Congenital chloride diarrhoea in a Chinese infant with a compound heterozygous SLC26A3 mutation.

INTRODUCTION: Congenital chloride diarrhoea (CCD) is an autosomal recessive condition that causes secretory diarrhoea and potentially deadly electrolyte imbalances in infants because of solute carrier family 26 member 3 (SLC26A3) gene mutations. CASE PRESENTATION: A 7-month-old Chinese infant with a history of maternal polyhydramnios presented with frequent watery diarrhoea, severe dehydration, hypokalaemia, hyponatraemia, failure to thrive, metabolic alkalosis, hyperreninaemia, and hyperaldosteronaemia. Genetic testing revealed a compound heterozygous SLC26A3 gene mutation in this patient (c.269_270dup and c.2006 C > A). Therapy was administered in the form of oral sodium and potassium chloride supplements, which decreased stool frequency. CONCLUSIONS: CCD should be considered when an infant presents with prolonged diarrhoea during infancy, particularly in the context of maternal polyhydramnios and dilated foetal bowel loops.

Neuronal activity rapidly reprograms dendritic translation via eIF4G2:uORF binding.

Learning and memory require activity-induced changes in dendritic translation, but which mRNAs are involved and how they are regulated are unclear. In this study, to monitor how depolarization impacts local dendritic biology, we employed a dendritically targeted proximity labeling approach followed by crosslinking immunoprecipitation, ribosome profiling and mass spectrometry. Depolarization of primary cortical neurons with KCl or the glutamate agonist DHPG caused rapid reprogramming of dendritic protein expression, where changes in dendritic mRNAs and proteins are weakly correlated. For a subset of pre-localized messages, depolarization increased the translation of upstream open reading frames (uORFs) and their downstream coding sequences, enabling localized production of proteins involved in long-term potentiation, cell signaling and energy metabolism. This activity-dependent translation was accompanied by the phosphorylation and recruitment of the non-canonical translation initiation factor eIF4G2, and the translated uORFs were sufficient to confer depolarization-induced, eIF4G2-dependent translational control. These studies uncovered an unanticipated mechanism by which activity-dependent uORF translational control by eIF4G2 couples activity to local dendritic remodeling.

The potential for current sodium and potassium production to support a global switch to the use of potassium-enriched salt: a desktop research study.

OBJECTIVE: Switching regular salt (sodium chloride) to salt enriched with potassium chloride (25 % potassium chloride, 75 % sodium chloride) has been shown to reduce blood pressure and the risk of cardiovascular diseases. We sought to define the potential for the current production of sodium chloride and potassium chloride to support a global switch to the use of potassium-enriched salt. DESIGN: We summarised data from geological surveys, government reports and trade organisations describing the global production and supply of sodium chloride and potash (the primary source of potassium chloride) and compared this to potential requirements for potassium-enriched salt. SETTING: Global. PARTICIPANTS: Not applicable. RESULTS: Approximately 280 million tonnes of sodium chloride were produced in 2020 with China and the USA the main producers. Global production of potash from which potassium chloride is extracted was about forty-four million tonnes with Canada, Belarus, Russia and China providing 77 % of the world's supply. There were forty-eight countries in which potassium-enriched salt is currently marketed with seventy-nine different brands identified. Allowing for loss of salt between manufacture and consumption, a full global switch from regular salt to potassium-enriched salt would require about 9·7 million tonnes of sodium chloride to be replaced with 9·7 million tonnes of potassium chloride annually. CONCLUSIONS: Significant upscaling of the production of potassium chloride and the capacity of companies able to manufacture potassium-enriched salt, as well as a robust business case for the switch to potassium chloride, would be required.

Comparison of modified Del Nido and Custodiol® cardioplegia in minimally invasive mitral valve surgery.

