiated on SGLT2-i
in Hospital Putrajaya (2020–2024). Electronic records were
reviewed for demographics, comorbidities, medications,
and biochemical parameters. Outcomes at 6–12 months
assessed glycemic control and safety. Adverse events
and discontinuation rates were recorded. Patients with
incomplete data, type 1 diabetes, active malignancy, or
severe renal impairment were excluded.
Results:
A total of 104 patients (mean age 78.2 years; 54% female)
were included with a high proportion (76.9%) classified as at
high cardiovascular risk due to established macrovascular
disease (57.7%) or nephropathy (53.8%). Indications for
SGLT2-i initiation were glycemic control alone (69.2%) and
together with cardiorenal protection (58.7%). Glycemic
control remained stable (hemoglobin A1c: 7.66–7.45%; p =
0.076), with preserved renal function (estimated glomerular
filtration rate: 58.65–58.11 mL/min/1.73 m²; p = 0.575).
Overall safety was favorable, with 90.4% experiencing no
adverse events. Minor adverse events included urinary
tract infections (2.9%) and polyuria (1.9%). ASCVD-related
hospitalizations occurred in 4.8% of patients, with a low
discontinuation rate (7.7%). A statistically significant
weight reduction was observed (baseline 66.67 kg, −1.01
kg; p = 0.005) but was not clinically significant. Proteinuria
improvement was noted in 15.7% of patients.
Conclusion
SGLT2-i are safe and well-tolerated in elderly T2DM
patients (≥75 years), with stable glycemic control, preserved
renal function, and minimal adverse events, supporting
their use in very elderly Asian populations.
Aged
;
Diabetes Mellitus, Type 2
;
Sodium-Glucose Transporter 2 Inhibitors
3.The Hidden Risk of a First-Line Therapy: Renal Abscess With SGLT2 Inhibitor Use
Wei Ton Wong ; Khairi Syazwan Rashid ; Afiq Hazim Ab Rahim
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):52-53
Introduction:
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are
cornerstone therapies for heart failure and diabetes,
offering proven cardiorenal benefits. However, expanded
use necessitates vigilance regarding adverse effects,
particularly genitourinary infections. While mild cystitis is
common, serious upper urinary tract infections remain rare
and potentially life-threatening. We describe a case of renal
abscess presenting as recurrent urinary tract infections
(UTI) following SGLT2 inhibitor initiation, emphasizing
the need for clinical vigilance.
Case:
A 69-year-old male with a significant cardiovascular
history, including heart failure with reduced ejection
fraction (HFrEF), hypertrophic cardiomyopathy with an
implantable cardioverter-defibrillator for non-sustained
ventricular tachycardia, diabetes mellitus, hypertension,
and hyperlipidemia, presented with a 1-week history of
right flank pain, dysuria, urinary frequency, and fever.
Initial labs confirmed infection: leukocytosis (22.6 × 10³/ µL),
markedly elevated CRP (200 mg/L), and bacteriuria. He was
diagnosed with a UTI and started on IV Cefuroxime. This
marked his third UTI admission in 5 months, following
discharge just 3 weeks prior for septic shock secondary
to UTI, establishing a relapsing pattern. Subsequent urine
and blood cultures were unremarkable. Medication review
revealed Dapagliflozin had been initiated for HFrEF
8 months ago. Following clinical improvement from each prior UTI episode, Dapagliflozin was consistently
restarted. Despite an initial antibiotic response, symptoms
recurred after discharge each time. The recurrent nature
of his infections prompted a renal ultrasound revealing a
large (5.3 × 7.5 × 7.4 cm), non-drainable, heterogeneously
hypoechoic collection at the left kidney’s mid-lower pole,
diagnostic of an early renal abscess.
Conclusion
This report highlights renal abscess as a rare and severe
complication of SGLT2 inhibitor therapy. It serves as a
critical reminder that recurrent or relapsing UTIs in patients
on these agents should prompt immediate investigation
with renal imaging to rule out deep-seated pathology
rather than simple cystitis. While these drugs offer proven
cardiorenal benefits, their role in promoting urological
infections necessitates a cautious approach.
