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Precise regulation of the acid-base balance is essential for the functioning of various organs and physiological processes. Acid retention and metabolic acidosis (MA) are frequent complications of chronic kidney disease (CKD) and can also occur following kidney transplantation. In addition to dietary modifications, pharmacological interventions, most notably sodium bicarbonate, are employed to correct MA. While several studies have reported a beneficial effect of MA correction on the progression of CKD, the results remain inconsistent and the magnitude of the treatment effect may be limited. Importantly, no beneficial effect on graft function has been demonstrated after kidney transplantation. The MA is associated with impaired bone quality and although alkali treatment has generally shown positive effects on markers of bone metabolism, consistent changes in bone density have not been observed. Additionally, MA is linked to an increased incidence of cardiovascular events but so far there is a lack of interventional studies with definitive cardiovascular endpoints. Sodium bicarbonate may lead to sodium retention, potentially increasing blood pressure, although the data on this are inconclusive. One interventional study with notable limitations reported a positive effect of alkali treatment on mortality. Correction of MA has been suggested to positively impact protein and muscle catabolism, although no improvement in physical performance was observed in a geriatric population. Limited studies exist on the endocrinological effects of alkali treatment but these indicate a favorable impact on glucose metabolism and potential benefits for thyroid function in predialysis CKD patients. Given the overall low to moderate level of evidence supporting the benefits of alkali treatment, the current guidelines from Kidney Disease: Improving Global Outcomes (KDIGO) propose alkali treatment to prevent serum bicarbonate levels < 18 mmol/l (prior < 22 mmol/l) in adults and the resulting complications., Competing Interests: Einhaltung ethischer Richtlinien. Interessenkonflikt: A. Ritter, C. Kuhn und N. Mohebbi geben an, dass kein Interessenkonflikt besteht. Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien., (© 2024. The Author(s).)

The case of a 72-year-old female patient with arrhythmogenic syncope associated with a combination therapy of flecainide and lacosamide is presented. The authors believe in an additive effect of both drugs on myocardial voltage-gated sodium channels with extraordinary QRS widening, exit block with temporary pacing and complete reversibility through infusion of sodium bicarbonate as bail-out therapy., Competing Interests: Einhaltung ethischer Richtlinien. Interessenkonflikt: A. Gallinger, R. Osei-Davies und F. Hennersdorf geben an, dass kein Interessenkonflikt besteht. Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien. Für Bildmaterial oder anderweitige Angaben innerhalb des Manuskripts, über die Patient/-innen zu identifizieren sind, liegt von ihnen und/oder ihren gesetzlichen Vertretern/Vertreterinnen eine schriftliche Einwilligung vor., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Aims/Background Hyperuricemia is a metabolic disorder characterized by elevated levels of uric acid in the blood. If left untreated, hyperuricemia can progress to gout, which manifests as acute arthritic attacks, and may also lead to uric acid nephrolithiasis and other renal conditions. This widespread condition poses significant risks to human health and quality of life. This study retrospectively evaluated the effectiveness and safety of using benzbromarone in combination with sodium bicarbonate tablets for the treatment of gout associated with hyperuricemia. Methods The study reviewed the electronic medical records (EMR) of 150 patients with gout and hyperuricemia who were admitted to our hospital between May 2018 and December 2023. These patients were divided into two groups: a control group and a research group. The control group received oral sodium bicarbonate tablets, while the research group was treated with oral benzbromarone tablets in addition to sodium bicarbonate tablets. The study compared the treatment outcomes and adverse reactions between the two groups, as well as assessed changes in blood-related indicators, the number of tophi, pain levels, and quality of life before and after treatment. Results The research group demonstrated a higher total effective rate compared to the control group ( p < 0.05). Post-treatment, the research group exhibited significantly lower levels of serum uric acid (UA), serum creatinine (Scr), and urea ( p < 0.05). Additionally, this group had fewer tophi and lower visual analog scale (VAS) scores compared to the control group ( p < 0.05). Quality of life scores were also significantly higher in the research group ( p < 0.05). No statistically significant difference was found in the incidence of adverse drug reactions between the two groups ( p > 0.05). Conclusion The combination of benzbromarone and sodium bicarbonate tablets is highly effective in treating gout associated with hyperuricemia. This treatment not only reduces uric acid levels and the number of tophi but also enhances renal function, alleviates pain, and improves the overall quality of life for patients.

