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

Introduction: Accounting for less than 2% of all pituitary adenomas, TSHsecreting pituitary adenomas (TSHoma) are an uncommon cause of hyperthyroidism. Majority are macroadenomas with delayed diagnosis as most patients are unwittingly treated for primary hyperthyroidism. Recurring discordant thyroid function test (TFT) with elevated thyroidstimulating hormone (TSH) and Free T4 is a hint and warrants additional investigation to facilitate diagnosis. Case: We report a case of a 48-year-old female who was treated for primary hyperthyroidism since her late 20s with multiple admissions for recurrent congestive heart failure and atrial fibrillation. The cardiac issue was preceded by worsening thyrotoxicosis. Previous thyroid autoantibodies were negative. Of note, she had recurring discordant TFT results from two different assays (TSH:84.7, free thyroxine 4 [FT4]:75.43) (TSH:37.86, FT4:27.34) during admission, excluding assay interference and prompting toward TSHoma or Resistance to Thyroid Hormone (RTH). Examination revealed a large goiter (10 × 8 cm) hard in consistency, and pansystolic murmur over tricuspid area. No thyroid eye disease nor bitemporal hemianopia or clinical sign of acromegaly. Echocardiography showed dilated left atrium and mild to moderate tricuspid regurgitation with preserved ejection fraction. Thyroid-releasing hormone (TRH) stimulation test demonstrated blunted TSH response confirming TSHoma. Anterior pituitary hormone profile revealed normal insulin-like growth factor-1 level with suppressed sex hormones and prolactin, thus excluding co-secreting hormone. Sex hormone-binding globulin level, α-subunit, and T3 suppression test were not done due to unavailability. Magnetic resonance imaging pituitary uncovered pituitary mass measuring (2.6 × 3.3 × 2.2 cm) suggestive of macroadenoma with encasement of cavernous internal carotid arteries and cavernous sinus compression. Computed tomography neck revealed diffuse thyroid enlargement with compressive mass effects onto adjacent structure with trachea narrowing. After discussing with a multidisciplinary team, we planned her for total thyroidectomy followed by transsphenoidal surgery. Conclusion Late presentation and diagnosis in TSHoma remain a major challenge. TFT interpretation is fundamental in identifying the causes of secondary hyperthyroidism to avert detrimental sequalae and to guide optimal treatment.
Atrial Fibrillation ; Thyrotropin

Introduction: Macro-thyroid-stimulating hormone (macro-TSH) is a rare complex formed by monomeric TSH with anti-TSH autoantibodies. Macromolecules of TSH are not renally excreted due to its large size, leading to elevated TSH measurements without clinical consequences. This rare condition frequently mimics subclinical hypothyroidism, often leading to misdiagnosis and inappropriate levothyroxine therapy. Case: A 17-year-old female with major depressive disorder was biochemically diagnosed with subclinical hypothyroidism (TSH 39.06 mIU/L, free thyroxine 4 12.9 pmol/L, antithyroid peroxidase negative) and commenced on levothyroxine. Over 5 years, her TSH levels heavily fluctuated (0.48–82.59 mIU/L) and remained persistently elevated with high-normal free T4 levels despite treatment adherence. An endocrinology consult was obtained, and clinical evaluation revealed a clinically asymptomatic and euthyroid patient, with no family history of thyroid disease or supplement use, and there was no goiter. Assay interference was excluded by analyzing her thyroid function tests on a different platform, which yielded similar biochemical results. Subsequently, a polyethylene glycol (PEG) precipitation test was performed. Her pre-PEG TSH of 29.24 mIU/L decreased significantly to 2.78 mIU/L post-PEG. This yielded a remarkably low TSH recovery rate of 9.5%, strongly indicating the presence of macroTSH. Levothyroxine was then stopped, and she remained clinically euthyroid. Conclusion While gel filtration chromatography remains the gold standard for diagnosing this condition, PEG precipitation is a more accessible, cost-effective, and reliable screening method in clinical practice. A TSH recovery rate below 20% is considered highly suggestive of macro-TSH. Clinicians should maintain a high index of suspicion for macro-TSH in asymptomatic patients presenting with isolated TSH elevations that do not respond to thyroxine therapy. Prompt recognition prevents misdiagnosis and avoids the potential risks of unnecessary thyroid hormone replacement.
Hypothyroidism ; Thyrotropin

