Potassium reduction with sodium zirconium cyclosilicate in patients with heart failure.

AIMS: Several patients with heart failure and reduced ejection fraction (HFrEF) do not receive renin-angiotensin-aldosterone system (RAAS) inhibitors at the recommended dose or at all, frequently due to actual or feared hyperkalaemia. Sodium zirconium cyclosilicate (SZC) is an orally administered non-absorbed intestinal potassium binder proven to lower serum potassium concentrations. METHODS AND RESULTS: PRIORITIZE-HF was an international, multicentre, parallel-group, randomized, double-blind, placebo-controlled study to evaluate the benefits and risks of using SZC to intensify RAAS inhibitor therapy. Patients with symptomatic HFrEF were eligible and randomly assigned to receive SZC 5 g or placebo once daily for 12 weeks. Doses of study medication and RAAS inhibitors were titrated during the treatment period. The primary endpoint was the proportion of patients at 12 weeks in the following categories: (i) any RAAS inhibitor at less than target dose, and no MRA; (ii) any RAAS inhibitor at target dose and no MRA; (ii) MRA at less than target dose; and (iv) MRA at target dose. Due to challenges in participant management related to the COVID-19 pandemic, the study was prematurely terminated with 182 randomized patients. There was no statistically significant difference in the distribution of patients by RAAS inhibitor treatment categories at 3 months (P = 0.43). The proportion of patients at target MRA dose was numerically higher in the SZC group (56.4%) compared with the placebo group (47.0%). Overall, SZC was well tolerated. CONCLUSIONS: PRIORITIZE-HF was terminated prematurely due to COVID-19 and did not demonstrate a statistically significant increase in the intensity of RAAS inhibitor therapies with the potassium-reducing agent SZC compared with placebo.

A Potassium-Based Quality-of-Service Metric Reduces Phlebotomy Errors, Resulting in Improved Patient Safety and Decreased Cost.

OBJECTIVES: Poor phlebotomy technique can introduce pseudohyperkalemia without hemolysis, requiring additional workup and placing a significant burden on patients, clinical teams, and laboratories. Such preanalytical biases can be detected through systematic evaluation of potassium concentrations on a per-phlebotomist basis. We report our long-term experience with a potassium-based quality-of-service phlebotomy metric and its effects on resource utilization. METHODS: Potassium monitoring and retraining of 26 full-time phlebotomists were piloted as a quality-of-service intervention. Changes in potassium concentrations and impact on resource utilization were assessed. An algorithm for data monitoring and phlebotomist feedback was developed, followed by institution-wide implementation. RESULTS: Systematic intervention and retraining normalized K+ concentrations and lowered the percentage of venipunctures with K+ above 5.2 mmol/L, leading to a marked increase in phlebotomist compliance. This change resulted in resources savings of 13% to 100% for individual phlebotomists, reducing the total extra laboratory time required for repeat phlebotomies to determine hyperkalemia, mostly in the high-volume phlebotomist group. CONCLUSIONS: A quality-of-service algorithm that involved monitoring potassium concentrations on a per-phlebotomist basis with feedback and retraining contributed to a concrete, data-based quality improvement plan. The institution-wide implementation of this metric allowed for significant cost savings and a reduction in critical value alerts, directly affecting the quality of patient care.

Refractoriness of Hyperkalemia and Hyperphosphatemia in Dialysis-Dependent AKI Associated with COVID-19.