Many dogmas influence daily clinical practice, and critical care medicine is no exception. We previously highlighted the weak, questionable, and often contrary evidence base underpinning four established medical managements-loop diuretics for acute heart failure, routine use of heparin thromboprophylaxis, rate of sodium correction for hyponatremia, and 'every hour counts' for treating bacterial meningitis. We now provide four further examples in this "Dogma II" piece (a week's course of antibiotics, diabetic ketoacidosis algorithms, sodium bicarbonate to improve ventricular contractility during severe metabolic acidosis, and phosphate replacement for hypophosphatemia) where routine practice warrants re-appraisal., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: High fruit and vegetable diets are associated with reduced chronic kidney disease and cardiovascular disease but are infrequently used in hypertension treatment. Low acid diets are also associated with reduced chronic kidney disease and cardiovascular disease, and fruits and vegetables or oral sodium bicarbonate (NaHCO 3 ) lowers dietary acid., Methods: We randomized 153 hypertensive macroalbuminuric patients receiving pharmacologic chronic kidney disease and cardiovascular disease protection to get fruits and vegetables, oral NaHCO 3 , or Usual Care. We assessed the course of kidney disease progression and cardiovascular disease risk indices over five years., Results: Chronic kidney disease progression was slower in participants receiving fruits and vegetables or oral NaHCO 3 than Usual Care [mean (SE)] [-1.08 (0.06) and -1.17 (0.07) vs. -1.94 (0.11) mL/min/1.73m 2 / year, respectively, P's< .001). Yet, systolic blood pressure was lower, and cardiovascular disease risk indices improved more in participants receiving fruits and vegetables than in those receiving NaHCO 3 or Usual Care. These cardiovascular benefits of fruits and vegetables were achieved despite lower doses of pharmacologic chronic kidney disease and cardiovascular disease protection., Conclusion: The trial supports fruits and vegetables as foundational hypertension treatment to reduce chronic kidney disease progression and cardiovascular disease risk., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract: Electrical muscle stimulation (EMS) training has been recognized as an effective modality for improving body composition, enhancing body strength, and facilitating injury recovery. However, individuals who are new to EMS training and those with certain chronic diseases should exercise caution due to the increased risk of rhabdomyolysis. This case report describes the occurrence of rhabdomyolysis and gluteal compartment syndrome following a single session of EMS training in a 46-year-old Caucasian female professional athlete. The patient was successfully managed with intensive intravenous fluid therapy and sodium bicarbonate supplementation, along with close monitoring of electrolytes and renal function. Electrical muscle stimulation training poses an increased risk of severe complications in individuals with chronic diseases and myopathy. Therefore, careful subject selection is required for EMS training in individuals with chronic diseases and myopathy to prevent common side effects. For individuals trying EMS training for the first time, it is recommended to avoid high-frequency EMS exercises., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Our objectives were to characterize variations from standardized, evidence-based guidelines in the management of pediatric patients with diabetic ketoacidosis (DKA) based on initial presentation to a tertiary pediatric emergency department (PED) versus a community emergency department (OSH) and compare clinical outcomes., Methods: We conducted a retrospective study on children 18 years and younger with DKA who presented to an OSH or PED over a 3-year period. Treatments monitored for variation included intravenous fluid management, insulin delivery, and sodium bicarbonate administrations. Clinical outcomes included time to anion gap correction and on insulin infusion, hypokalemia, hypoglycemia, rapid serum glucose decline, cerebral edema, mechanical ventilation, mortality, and time from initial presentation to hospital discharge., Results: Children with DKA who presented to an OSH (n = 250) were more acidotic (pH 7.11 vs. 7.13, P = 0.001) and had larger anion gaps (28.8 vs. 25.5, P < 0.001) compared with children presenting to the PED (n = 237). The OSH patients were more likely to receive larger fluid boluses (>20 cc/kg or >1000 ml, 43% vs. 4%, P < 0.001), sodium bicarbonate (5% vs. 0%, P < 0.001), and intravenous bolus insulin (28% vs. 0%, P < 0.001). The OSH group were less likely to be started on maintenance intravenous fluids (70% vs. 99%, P < 0.001) or receive potassium in maintenance intravenous fluids (14% vs. 42%, P < 0.001). The OSH group had longer anion gap correction times (754 vs. 541 mins, P < 0.001), insulin infusion times (1018 vs. 854 min, P = 0.003), and times to hospital discharge (3358 vs. 3045 mins, P < 0.001). Incidence of hypokalemia, hypoglycemia, rapid glucose decline, cerebral edema, and deaths were similar between the 2 groups., Conclusions: Our study demonstrated significant variations in the initial management of pediatric DKA patients by OSH facilities that deviated from an evidence-based treatment pathway utilized by a PED. Statewide quality improvement initiatives could help improve the overall clinical care provided to pediatric DKA patients., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To