OBJECTIVES: In this study, we evaluated if modified Del Nido cardioplegia delivers comparable cardiac protection in comparison to Custodiol® in patients undergoing isolated minimally invasive mitral valve repair. METHODS: From January 2018 to October 2021, all patients undergoing non-emergent isolated minimally invasive mitral valve repair were included in this study. The cardioplegia was chosen at the surgeons' discretion. The primary end points of this study were peak postoperative cardiac enzyme levels. Secondary end points were in-hospital mortality, hospital stay, occurrence of cardiac arrhythmias, pacemaker implantations, postoperative lactate and sodium levels and postoperative incidence of renal failure requiring dialysis. RESULTS: A total of 355 patients were included in this study. The mean age of patients was 57. After propensity score matching, a total of 156 pairs were identified. There was no difference in cross-clamp time between both groups. Postoperative creatine kinase levels were higher in patients receiving Custodiol on the 1st and 2nd postoperative days. Creatine kinase isoenzyme MB levels were higher in patients receiving Custodiol on the 2nd postoperative day (0.5 ± 0.2 vs 0.4 ± 0.1 µmol/l s; P < 0.001). Postoperative Troponin T concentrations were similar between both groups. Maximum lactate concentrations were higher in patients receiving Custodiol on the day of surgery (2.4 ± 1.9 vs 2.0 ± 1.1 mmol/l; P = 0.04). The overall hospital stay was longer in patients receiving Del Nido cardioplegia (10.6 ± 3.2 vs 8 ± 4.1 days; P < 0.01). CONCLUSIONS: Modified Del Nido cardioplegia based on Ionosteril® solution offers equivalent protection compared to Custodiol for isolated minimally invasive mitral valve repair.

Del nido cardioplegia in adults: a retrospective observational study in comparison to modified St. Thomas cardioplegia in cardiac surgery.

BACKGROUND: St. Thomas cardioplegia is commonly administered to adults, yet repeated dosing at brief intervals is required. Del Nido's cardioplegic solution provides a prolonged duration of safe myocardial arrest, yet it was primarily intended for pediatric cardiac surgery. Recently, there has been an increasing interest in using Del Nido's in adults; this might be due to its ease of administration and extended re-dosing intervals. This study contrasted Del Nido's to modified St. Thomas cardioplegia in adults. METHODS: This study was conducted on 200 patients. Troponin-T was the primary outcome within the first 24 and 48 h post-surgery. Cardiopulmonary bypass time, cross-clamp time, intraoperative use of inotropic support, defibrillator and/or intra-aortic balloon were the secondary outcomes of the study. RESULTS: There was a significant reduction in post-operative Troponin-T levels in the first 24 and 48 h within Del Nido's group compared to the modified St. Thomas group. The cross-clamp and cardiopulmonary bypass times were also found to be lower within Del Nido's group. CONCLUSION: This study has demonstrated a significant reduction in early postoperative Troponin-T levels as well as operative times favoring Del Nido's in adults.

Evaluation of Chronic Effects of Potassium Chloride and Nickel on Survival, Growth, and Reproduction of a Unionid Mussel (Lampsilis siliquoidea).

The ASTM International standard test method for freshwater mussels (E2455-13) recommends 4-week toxicity testing with juveniles to evaluate chronic effects on survival and growth. However, concerns remain that the method may not adequately address the sensitivity of mussels to longer term exposures (>4 weeks), particularly in relation to potential reproductive impairments. No standard method directly evaluates toxicant effects on mussel reproduction. The objectives of the present study were to (1) evaluate toxicity endpoints related to reproduction in fatmucket (Lampsilis siliquoidea) using two common reference toxicants, potassium chloride (KCl) and nickel (Ni); (2) evaluate the survival and growth of juvenile fatmucket in standard 4-week and longer term (12-week) KCl and Ni tests following a method refined from the standard method; and (3) compare the sensitivity of the reproductive endpoints with the endpoints obtained from the juvenile mussel tests. Reproductive toxicity tests were conducted by first exposing female fatmucket brooding mature larvae (glochidia) to five test concentrations of KCl and Ni for 6 weeks. Subsamples of the glochidia were then removed from the adults to determine three reproductive endpoints: (1) the viability of brooded glochidia; (2) the viability of free glochidia in a 24-h exposure to the same toxicant concentrations as their mother; and (3) the success of glochidia parasitism on host fish. Mean viability of brooded glochidia was significantly reduced in the high KCl concentration (26 mg K/L) relative to the control, with a 20% effect concentration (EC20) of 14 mg K/L, but there were no significant differences between the control and any Ni treatment (EC20 > 95 µg Ni/L). The EC20s for viability of free glochidia after the additional 24-h exposure and parasitism success were similar to the EC20s of brooded glochidia. The EC20s based on the most sensitive biomass endpoint in the 4-week juvenile tests were 15 mg K/L and 91 µg Ni/L, similar to or greater than the EC20s from the reproductive KCl and Ni tests, respectively. When exposure duration in the juvenile tests was extended from 4 to 12 weeks, the EC20s decreased by more than 50% in the KCl test but by only 8% in the Ni test. Overall, these results indicate that a standard 4-week test with juvenile mussels can prove effective for estimating effects in chronic exposures with different life stages although a longer term 12-week exposure with juvenile mussels may reveal higher sensitivity of mussels to some toxicants, such as KCl. Environ Toxicol Chem 2024;43:1097-1111. © 2024 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Harmonising IV Oxycodone with Paediatric Perioperative Medications: A Compatibility Study Through Y-Type Connectors.