Background: Persistent hyperkalemia (hyperK) and hyperphosphatemia (hyperP) despite renal replacement therapy (RRT) was anecdotally reported in COVID-19 and acute kidney injury (AKI) requiring RRT (CoV-AKI-RRT). However, observation bias could have accounted for the reports. Thus, we systematically examined the rate and severity of hyperK and hyperP in patients with CoV-AKI-RRT in comparison with the pre-COVID-19 era. Methods: We identified patients with CoV-AKI-RRT treated with sustained low-efficiency dialysis (SLED) for ≥2 days in March-April 2020. As pre-COVID-19 control, we included patients with AKI treated with SLED in December 2019. We examined the rates of hyperK (serum potassium [sK] ≥5.5 mEq/L), severe hyperK (sK ≥6.5 mEq/L), hyperP (serum phosphate [sP] ≥4.5 mg/dl), and moderate or severe hyperP (sP ≥7-10 and >10 mg/dl, respectively) as %SLED-days with an event. Results: Along the duration of SLED, the incidence of hyperK was greater in CoV-AKI-RRT (n=64; mean 19%±2% versus 14%±3% SLED-days, P=0.002) compared with control (n=60). The proportion of patients with one or more event of severe hyperK was greater in CoV-AKI (33% versus 7%, P<0.001). The incidence of hyperP was similar between groups (mean 56%±4% versus 53%±5% SLED-days, P=0.49). However, the proportion of patients with one or more event of moderate and severe hyperP was greater in CoV-AKI-RRT (86% versus 60%, P=0.001, and 50% versus 18%, P<0.001, respectively). Among those with CoV-AKI-RRT, sK and sP correlated with lactate dehydrogenase (LDH; r=0.31, P=0.04, and r=0.31, P=0.04, respectively), whereas hyperP also correlated with shorter SLED runs (hours/run; r=-0.27, P=0.05). Conclusions: Refractory hyperK and hyperP were more frequent in CoV-AKI-RRT compared with the pre-COVID-19 era. Because of the correlation of sK and sP with higher LDH and sP with shorter SLED runs, intracellular ion release from cell injury due to cytokine storm and RRT interruptions may account for the findings.

Dehydration is associated with production of organic osmolytes and predicts physical long-term symptoms after COVID-19: a multicenter cohort study.

BACKGROUND: We have previously shown that iatrogenic dehydration is associated with a shift to organic osmolyte production in the general ICU population. The aim of the present investigation was to determine the validity of the physiological response to dehydration known as aestivation and its relevance for long-term disease outcome in COVID-19. METHODS: The study includes 374 COVID-19 patients from the Pronmed cohort admitted to the ICU at Uppsala University Hospital. Dehydration data was available for 165 of these patients and used for the primary analysis. Validation was performed in Biobanque Québécoise de la COVID-19 (BQC19) using 1052 patients with dehydration data. Dehydration was assessed through estimated osmolality (eOSM = 2Na + 2 K + glucose + urea), and correlated to important endpoints including death, invasive mechanical ventilation, acute kidney injury, and long COVID-19 symptom score grouped by physical or mental. RESULTS: Increasing eOSM was correlated with increasing role of organic osmolytes for eOSM, while the proportion of sodium and potassium of eOSM were inversely correlated to eOSM. Acute outcomes were associated with pronounced dehydration, and physical long-COVID was more strongly associated with dehydration than mental long-COVID after adjustment for age, sex, and disease severity. Metabolomic analysis showed enrichment of amino acids among metabolites that showed an aestivating pattern. CONCLUSIONS: Dehydration during acute COVID-19 infection causes an aestivation response that is associated with protein degradation and physical long-COVID. TRIAL REGISTRATION: The study was registered à priori (clinicaltrials.gov: NCT04316884 registered on 2020-03-13 and NCT04474249 registered on 2020-06-29).

SARS-COV-ATE risk assessment model for arterial thromboembolism in COVID-19.

Patients with SARS-CoV-2 infection are at an increased risk of cardiovascular and thrombotic complications conferring an extremely poor prognosis. COVID-19 infection is known to be an independent risk factor for acute ischemic stroke and myocardial infarction (MI). We developed a risk assessment model (RAM) to stratify hospitalized COVID-19 patients for arterial thromboembolism (ATE). This multicenter, retrospective study included adult COVID-19 patients admitted between 3/1/2020 and 9/5/2021. Among 3531 patients from the training cohort, 15.5% developed acute in-hospital ATE, including stroke, MI, and other ATE, compared to 13.4% in the validation cohort. The 16-item final score was named SARS-COV-ATE (Sex: male = 1, Age [40-59 = 2, > 60 = 4], Race: non-African American = 1, Smoking = 1 and Systolic blood pressure elevation = 1, Creatinine elevation = 1; Over the range: leukocytes/lactate dehydrogenase/interleukin-6, B-type natriuretic peptide = 1, Vascular disease (cardiovascular/cerebrovascular = 1), Aspartate aminotransferase = 1, Troponin-I [> 0.04 ng/mL = 1, troponin-I > 0.09 ng/mL = 3], Electrolytes derangement [magnesium/potassium = 1]). RAM had a good discrimination (training AUC 0.777, 0.756-0.797; validation AUC 0.766, 0.741-0.790). The validation cohort was stratified as low-risk (score 0-8), intermediate-risk (score 9-13), and high-risk groups (score ≥ 14), with the incidence of ATE 2.4%, 12.8%, and 33.8%, respectively. Our novel prediction model based on 16 standardized, commonly available parameters showed good performance in identifying COVID-19 patients at risk for ATE on admission.

