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.

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.

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.

CAPOS syndrome is an autosomal dominant neurological disorder caused by mutations in the ATP1A3 gene. Initial symptoms, often fever-induced, include recurrent acute ataxic encephalopathy in childhood, featuring cerebellar ataxia, optic atrophy, areflflexia, sensorineural hearing loss, and in some cases, pes cavus. This report details a case of CAPOS syndrome resulting from a maternal ATP1A3 gene mutation. Both the child and her mother exhibited symptoms post-febrile induction,including severe sensorineural hearing loss in both ears, ataxia, areflexia, and decreased vision. Additionally, the patient's mother presented with pes cavus. Genetic testing revealed a c. 2452G>A（Glu818Lys） heterozygous mutation in theATP1A3 gene in the patient . This article aims to enhance clinicians' understanding of CAPOS syndrome, emphasizing the case's clinical characteristics, diagnostic process, treatment, and its correlation with genotypeic findings.
Humans ; Child ; Female ; Cerebellar Ataxia/diagnosis* ; Talipes Cavus ; Hearing Loss, Sensorineural/diagnosis* ; Optic Atrophy/diagnosis* ; Mutation ; Phenotype ; Sodium-Potassium-Exchanging ATPase/genetics* ; Foot Deformities, Congenital ; Reflex, Abnormal

BACKGROUND: Sacubitril/valsartan is currently a standard medication in the treatment of reduced ejection fraction heart failure (HFrEF), and studies have also shown its efficacy for controlling hypertension. However, its efficacy varies between populations, and current recommendations are predominantly based on non Asian data. Hence, this study synthesizes the available evidence to determine its overall efficacy and safety among Asians. METHODS: A systematic search through PubMed, ScienceDirect, Cochrane, HERDIN PLUS, and ClinicalTrials.gov was done to include randomized controlled trials with Asian data comparing sacubitril/valsartan against an active control. The Cochrane Risk of Bias 2.0 was used to assess each article for bias. Forest plots in fixed-effects model for major adverse cardiovascular events (MACEs), hypertension control, and safety were created using RevMan 5.4. RESULTS AND DISCUSSION: Ten articles with an overall low risk of bias were included involving 6120 Asians. Sacubitril/valsartan showed better hypertension control against conventional angiotensin blocker (odds ratio [OR], 1.63; confidence interval [CI], 1.38–1.92; I2 = 7%). However, MACE reduction was not significant in HFrEF (hazard ratio, 0.89; CI, 0.73–1.08; I2 = 0%) or acute myocardial infarction (hazard ratio, 0.90; CI, 0.65–1.24; I2 = 0%). Safety was comparable to conventional angiotensin-converting enzyme inhibitors angiotensin receptor blocker (ARB) with a severe adverse event OR of 0.81 (CI, 0.44–1.50; I2 = 38%) and nonsevere adverse event OR of 1.09 (CI, 0.88–1.35; I2 = 44%). These results implicate the nee for efficacy studies focused on Asians, reassessment of the strength of recommendations in the treatment of heart failure, and consideration of sacubitril/valsartan as a treatment option for hypertension. CONCLUSION Among Asians, better hypertension control is seen with LCZ696 than conventional ARB. However, MACE reduction in HFrEF or acute myocardial infarction is insignificant, although there is a trend toward benefit. Finally, safety is comparable to conventional angiotensin-converting enzyme inhibitors/ARBs.\.
Asian ; Heart Failure ; Hypertension ; LCZ696 ; sacubitril and valsartan sodium hydrate drug combination

Sodium ; Wastewater ; Potassium ; Diet ; Blood Pressure ; China ; Sodium, Dietary ; Sodium Chloride, Dietary

Sodium nitrite (SN, NaNO2) is a water-soluble, white-yellow crystalline powder with broad applications in food preservation, automotive maintenance, and animal control. It is a strong oxidizing agent that can oxidize hemoglobin iron (Fe) to its oxidized state, leading to methemoglobin formation. An increasing trend of suicide cases by SN ingestion has been reported globally following its popularization in online suicide forums providing detailed instructions of its use solely or as part of a “suicide kit.” We report a case of a 21-year-old male who was found continuously vomiting, with blood per orem and cyanosis of the mouth and digits. Within minutes of the onset of symptoms, the patient lost consciousness and was pronounced dead on arrival at the nearest emergency room. Autopsy findings showed lip erosions, hemorrhage, and perioral and peripheral cyanosis. Internal examination showed characteristic bright red muscle discoloration, dark brown arterial blood, red-brown congested visceral organs, and hyperemic esophageal and gastric mucosa. Methemoglobin studies from sampled arterial blood showed elevated levels (17.5%). Further investigation of the decedent’s belongings, social media posts, and recent online purchases reinforced the intentional sodium nitrite ingestion. While there are plenty of reported SN poisoning in suicide cases internationally, limited reports have been published locally. Death by SN poisoning is preventable with Methylene blue. The role of forensic pathologists through autopsy may be the last chance to detect such cases. The lack of systemic death investigation, experts, and local laboratories to reliably detect the signs of SN poisoning may have affected the low detection rate of cases locally. Further reporting of cases can raise the awareness of medical professionals that is fundamental to the ultimate saving of lives.