Purpose: Co-administering multiple intravenous (IV) agents via Y-connectors is a common practice in hospitalised and fasting surgical patients. However, there is a lack of reliable data confirming the physical compatibility of some combinations including IV oxycodone, a drug that is gaining increasing popularity in the perioperative period. Concern regarding physical drug incompatibilities precludes concurrent coadministration with other common drugs through a single lumen. This can result in the cessation of infusions to allow the administration of other medications, resulting in exacerbation of acute pain. This study aims to evaluate the physical compatibility of IV oxycodone with some commonly co-administered drugs and IV fluids. Methods: Mixtures of oxycodone (1mg.mL-1) and the tested drugs and IV fluids were prepared in a ratio of 1:1. The mixtures were examined at 0 and 60 minutes from mixing and assessed using the European Conference Consensus Standards. This involved visual inspection (precipitation, turbidity, colour change, gas formation), spectrophotometry, and pH change. The tested drugs included ketamine, tramadol, clonidine, vancomycin, piperacillin/tazobactam, dexmedetomidine, cefotaxime, gentamicin, and paracetamol. In addition, the commonly used IV fluids tested included glucose 5% + sodium chloride 0.9% + 60 mmol potassium chloride, plasmalyte + dextrose 5%;plasmalyte + dextrose 5% + 55 mmol potassium chloride, plasmalyte + dextrose 5% + 55mmol potassium acetate, plasmalyte + dextrose 5% + 55mmol potassium dihydrogen phosphate, Hartmann's solution, Standard pediatric Total Parenteral Nutrition (TPN) 20/100 and TPN 25/150. Results: IV oxycodone (1 mg.mL-1) showed no visual changes; no spectrophotometric absorption variability at 350, 410, or 550nm; and no pH changes of >0.5 at 0 or 60 minutes with any of the tested drugs or fluids in the concentrations tested. Conclusion: According to European Consensus Conference Standards, IV Oxycodone at 1 mg.mL-1 is physically compatible in a ratio of 1:1 v/v with all investigated drugs and fluids tested for at least 60 minutes.

Potassium Intake and Human Health.

Potassium is a monovalent cation widely present in nature, where it is not in metallic form, but always in combination with other substances, especially chloride [...].

Partial Replacement of NaCl with KCl in Cooked Meat Could Reduce the Liver Damage Through Renin-Angiotensin System in Mice.

SCOPE: Dietary salt (sodium chloride, NaCl) is necessary for processed meat products, but intake of a high-sodium diet carries serious health risks. Considerable studies indicate that the partial substitution of NaCl with potassium chloride (KCl) can produce sodium-reduced cooked meat. However, most studies of sodium-reduced cooked meat focus on the production process in vitro, and the effect of cooked meat on health has not been well clarified in vivo. METHODS AND RESULTS: This study finds that compared to the high-sodium group (HS), serum renin, angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and the levels of some indicators of dyslipidemia are decreased in the reduced salt by partial substitution of NaCl with KCl group (RS + K). Furthermore, RS + K increases the antioxidation abilities, inhibits the renin-angiotensin system (RAS) through ACE/Ang II/Ang II type 1 receptor axis pathway, reduces synthesis of triglyceride and cholesterol and protein expressions of inflammatory factors interleukin-17A and nuclear factor-kappa B in the liver. CONCLUSION: Partial substitution of NaCl with KCl in cooked meat can be a feasible approach for improving the health benefits and developing novel functional meat products for nutritional health interventions.