Introduction: Isolated hypothyroxinemia (IH) in pregnancy, characterized by low free thyroxine 4 (FT4) with normal thyroidstimulating hormone (TSH), has a reported prevalence of 1.3–8%. We present a diagnostically challenging case that initially mimicked central hypothyroidism before evolving into classic IH. Case: A 37-year-old G4P3 female at 22 + 3 weeks gestation with &beta;-thalassemia trait presented with palpitations and tachycardia (150–184 bpm). A bedside echocardiogram showed volume depletion. Her heart rate improved to 108– 116 bpm following a 1.5 L normal saline bolus. Incidentally, thyroid function tests (TFTs) revealed both low FT4 6.04 pmol/L (7.86–14.41) and low TSH 0.009 mIU/L (0.38–5.33). Anti-thyroid peroxidase antibody was markedly elevated at 360 IU/mL (<35). At 24 + 4 weeks, TFTs showed persistently low FT4 (5.84 pmol/L) and TSH (0.022 mIU/L). Differential diagnoses included central hypothyroidism or assay interference. Tests were repeated using different platforms. Both the Beckman system (FT4: 5.73 pmol/L, TSH: 0.086 mIU/L) and Roche system (FT4: 8.83 pmol/L [12.0–22.0], TSH: 0.11 mIU/L [0.27–4.20]) confirmed low values, ruling out assay interference. Following endocrinology consultation and given her asymptomatic status, IH was considered most likely, and a plan for close monitoring was initiated. Serial follow-up demonstrated biochemical evolution. By 31 + 6 weeks, TFTs showed a low TSH (0.753 mIU/L) with an FT4 level (5.86 pmol/L) within the normal reference range, a pattern typical of IH in pregnancy. Repeat TFTs 6 weeks postpartum showed both TSH and FT4 within normal range. Conclusion This case illustrates a rare and unexpected biochemical progression of IH in pregnancy, initially presenting with a pattern indistinguishable from central hypothyroidism. It underscores that in an asymptomatic, fertile patient, IH can manifest with an atypical pattern early in gestation. The findings suggest that vigilant serial monitoring, rather than immediate extensive pituitary workup, may be a prudent initial approach in such scenarios, as the biochemical profile can normalize toward the classic IH pattern as pregnancy advances.
Female ; Pregnancy ; Thyrotropin

Introduction: Thyroid stimulating hormone (TSH) suppression following differentiated thyroid carcinoma is widely recommended to reduce recurrence risk. However, this strategy assumes cardiovascular tolerance to supraphysiologic thyroid hormone exposure. In patients with advanced structural heart disease, this assumption may fail, exposing a critical limitation of guideline-directed TSH suppression. Case: We report a 71-year-old male with end-stage renal failure on hemodialysis and severe ischemic cardiomyopathy (ejection fraction 23%) who presented with acute decompensation characterized by dyspnea, rapid atrial fibrillation, and non–ST-elevation myocardial infarction. He had a history of papillary thyroid carcinoma treated with total thyroidectomy and radioactive iodine over 20 years prior and was maintained on levothyroxine 200 mcg daily for TSH suppression. Despite biochemically euthyroid indices (TSH 1.8 mIU/L, free thyroxine 4 17 pmol/L), he developed recurrent arrhythmia with heart failure decompensation. This case highlights a dissociation between biochemical euthyroidism and tissue-level thyrotoxicity in a structurally compromised myocardium. Papillary thyroid carcinoma after definitive therapy typically follows an indolent course with low short-term mortality. In contrast, in severe left ventricular dysfunction, excess thyroid hormone increases adrenergic sensitivity and myocardial oxygen demand, precipitating arrhythmia and ischemia. This risk is amplified in end-stage renal disease, where altered hormone handling renders biochemical indices less reliable. Conclusion Biochemical euthyroidism does not equate to physiological safety. In patients with advanced cardiovascular disease, thyroid hormone therapy should be titrated to cardiovascular tolerance rather than oncologic targets alone, and routine TSH suppression may be inappropriate.
Thyroxine ; Heart Failure ; Thyrotropin