Abscess
;
Sodium-Glucose Transporter 2 Inhibitors
4.Pharmacological inhibition of ENaC or NCX can attenuate hepatic ischemia-reperfusion injury exacerbated by hypernatremia.
Yabin CHEN ; Hao LI ; Peihao WEN ; Jiakai ZHANG ; Zhihui WANG ; Shengli CAO ; Wenzhi GUO
Journal of Zhejiang University. Science. B 2025;26(5):461-476
Donors with a serum sodium concentration of >155 mmol/L are extended criteria donors for liver transplantation (LT). Elevated serum sodium of donors leads to an increased incidence of hepatic dysfunction in the early postoperative period of LT; however, the exact mechanism has not been reported. We constructed a Lewis rat model of 70% hepatic parenchymal area subjected to ischemia-reperfusion (I/R) with hypernatremia and a BRL-3A cell model of hypoxia-reoxygenation (H/R) with high-sodium (HS) culture medium precondition. To determine the degree of injury, biochemical analysis, histological analysis, and oxidative stress and apoptosis detection were performed. We applied specific inhibitors of the epithelial sodium channel (ENaC) and Na+/Ca2+ exchanger (NCX) in vivo and in vitro to verify their roles in injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels and the area of hepatic necrosis were significantly elevated in the HS+I/R group. Increased reactive oxygen species (ROS) production, myeloperoxidase (MPO)-positive cells, and aggravated cellular apoptosis were detected in the HS+I/R group. The HS+H/R group of BRL-3A cells showed significantly increased cellular apoptosis and ROS production compared to the H/R group. The application of amiloride (Amil), a specific inhibitor of ENaC, reduced ischemia-reperfusion injury (IRI) aggravated by HS both in vivo and in vitro, as evidenced by decreased serum transaminases, inflammatory cytokines, apoptosis, and oxidative stress. SN-6, a specific inhibitor of NCX, had a similar effect to Amil. In summary, hypernatremia aggravates hepatic IRI, which can be attenuated by pharmacological inhibition of ENaC or NCX.
Animals
;
Reperfusion Injury/drug therapy*
;
Hypernatremia/complications*
;
Rats
;
Liver/metabolism*
;
Rats, Inbred Lew
;
Male
;
Apoptosis
;
Sodium-Calcium Exchanger/antagonists & inhibitors*
;
Reactive Oxygen Species/metabolism*
;
Oxidative Stress
;
Epithelial Sodium Channel Blockers/pharmacology*
;
Epithelial Sodium Channels
;
Cell Line
;
Liver Transplantation
5.Human Cortical Organoids with a Novel SCN2A Variant Exhibit Hyperexcitability and Differential Responses to Anti-Seizure Compounds.
Yuling YANG ; Yang CAI ; Shuyang WANG ; Xiaoling WU ; Zhicheng SHAO ; Xin WANG ; Jing DING
Neuroscience Bulletin 2025;41(11):2010-2024
Mutations in ion channel genes have long been implicated in a spectrum of epilepsy syndromes. However, therapeutic decision-making is relatively complex for epilepsies associated with channelopathy. Therefore, in the present study, we used a patient-derived organoid model with a novel SCN2A mutation (p.E512K) to investigate the potential of utilizing such a model as a platform for preclinical testing of anti-seizure compounds. The electrophysiological properties of the variant Nav1.2 exhibited gain-of-function effects with increased current amplitude and premature activation. Immunofluorescence staining of patient-derived cortical organoids (COs) displayed normal neurodevelopment. Multielectrode array (MEA) recordings of patient-derived COs showed hyperexcitability with increased spiking and remarkable network bursts. Moreover, the application of patient-derived COs for preclinical drug testing using the MEA showed that they exhibit differential responses to various anti-seizure drugs and respond well to carbamazepine. Our results demonstrate that the individualized organoids have the potential to serve as a platform for preclinical pharmacological assessment.