The expression system influences stability, maturation efficiency, and oligomeric properties of the potassium-chloride co-transporter KCC2.

The neuron-specific K+/Cl- co-transporter 2, KCC2, which is critical for brain development, regulates γ-aminobutyric acid-dependent inhibitory neurotransmission. Consistent with its function, mutations in KCC2 are linked to neurodevelopmental disorders, including epilepsy, schizophrenia, and autism. KCC2 possesses 12 transmembrane spans and forms an intertwined dimer. Based on its complex architecture and function, reduced cell surface expression and/or activity have been reported when select disease-associated mutations are present in the gene encoding the protein, SLC12A5. These data suggest that KCC2 might be inherently unstable, as seen for other complex polytopic ion channels, thus making it susceptible to cellular quality control pathways that degrade misfolded proteins. To test these hypotheses, we examined KCC2 stability and/or maturation in five model systems: yeast, HEK293 cells, primary rat neurons, and rat and human brain synaptosomes. Although studies in yeast revealed that KCC2 is selected for endoplasmic reticulum-associated degradation (ERAD), experiments in HEK293 cells supported a more subtle role for ERAD in maintaining steady-state levels of KCC2. Nevertheless, this system allowed for an analysis of KCC2 glycosylation in the ER and Golgi, which serves as a read-out for transport through the secretory pathway. In turn, KCC2 was remarkably stable in primary rat neurons, suggesting that KCC2 folds efficiently in more native systems. Consistent with these data, the mature glycosylated form of KCC2 was abundant in primary rat neurons as well as in rat and human brain. Together, this work details the first insights into the influence that the cellular and membrane environments have on several fundamental KCC2 properties, acknowledges the advantages and disadvantages of each system, and helps set the stage for future experiments to assess KCC2 in a normal or disease setting.

Maximum serum K+ concentration within 1 hour with enteral replacement in severe hypokalemia.

Introduction: Introduction: we report two cases with severe hypokalemia. Patients and methods: a 68-year-old woman was admitted with lower limb swelling and urinary symptoms; on the fourth day serum K+ concentration (s[K+]) was 2.3 mmol/L. A 64-year-old woman was admitted with pain in the lumbosacral spine, she was diagnosed with multiple myeloma. After receiving specific therapy she showed s[K+] at 2.4 mmol/L. A KCl solution containing 26.8 mEq of K+ was administered enterally, which increased s[K+] by 0.7 mmol/L within 1 h. Results and conclusion: these cases reveal that peak s[K+] may be achieved within 1 hour after KCl intake in severe hypokalemia, which is probably faster than IV administration.

Introducción: Introducción: se presentan dos casos clínicos con hipopotasemia severa. Pacientes y métodos: mujer de 68 años que ingresó por edema en miembros inferiores y síntomas urinarios; al cuarto día, el nivel sérico de K+ ([K+]s) era de 2,3 mmol/L. Una mujer de 64 años ingresó por dolor en la columna lumbosacra y fue diagnosticada de mieloma múltiple; luego de recibir terapia específica, presentó una [K+]s de 2.4 mmol/L. Se administró por vía enteral una solución de KCl que contenía 26,8 mEq de K+, aumentando la [K+]s en 0,7 mmol/L en 1 h. Resultados y conclusión: estos casos revelan que la [K+]s máxima se alcanzaría 1 hora después de la ingestión de KCl en la hipopotasemia grave, probablemente en menos tiempo que por vía intravenosa.

Comparing a range of potassium-enriched low sodium salt substitutes to common salt: Results of taste and visual tests in South African adults.