determine the safety and effectiveness of sodium bicarbonate administration in the management of metabolic acidemia and short-term outcomes in neonates with hypoxic-ischemic encephalopathy (HIE)., Study Design: Retrospective cohort study of neonates born at ≥35 weeks of gestation and receiving therapeutic hypothermia. Demographics, pH, lactate, base deficit, treatment, MRI findings, seizure incidence, death prior to discharge were collected., Results: There was higher mortality (p = 0.010) and injury on MRI (p = 0.008)-primarily deep gray matter (p < 0.001) and cortical injury (p = 0.003)-in the bicarbonate group compared to controls in univariate analysis. The combined outcome of death or abnormal MRI was not significantly associated (OR 1.97, 95% CI 0.80-4.87, p = 0.141) with bicarbonate administration when adjusting for sex, 5-minute Apgar, and initial base deficit., Conclusion: This study demonstrated association between bicarbonate use after HIE and negative short-term outcomes. Future prospective trials could overcome the treatment bias limitation demonstrated in this retrospective study., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Sjogren's syndrome is a known cause of renal tubular acidosis (RTA). However, osteomalacia associated with Sjogren's syndrome is rare and seldom reported in literature. We report a case of pseudofractures of both femora due to osteomalacia as a result of RTA secondary to Sjogren's syndrome, which was initially misdiagnosed as a stress fracture. A man in his 30s presented with hip pain and was initially misdiagnosed to have stress fractures because of the 'through and through' extension of the 'fracture' lines at the neck of both femora. The patient had a normal serum biochemistry profile except for elevated alkaline phosphatase levels. On further evaluation, he was found to have distal RTA secondary to Sjogren's syndrome. The patient responded to sodium bicarbonate therapy with clinical, biochemical and radiological improvement. A high index of suspicion for RTA should be kept in a patient with osteomalacia with a normal calcium profile and vitamin D level., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Flecainide is a medication used to treat supraventricular and ventricular tachyarrhythmias. Cases of overdoses are rare, however, can lead to significant cardiac effects. In previous cases of flecainide toxicity, treatment with sodium bicarbonate, intravenous lipid emulsion and amiodarone have been reported to be effective in preventing cardiovascular collapse and reestablishing baseline rhythm. Here, we present a case of a man in his 40s presented with flecainide overdose with wide-complex tachycardia that was treated with intravenous sodium bicarbonate following failure of amiodarone to normalise QRS interval., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: In the presence of infection, acidic pH of a lignocaine local anesthetic causes undesirable effects such as burning on injection, relatively slow onset, and lack of numbness. Buffered lignocaine will increase the pH of the solution and may resolve above problems. Thus, the objective of this study is to compare the efficacy of buffered lignocaine with that of commercial lignocaine., Method: Seventy patients with infected teeth were randomly divided into two equal groups. The study group received buffered lignocaine (8.4% sodium bicarbonate added to 2% lignocaine mixture) while the control received commercial lignocaine preparation (2% lignocaine with 1:80,000 adrenaline). Burning while injection, pain using VAS scale and onset of action with EPT (electric pulp tester) were recorded., Results: In the study group, the VAS score after injection was 1.20 ± 0.68 and the control group was 2.57 ± 0.92 (p = 0.001). There was a statistically significant reduction in pain reduction in the study group. The time of onset was 3.97 ± 0.71 and 5.67 ± 1.15 min, respectively, and the difference was statically significant. Only one-third of the study group experienced burning on injection as compared to two-thirds in the control group., Conclusion: Buffered lignocaine is more effective as compared to commercial lignocaine in the extraction of infected teeth., Ctri Number: CTRI/2022/01/039476., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To determine whether initiating saline nasal irrigation after COVID-19 diagnosis reduces hospitalization and death in high-risk outpatients compared with observational controls, and if irrigant composition impacts severity., Methods: Participants 55 and older were enrolled within 24 hours of a + PCR COVID-19 test between September 24 and December 21, 2020. Among 826 screened, 79 participants were enrolled and randomly assigned to add 2.5 mL povidone-iodine 10% or 2.5 mL sodium bicarbonate to 240 mL of isotonic nasal irrigation twice daily for 14 days. The primary outcome was hospitalization or death from COVID-19 within 28 days of enrollment by daily self-report confirmed with phone calls and hospital records, compared to the CDC Surveillance Dataset covering the same time. Secondary outcomes compared symptom resolution by irrigant additive., Results: Seventy-nine high-risk participants were enrolled (mean [SD] age, 64 [8] years; 36 [46%] women; 71% Non-Hispanic White), with mean BMI 30.3. Analyzed by intention-to-treat, by day 28, COVID-19 symptoms resulted in one ED visit and no hospitalizations in 42 irrigating with alkalinization, one hospitalization of 37 in the povidone-iodine group, (1.27%) and no deaths. Of nearly