BACKGROUND

Caustic ingestion is a major public health problem worldwide [1]. It imposes huge economic burden in terms of medical cost to poorly resourced health system of developing countries [2]. Household cleaning products, such as sodium hypochlorite (NaOCI), are the most common cause of caustic exposure [3]. NaOCI ingestion consistently ranks second in caustic ingestion cases in Northern Mindanao Medical Center (NMMC) based on toxicology census from 2015 to 2018. The aim of this study is to determine the epidemiologic profile, clinical findings and outcome of admitted patients who ingested NaOCI.

This a single-center descriptive, cross-sectional study of 40 cases of sodium hypochlorite ingestion admitted at NMMC from January 2015 to December 2018.

There were a total of 17 males and 23 females. Majority of patients were 0-5 years of age (46.5%; mean age of 2), followed by age range of 18-64 years old (40.0%; mean age of 35). Twenty-nine cases (72. 5%) cases of NaOCI ingestion were accidental and the remaining 11 (27.5%) were non-accidental. The non-accidental cases belong to the 12-17 (mean age 15.3) and 18-64 (mean age 31) years old age groups at 33.3% and 66.7%, respectively, with prevalence in females at 81.8%. Non-accidental cases increase with age, and among females. Majority of all ingested less than 50 ml of NaOCI. Two non-accidental cases (18.2%) ingested more than 100 ml of NaOCI were observed to have more than 2 signs and symptoms. Majority of patients presented with vomiting. Greater portion of non- accidental cases complained of abdominal or epigastric pain (54.5% vs 10%), oropharyngeal erythema (9.1 % vs 6.9), and odynophagia (45.5% vs 0). None of the patients had serious signs and symptoms. All patients were discharged improved and without sequelae.

Most NaOCI cases were accidental especially in children. Non-accidental cases increase significantly with age, with most cases found among adolescents and young adults, with higher prevalence among females. Majority of patients only ingested less than 50 ml, and that ingestion of 100 ml or more of NaOCI is associated with more than 2 signs and symptoms. The most predominant symptom is vomiting. Greater portion of non-accidental cases complained of abdominal or epigastric pain and odynophagia. None of the patients exhibit severe signs and symptoms. This study showed that all 40 cases of sodium hypochlorite ingestion did not have sequelae upon discharge.

Humans ; Consensus ; Hypertension/therapy* ; Sodium Chloride, Dietary/adverse effects* ; China

Humans ; Heart Failure/drug therapy* ; Diabetes Mellitus, Type 2/drug therapy* ; Glucose ; Sodium

Renal outer medullary potassium (ROMK) channel is an important K⁺ excretion channel in the body, and K⁺ secreted by the ROMK channels is most or all source of urinary potassium. Previous studies focused on the ROMK channels of thick ascending limb (TAL) and collecting duct (CD), while there were few studies on the involvement of ROMK channels of the late distal convoluted tubule (DCT2) in K⁺ excretion. The purpose of the present study was mainly to record the ROMK channels current in renal DCT2 and observe the effect of high potassium diet on the ROMK channels by using single channel and whole-cell patch-clamp techniques. The results showed that a small conductance channel current with a conductance of 39 pS could be recorded in the apical membrane of renal DCT2, and it could be blocked by Tertiapin-Q (TPNQ), a ROMK channel inhibitor. The high potassium diet significantly increased the probability of ROMK channel current occurrence in the apical membrane of renal DCT2, and enhanced the activity of ROMK channel, compared to normal potassium diet (P < 0.01). Western blot results also demonstrated that the high potassium diet significantly up-regulated the protein expression levels of ROMK channels and epithelial sodium channel (ENaC), and down-regulated the protein expression level of Na⁺-Cl^- cotransporter (NCC). Moreover, the high potassium diet significantly increased urinary potassium excretion. These results suggest that the high potassium diet may activate the ROMK channels in the apical membrane of renal DCT2 and increase the urinary potassium excretion by up-regulating the expression of renal ROMK channels.
Potassium Channels, Inwardly Rectifying/metabolism* ; Kidney Tubules, Distal/metabolism* ; Potassium/metabolism* ; Epithelial Sodium Channels/metabolism* ; Diet