Durable antibody and effector memory T cell responses in breastmilk from women with SARS-CoV-2.

Background: Given that only 25% of pregnant women elect to receive a COVID-19 vaccine, maternal SARS-CoV-2 infection remains an important route of conferring protective passive immunity to breastfed infants of mothers who are not vaccinated. Methods: We enrolled 30 lactating participants between December 2020 and March 2021 who had a positive PCR-test and their first COVID-19 symptoms within the previous 21 days. Participants were asked to provide serial bilateral milk samples at 12 timepoints (~ every 3 days) over a period of 35 days. A second set of samples was collected at least four months after the beginning of the first set. Participants also were asked to provide their dried blood spots and infant stool samples. All samples were tested for receptor-binding domain (RBD)-specific immunoglobulin (Ig)A, IgG, and IgM. Milk samples were assessed for neutralizing ability against the spike protein and four SARS-CoV-2 variants: D614G, Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P.1). Permeability of the breast epithelium was assessed by measuring the sodium to potassium ions (Na:K) in milk. Using flow cytometry, memory CD4 and CD8 T cells (CD45RO+ and CCR7+/-) and mucosal-homing CD4 and CD8 T cells (CD103+) were determined in cells from milk expressed at 35 days and at least 4 months after their first milk donation. Results: Milk antibodies from SARS-CoV-2 positive participants neutralized the spike complex. Milk from 73, 90, and 53% of participants had binding reactivities to RBD-specific IgA, IgG, and IgM, respectively. In contrast to blood spots, which showed increased levels of IgG, but not IgA or IgM, the COVID-19 response in milk was associated with a robust IgA response. Twenty-seven percent of participants had increased breast-epithelium permeability, as indicated by Na:K ≥ 0.6. The percentage of CD45RO+CCR7- effector-memory T cells in the day ≥120 milk samples was significantly higher than day 35 samples (P< 0.05). Conclusions: Antibodies in milk from participants with recent SARS-CoV-2 infection and those who recovered can neutralize the spike complex. For the first time we show that breastmilk T cells are enriched for mucosal memory T cells, further emphasizing the passive protection against SARS-CoV-2 conferred to infants via breastmilk.

Assessment of hypokalemia and clinical prognosis in Patients with COVID-19 in Yangzhou, China.

BACKGROUND: Hypokalemia is a frequent electrolyte imbalance in patients with COVID-19. The aim of this study was to estimate the association between hypokalemia and clinical prognosis in patients with moderate COVID-19. METHODS: A single-center, retrospective, observational study was conducted on 81 non-ICU admitted patients with moderate COVID-19 according to the criteria issued by the Chinese Health Bureau in the Third People's Hospital of Yangzhou (Northern Jiangsu People's Hospital New District Branch) from 4th to 25th August 2021. The demographic, clinical, and laboratory data were reviewed and collected, then the correlation between hypokalemia and prognosis was determined. RESULTS: The level of serum potassium of patients ranged from 2.80 mmol/L to 4.70 mmol/L. Hypokalemia was detected in 39 out of the 81 included patients (48.15%) during hospitalization. Patients with hypokalemia had prolonged days of negative nucleic acid conversion and hospital stay. Correlation analysis showed that the level of serum potassium was negatively correlated with days of negative nucleic acid conversion and length of hospital stay. Bivariate logistic regression analysis proved that hypokalemia was a risk factor for prolonged hospital stay in patients with moderate COVID-19. CONCLUSION: Hypokalemia was prevalent in patients with moderate COVID-19 in Yangzhou, China. Hypokalemia was associated with the prolonged hospital stay in patients with moderate COVID-19.

A 77-Year-Old Man with Heparin-Induced Aldosterone Suppression Causing Hyperkalemia.