Introduction: Discordant thyroid function tests (TFTs), characterized by elevated free thyroxine 4 (FT4) with non-suppressed thyroid-stimulating hormone (TSH), pose a significant diagnostic challenge. Differentiating between Resistance to Thyroid Hormone (RTH) and TSH-secreting pituitary adenoma (TSH-oma) is essential, as management strategies differ substantially. Case: A female with a history of hyperthyroidism diagnosed in 2011 was treated with antithyroid drugs for 1 year before defaulting on follow-up. She was later found to have discordant TFTs at a private centre, where a brain computed tomography scan was reportedly normal. She was referred to our centre for optimization of thyroid function prior to planned thyroidectomy for a solitary large right thyroid nodule measuring 4.2 × 2.8 × 4.7 cm. Fine-needle aspiration cytology demonstrated a benign follicular lesion (Bethesda II). Despite restarting antithyroid medication, she remained clinically euthyroid with no overt thyrotoxic symptoms apart from intermittent palpitations without documented tachycardia. Antithyroid therapy was discontinued. Serial TFTs across multiple assay platforms consistently demonstrated elevated FT4 with inappropriately normal TSH levels. Thyroid autoantibodies, including TSH receptor and anti-thyroid peroxidase antibodies, were negative. Pituitary magnetic resonance imaging showed no evidence of adenoma, and serum &alpha;-subunit level was normal (0.3 ng/ mL), making TSH-oma unlikely. Dynamic testing was not performed as thyrotropin-releasing hormone stimulation was unavailable at our centre, while T3 suppression testing was deemed inappropriate due to symptomatic palpitations. Family screening was not possible as the patient was not in contact with her relatives. In the absence of pituitary pathology and given her largely euthyroid clinical status, RTH was considered the most likely diagnosis. Conclusion This case highlights the importance of considering RTH in patients with persistent discordant TFTs, particularly when clinical findings do not correlate with biochemical abnormalities. Early recognition and appropriate pituitary evaluation are essential to prevent misdiagnosis and avoid unnecessary antithyroid therapy or thyroidectomy.
Pituitary Neoplasms ; Thyroid Hormones ; Thyrotropin

OBJECTIVES: To explore the effects of exogenous trigger (hCG/GnRHa) versus endogenous LH surge in natural cycle IVF/ICSI (NC-IVF/ICSI) for patients with diminished ovarian reserve (DOR). METHODS: A retrospective analysis was conducted on 1,118 NC-IVF/ICSI cycles from two reproductive centers between 2013 and 2024. Propensity score matching (PSM) and multivariate logistic regression were used to adjust for confounding factors. The trigger-day hormone threshold was determined using receiver operating characteristic (ROC) curve analysis. Outcome measures included oocyte retrieval rate, 2PN fertilization rate, clinical available embryo rate, high-quality embryo rate, fresh cycle clinical pregnancy rate (CPR), and live birth rate (LBR). RESULTS: After adjusting for confounders via PSM and logistic regression, the exogenous trigger group demonstrated significantly better outcomes across all the evaluated parameters (oocyte retrieval rate, 2PN fertilization rate, transferable embryo rate, high-quality embryo rate, fresh cycle CPR, and LBR) than the endogenous LH surge group (P<0.05). Age-stratified analysis revealed that for the entire cohort, exogenous triggering significantly increased the number of transferable embryos and high-quality embryos (P<0.001). In the 35-39 years old subgroup, exogenous triggering showed significant advantages in oocyte yield, high-quality embryo rate, CPR, and LBR (P<0.05) and resulted in the most pronounced improvement in LBR (OR=6.25, 95% CI: 1.34-29.23). ROC analysis established a decision-day LH threshold of 19.055 mIU/mL (AUC=0.945, specificity=93.3%) for precise stratification of the clinical pathways. CONCLUSIONS For DOR patients undergoing NC-IVF/ICSI, exogenous triggering comprehensively improves the treatment outcomes, particularly providing significant live birth benefits for women aged 35-40 years. An individualized protocol incorporating the LH threshold (19.055 mIU/mL) effectively enhances embryonic developmental potential and live birth rates.
Humans ; Female ; Ovarian Reserve ; Pregnancy ; Propensity Score ; Retrospective Studies ; Fertilization in Vitro ; Sperm Injections, Intracytoplasmic ; Chorionic Gonadotropin ; Pregnancy Rate ; Logistic Models ; Ovulation Induction/methods* ; Gonadotropin-Releasing Hormone ; Adult ; Oocyte Retrieval