three million CDC cases, 9.47% were known to be hospitalized, with an additional 1.5% mortality in those without hospitalization data. Age, sex, and percentage with pre-existing conditions did not significantly differ by exact binomial test from the CDC dataset, while reported race and hospitalization rate did. The total risk of hospitalization or death (11%) was 8.57 times that of enrolled nasal irrigation participants (SE = 2.74; P = .006). Sixty-two participants completed daily surveys (78%), averaging 1.8 irrigations/day. Eleven reported irrigation-related complaints and four discontinued use. Symptom resolution was more likely for those reporting twice daily irrigation ( X 2 = 8.728, P = .0031) regardless of additive., Conclusion: SARS-CoV-2+ participants initiating nasal irrigation were over 8 times less likely to be hospitalized than the national rate., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Metabolic acidosis is a frequent complication of chronic kidney disease and is associated with a number of adverse outcomes, including worsening kidney function, poor musculoskeletal health, cardiovascular events, and death. Mechanisms that prevent metabolic acidosis detrimentally promote further kidney damage, creating a cycle between acid accumulation and acid-mediated kidney injury. Disrupting this cycle through the provision of alkali, most commonly using sodium bicarbonate, is hypothesized to preserve kidney function while also mitigating adverse effects of excess acid on bone and muscle. However, results from clinical trials have been conflicting. There is also significant interest to determine whether sodium bicarbonate might improve patient outcomes for those who do not have overt metabolic acidosis. Such individuals are hypothesized to be experiencing acid-mediated organ damage despite having a normal serum bicarbonate concentration, a state often referred to as subclinical metabolic acidosis. Results from small- to medium-sized trials in individuals with subclinical metabolic acidosis have also been inconclusive. Well-powered clinical trials to determine the efficacy and safety of sodium bicarbonate are necessary to determine if this intervention improves patient outcomes.

Background: Oral mucositis is one of the side effects developed post-hematopoietic stem cell transplant. This retrospective study aimed to assess the efficacy of a mouthwash mixture (lidocaine, sodium alginate, sucralfate, pheniramine) versus hyaluronic acid and a solution of sodium bicarbonate in terms of healing time and weight gain in the treatment of oral mucositis in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation with hemato-oncological malignancies., Methods: A total of 171 patients that received chemotherapy for the hematopoietic stem cell transplant were divided into three groups; group 1, treated with a mixed mouthwash of lidocaine, sodium alginate, sucralfate, and pheniramine; group 2, treated with hyaluronic acid; and group 3, treated with an aqueous solution of 5% sodium bicarbonate. Weight and mucositis scale scores derived from medical records of patients., Results: There was a statistically significant difference in the mucositis scale scores between the groups on the transplant day and days 5, 10, 15 and 20 after the transplantation. At these measurement points, Group 2 (receiving hyaluronic acid) had a lower score, and Group 3 (who received sodium bicarbonate) had a higher score, especially on days 5 and 10 after the transplantation., Conclusion: The results suggest that hyaluronic acid is a more effective treatment option than the other oral care solutions that are frequently used for prophylaxis and treatment of oral mucositis., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Abstract: Background : This study aims to determine the impact and mechanism of miR-21-3p on intestinal injury and intestinal glycocalyx during fluid resuscitation in traumatic hemorrhagic shock (THS), and the different impacts of sodium lactate Ringer's solution (LRS) and sodium bicarbonate Ringer's solution (BRS) for resuscitation on intestinal damage. Methods : A rat model of THS was induced by hemorrhage from the left femur fracture. The pathological changes of intestinal tissues and glycocalyx structure were observed by hematoxylin-eosin staining and transmission electron microscope. MiR-21-3p expression in intestinal tissues was detected by real-time quantitative polymerase chain reaction. The expression of glycocalyx-, cell junction-, and PI3K/Akt/NF-κB signaling pathway-related proteins was analyzed by western blot. Results : MiR-21-3p expression was increased in THS rats, which was suppressed by resuscitation with BRS. BRS or LRS aggravated the intestinal injury and damaged intestinal glycocalyx in THS rats. The expression of SDC-1, HPA, β-catenin, MMP2, and MMP9 was upregulated, the expression of E-cad was downregulated, and the PI3K/Akt/NF-κB signaling pathway was activated in THS rats, which were further aggravated by BRS or LRS. The adverse effect of LRS was more serious than BRS. MiR-21-3p overexpression deteriorated the injury of intestinal tissues and intestinal glycocalyx; increased the expression of SDC-1, HPA, β-catenin, MMP2, and MMP9 while decreasing E-cad expression; and activated the PI3K/Akt/NF-κB signaling pathway in BRS-resuscitated THS rats. Conclusion : MiR-21-3p aggravated intestinal tissue injury and intestinal glycocalyx damage through activating PI3K/Akt/NF-κB signaling pathway in rats with THS resuscitated with BRS., (Copyright © 2024 by the Shock Society.)