Organoids/physiology*
;
NAV1.2 Voltage-Gated Sodium Channel/genetics*
;
Humans
;
Anticonvulsants/pharmacology*
;
Epilepsy/drug therapy*
;
Mutation
;
Cerebral Cortex/drug effects*
;
Action Potentials/drug effects*
;
Carbamazepine/pharmacology*
6.The relationship between serum sodium concentration and the risk of delirium in sepsis patients.
Chinese Critical Care Medicine 2025;37(5):424-430
OBJECTIVE:
To explore the relationship between serum sodium level and the risk of delirium in patients with sepsis.
METHODS:
Based on the Medical Information Mart for Intensive Care-IV (MIMIC-IV), adult patients with sepsis in the intensive care unit (ICU) were enrolled. The serum sodium level prior to the onset of sepsis during hospitalization was used as the exposure variable. Delirium was assessed using the ICU-confusion assessment method (ICU-CAM) as the primary outcome. Patients were divided into delirium and non-delirium groups based on the occurrence of delirium. The relationship between serum sodium level and delirium risk was described using restricted cubic spline (RCS) to determine the optimal reference range for serum sodium. Logistic regression analysis was used to evaluate the effect of blood sodium levels on delirium in sepsis patients. Subgroup analyses were performed to explore potential interactions and further validate the robustness of the results. Receiver operator characteristic curve (ROC curve) analysis was performed to assess the predictive value of serum sodium level for delirium occurrence in patients with sepsis.
RESULTS:
A total of 13 889 patients with sepsis were included, of which 4 831 experienced delirium. The maximum and mean serum sodium values were significantly higher in the delirium group compared to the non-delirium group, while there were no statistically significant differences in terms of initial and minimum serum sodium values between the two groups. Compared with the non-delirium group, the delirium group had a higher mortality and longer hospital stay. The RCS curve showed that a "U"-shaped relationship between serum sodium level and delirium risk in patients with sepsis, with the optimal reference range for average serum sodium was 135.3-141.3 mmol/L. Group based on this reference range, compared to the group with 135.3 mmol/L ≤ serum sodium ≤ 141.3 mmol/L, the delirium incidence and mortality were significantly higher, and the hospital stay was longer in the groups with serum sodium < 135.3 mmol/L and serum sodium ≥ 141.3 mmol/L [delirium incidence: 36.92%, 40.88% vs. 31.22%; 28-day mortality: 23.08%, 20.15% vs. 13.39%; 90-day mortality: 30.75%, 24.81% vs. 18.26%; in-hospital mortality: 19.53%, 17.48% vs. 11.61%; ICU mortality: 14.35%, 14.05% vs. 9.00%; hospital length of stay (days): 10.1 (6.1, 17.7), 9.4 (5.4, 17.0) vs. 8.9 (5.5, 15.4), length of ICU stay (days): 3.7 (2.1, 7.1), 4.0 (2.1, 8.9) vs. 3.2 (1.9, 6.8); all P < 0.01]. Logistic regression analysis showed that, in the initial model and each factor-adjusted models, compared to the reference group with 135.3 mmol/L ≤ serum sodium < 141.3 mmol/L, serum sodium < 135.3 mmol/L increased the risk of delirium in septic patients by 21% to 29% [odds ratio (OR) was 1.21-1.29, all P < 0.01], while serum sodium ≥ 141.3 mmol/L increased the delirium risk by 28%-52% (OR was 1.28-1.52, all P < 0.01). Subgroup analyses based on gender, age, race, diuretic use, and sequential organ failure assessment (SOFA) score revealed there was no significant interactions between subgroup variables and serum sodium, and the results supported that both serum sodium < 135.3 mmol/L and serum sodium ≥ 141.3 mmol/L were risk factors for delirium in septic patients. ROC curve analysis showed that the area under the curve (AUC) for predicting delirium in septic patients based on serum sodium was 0.614, with a cut-off value of 139.5 mmol/L yielding a specificity of 67.5% and sensitivity of 50.9%.
