1.Acute lithium toxicity in a patient with multinodular toxic goiter and methimazole-induced agranulocytosis: A case report.
Emmanuel Martin S. DIZON ; Kristian PUNZALAN ; Romulo RAMOS ; Harold Henrison CHIU
Philippine Journal of Internal Medicine 2026;64(1):86-88
BACKGROUND
Lithium has been known as a second-line treatment for hyperthyroidism. However, it has a narrow therapeutic range especially in patients with impaired renal function. Toxicity can cause neurological, gastrointestinal, cardiovascular, and renal symptoms, including rare cases of renal failure needing renal replacement therapy. This case report highlights a rare instance of acute lithium toxicity in a patient with multinodular goiter and chronic kidney disease, following methimazole-induced agranulocytosis.
CASE SUMMARYA 55-year-old Filipino woman with chronic kidney disease and multinodular toxic goiter who developed methimazole-induced agranulocytosis presented with altered mental status after pre-treatment with lithium. Laboratory tests confirmed elevated lithium levels, consistent with acute lithium toxicity. She developed acute kidney injury, necessitating urgent hemodialysis with hemoperfusion. After two sessions, her neurological status and renal function improved. The patient resumed pre-treatment with carbimazole and subsequently underwent successful RAI then maintained on levothyroxine for long-term thyroid management
CONCLUSIONLithium toxicity is rare but can cause life-threatening complications, particularly in patients with pre-existing kidney disease. Hemodialysis remains the treatment of choice for severe toxicity, significantly improving patient outcomes. Lithium toxicity can occur even within therapeutic levels, emphasizing the need for careful monitoring. This case highlights the importance of clinical vigilance when using lithium.
Human ; Female ; Middle Aged: 45-64 Yrs Old ; Agranulocytosis ; Goiter ; Lithium ; Methimazole ; Patients ; Research Report
2.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
3.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
4.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
5.Synergistic Use of Plasmapheresis and Lithium in Refractory Thyroid Storm
Humaira Nuraqilah Mohd Yusof ; Nur Aini Eddy Warman ; Nur Haziqah Baharum ; Aimi Fadilah Mohamad ; Mohd Hazriq Awang ; Fatimah Zaherah Mohamed Shah ; Rohana Abdul Ghani
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):118-
Introduction:
Thyroid storm is a life-threatening endocrine emergency
with a mortality rate of 8–25% despite optimal therapy.
Some patients exhibit a refractory phenotype characterized
by rapid clinical deterioration and failure of conventional
treatment, necessitating early escalation. Therapeutic
plasmapheresis and lithium represent adjunctive therapies
targeting different aspects of thyroid hormone physiology,
yet their combined use remains underexplored.
Case:
A 55-year-old male with Graves’ disease, non-adherent to
treatment since 2020, presented with fever, palpitations,
and dyspnea for 2 days. He recently started on carbimazole
30 mg daily and propranolol 1 week prior. On examination,
blood pressure was 158/74 mmHg, heart rate 180 bpm,
Glasgow Coma Scale 15/15 with bibasal crepitations.
Electrocardiogram showed atrial fibrillation at 168 bpm.
His Burch-Wartofsky score was 95, consistent with thyroid
storm. Standard therapy with propylthiouracil 250 mg QID,
Lugol’s iodine, intravenous hydrocortisone 100 mg TDS,
and carvedilol was commenced. However, after 3 days of
treatment, he developed acute confusion and persistent
fast atrial fibrillation requiring cardioversion. Liver
function remained normal. Plasmapheresis was initiated
on day 4 for six sessions. Propylthiouracil was switched to
methimazole due to a declining white cell count from (5.5–
3.2 ×10⁹/L). Lithium 300 mg BD was added on day 13 due to
inadequate free thyroxine 4 (FT4) reduction. After 1 week
of combined therapy, FT4 decreased from 70 to 35 pmol/L.
Conclusion
Early recognition of refractory disease and timely escalation
are critical as refractory thyroid storm carries high
mortality, especially with cardiovascular and neurological
involvement. When conventional therapy fails, plasmapheresis facilitates rapid clearance of circulating thyroid
hormones and inflammatory mediators, while lithium
inhibits thyroid hormone release, providing an alternative
mechanism when thionamides alone are insufficient. Their
combined use offers a synergistic approach and targets both
circulating and intrathyroidal hormone pools, suggesting
that early dual-modality intervention is essential to
overcome therapeutic resistance and improve overall
outcomes in refractory disease.
Lithium
;
Thyroid Crisis
;
Plasmapheresis
6.CDK5-Induced HCN2 Channel Dysfunction in the Prelimbic Cortex Drives Allodynia and Anxiety-Like Behaviors in Neuropathic Pain.