Purpose of This Review: Metabolic acidosis is frequently encountered in patients with chronic kidney disease (CKD), with increasing prevalence as kidney function worsens. Treating electrolyte disturbances is the sine qua non of Nephrologists, and alkali therapy to normalize serum bicarbonate levels and slow progression of kidney disease has been embedded in clinical practice guidelines for decades on the basis of animal models and controversial clinical trials. This review will critically appraise the literature base for this recommendation and determine whether the available evidence supports this common practice, which is a timely endeavor considering the impending demotion of metabolic acidosis treatment from recommendation to practice point in forthcoming KDIGO guidelines., Recent Findings: Earlier, open-label, studies supporting the utility of sodium bicarbonate therapy to slow progression of chronic kidney disease have been challenged by more recent, blinded, studies failing to show benefit on CKD progression. This was further demonstrated in the absence of concomitant sodium administration with the hydrochloric acid binder veverimer, which failed to demonstrate benefit on renal death, end stage kidney disease or 40% reduction in estimated glomerular filtration rate in a large multicenter trial., Summary: The current body of literature does not support the routine treatment of metabolic acidosis in patients with CKD and the authors agree with the forthcoming KDIGO guidelines to de-emphasize this common practice., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: To analyze efficacy of endoscopic lithotripsy combined with drug lithotripsy as compared with drug lithotripsy for the treatment of phytobezoars., Methods: We collected and evaluated case records of 165 patients with phytobezoars from 2014 to 2023. And we analyzed demographic and clinical characteristics, imaging features, endoscopic features, complications of phytobezoars, and compared efficacy between endoscopic lithotripsy combined with drug lithotripsy (Group A) and drug lithotripsy (sodium bicarbonate combined with proton pump inhibitor) (Group B)., Results: The median age of patients with phytobezoars was 67.84 ± 4.286 years old. Abdominal pain was the most common symptom and peptic ulcers (67.5%) were the most common complication. Bezoar-induced ulcers were more frequent in the gastric angle. The success rate of phytobezoars vanishing in Group A and Group B were similar (92.3% vs. 85.1% within 48 h, 98.7% vs. 97.7% within a week), while the average hospitalization period, average hospitalization cost, second endoscopy rate, and average endoscopic operation time were significantly lower in patients in Group B than in Group A., Conclusion: Drug lithotripsy is the preferred effective and safe treatment option for phytobezoars. We advise that an endoscopy should be completed after 48 h for drug lithotripsy., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Hypertonic sodium bicarbonate is advocated for the treatment of sodium channel blocker poisoning, but its efficacy varies amongst different sodium channel blockers. This Commentary addresses common pitfalls and appropriate usage of hypertonic sodium bicarbonate therapy in cardiotoxic drug poisonings., Sodium Bicarbonate Works Synergistically With Hyperventilation: Serum alkalinization is best achieved by the synergistic effect of hypertonic sodium bicarbonate and hyperventilation (PCO 2 ∼ 30-35 mmHg [0.47-0.6 kPa]). This reduces the dose of sodium bicarbonate required to achieve serum alkalinization (pH ∼ 7.45-7.55) and avoids adverse effects from excessive doses of hypertonic sodium bicarbonate., Variability in Response to Sodium Bicarbonate Treatment: Tricyclic antidepressant poisoning responds well to sodium bicarbonate therapy, but many other sodium channel blockers may not. For instance, drugs that block the intercellular gap junctions, such as bupropion, do not respond well to alkalinization. For sodium channel blocker poisonings in which the expected response is unknown, a bolus of 1-2 mmol/kg sodium bicarbonate can be used to assess the response to alkalinization., Sodium Bicarbonate Can Exacerbate Toxicity From Drugs Acting on Multiple Cardiac Channels: Hypertonic sodium