BACKGROUND AND AIMS: Potassium-enriched low sodium salt substitutes (LSSS), which replace a proportion of sodium chloride (NaCl) with potassium chloride (KCl), have been shown to reduce blood pressure and offer a potential solution to address the high burden of hypertension in South Africa. However, it is unknown which proportions of KCl in LSSS are acceptable. We compared the taste and visual acceptability of various LSSS in South African adults. METHODS AND RESULTS: Fifty-six adults underwent double-blind taste and visual tests of four LSSS (35%KCl/65%NaCl; 50%KCl/50%NaCl; 66%KCl/34%NaCl; 100%KCl) in comparison to 100%NaCl (common salt). Participants scored each product by taste ranking, taste perception and likeliness to use. Participants then visually inspected the five products and attempted to identify which was which. Almost half (45 %) of participants ranked the taste of 50%KCl/50 %NaCl as fantastic or really good. Furthermore, 62 % of participants liked and would be happy to use the 50 %KCl/50 %NaCl or felt this tasted like common salt. Only 12 % rated the 100%KCl highly for taste, and over half reported being unlikely to use this. Most participants (57.3 % and 36.4 %) were able to visually identify 100%NaCl and 100%KCl, while identification of other blends was generally poor. Responses were similar for 35%KCl/65%NaCl and 66%KCl/34%NaCl throughout. CONCLUSION: Our findings suggest that the taste of the 50%KCl salt substitute would be well tolerated by South African adults, most of which could not visually differentiate between this salt substitute and common salt.

Anesthesia and humane euthanasia methods for king worm larvae (Zophobas morio).

A growing spotlight on insect welfare as research subjects, fodder for vertebrate animals, and patients for veterinarians highlights the need to establish humane euthanasia methods for these species. An insect of increasing commercial importance is the king worm (Zophobas morio), a type of darkling beetle larvae. The initial objective of this study was to determine if prolonged exposure to isoflurane would lengthen anesthetic recovery and lead to euthanasia. Larvae were exposed to isoflurane for 10 min, 40 min, 70 min, 190 min, 13 h, and 24 h (n = 10 for each treatment duration group), and time to recovery was subsequently monitored in room air. The second objective was to determine effectiveness of secondary euthanasia methods: injectable potassium chloride at 1 mg/g body weight (n = 5) and 3 mg/g body weight (n = 5) doses; immersion in 200 proof ethanol (n = 10), 10% buffered formalin (n = 10), and water (n = 10); and freezing at -18°C (n = 10). Prolonged exposure to isoflurane led to extended recovery times, but 100% mortality was not achieved. Submersion in ethanol and injection of potassium chloride at a 3 mg/g body weight dose resulted in 100% mortality. If these larvae are to be used as future food sources, a humane euthanasia method that preserves the ability to be consumed is required.

Potassium-Enriched Salt Substitutes: A Review of Recommendations in Clinical Management Guidelines.

Excess dietary sodium intake and insufficient dietary potassium intake are both well-established risk factors for hypertension. Despite some successful initiatives, efforts to control hypertension by improving dietary intake have largely failed because the changes required are mostly too hard to implement. Consistent recent data from randomized controlled trials show that potassium-enriched, sodium-reduced salt substitutes are an effective option for improving consumption levels and reducing blood pressure and the rates of cardiovascular events and deaths. Yet, salt substitutes are inconsistently recommended and rarely used. We sought to define the extent to which evidence about the likely benefits and harms of potassium-enriched salt substitutes has been incorporated into clinical management by systematically searching guidelines for the management of hypertension or chronic kidney disease. We found incomplete and inconsistent recommendations about the use of potassium-enriched salt substitutes in the 32 hypertension and 14 kidney guidelines that we reviewed. Discussion among the authors identified the possibility of updating clinical guidelines to provide consistent advice about the use of potassium-enriched salt for hypertension control. Draft wording was chosen to commence debate and progress consensus building: strong recommendation for patients with hypertension-potassium-enriched salt with a composition of 75% sodium chloride and 25% potassium chloride should be recommended to all patients with hypertension, unless they have advanced kidney disease, are using a potassium supplement, are using a potassium-sparing diuretic, or have another contraindication. We strongly encourage clinical guideline bodies to review their recommendations about the use of potassium-enriched salt substitutes at the earliest opportunity.

Comparison of Bretschneider HTK and Blood Cardioplegia (4:1): A Prospective Randomized Study.