Lu CHEN ; Shuai CAO ; Yun-Ze LIU ; Qi-Fan YANG ; Jin-Yu YANG ; Dan-Yang ZHANG ; Guo-Guang XIE ; Xiang-Sha YIN ; Ying ZHANG ; Yun WANG
Neuroscience Bulletin 2025;41(12):2254-2271
The prelimbic cortex (PL) plays a critical role in processing both the sensory and affective components of pain. However, the underlying molecular mechanisms remain poorly understood. In this study, we observed a reduction in hyperpolarization-activated cation current (Ih) in layer V pyramidal neurons of the contralateral PL in a mouse model of spared nerve injury (SNI). The expression of hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) channels was also decreased in the contralateral PL. Conversely, microinjection of fisetin, a partial agonist of HCN2, produced both analgesic and anxiolytic effects. Additionally, we found that cyclin-dependent kinase 5 (CDK5) was activated in the contralateral PL, where it formed a complex with HCN2 and phosphorylated its C-terminus. Knockdown of CDK5 restored HCN2 expression and alleviated both pain hypersensitivity and anxiety-like behaviors. Collectively, these results indicate that CDK5-mediated dysfunction of HCN2 in the PL underlies nerve injury-induced mechanical hypersensitivity and anxiety.
Animals
;
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/metabolism*
;
Hyperalgesia/metabolism*
;
Cyclin-Dependent Kinase 5/metabolism*
;
Neuralgia/metabolism*
;
Male
;
Anxiety/metabolism*
;
Mice
;
Potassium Channels/metabolism*
;
Mice, Inbred C57BL
;
Disease Models, Animal
;
Pyramidal Cells/metabolism*
7.Association of serum potassium trajectory with 30-day death risk in patients with sepsis in intensive care unit: a retrospective cohort study.
Shaoxu DENG ; Rui HUANG ; Fei XIA ; Tian ZHANG ; Longjiu ZHANG ; Jiangquan FU
Chinese Critical Care Medicine 2025;37(4):324-330
OBJECTIVE:
To investigate the relationship between the trajectories of serum potassium changes after intensive care unit (ICU) admission and 30-day death risk in patients with sepsis.
METHODS:
A retrospective cohort study was conducted, including adult patients with sepsis admitted to the comprehensive ICU, medical intensive care unit (MICU) and emergency intensive care unit (EICU) of Guizhou Medical University Affiliated Hospital from January 2020 to January 2024. The patients who had a minimum of 5 days' hospitalisation in the ICU and who had at least 7 consecutive days of the serum potassium measurements were classified into five trajectories groups according to group-based trajectory modelling (GBTM) using SAS software. This was based on tendency changes in serum potassium levels in patients after admission to the ICU, which was categorized as follows: slowly increased from a low level group, slowly increased from a medium level of normal range group, slowly decreased from a medium level of normal range group, slowly decreased from a high level group, and slowly increased from a high level of normal range group. The patient's gender, age, medical history, and white blood cell count (WBC), platelet count (PLT), procalcitonin (PCT), activated partial thromboplastin time (APTT), prothrombin time (PT), blood sodium, and serum creatinine (SCr) at the time of admission to the ICU were collected. At the same time, the patient's worst sequential organ failure assessment (SOFA) score within 24 hours of admission to the ICU, length of ICU stay, and 30-day outcome were record. The differences in clinical data among different groups of patients were compared. The 30-day cumulative survival rates of the various serum potassium trajectories were plotted using Kaplan-Meier survival curves, the groups were then compared using the Log-Rank test. A multivariate Cox proportional risk regression analysis was developed to evaluate the independent effect of serum potassium trajectory on 30-day death risk.
RESULTS:
Finally, 342 ICU sepsis patients were enrolled, of which 42 patients in the slowly increased from a low level group (12.28%), 127 patients in the slowly increased from a medium level of normal range group (37.14%), 118 patients in the slowly decreased from a medium level of normal range group (34.50%), 28 patients in the slowly decreased from a high level group (8.19%), and 27 patients in the slowly increased from a high level of normal range group (7.89%). Except for age and APTT differences, there were no statistically significant differences in other clinical characteristics among the patients in the different serum potassium trajectories groups. Kaplan-Meier survival curves showed that there was statistically significant difference in the 30-day cumulative survival rate among the patients in the different serum potassium trajectories groups (Log-Rank test: χ2 = 14.696, P = 0.005), with the lowest in the slowly increased from a high level of normal range group (39.3%). Multivariate Cox proportional risk regression analysis showed that the patients with the serum potassium trajectory of slowly increased from a high level of normal range had the highest 30-day death risk [hazard ratio (HR) = 2.341, 95% confidence interval (95%CI) was 1.049-5.226, P = 0.038]. This association persisted after adjustment for variables such as gender, age, medical history, SOFA score, WBC, PLT, PCT, APTT, PT, blood sodium, and SCr (HR = 3.058, 95%CI was 1.249-7.488, P = 0.014).
CONCLUSION
Compared with the patients whose serum potassium fluctuated within the normal range, the sepsis patients in the ICU with a serum potassium trajectory that slowly increased from a high level of normal range had a significantly higher 30-day death risk.
Humans
;
Retrospective Studies
;
Intensive Care Units
;
Sepsis/blood*
;
Potassium/blood*
;
Male
;
Female
;
Middle Aged
;
Aged
;
Risk Factors
;
Hospital Mortality
;
Prognosis
8.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
9.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
10.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


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