BACKGROUND Anticoagulation with heparin infrequently causes elevated serum potassium via a reduction in the number and affinity of adrenal angiotensin II receptors, causing reversible aldosterone suppression, thereby leading to enhanced sodium excretion and hyperkalemia. CASE REPORT A 77 year-old man presented with productive cough and shortness of breath and was subsequently found to have non-ST-elevation myocardial infarction and concomitant symptomatic COVID-19 infection, for which he was started on a high-dose unfractionated heparin infusion. A gradual increase in serum potassium followed, with a subsequent return to a normal potassium level after stopping treatment with heparin. An evaluation for hemolysis was unrevealing, and the patient was not on any other medications known to cause hyperkalemia. On day 6, heparin was restarted owing to a high suspicion of pulmonary embolism. There was a subsequent increase in serum potassium level, which was followed by a return to baseline after discontinuation of heparin, thereby confirming the suspected diagnosis. CONCLUSIONS Acute increases in serum potassium levels in hospitalized patients can result in weakness, paralysis, conduction abnormalities, and cardiac arrhythmias that, if left untreated, can result in serious morbidity and potentially death in a short period of time. As this clinical entity is infrequently encountered in clinical practice, it can easily be overlooked by clinicians. The prompt exclusion of alternative causes of acutely elevated serum potassium levels and the identification of heparin administration as an easily reversible trigger is imperative and can potentially be life-saving.

Diuretic-induced hypokalaemia: an updated review.

Diuretic-induced hypokalaemia is a common and potentially life-threatening adverse drug reaction in clinical practice. Previous studies revealed a prevalence of 7%-56% of hypokalaemia in patients taking thiazide diuretics. The clinical manifestations of hypokalaemia due to diuretics are non-specific, varying from asymptomatic to fatal arrhythmia. Diagnosis of hypokalaemia is based on the level of serum potassium. ECG is useful in identifying the more severe consequences. A high dosage of diuretics and concomitant use of other drugs that increase the risk of potassium depletion or cardiac arrhythmias can increase the risk of cardiovascular events and mortality. Thiazide-induced potassium depletion may cause dysglycaemia. The risk of thiazide-induced hypokalaemia is higher in women and in black people. Reducing diuretic dose and potassium supplementation are the most direct and effective therapies for hypokalaemia. Combining with a potassium-sparing diuretic or blocker of the renin-angiotensin system also reduces the risk of hypokalaemia. Lowering salt intake and increasing intake of vegetables and fruits help to reduce blood pressure as well as prevent hypokalaemia.

[Relationship between blood electrolytes and prognosis of patients with severe coronavirus disease 2019].