CONCLUSIONS
The risk of delirium in patients with sepsis is associated with serum sodium level in a "U"-shaped manner. Both high and low serum sodium levels are associated with increased risk of delirium, higher all-cause mortality, and prolonged hospital stays in patients with sepsis. Abnormal serum sodium levels may have predictive value for sepsis-associated delirium and could serve as an early biomarker for identifying delirium in septic patients, although further validation is needed.
Humans
;
Delirium/etiology*
;
Sepsis/complications*
;
Sodium/blood*
;
Intensive Care Units
;
Risk Factors
;
Male
;
Middle Aged
;
Female
;
Aged
;
Logistic Models
;
Adult
7.Effect of YTH Domain Family Protein 2 on the Sodium Arsenite-Induced Malignant Transformation of Skin Cells.
Wen-Xiao XIONG ; Tian-He ZHAO ; Ke-Yan LONG ; Zun-Zhen ZHANG
Acta Academiae Medicinae Sinicae 2025;47(3):333-342
Objective To investigate the effect of liquid-liquid phase separation(LLPS)of YTH domain family protein 2(YTHDF2)on the sodium arsenite-induced malignant transformation of skin cells,providing a new intervention target for the prevention and control of sodium arsenite-induced carcinogenesis.Methods The HaCaT cell model of malignant transformation was constructed by continuous treatment with 1 μmol/L sodium arsenite for 22 weeks,including cells with normal YTHDF2 LLPS(YTHDF2-wt)and cells with inhibited YTHDF2 LLPS(YTHDF2-mut).Confocal microscopy was employed to observe and characterize the LLPS droplets formed by YTHDF2 during sodium arsenite-induced malignant transformation of skin cells.Cell proliferation,scratch healing,and colony formation assays were performed to detect malignant phenotypes.Western blotting,quantitative reverse transcription PCR,and immunofluorescence experiments were conducted to examine the effects of YTHDF2 LLPS on the mRNA and protein levels of phosphatase and tensin homolog deleted on chromosome ten(PTEN)during sodium arsenite-induced malignant transformation of skin cells.Results After 4 weeks of sodium arsenite treatment,LLPS droplets of YTHDF2 appeared in YTHDF2-wt cells,and the number of droplets gradually increased as the treatment time was prolonged(F=35.252,P<0.001),while no phase-separated droplets were observed in YTHDF2-mut cells.Compared with YTHDF2-mut cells,YTHDF2-wt cells showed enhanced proliferation at the time points of 48 h(t=3.654,P=0.006)and 72 h(t=5.458,P<0.001)after 22 weeks of sodium arsenite treatment.The scratch healing rate of YTHDF2-wt cells was increased at the 8th(t=12.137,P<0.001)and 22th(t=4.484,P=0.011)weeks of sodium arsenite treatment.The number of colonies formed by YTHDF2-wt cells was higher at the 4th(t=3.365,P=0.027),8th(t=5.580,P=0.005),and 22th(t=3.328,P=0.029)weeks of sodium arsenite treatment.Compared with YTHDF2-mut cells,YTHDF2-wt cells showed down-regulated protein(t=-3.119,P=0.036)and mRNA(t=4.051,P=0.015) levels of PTEN after 22 weeks of sodium arsenite treatment.Immunofluorescence results showed that after 4 weeks of sodium arsenite treatment,YTHDF2 LLPS droplets in YTHDF2-wt cells were localized to stress granules,translation-related membrane-less organelles.Conclusions During sodium arsenite-induced malignant transformation of skin cells,YTHDF2 undergoes LLPS and localizes to stress granules,translation-related membrane-less organelles.YTHDF2 LLPS participates in sodium arsenite-induced malignant transformation of skin cells by down-regulating the mRNA level of the key tumor suppressor PTEN.
