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.

METHODS

This 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.

RESULTS

Two 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.

CONCLUSION

Overall 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

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*

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

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

BACKGROUND

Congruent with the increasing prevalence of diabetes, a growing armamentarium of anti-diabetes medications has been introduced. Among these are sodium glucose co-transporter-2 inhibitors (SGLT2i).

OBJECTIVES

SGLT2i use has been linked to an increased incidence of urogenital infections. The study aims to compare resistance patterns of urinary tract isolates among patients with diabetes who are on SGLT2i and not on SGLT2i.

METHODOLOGY

Single-center retrospective cohort study. A total of 464 patients (75 on SGLT2i, 389 not on SGLT2i) with DM type 2 and urinary tract infection were included. Urine culture results were compared.

RESULTS

A similar pattern of urinary tract isolates was found between groups except for C. albicans being more common in the SGLT2i group. There was no significant association between the presence of resistant urinary tract pathogens and the use of SGLT2i. There was no statistically significant difference in resistance rates between groups, except for Imipenem (p = 0.015).

CONCLUSION

SGLT2i use per se does not play a pivotal role in mediating bacterial resistance in urinary tract pathogens among patients with DM type 2. We do not recommend for or against the use of specific antimicrobials based on SGLT2 inhibitor alone. Patient’s clinical profile along with urine culture test results remain key factors in patient management.

Human ; Sodium-glucose Transporter 2 Inhibitors ; Urinary Tract Infections

Although salt-related behaviors may influence urinary salt excretion in early childhood, this relationship remains unclear. This study aimed to examine salt-related behaviors using data from a salt check sheet and urinary salt excretion parameters using spot urine samples from 4-year-old children. This cross-sectional study included all 4-year-old children who underwent health checkups in Ohnan Town, Shimane Prefecture. The study sample consisted of 109 children (49 boys). Measures from spot urine samples included estimated salt excretion (g/day) and the sodium-potassium (Na/K) ratio. Salt-related behaviors were assessed using a salt check sheet that was completed by the parents or guardians. The associations between salt-related behaviors and urinary salt excretion parameters were analyzed using a generalized linear model. The median (M) and interquartile range (IQR) for urinary measures in 4-year-old children were as follows: estimated salt excretion (M = 4.4, IQR: 3.3-6.2) and Na/K ratio (M = 2.3, IQR: 1.4-3.3). The low frequency of consumption of high-salt foods ("such as pickles, pickled plums, etc." and "noodles such as udon and ramen") was associated with low salt excretion and low Na/K ratio. However, in the case of "consumption of udon, ramen, or other soups", the Na/K ratio was higher for "About half a bowl" and "Some" than for "An entire bowl." Additionally, for "eating out or having convenience-store-bought bento (lunch plate) for lunch", the Na/K ratio was higher for "No" than for "Almost every day." In conclusion, the frequency of high-sodium food intake was associated with both urinary sodium excretion and the Na/K ratio in 4-year-old children. Longitudinal investigations using the 24-hour urine collection method are needed to confirm these salt-related behaviors.
Humans ; Child, Preschool ; Male ; Cross-Sectional Studies ; Female ; Sodium Chloride, Dietary/urine* ; Parents ; Sodium/urine* ; Japan ; Potassium/urine*

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

OBJECTIVE: To analyze the clinical characteristics and genetic etiology of a child with Christianson syndrome (CS). METHODS: A 1-year-and-5-month-old boy with CS diagnosed at the First Affiliated Hospital of Zhengzhou University in April 2021 was selected as the study subject. Clinical data were retrospectively analyzed. Peripheral blood samples were obtained from the child and his parents, followed by genomic DNA extraction and whole exome sequencing (WES). Candidate variant was validated by Sanger sequencing. This study has been approved by the Medical Ethics Committee of the Hospital of Zhengzhou University (Ethics No. 2024-KY-1103-001). RESULTS: The child has manifested with seizures, microcephaly, and global developmental delay. WES revealed that he has harbored a novel de novo hemizygous nonsense variant of the SLC9A6 gene, namely c.1014G>A (p.W338*). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic. CONCLUSION The hemizygous c.1014G>A nonsense variant of the SLC9A6 gene probably underlay the pathogenesis in this child. Above discovery has expanded mutational spectrum of the SLC9A6 gene and enabled definite diagnosis of the child.
Humans ; Male ; Infant ; Microcephaly/genetics* ; Spasms, Infantile/genetics* ; Sodium-Hydrogen Exchangers/genetics* ; Exome Sequencing ; Intellectual Disability/genetics* ; Genetic Diseases, X-Linked/genetics* ; Mutation ; Seizures/genetics* ; Ataxia ; Epilepsy ; Ocular Motility Disorders

OBJECTIVE: To evaluate the clinical significance of a hemizygous c.1042-10G>C variant of the SLC9A7 gene NM_001257291.2) previously identified in individuals with neurodevelopmental disorders, and to provide an evidence-based guidance for prenatal genetic counseling. METHODS: Four families presented at the Medical Genetics Center of Henan Provincial People's Hospital between December 2022 and July 2024 were included in this study. Phenotypic information and biological samples were collected from family members. Genomic DNA was extracted and subjected to whole-exome sequencing and copy number variation analysis to identify candidate pathogenic variants. Sanger sequencing was performed for familial co-segregation analysis. Reverse-transcription PCR was used to assess the RNA splicing pattern of the variant in peripheral blood samples. Quantitative PCR was employed to analyze the expression profiles of various SLC9A7 transcripts in fetal brain tissue and peripheral blood samples. Pathogenicity of the variant was classified based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Henan Provincial People's Hospital (Ethics No.: 2021-171). RESULTS: Six hemizygous males carrying the SLC9A7 c.1042-10G>C variant were identified among the four families, which included three adult males and two male infants with normal phenotypes. Only one affected male from family 3 exhibited global developmental delay, short neck, webbed neck, ocular dysplasia, and congenital corneal leukoma. He also had a history of perinatal asphyxia and carried an additional hemizygous variant HUWE1 c.12283C>G. Reverse-transcription PCR showed no aberrant splicing in heterozygous or hemizygous carriers compared to healthy controls, suggesting that the variant does not affect RNA splicing. Quantitative PCR revealed that NM_001257291.2 is the predominant transcript expressed in fetal brain tissue and peripheral blood. CONCLUSION The SLC9A7 c.1042-10G>C variant does not alter RNA splicing and is present in multiple phenotypically normal males, which supported its classification as a benign variant.
Humans ; Male ; Female ; Genetic Counseling ; Pedigree ; Adult ; DNA Copy Number Variations/genetics* ; Sodium-Hydrogen Exchangers/genetics* ; Exome Sequencing

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.

DISCUSSION

An 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.

CONCLUSION

The 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