OBJECTIVE: To analyze the relationship between blood electrolytes and the prognosis of patients with severe coronavirus disease 2019 (COVID-19) and to provide assistance for clinical decision-making. METHODS: The clinical data of patients with severe COVID-19 admitted to intensive care unit (ICU) of the Wuhan Third Hospital by the Shanghai aid-Hubei medical team from January 21 to March 4, 2020 were collected. Excluding ineligible patients, 110 patients were finally enrolled. The patients' gender, age, temperature, heart rate, systolic and diastolic blood pressure, clinical symptoms at admission, time of symptom onset, duration of fever, and relevant indicators at admission to ICU (including blood potassium, chloride, sodium, calcium, phosphorus, and magnesium, etc.) and prognosis were analyzed. The patients were grouped by blood potassium or calcium levels or blood potassium/calcium ratio. The Kaplan-Meier survival curves were used to analyze the survival of patients in each group. The relationship between the potassium/calcium ratio and the prognosis was analyzed using restricted cubic spline plots. The relationship between each index in the different models and the prognosis was analyzed using Cox regression models. RESULTS: Among 110 severe COVID-19 patients, 78 cases survived, and 32 cases died. Compared with the surviving group, patients in the death group had higher blood potassium levels [mmol/L: 4.25 (3.80, 4.65) vs. 3.90 (3.60, 4.20), P < 0.05] and lower blood calcium levels (mmol/L: 2.00±0.14 vs. 2.19±0.18, P < 0.05). The Kaplan-Meier survival curves showed that patients in the potassium > 4.2 mmol/L group had a worse prognosis than the potassium < 3.8 mmol/L group and the potassium 3.8-4.2 mmol/L group (P = 0.011), patients in the calcium > 2.23 mmol/L group had a better prognosis than the calcium < 2.03 mmol/L group and the calcium 2.03-2.23 mmol/L group, and the lower calcium group had a worse prognosis (P = 0.000 15). Cox regression analysis showed that the hazard ratio (HR) of blood potassium and calcium were 2.08 and 0.01, respectively, in model 1 (single blood potassium or calcium) and in model 2 (model 1 plus age and gender), the HR of blood potassium and calcium were 1.98 and 0.01 respectively, which were significantly associated with patient prognosis (all P < 0.05). Patients in the group with the potassium/calcium ratio > 1.9 had higher blood potassium levels and a higher proportion of mechanical ventilation, lower calcium levels and lower proportion of survival, and longer time of ICU admission compared with the groups with the potassium/calcium ratio < 1.7 and 1.7-1.9. The Kaplan-Meier survival curves showed that the survival rate of the potassium/calcium ratio > 1.9 group was the lowest (P < 0.000 1), and there was no statistically significant difference in survival between the potassium/calcium ratio < 1.7 group and the potassium/calcium ratio 1.7-1.9 group. A restricted cubic spline plot corrected for age and gender showed that patients in the potassium/calcium ratio > 1.8 group had HR values > 1. Cox regression analysis corrected for other indicators showed that the potassium/calcium ratio was still associated with patient prognosis (HR = 4.85, P = 0.033). CONCLUSION: Blood potassium, calcium, and the potassium/calcium ratio at ICU admission are related to the prognosis of patients with severe COVID-19, and the potassium/calcium ratio is an independent risk factor for the death of patients. The higher the potassium/calcium ratio, the worse the prognosis of patients.

Influence of Coronavirus Disease 2019 on some Physiological Blood Parameters in Patients with Kidney Failure in Iraq.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a novel coronavirus (Severe Acute Respiratory Syndrome Coronavirus 2; SARS-CoV-2), which is related to the SARS-CoV-2 and the Middle East Respiratory Syndrome Coronavirus, which caused serious outbreaks in 2003 and 2012. This study aimed to determine if there is an association between ABO blood types/renal failure and infection with COVID-19. Furthermore, the effects of COVID-19 infection on some blood parameters and electrolyte levels were investigated in this study. In the current study, 90 samples were obtained from males and females aged between 21-68 years old. The data were collected from September to February 2021 in a Kidney Center of Alsaader Teaching Hospital. The participants were divided into three groups (n=30) of A) kidney failure, B) kidney failure with COVID-19, and C) kidney failure with COVID-19 recovery after one month. The variables of this study included blood group types, blood electrolytes, and some blood biochemical parameters. According to the results, regarding the frequency of blood groups, in the control group, 34, 20, 14, and 36 participants belonged to the A , B, AB, and O blood groups, respectively. The recorded data showed that participants who had suffered from kidney failure and were infected with COVID-19 belonged to the A, B, AB, and O blood groups (25%, 10%, 27%, and 45%), respectively, while kidney failure patients who had recovered after one month from COVID-19 had blood groups of A, B, AB, and O (25%, 22%, 105%, and 45%, respectively). The recorded data showed a significant decrease (P<0.05) in the levels of Potassium (K), Sodium (Na), and Calcium (Ca) in the B group, compared to the A group, while the levels of K, Na, and Ca had significantly improved in group C (P<0.05), compared to group B. The Chloride level showed no significant differences among the groups. Furthermore, non-significant differences (P>0.05) were observed in the red blood cells (RBC), hemoglobin (Hb), and white blood cell count (WBC) in the COVID-19 group (Group B), compared to group A; however, there was a significant raise (P<0.05) in WBC and platelet (PLT), as well as a significant decrease (P<0.05) in lymphocyte (LYM), RBC, Hb, and hematocrit (HCT) in group C, compared to groups A and B. In conclusion, blood group O obtained the lowest level of resistance to COVID-19, compared to blood group A which had the highest response to recovery. The COVID-19 patients with kidney failure showed a significant decrease in blood parameters, such as RBCs, Hb, LYM, PLT, HCT, and electrolytes.

