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

OBJECTIVES

In Asia, younger individuals (below age 45) are diagnosed to have type 2 diabetes with increased rates of obesity defined by lower BMI yet with greater visceral adiposity (waist circumference and waisthip ratios). The prevalence data on type 1 diabetes is not well established, considered to be low, but is seen to be increasing as well. This changing phenotype therefore, presents a clinical dilemma in terms of correctly classifying diabetes and deciding on the consequent appropriate treatment. Distinguishing type 1 from type 2 diabetes has become more difficult with type 2 diabetes dramatically increasing in young adults and children. This study aims to define the characteristics of diabetes among young adults in the Philippines to provide a basis for appropriate management amidst changes in diabetes phenotypes seen globally.

METHODS

In this cross-sectional analytic study, we characterized the demographic, metabolic, and autoimmune features of diabetes among young adult Filipinos aged 18 to 45 years old consulting at a tertiary referral center in Manila, Philippines. Baseline serum A1c, FBS, 75-g oral glucose tolerance test, insulin, serum C-peptide, insulin autoantibodies, leptin, adiponectin, lipid profile, and thyroid function tests were obtained from the participants and analyzed. The homeostasis model assessment (HOMA) was used to estimate the insulin sensitivity.

RESULTS

A total of 348 patients with diabetes were included, with females comprising two-thirds of the participants. The mean age at diagnosis of diabetes was 35.9±7.22 years. The mean BMI was 28.12 kg/m2, with median waist to hip ratio (WHR) of 0·93. Metabolic syndrome was found in 60% of participants and 67.82% were obese by body mass index. The mean A1c was 9.07±2.52%. Good glucose control (A1c less than 7.0%) was seen in 23% of participants  while nearly half (48%) had HbA1c which was >9.0%. The median levels of fasting insulin and C-peptide were 12.62 (range 1.33–90.42) mIU/L and 0.78 ng/mL (range 0–16.2), respectively. 

Included participants were diagnosed with diabetes within a year and as such, majority did not have any micro- or macrovascular complications. The most common diabetes complication was sensory neuropathy detected by monofilament testing, which was found in 28% of participants, followed by non-proliferative diabetic retinopathy in 13%. A history of previous diabetic ketoacidosis was found in 10 patients (2.87%). Glutamic acid decarboxylase (GAD) and insulin auto-antibodies were found in 3.2% and 19.3% of participants, respectively. Approximately half (51.73%) of the participants were insulin resistant by HOMA-IR.

CONCLUSION

In contrast with Caucasians and other Asians, diabetes among young Filipino adults is associated with lower BMI but with a similarly high visceral adiposity as shown by an elevated WHR. Metabolic syndrome with insulin resistance as defined by a variety of indices is predominant. Type 1 diabetes with autoantibodies occur in only a small fraction of this population. Data derived from this work can provide a framework for cluster analysis towards personalized management specific to this population.

Human ; Acids ; Adiponectin ; Adiposity ; Adult ; Aged ; Antibodies ; Asia ; Asian ; Asian Continental Ancestry Group ; Autoantibodies ; Body Mass Index ; C-peptide ; Carboxy-lyases ; Child ; Cluster Analysis ; Demography ; Diabetes Complications ; Diabetes Mellitus ; Diabetes Mellitus, Type 1 ; Diabetes Mellitus, Type 2 ; Diabetic Ketoacidosis ; Diabetic Retinopathy ; Diagnosis ; Fasting ; Female ; Glucose ; Glucose Tolerance Test ; Glutamate Decarboxylase ; Glutamic Acid ; Insulin ; Insulin Resistance ; Ketosis ; Leptin ; Lipids ; Metabolic Syndrome ; Obesity ; Patients ; Peptides ; Phenotype ; Philippines ; Population ; Prevalence ; Serum ; Therapeutics ; Thyroid Gland ; Thyroid Function Tests ; Young Adult