Arsenites/toxicity*
;
Sodium Compounds/toxicity*
;
Humans
;
Cell Transformation, Neoplastic/drug effects*
;
PTEN Phosphohydrolase/metabolism*
;
Cell Proliferation
;
Skin/cytology*
;
RNA-Binding Proteins
;
Skin Neoplasms/chemically induced*
;
Cell Line
8.The trojan horse - A case of transthyretin cardiac amyloidosis diagnosed via multi-modality imagin
Gwen R. Marcellana ; Lynnette Marie C. Tan ; Jared Alphonse S. Cordero ; Carmen N. Chungunco ; Christian Michael H. Pahway ; Nathania S. Fajardo
Philippine Journal of Cardiology 2025;53(1):115-120
BACKGROUND
Observational studies have increasingly reported transthyretin amyloid cardiomyopathy (ATTR-CM) as an under-recognized cause of heart failure. We report the first ATTR-CM diagnosed via multi-modality imaging in the Philippines signifying an important milestone in recognition and management of this formerly believed rare disease, locally. Utilization of non-invasive imaging such as echocardiography, cardiac MRI and technetium-99m pyrophosphate scintigraphy (PYP) demonstrates the potential for accurate diagnosis as well as timely and appropriate treatment strategies.
DISCUSSIONAn 81/M Filipino with a history of carpal tunnel surgery, post-percutaneous coronary intervention (PCI), had three months’ history of refractory heart failure symptoms despite optimized medical treatment. His 2D-echo showed an ejection fraction (EF): 45%-50%, increased left ventricular (LV) posterior wall thickness with mild basal inferior wall hypokinesia and ECG: atrial fibrillation with low voltage. Speckle tracking imaging showed average global longitudinal strain: - 6.5% with cherry-on-top pattern on polar strain map. Cardiac MRI demonstrated diffuse late gadolinium enhancement from endocardial to transmural layers of biventricular and biatrial walls, highly suggestive of cardiac amyloidosis (CA). Light-chain amyloidosis was excluded by negative serum/urine protein electrophoresis/immunofixation. Tc-99m PYP scan revealed greater myocardial-than-bone uptake with a Perugini score 3 and calculated heart-to-contralateral ratio of 1.7. Congestion was controlled with intravenous loop diuretics and he was discharged stable with metoprolol succinate, dapagliflozin and apixaban. At the time of paper submission, he is currently being evaluated for tafamidis treatment.
CONCLUSIONThe case highlighted the advantage of multi-modality imaging for noninvasive yet accurate identification of the disease. A tailored approach is required in slowing the disease progression and improving outcomes.
Human ; Male ; Amyloidosis ; Cardiomyopathies ; Percutaneous Coronary Intervention ; Sodium Potassium Chloride Symporter Inhibitors
9.Pharmacotherapy in patients with heart failure with reduced ejection fraction: A systematic review and meta-analysis.
Jia TANG ; Ping WANG ; Chenxi LIU ; Jia PENG ; Yubo LIU ; Qilin MA
Chinese Medical Journal 2025;138(8):925-933
BACKGROUND:
Angiotensin receptor neprilysin inhibitors (ARNIs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) are the cornerstones in treating heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) are included in HFrEF treatment guidelines. However, the effect of SGLT-2i and the five drugs on HFrEF have not yet been systematically evaluated.
METHODS:
PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) from inception dates to September 23, 2022. Additional trials from previous relevant reviews and references were also included. The primary outcomes were changes in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter/dimension (LVEDD), left ventricular end-systolic diameter/dimension (LVESD), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV), left ventricular end-systolic volume index (LVESVI), and left ventricular end-diastolic volume index (LVEDVI). Secondary outcomes were New York Heart Association (NYHA) class, 6-min walking distance (6MWD), B-type natriuretic peptide (BNP) level, and N-terminal pro-BNP (NT-proBNP) level. The effect sizes were presented as the mean difference (MD) with 95% confidence interval (CI).