Comparison of Laboratory and Hemodynamic Time Series Data Across Original, Alpha, and Delta Variants in Patients With Multisystem Inflammatory Syndrome in Children.

OBJECTIVES: To compare the clinical, laboratory, and hemodynamic parameters during hospitalization for patients with multisystem inflammatory syndrome in children (MIS-C), across the Original/Alpha and the Delta variants of severe acute respiratory syndrome coronavirus 2 infection. DESIGN: Retrospective cohort study. SETTING: Single-center quaternary children's hospital. PATIENTS: Children with MIS-C admitted from May 2020 to February 2021(Original and Alpha variant cohort) and August 2021 to November 2021 (Delta variant cohort). MEASUREMENTS AND MAIN RESULTS: Continuous vital sign measurements, laboratory results, medications data, and hospital outcomes from all subjects were evaluated. Of the 134 patients (102 with Original/Alpha and 32 with Delta), median age was 9 years, 75 (56%) were male, and 61 (46%) were Hispanics. The cohort with Original/Alpha variant had more males (61% vs 41%; p = 0.036) and more respiratory/musculoskeletal symptoms on presentation compared with the Delta variant ( p < 0.05). More patients in the Original/Alpha variant cohort received mechanical ventilation (16 vs 0; p = 0.009). Median hospital length of stay (LOS) was 7 days, and ICU LOS was 3 days for the entire cohort. ICU LOS was shorter in cohort with the Delta variant compared with the Original/Alpha variant (4 vs 2 d; p = 0.001). Only one patient had cardiac arrest, two needed extracorporeal membrane oxygenation, and two needed left ventricular assist device (Impella, Danvers, MA), all in the Original/Alpha variant cohort; no mortality occurred in the entire cohort. MIS-C cohort associated with the Delta variant had lower INR, prothrombin time, WBCs, sodium, phosphorus, and potassium median values ( p < 0.05) during hospitalization compared with the Original/Alpha variants. Hemodynamic assessment showed significant tachycardia in the Original/Alpha variants cohort compared with the Delta variant cohort ( p < 0.05). INTERVENTIONS: None. CONCLUSIONS: Patients with MIS-C associated with the Delta variants had lower severity during hospitalization compared with the Original/Alpha variant. Analysis of distinct trends in clinical and laboratory parameters with future variants of concerns will allow for potential modification of treatment protocol.

In-hospital mortality, length of stay, and hospitalization cost of COVID-19 patients with and without hyperkalemia.

BACKGROUND: Hyperkalemia (HK) may be associated with poor clinical outcomes among COVID-19 patients. This study aimed to describe the prevalence of HK and evaluate the associations between HK and in-hospital mortality, intensive care unit (ICU) admission, length of hospital stay (LOS), and hospitalization cost among COVID-19 inpatients. METHODS: A retrospective cohort study was conducted using a large hospital discharge database (PINC AI Healthcare Database) for COVID-19 inpatients discharged between April 1 and August 31, 2020. HK was defined with discharge diagnosis and potassium binder use. RESULTS: Of 192,182 COVID-19 inpatients, 12% (n = 22,702) had HK. HK patients were more likely to be older (median age 67 vs 63 years), male (63% vs 50%), black (30% vs 22%), and have a history of chronic kidney disease (45% vs 16%) or diabetes mellitus (55% vs 35%) than non-HK patients (all p<.001). A significantly higher proportion of patients with HK had in-hospital mortality (42% vs 11%, p<.001) than those without HK; this was persistent after adjusting for confounders (adjusted odds ratio [aOR] 1.69, 95% confidence interval [CI]1.62-1.77). Patients with HK were also more likely to be admitted to ICU (aOR 1.05, 95% CI 1.01-1.09), incur higher cost of care (adjusted mean difference $5,389) and have longer LOS (adjusted mean difference 1.3 days) than non-HK patients. CONCLUSIONS: Presence of HK was independently associated with higher in-hospital mortality, LOS, and cost of care among COVID-19 inpatients. Detecting and closely monitoring HK are recommended to improve clinical outcomes and reduce LOS and healthcare cost among COVID-19 patients.

SARS-CoV-2 viroporin encoded by ORF3a triggers the NLRP3 inflammatory pathway.