Virtually all of the dietary potassium intake is absorbed in the intestine, over 90% of which is excreted by the kidneys regarded as the most important organ of potassium excretion in the body. The renal excretion of potassium results primarily from the secretion of potassium by the principal cells in the aldosterone-sensitive distal nephron (ASDN), which is coupled to the reabsorption of Na⁺ by the epithelial Na⁺ channel (ENaC) located at the apical membrane of principal cells. When Na⁺ is transferred from the lumen into the cell by ENaC, the negativity in the lumen is relatively increased. K⁺ efflux, H⁺ efflux, and Cl^- influx are the 3 pathways that respond to Na⁺ influx, that is, all these 3 pathways are coupled to Na⁺ influx. In general, Na⁺ influx is equal to the sum of K⁺ efflux, H⁺ efflux, and Cl^- influx. Therefore, any alteration in Na⁺ influx, H⁺ efflux, or Cl^- influx can affect K⁺ efflux, thereby affecting the renal K⁺ excretion. Firstly, Na⁺ influx is affected by the expression level of ENaC, which is mainly regulated by the aldosterone-mineralocorticoid receptor (MR) pathway. ENaC gain-of-function mutations (Liddle syndrome, also known as pseudohyperaldosteronism), MR gain-of-function mutations (Geller syndrome), increased aldosterone levels (primary/secondary hyperaldosteronism), and increased cortisol (Cushing syndrome) or deoxycorticosterone (hypercortisolism) which also activate MR, can lead to up-regulation of ENaC expression, and increased Na⁺ reabsorption, K⁺ excretion, as well as H⁺ excretion, clinically manifested as hypertension, hypokalemia and alkalosis. Conversely, ENaC inactivating mutations (pseudohypoaldosteronism type 1b), MR inactivating mutations (pseudohypoaldosteronism type 1a), or decreased aldosterone levels (hypoaldosteronism) can cause decreased reabsorption of Na⁺ and decreased excretion of both K⁺ and H⁺, clinically manifested as hypotension, hyperkalemia, and acidosis. The ENaC inhibitors amiloride and Triamterene can cause manifestations resembling pseudohypoaldosteronism type 1b; MR antagonist spironolactone causes manifestations similar to pseudohypoaldosteronism type 1a. Secondly, Na⁺ influx is regulated by the distal delivery of water and sodium. Therefore, when loss-of-function mutations in Na⁺-K⁺-2Cl^- cotransporter (NKCC) expressed in the thick ascending limb of the loop and in Na⁺-Cl^- cotransporter (NCC) expressed in the distal convoluted tubule (Bartter syndrome and Gitelman syndrome, respectively) occur, the distal delivery of water and sodium increases, followed by an increase in the reabsorption of Na⁺ by ENaC at the collecting duct, as well as increased excretion of K⁺ and H⁺, clinically manifested as hypokalemia and alkalosis. Loop diuretics acting as NKCC inhibitors and thiazide diuretics acting as NCC inhibitors can cause manifestations resembling Bartter syndrome and Gitelman syndrome, respectively. Conversely, when the distal delivery of water and sodium is reduced (e.g., Gordon syndrome, also known as pseudohypoaldosteronism type 2), it is manifested as hypertension, hyperkalemia, and acidosis. Finally, when the distal delivery of non-chloride anions increases (e.g., proximal renal tubular acidosis and congenital chloride-losing diarrhea), the influx of Cl^- in the collecting duct decreases; or when the excretion of hydrogen ions by collecting duct intercalated cells is impaired (e.g., distal renal tubular acidosis), the efflux of H⁺ decreases. Both above conditions can lead to increased K⁺ secretion and hypokalemia. In this review, we focus on the regulatory mechanisms of renal potassium excretion and the corresponding diseases arising from dysregulation.
Humans ; Bartter Syndrome/metabolism* ; Pseudohypoaldosteronism/metabolism* ; Potassium/metabolism* ; Aldosterone/metabolism* ; Hypokalemia/metabolism* ; Gitelman Syndrome/metabolism* ; Hyperkalemia/metabolism* ; Clinical Relevance ; Epithelial Sodium Channels/metabolism* ; Kidney Tubules, Distal/metabolism* ; Sodium/metabolism* ; Hypertension ; Alkalosis/metabolism* ; Water/metabolism* ; Kidney/metabolism*