Introduction: The growing popularity of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for weight management has inadvertently perpetuated demand for unregulated experimental peptides procured through gray markets. Retatrutide, a novel triple GLP-1/glucose-dependent insulinotropic polypeptide (GIP)/glucagon receptor agonist undergoing Phase III trials; AOD -9604, an abandoned synthetic human growth hormone fragment; and tesamorelin, a synthetic GHRH analogue, are increasingly self-administered without medical supervision. Their combined metabolic and thromboembolic risks remain unknown and unreported. Case: A 50-year-old Malaysian female with morbid obesity and poorly controlled type 2 diabetes mellitus (hemoglobin A1c 13%) presented with acute dyspnea, chest tightness, syncope, and cardiogenic shock. Three weeks prior, she had self-initiated subcutaneous retatrutide, AOD-9604, and tesamorelin procured through unregulated online platforms, achieving rapid weight loss of 10 kg. Despite markedly reduced oral intake from GLP-1-mediated gastrointestinal side effects, she continued her prescribed high-dose insulin regimen and sodium-glucose cotransporter-2 (SGLT2) inhibitor without dose adjustment. She developed concurrent diabetic ketoacidosis, confirmed biochemically, alongside massive saddle pulmonary embolism with right ventricular strain on echocardiography and computed tomography pulmonary angiography. She was successfully treated with systemic thrombolysis using alteplase, guideline-directed diabetic ketoacidosis management including fixed-rate insulin infusion and fluid resuscitation, and anticoagulation. The SGLT2 inhibitor was withheld throughout admission. She was discharged on rivaroxaban with counseling to cease all unregulated compounds. All three agents were submitted to the National Pharmaceutical Regulatory Authority/Malaysian Adverse Drug Reactions Advisory Committee for adverse drug reaction reporting. Conclusion To our knowledge, this is the first reported case of concurrent massive pulmonary embolism and diabetic ketoacidosis precipitated by unsupervised gray-market retatrutide, AOD-9604, and tesamorelin. Clinicians should enquire about unregistered supplement use, counsel insulin-dependent patients on sick-day rules when appetitesuppressing agents are initiated, and report adverse events to pharmacovigilance authorities.
AOD 9604 ; tesamorelin ; Diabetic Ketoacidosis ; Pulmonary Embolism ; Peptides

Rosacea is a common chronic inflammatory skin disease that predominantly affects the central face. It can impair appearance and cause various discomforts, thus negatively impacting patients' physical and mental well-being as well as their quality of life. Its pathophysiological mechanisms involve multiple factors. Studies have confirmed that ultraviolet radiation plays a significant role in the pathogenesis of rosacea, affecting skin tissues, cells, DNA, and proteins, and inducing oxidative damage. Ultraviolet can lead to the occurrence and development of rosacea by up-regulating the expression of LL-37, matrix metalloproteinase, vascular endothelial growth factor, and reactive oxygen species, and influence their interactions, thereby triggering inflammatory responses, altering the dermal matrix, and promoting capillary dilation and neovascularization, which contribute to the onset and progression of rosacea. Exploring the role of ultraviolet in the pathogenesis of rosacea can provide new strategies for protection and treatment, and enhance awareness of ultraviolet protection among patients with rosacea.
Humans ; Rosacea/metabolism* ; Ultraviolet Rays/adverse effects* ; Cathelicidins ; Reactive Oxygen Species/metabolism* ; Antimicrobial Cationic Peptides/metabolism* ; Matrix Metalloproteinases/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Skin/metabolism*

Peptide-based drugs possess several advantages, including high specificity, low immunogenicity, minimal accumulation, and fewer drug-drug interactions, making them a novel and efficient therapeutic class for various diseases. In recent years, peptide-based drugs have shown great potential and broad application prospects in the treatment of oral infectious diseases, tissue injury and repair, tumors, and complex oral mucosal disorders, acting either through direct mechanisms or indirect modulation. Oral administration remains the preferred route due to its non-invasive, painless nature and ease of management; however, gastrointestinal pH can inactivate or even degrade peptide drugs. In the treatment of oral diseases, local administration is commonly employed, avoiding gastrointestinal degradation and first-pass metabolism. Nevertheless, limitations in current theoretical research and the high cost of peptide synthesis hinder their clinical application. Future efforts should focus on advancing related studies to promote the practical application of peptide-based drugs in the field of oral medicine.
Humans ; Peptides/administration & dosage* ; Mouth Diseases/drug therapy* ; Administration, Oral