Heightened inflammatory response is a prominent feature of severe COVID-19 disease. We report that the SARS-CoV-2 ORF3a viroporin activates the NLRP3 inflammasome, the most promiscuous of known inflammasomes. Ectopically expressed ORF3a triggers IL-1ß expression via NFκB, thus priming the inflammasome. ORF3a also activates the NLRP3 inflammasome but not NLRP1 or NLRC4, resulting in maturation of IL-1ß and cleavage/activation of Gasdermin. Notably, ORF3a activates the NLRP3 inflammasome via both ASC-dependent and -independent modes. This inflammasome activation requires efflux of potassium ions and oligomerization between the kinase NEK7 and NLRP3. Importantly, infection of epithelial cells with SARS-CoV-2 similarly activates the NLRP3 inflammasome. With the NLRP3 inhibitor MCC950 and select FDA-approved oral drugs able to block ORF3a-mediated inflammasome activation, as well as key ORF3a amino acid residues needed for virus release and inflammasome activation conserved in the new variants of SARS-CoV-2 isolates across continents, ORF3a and NLRP3 present prime targets for intervention.

Massive Nonfatal Hydroxychloroquine Ingestion in a Pediatric Patient.

BACKGROUND: Hydroxychloroquine overdose is rare but potentially lethal. Hydroxychloroquine overdose symptoms are characterized by central nervous system toxicity, cardiac toxicity, and hypokalemia. Recommended treatment consists of epinephrine, high-dose diazepam, and careful potassium repletion. Few pediatric hydroxychloroquine overdoses have been reported. CASE REPORT: We describe a 14-year-old girl who ingested 10 g (172 mg/kg) of hydroxychloroquine. She developed tachycardia, hypotension, and hypokalemia. She was intubated and treated with diazepam and epinephrine infusions and potassium supplementation. Her serum hydroxychloroquine concentration obtained 10 h after ingestion was 13,000 ng/mL (reference range 500-2000 ng/mL). The patient made a full medical recovery. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Pediatric hydroxychloroquine overdoses are reported rarely, and the toxic and lethal doses of hydroxychloroquine ingestion have not been established. This case of a teenaged patient who ingested 10 g of hydroxychloroquine and survived provides additional information that may be used to help establish toxic and lethal doses of ingestion.

Serum magnesium: time for a standardized and evidence-based reference range.

Magnesium deficiency can have serious health consequences. Low magnesium intake or low serum levels are risk factors for e.g. type 2 diabetes and cardiovascular diseases. Despite its scientifically recognized importance, too little attention is paid to magnesium in clinical practice. This may be due to the fact that there is no uniform and evidence-based reference range for serum magnesium as is the case for other electrolytes such as sodium and potassium. The serum magnesium concentration is also of a limited informative value, as it is maintained for a long time by releasing magnesium from body pools. A low serum magnesium is a definite sign of magnesium deficiency; however, values within the reference range do not rule out deficiencies. Nevertheless, serum magnesium should become part of routine diagnostics in order to be able to better detect deficiency states. For serum magnesium, a reference range of 0.75 to 0.95 mmol/L (1.82 to 2.31 mg/dL) can often be found. However, according to the current data situation, serum magnesium values of less than 0.85 mmol/L are associated with increased health risks. Therefore, the lower limit of the reference range should be raised to 0.85 mmol/L (2.07 mg/dL).

Efficacy of standard- vs reduced-dose insulin for treatment of hyperkalemia: A quasi-experiment.