Renal ischemia-reperfusion injury (IRI) is a major contributor to acute kidney injury (AKI), leading to substantial morbidity and mortality. Spexin (SPX), a 14-amino acid endogenous peptide involved in metabolic regulation and immune modulation, has not yet been studied in the context of chronic treatment and renal IRI. This study evaluated the effects of exogenous SPX on renal function, histopathological changes, and molecular pathways in both IRI-induced injured and healthy kidneys. Twenty-eight male BALB/c mice were divided into four groups: control, SPX, IRI, and SPX+IRI. IRI was induced by 30 minutes of bilateral renal ischemia followed by 6 hours of reperfusion. Renal injury markers, histopathological changes, inflammatory mediators, apoptotic markers, and fibrosis-related proteins were analyzed. SPX significantly exacerbated IRI-induced kidney injury by activating the Wnt/β-catenin signaling pathway and promoting the upregulation of pro-inflammatory, pro-apoptotic, and pro-fibrotic mediators. It is noteworthy that SPX exerted more severe deleterious nephrotoxic effects in the healthy kidney compared to those observed in the IRI-induced injured kidney. These findings indicate that chronic treatment with SPX administration may have intrinsic pro-inflammatory, pro-apoptotic and fibrotic properties, raising concerns about its therapeutic potential. Further research is needed to clarify its physiological role and therapeutic implications in kidney diseases.
Animals ; Reperfusion Injury/chemically induced* ; Male ; Mice, Inbred BALB C ; Mice ; Acute Kidney Injury/metabolism* ; Kidney/blood supply* ; Peptide Hormones/adverse effects* ; Apoptosis/drug effects* ; Wnt Signaling Pathway/drug effects* ; Disease Models, Animal

BACKGROUND AND OBJECTIVE

Prolactinoma is the most common functioning tumor of the pituitary gland. While its clinical course and outcomes among different populations have been vastly described in the past, data of prolactinoma among Filipinos has not been explored. This paper aims to describe the clinical profile and outcome of prolactinoma among adult Filipino patients.

METHODS

We conducted a retrospective cohort study including 41 patients with prolactinoma seen at the Philippine General Hospital. The clinical profile, cranial imaging features, treatment modalities given, and their outcomes over a mean follow up of 16 months were evaluated.

RESULTS

The mean age at diagnosis was 36.76 ± 13.99 years. Majority of our cohort were females. Macroprolactinoma were found in 75.61% and giant prolactinoma in 9.76%. The remaining 12.2% were mixed GH and PRL secreting tumors. Most common symptoms at presentation were blurring of vision, headache, and amenorrhea. Median PRL levels was 353 (200-470) ng/ml. Medical therapy with Bromocriptine was the primary treatment modality used in 78% of patients. We found no significant difference between patients who underwent surgical and medical primary treatment modalities in terms of outcomes. At the end of follow up, 82.6% of patients achieved at least more than 50% reduction in their prolactin levels.

CONCLUSION

Overall, our study showed that adult Filipino patients with prolactinoma have a larger tumor size at diagnosis and a lower rate of improvement of gonadal function after treatment. There were no statistically significant differences in clinical and biochemical outcomes between the treatment modalities used.