BACKGROUND: We compared the effect of intermittent blood and histidine-tryptophan-ketoglutarate (HTK) solution of Bretschneider on myocardial histopathology and perioperative outcome. METHODS: Forty adult cardiac surgery patients were grouped into two (n = 20 for each): (1) Intermittent blood cardioplegia (IBC): had repeated cold 4:1 blood cardioplegia and (2) HTK: had a single dose of cold HTK for cardioprotection. Creatine kinase (CK)-MB, Troponin-I (cTn-I), pH, and lactate were studied in coronary sinus blood before and after aortic cross-clamping (AXC) and systemic blood at postoperative 6th, 24th, and 48th hours. Myocardial biopsy was performed before and after AXC for light microscopy. Vacuolation, inflammation, edema, and glycogen were graded semiquantitatively (from 0 to 3). The myocardial apoptotic index was evaluated via the terminal deoxynucleotidyl transferase dUTP nick end labeling. RESULTS: There were no differences in perioperative clinical outcomes between the groups. The coronary sinus samples after AXC were more acidotic (7.15 ± 0.14 vs. 7.32 ± 0.07, p = 0.001) and revealed higher CK-MB (21.0 ± 12.81 vs. 12.60 ± 11.80, p = 0.008) in HTK compared with IBC. The HTK had significantly a higher amount of erythrocyte suspension intraoperatively compared with IBC (0.21 ± 0.53 vs. 1.68 ± 0.93 U, p = 0.001). Microscopically, myocardial edema was more pronounced in HTK compared with IBC after AXC (2.25 ± 0.91 vs. 1.50 ± 0.04, p = 0.013). While a significant increase in the apoptotic index was seen after AXC in both groups (p = 0.001), no difference was detected between the groups (p = 0.417). CONCLUSION: IBC and HTK have a similar clinical outcome and protective effect, except for more pronounced myocardial edema and increased need for intraoperative transfusion with HTK.

The effect of potassium supplementation and concomitant medications on potassium homeostasis for hospitalized patients.

PURPOSE: Hospitalized patients receive potassium (K+) supplementation for hypokalemia, with clinicians often estimating a rise in serum K+ levels of 0.1 mEq/L per 10 mEq delivered. However, there is limited evidence to support this expectation. Patients also concomitantly take medications that may alter K+ levels, and it is not known to what degree these may impact interventions to correct K+ levels via supplementation. The objective of this study was to identify the impact of oral and/or intravenous K+ supplementation on serum K+ levels, including the influence of selected concomitant medications, in adult hospitalized patients. METHODS: A single-center, retrospective descriptive study of adult hospitalized patients receiving K+ supplementation at a tertiary hospital between 2021 and 2022 was conducted. Patients were included if they received at least one dose of potassium chloride while admitted to the general medicine ward. The primary outcome was the daily median change in serum K+, normalized per 10 mEq of supplementation administered. The secondary outcome was the impact of selected concomitant medication use on supplement-induced changes in serum K+. RESULTS: A total of 800 patients and 1,291 daily episodes of K+ supplementation were evaluated. The sample was approximately 53% women, was 78% white, and had a median age of 68 years. The overall daily median change in serum K+ level was 0.05 mEq/L per 10 mEq of supplementation delivered. Patients received a median of 40 mEq of supplementation per day, primarily via the oral route (80.6%). Among the concomitant medications assessed, loop diuretics significantly dampened the impact of K+ supplementation. CONCLUSION: Supplementation of K+ in non-critically ill hospitalized patients is variable and dependent on concomitant medication use.

A propensity score matched analysis of liver transplantation outcomes in the setting of preservation solution shortage.

The recent shortage of the University of Wisconsin (UW) solution prompted increased utilization of histidine-tryptophan-ketoglutarate (HTK) solution for liver graft preservation. This contemporary study analyzed deceased donor liver transplant outcomes following preservation with HTK vs UW. Patients receiving deceased donor liver transplantations between January 1, 2019, and June 30, 2022, were retrospectively identified utilizing the Organ Procurement and Transplant Network database, stratified by preservation with HTK vs UW, and a propensity score matching analysis was performed. Outcomes assessed included rates of primary nonfunction, graft survival, and patient survival. There were 4447 patients in each cohort. Primary nonfunction occurred in 60 (1.35%) patients in the HTK group vs 25 (0.54%) in the UW group (P < .001). HTK was associated with lower 90-day graft survival (94.39% vs 96.09%; P < .001) and 90-day patient survival (95.97% vs 97.38%; P = .001). Unmatched donation after cardiac death-specific analysis of HTK vs UW demonstrated respective rates of primary nonfunction of 1.63% vs 0.82% (P = .20), 90-day graft survival of 92.50% vs 95.29% (P = .069), and 90-day patient survival of 93.90% vs 96.35% (P = .077). These results suggest that HTK may not be an equivalent preservation solution for deceased donor liver transplantation.