PURPOSE: Hyperkalemia more commonly affects patients with a glomerular filtration rate of less than 60 mL/min. Using intravenous (IV) insulin to shift potassium intracellularly may cause hypoglycemia, requiring additional treatment or longer hospitalization. Literature on insulin dosing in this context is limited, with one previous study indicating that 5 units of IV insulin might be as effective and result in less hypoglycemia than the standard dose of 10 units of IV insulin. The hyperkalemia treatment pathway at our institution was revised in May 2018 to include a reduced-dose option (5 units of insulin) for patients with end-stage renal disease. This study aimed to compare the prevalence of hypoglycemia between patients who received standard-dose vs reduced-dose IV insulin. METHODS: This single-center, retrospective, quasi-experimental study evaluated the impact of revision of the hyperkalemia treatment pathway by assessing rates of hypoglycemia during the 6 months before and after implementation of the revised pathway. The primary endpoint was prevalence of hypoglycemia, defined as a blood glucose level of less than or equal to 70 mg/dL. RESULTS: There was no statistically significant difference in the occurrence of hypoglycemia when comparing the pre- and postimplementation groups (36 [17.7%] patients vs 34 [18.7%] patients; P = 0.7924). The postimplementation group had a statistically significant lower reduction in potassium levels after treatment than the preimplementation group (mean [interquartile range], -0.9 [-1.3, -0.5] mEq/L vs -0.6 [-1.2, -0.2] mEq/L; P = 0.0095). Baseline potassium levels were similar between the groups. CONCLUSION: Administration of reduced-dose IV insulin for treatment of hyperkalemia was significantly less effective in lowering serum potassium levels and did not decrease prevalence of hypoglycemia. When accounting for potential confounders, the only variable that was associated with hypoglycemia was pretreatment glucose level.

How SARS-CoV-2 might affect potassium balance via impairing epithelial sodium channels?

Severe acute respiratory syndrome coronaviruses 2 (SARS-CoV-2) is the causative agent of current coronavirus disease 2019 (COVID-19) pandemic. Electrolyte disorders particularly potassium abnormalities have been repeatedly reported as common clinical manifestations of COVID-19. Here, we discuss how SARS-CoV-2 may affect potassium balance by impairing the activity of epithelial sodium channels (ENaC). The first hypothesis could justify the incidence of hypokalemia. SARS-CoV-2 cell entry through angiotensin-converting enzyme 2 (ACE2) may enhance the activity of renin-angiotensin-aldosterone system (RAAS) classical axis and further leading to over production of aldosterone. Aldosterone is capable of enhancing the activity of ENaC and resulting in potassium loss from epithelial cells. However, type II transmembrane serine protease (TMPRSS2) is able to inhibit the ENaC, but it is utilized in the case of SARS-CoV-2 cell entry, therefore the ENaC remains activated. The second hypothesis describe the incidence of hyperkalemia based on the key role of furin. Furin is necessary for cleaving both SARS-CoV-2 spike protein and ENaC subunits. While the furin is hijacked by the virus, the decreased activity of ENaC would be expected, which causes retention of potassium ions and hyperkalemia. Given that the occurrence of hypokalemia is higher than hyperkalemia in COVID-19 patients, the first hypothesis may have greater impact on potassium levels. Further investigations are warranted to determine the exact role of ENaC in SARS-CoV-2 pathogenesis.

Dietary Advice in Hemodialysis Patients: Impact of a Telehealth Approach During the COVID-19 Pandemic.

OBJECTIVE: The purpose of this study was to assess the effect of a telehealth-delivered nutritional intervention via telephone in maintenance hemodialysis (HD) patients during the coronavirus outbreak. METHODS: This was a multicenter, observational, prospective, and longitudinal study of 156 patients undergoing maintenance HD from 15 dialysis units conducted during the COVID-19 pandemic. We assigned patients to receive dietary counseling through a phone call, according to their biochemical and nutritional parameters. Dry weight, intradialytic weight gain percentage (%IDWG), body mass index, potassium, phosphorus, calcium, calcium/phosphorus product, normalized protein catabolic rate, albumin, and hemoglobin were recorded at baseline and 1 month after nutrition counseling. RESULTS: The prevalence of hyperkalemia and hyperphosphatemia decreased significantly after dietary advice. A statistically significant reduction in serum potassium and phosphorus levels was observed in patients receiving counseling for hyperkalemia and hyperphosphatemia. In addition, there was a statistically significant decrease in the prevalence of hypophosphatemia. We also observed a significant decrease in %IDWG, although no statistically significant differences were detected in patients with high %IDWG. The data demonstrated statistically significant differences in potassium and phosphorus values when the person receiving the phone contact was the patient or the caregiver. The main statistically significant differences in hypophosphatemia %IDWG were only observed when contact was made directly with the patient. No differences were observed when the contact was made through nursing homes. CONCLUSION: Our results suggest that telehealth-delivered dietary interventions can improve the clinical and nutritional parameters of HD patients. Consequently, this strategy may be effective for promoting continuous nutritional monitoring in these patients, in particular when conducting a face-to-face option is not crucial.