Human ; Prolactinoma ; Pituitary Neoplasms ; Prolactin

OBJECTIVE: To observe the effects of the "Zhibian" (BL54)-toward-"Shuidao" (ST28) acupuncture on key regulatory factors during mitochondrial apoptosis of testicular tissue in asthenozoospermia mice, and explore the potential mechanism of the protective effect of acupuncture on reproductive function. METHODS: Thirty C57BL/6 male mice were randomly divided into a blank group, a model group and an acupuncture group, 10 mice in each group. In the model and the acupuncture groups, the intraperitoneal injection of cyclophosphamide (30 mg•kg^-1•d^-1) was delivered for 7 days to prepare the asthenozoospermia model. After the success of modeling, the modeled mice in the acupuncture group were intervened with "Zhibian" (BL54)-toward-"Shuidao" (ST28) acupuncture, once daily and the needles were retained for 20 min. The duration of the intervention was 2 weeks. The general condition of each mouse was observed, and the body mass was recorded before modeling, after modeling and after intervention completion. After intervention, the testicular mass was recorded and the weight coefficient was calculated, and the mouse sperm quality was examined; the serum contents of testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were detected using ELISA, the morphology of testicular tissue was observed using HE, the mitochondrial ultra-microstructure of testicular tissue was observed under transmission electrone microscopy, the mitochondrial membrane potential level of testicular tissue was detected using JC-1 staining, the positive rate of apoptosis cell of testicular tissue was observed using TUNEL; and the mRNA and protein expression of b-cell lymphocytoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), cytochrome c (Cyt C), apoptotic protease-activating factor1 (Apaf-1), Caspase-9 and Caspase-3 of testicular tissue was detected using real-time quantitative fluorescence PCR and Western blot methods separately; and the positive expression of Cleaved Caspase-3 of the testicular tissue was detected using immunohistochemistry. RESULTS: Compared with the blank group, the mice were in listless spirits, had shaggy hairs, the reduced appetite and movement, and weight loss in the model group (P<0.01); the testicular mass and the weight coefficient decreased (P<0.01); the total number of sperms, sperm motility, and sperm viability were declined (P<0.01); while the levels of serum T, FSH, and LH were dropped (P<0.01). The morphology of seminiferous tubules in testicular tissue was abnormal, the number of spermatogenic cells and the number of mitochondria decreased, the inner mitochondrial crest was fractured and lost, and vacuoles appeared. The level of mitochondrial membrane potential was reduced (P<0.01); and the positive rate of apoptosis cell in testicular tissue increased (P<0.01). The mRNA and protein expression of Bax, Cyt C, Apaf-1, Caspase-9 and Caspase-3 was elevated (P<0.01, P<0.05), the mRNA and protein expression of Bcl-2 was dropped (P<0.01), and the average absorbance value of Cleaved Caspase-3 increased (P<0.01). When compared with the model group, in the acupuncture group, the general condition of mice was improved, the testicular mass and the weight coefficient elevated (P<0.01); the total number of sperms, sperm motility, and sperm viability increased (P<0.01); while the levels of serum T, FSH, and LH rose (P<0.01). The pathological morphology of testicular tissue and the inner mitochondrial ultra-microstructure were ameliorated, the level of mitochondrial membrane potential was elevated (P<0.01); the positive rate of apoptosis cell was reduced (P<0.01). The mRNA and protein expression of Bax, Cyt C, Apaf-1, Caspase-9 and Caspase-3 was dropped (P<0.01, P<0.05), the mRNA and protein expression of Bcl-2 elevated (P<0.05), and the average absorbance value of Cleaved Caspase-3 declined (P<0.01). CONCLUSION "Zhibian" (BL54)-toward- "Shuidao" (ST28) acupuncture may ameliorate mouse reproductive function by inhibiting mitochondrial apoptosis pathway, alleviating testicular tissue damage in the asthenospermia mice induced by cyclophosphamide.
Animals ; Male ; Mice ; Apoptosis ; Acupuncture Therapy ; Mitochondria/metabolism* ; Asthenozoospermia/genetics* ; Humans ; Testis/metabolism* ; Mice, Inbred C57BL ; Spermatozoa/metabolism* ; Acupuncture Points ; Sperm Motility ; Testosterone/blood* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Caspase 3/genetics* ; Follicle Stimulating Hormone/blood* ; Reproduction ; Cytochromes c/genetics* ; bcl-2-Associated X Protein/genetics* ; Apoptotic Protease-Activating Factor 1/genetics*