RESULTS:
We included 68 RCTs involving 16,425 patients. Compared with placebo, ARNI + BB + MRA + SGLT-2i was the most effective combination to improve LVEF (15.63%, 95% CI: 9.91% to 21.68%). ARNI + BB + MRA + SGLT-2i (5.83%, 95% CI: 0.53% to 11.14%) and ARNI + BB + MRA (3.83%, 95% CI: 0.72% to 6.90%) were superior to the traditional golden triangle ACEI + BB + MRA in improving LVEF. ACEI + BB + MRA + SGLT-2i was better than ACEI + BB + MRA (-8.05 mL/m 2 , 95% CI: -14.88 to -1.23 mL/m 2 ) and ACEI + BB + SGLT-2i (-18.94 mL/m 2 , 95% CI: -36.97 to -0.61 mL/m 2 ) in improving LVEDVI. ACEI + BB + MRA + SGLT-2i (-3254.21 pg/mL, 95% CI: -6242.19 to -560.47 pg/mL) was superior to ARB + BB + MRA in reducing NT-proBNP.
CONCLUSIONS:
Adding SGLT-2i to ARNI/ACEI + BB + MRA is beneficial for reversing cardiac remodeling. The new quadruple drug "ARNI + BB + MRA + SGLT-2i" is superior to the golden triangle "ACEI + BB + MRA" in improving LVEF.
REGISTRATION
PROSPERO; No. CRD42022354792.
Humans
;
Heart Failure/physiopathology*
;
Stroke Volume/physiology*
;
Angiotensin Receptor Antagonists/therapeutic use*
;
Angiotensin-Converting Enzyme Inhibitors/therapeutic use*
;
Sodium-Glucose Transporter 2 Inhibitors/therapeutic use*
;
Randomized Controlled Trials as Topic
;
Mineralocorticoid Receptor Antagonists/therapeutic use*
;
Adrenergic beta-Antagonists/therapeutic use*
10.Acupuncture regulates dynamic flux of Ca2+, Na+, and H2O2 in skeletal muscle injury induced by eccentric exercise in rats.
Xue-Lin ZHANG ; Qian ZHAO ; Ai-Shan LIU ; Ming-Liang DUAN ; Jing-Jing DING ; Hua WANG
Acta Physiologica Sinica 2025;77(1):47-61
This study aimed to investigate the effects of acupuncture on dynamic changes in Ca2+, Na+, and H2O2 flux following eccentric exercise-induced muscle injury. The total of 324 healthy male Wistar rats were randomly divided into 6 groups: control group (C), eccentric exercise group (E), eccentric exercise with acupuncture group (EA), EA with TRP channel blocker group (EAT), EA with NOX2 blocker group (EAN) and EA with placebo group (EAP). Gastrocnemius muscles were subject to lengthening contractions with percutaneous electrical stimulation, followed by immediate pretreatment with blocking agents. After 30 min, acupuncture needling was administered to the gastrocnemius muscle, and real-time dynamic changes of Ca2+, Na+ and H2O2 flux were measured with non-invasive micro-test technique during the needle retention period, immediately, 3 h, 6 h, and 24 h post-extraction respectively. Results showed that compared with the E group, acupuncture significantly increased net Ca2+ efflux (P < 0.05), extended the period of net Na+ influx, and significantly decreased net H2O2 efflux (P < 0.05). However, these effects were significantly attenuated in the EAT and EAN groups, where excessive net H2O2 efflux was observed (P < 0.001). These findings indicate that acupuncture regulates the dynamic changes of Ca2+, Na+ and H2O2 flux by activating the TRP channels and interacting with NOX2 activity following eccentric exercise-induced skeletal muscle injury.
Animals
;
Muscle, Skeletal/metabolism*
;
Rats, Wistar
;
Rats
;
Male
;
Calcium/metabolism*
;
Hydrogen Peroxide/metabolism*
;
Physical Conditioning, Animal
;
Sodium/metabolism*
;
Acupuncture Therapy
;
NADPH Oxidase 2


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