The cosmetic sector is a multibillion-dollar industry that requires constant attention being paid to innovative product development and engagement. Notably, its market value is projected to exceed 750 billion U.S. dollars by 2025, and it is expanding as novel, climate-friendly, green, and sustainable components from natural sources are incorporated. This review is written based on the numerous reports on the potential applications of food-derived peptides while focusing on their possible uses in the formulation of cosmeceutical and skincare products. First, the production methods of bioactive peptides linked to cosmeceutical uses are described. Then, we discuss the obtainment and characterization of different anti-inflammatory, antimicrobial, antioxidant, anti-aging, and other pleiotropic peptides with their specific mechanisms, from various food sources. The review concludes with salient considerations of the cost of production and pilot scale operation, stability, compatibility, user safety, site-specificity, and delivery methods, when designing or developing biopeptide-based cosmeceutical products.
Cosmeceuticals/chemistry* ; Peptides/pharmacology* ; Humans ; Antioxidants/pharmacology* ; Anti-Inflammatory Agents/pharmacology* ; Anti-Infective Agents/pharmacology* ; Cosmetics ; Skin Aging/drug effects*

Hippo signaling is a highly conserved pathway central to diverse cellular processes. Dysregulation of this pathway not only leads to developmental abnormalities but is also closely related to the occurrence and progression of various cancers. Recent studies have uncovered that, in addition to the classical signaling cascade regulation, biomolecular condensates formed via phase separation play a key role in the spatiotemporal regulation of Hippo signaling. In this review, we provide a summary of the latest research progress on the regulation of the Hippo signaling pathway by phase separation, with a particular focus on transcriptional activation mediated by Yes-associated protein (YAP)/transcriptional coactivator with post-synaptic density-95, disks-large, and zonula occludens-1 (PDZ)-binding domain (TAZ) condensates. Furthermore, we discuss the utility of chemical crosslinking combined with mass spectrometry to analyze the TAZ condensate interactome and examine the role of the protein fused in sarcoma (FUS) in modulating the biophysical properties of TAZ condensates, which in turn influence their transcriptional activity and pro-tumorigenic functions. These insights not only advance our understanding of Hippo signaling but also offer new perspectives for therapeutic interventions targeting diseases linked to dysregulated YAP/TAZ activity.
Humans ; Signal Transduction ; Hippo Signaling Pathway ; Protein Serine-Threonine Kinases/physiology* ; Animals ; Biomolecular Condensates/metabolism* ; Transcription Factors/metabolism* ; YAP-Signaling Proteins ; Adaptor Proteins, Signal Transducing/metabolism* ; Neoplasms ; Transcriptional Activation ; Intracellular Signaling Peptides and Proteins/metabolism*

Food-derived bioactive peptides (FBPs), particularly those with ten or fewer amino acid residues and a molecular weight below 1300 Da, have gained increasing attention for their safe, diverse structures and specific biological activities. The development of FBP-based functional foods and potential medications depends on understanding their structure‒activity relationships (SARs), stability, and bioavailability properties. In this review, we provide an in-depth overview of the roles of FBPs in treating various diseases, including Alzheimer's disease, hypertension, type 2 diabetes mellitus, liver diseases, and inflammatory bowel diseases, based on the literature from July 2017 to Mar. 2023. Subsequently, attention is directed toward elucidating the associations between the bioactivities and structural characteristics (e.g., molecular weight and the presence of specific amino acids within sequences and compositions) of FBPs. We also discuss in silico approaches for FBP screening and their limitations. Finally, we summarize recent advancements in formulation techniques to improve the bioavailability of FBPs in the food industry, thereby contributing to healthcare applications.
Humans ; Peptides/therapeutic use* ; Structure-Activity Relationship ; Functional Food ; Diabetes Mellitus, Type 2/drug therapy* ; Biological Availability ; Alzheimer Disease/drug therapy* ; Inflammatory Bowel Diseases/drug therapy* ; Hypertension/drug therapy* ; Liver Diseases/drug therapy* ; Bioactive Peptides, Dietary