Mouse TMC4 is involved in the detection of chloride taste of salts.

Licking behavior with various salts in transmembrane channel-like 4 (Tmc4) knockout (KO) mice was observed. In Tmc4 KO mice, a significant decrease in sensitivity to chloride salts, such as NaCl, KCl, and NH4Cl, was observed, while no significant decrease in sensitivity to Na-gluconate was observed. This finding suggests that TMC4 may be involved in the detection of chloride taste.

Physical and Chemical Compatibility of Medications Commonly Used in Critically Ill Patients With Balanced Crystalloids: A Systematic Review.

OBJECTIVE: Evaluate available evidence of physical and/or chemical compatibility of commonly used medications in critically ill patients with balanced crystalloids. DATA SOURCES: Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews were queried from inception to September 2022. STUDY SELECTION AND DATA EXTRACTION: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. English-language studies reporting physical and/or chemical compatibility data between 50 selected medications and balanced crystalloids were included. A previously designed tool to assess risk of bias was adapted for use. DATA SYNTHESIS: Twenty-nine studies encompassing 39 (78%) medications and 188 unique combinations with balanced crystalloids were included. Combinations included 35 (70%) medications with lactated Ringer's, 26 (52%) medications with Plasma-Lyte, 10 (20%) medications with Normosol, and one (2%) medication with Isolyte. Studies commonly evaluated physical and chemical compatibility (55.2%). More medications were evaluated via Y-site than admixture. Incompatibilities were identified in 18% of combinations comprising 13 individual drugs. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This systematic review evaluates the compatibility of select critical care medications with balanced crystalloid solutions. Results may be used as a tool to guide clinicians on balanced crystalloid compatibility, potentially increasing ubiquitous use and reducing patient exposure to normal saline. CONCLUSION AND RELEVANCE: Data are limited regarding chemical/physical compatibility of commonly used medications in critically ill patients with balanced crystalloids. Additional compatibility studies are warranted, particularly methodologically rigorous studies assessing Plasma-Lyte, Normosol, and Isolyte. Of the evaluated medications, there was a low frequency of incompatibilities with balanced crystalloids.

A pragmatic, open-label, randomized controlled trial of Plasma-Lyte-148 versus standard intravenous fluids in children receiving kidney transplants (PLUTO).

Acute electrolyte and acid-base imbalance is experienced by many children following kidney transplant. This is partly because doctors give very large volumes of artificial fluids to keep the new kidney working. When severe, fluid imbalance can lead to seizures, cerebral edema and death. In this pragmatic, open-label, randomized controlled trial, we randomly assigned (1:1) pediatric kidney transplant recipients to Plasma-Lyte-148 or standard of care perioperative intravenous fluids (predominantly 0.45% sodium chloride and 0.9% sodium chloride solutions). We then compared clinically significant electrolyte and acid-base abnormalities in the first 72 hours post-transplant. The primary outcome, acute hyponatremia, was experienced by 53% of 68 participants in the Plasma-Lyte-148 group and 58% of 69 participants in the standard fluids group (odds ratio 0·77 (0·34 - 1·75)). Five of 16 secondary outcomes differed with Plasma-Lyte-148: hypernatremia was significantly more frequent (odds ratio 3·5 (1·1 - 10·8)), significantly fewer changes to fluid prescriptions were made (rate ratio 0·52 (0·40-0·67)), and significantly fewer participants experienced hyperchloremia (odds ratio 0·17 (0·07 - 0·40)), acidosis (odds ratio 0·09 (0·04 - 0·22)) and hypomagnesemia (odds ratio 0·21 (0·08 - 0·50)). No other secondary outcomes differed between groups. Serious adverse events were reported in 9% of participants randomized to Plasma-Lyte-148 and 7% of participants randomized to standard fluids. Thus, perioperative Plasma-Lyte-148 did not change the proportion of children who experienced acute hyponatremia compared to standard fluids. However fewer fluid prescription changes were made with Plasma-Lyte-148, while hyperchloremia and acidosis were less common.