OBJECTIVES: To investigate the protective effect of Yiqi Yangyin Huazhuo Tongluo Formula (YYHT) against high glucose-induced injury in mouse renal podocytes (MPC5 cells) and the possible mechanism. METHODS: Adult Wistar rats were treated with 19, 38, and 76 g/kg YYHT or saline via gavage for 7 days to prepare YYHT-medicated or blank sera for treatment of MPC5 cells cultured in high glucose (30 mmol/L) prior to transfection with a miR-21a-5p inhibitor or a miR-21a-5p mimic. The changes in miR-21a-5p expressions and the mRNA levels of FoxO1, PINK1, and Parkin in the treated cells were detected with qRT-PCR, and the protein levels of nephrin, podocin, FoxO1, PINK1, and Parkin were detected with Western blotting. Autophagic activity in the cells were evaluated with MDC staining. The effect of miR-21a-5p mimic on FoxO1 transcription and the binding of miR-21a-5p to FoxO1 were examined with luciferase reporter gene assay and radioimmunoprecipitation assay. RESULTS: MPC5 cells exposed to high glucose showed significantly increased miR-21a-5p expression, lowered expressions of FoxO1, PINK1, and Parkin1 mRNAs, and reduced levels of FoxO1, PINK1, parkin, nephrin, and podocin proteins and autophagic activity. Treatment of the exposed cells with YYHT-medicated sera and miR-21a-5p inhibitor both significantly enhanced the protein expressions of nephrin and podocin, inhibited the expression of miR-21a-5p, increased the mRNA and protein expressions of FoxO1, PINK1 and Parkin, and upregulated autophagic activity of the cells. Transfection with miR-21a-5p mimic effectively inhibited the transcription of FoxO1 and promoted the binding of miR-21a-5p to FoxO1 in MPC5 cells, and these effects were obviously attenuated by treatment with YYHT-medicated sera. CONCLUSIONS YYHT-medicated sera alleviate high glucose-induced injury in MPC5 cells by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.
Animals ; MicroRNAs/genetics* ; Podocytes/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Autophagy/drug effects* ; Rats, Wistar ; Protein Kinases/metabolism* ; Rats ; Forkhead Box Protein O1 ; Mice ; Mitochondria/drug effects* ; Ubiquitin-Protein Ligases/metabolism* ; Glucose ; Diabetic Nephropathies ; Male ; Membrane Proteins/metabolism* ; Intracellular Signaling Peptides and Proteins

OBJECTIVES: To investigate the changes in blood levels of calcium and bone metabolism biochemical markers in patients with primary osteoporosis receiving treatment with denosumab. METHODS: Seventy-three patients with primary osteoporosis treated in our Department between December, 2021 and December 2023 were enrolled. All the patients were treated with calcium supplements, vitamin D and calcitriol in addition to regular denosumab treatment every 6 months. Blood calcium, parathyroid hormone (PTH), osteocalcin (OC), type I procollagen amino-terminal propeptide (PINP), and type I collagen carboxy-terminal telopeptide β special sequence (β‑CTX) data before and at 3, 6, 9, and 12 months after the first treatment were collected from each patient. RESULTS: Three months after the first denosumab treatment, the bone turnover markers (BTMs) OC, PINP, and β-CTX were significantly decreased compared to their baseline levels by 39.5% (P<0.001), 56.2% (P<0.001), and 81.8% (P<0.001), respectively. At 6, 9, and 12 months of treatment, OC, PINP, and β-CTX remained significantly lower than their baseline levels (P<0.001). Blood calcium level was decreased (P<0.05) and PTH level increased (P<0.05) significantly in these patients at months of denosumab treatment, but their levels were comparable to the baseline levels at 6, 9, and 12 months of the treatment (P>0.05). CONCLUSIONS Denosumab can suppress BTMs and has a good therapeutic effect in patients with primary osteoporosis, but reduction of blood calcium and elevation of PTH levels can occur during the first 3 months in spite of calcium supplementation. Blood calcium and PTH levels can recover the baseline levels as the treatment extended, suggesting the importance of monitoring blood calcium and PTH levels during denosumab treatment.
Humans ; Denosumab/therapeutic use* ; Calcium/blood* ; Parathyroid Hormone/blood* ; Biomarkers/blood* ; Osteoporosis/blood* ; Osteocalcin/blood* ; Procollagen/blood* ; Female ; Collagen Type I/blood* ; Peptide Fragments/blood* ; Bone Density Conservation Agents/therapeutic use* ; Bone and Bones/metabolism* ; Male ; Middle Aged ; Vitamin D ; Peptides/blood* ; Aged