bicarbonate can cause electrolyte abnormalities such as hypokalaemia and hypocalcaemia, leading to QT interval prolongation and torsade de pointes in poisonings with drugs that have mixed sodium and potassium cardiac channel properties, such as hydroxychloroquine and flecainide., The Goal for Hypertonic Sodium Bicarbonate Is to Achieve the Alkalinization Target (∼ph 7.5), Not Complete Correction of Qrs Complex Prolongation: Excessive doses of hypertonic sodium bicarbonate commonly occur if it is administered until the QRS complex duration is < 100 ms. A prolonged QRS complex duration is not specific for sodium channel blocker toxicity. Some sodium channel blockers do not respond, and even when there is a response, it takes a few hours for the QRS complex duration to return completely to normal. In addition, QRS complex prolongation can be due to a rate-dependent bundle branch block. So, no further doses should be given after achieving serum alkalinization (pH ∼ 7.45-7.55)., Maximal Dosing for Hypertonic Sodium Bicarbonate: A further strategy to avoid overdosing patients with hypertonic sodium bicarbonate is to set maximum doses. Exceeding 6 mmol/kg is likely to cause hypernatremia, fluid overload, metabolic alkalosis, and cerebral oedema in many patients and potentially be lethal., Recommendation for the Use of Hypertonic Sodium Bicarbonate in Sodium Channel Blocker Poisoning: We propose that hypertonic sodium bicarbonate therapy be used in patients with sodium channel blocker poisoning who have clinically significant toxicities such as seizures, shock (systolic blood pressure < 90 mmHg, mean arterial pressure <65 mmHg) or ventricular dysrhythmia. We recommend initial bolus dosing of hypertonic sodium bicarbonate of 1-2 mmol/kg, which can be repeated if the patient remains unstable, up to a maximum dose of 6 mmol/kg. This is recommended to be administered in conjunction with mechanical ventilation and hyperventilation to achieve serum alkalinization (PCO 2 ∼30-35 mmHg [4-4.7 kPa]) and a pH of ∼7.45-7.55. With repeated bolus doses of hypertonic sodium bicarbonate, it is imperative to monitor and correct potassium and sodium abnormalities and observe changes in serum pH and on the electrocardiogram., Conclusions: Hypertonic sodium bicarbonate is an effective antidote for certain sodium channel blocker poisonings, such as tricyclic antidepressants, and when used in appropriate dosing, it works synergistically with hyperventilation to achieve serum alkalinization and to reduce sodium channel blockade. However, there are many pitfalls that can lead to excessive sodium bicarbonate therapy and severe adverse effects.

Objective: Temporary vascular access is mandatory for acute hemodialysis. Heparin lock solution is the standard of care worldwide. Many lock solutions were studied in terms of thrombosis and catheter-related infection prevention, but none replaced heparin as a standard measure. Our main aim is to investigate the effectiveness of sodium bicarbonate (NaHCO3), a ubiquitous and cheap option as a catheter lock solution, in comparison with traditionally used heparin in non-tunneled hemodialysis catheters., Methods: We conducted our prospective study between March 2021 and March 2022. Our study included 441 patients > 18 years old who needed either femoral or jugular non-tunneled dialysis catheters. Patients were assigned to either heparin (5000 IU/ml) or 8.4% sodium bicarbonate on a consecutive basis. Basic characteristics and information regarding catheters, dialysis sessions, and complications were recorded. We divided patients according to the catheter insertion site as well as the lock solution., Results: We analyzed 426 patients divided into four groups: jugular heparin (n = 113), jugular bicarbonate (n = 113), femoral heparin (n = 113), and femoral bicarbonate (n = 100). Basal characteristics were similar for all groups. The mean time to last effective dialysis in our institution was 10.7 ± 12.1 days for heparin vs 11.5 ± 10.8 days for the bicarbonate group. 25 (5.9%) patients had some kind of blood flow problems (13 in the heparin and 12 in the bicarbonate group). There was no significant difference in terms of catheter malfunction among groups (p = 0.50). Out of these 25 cases, only 12 (7 in heparin and 5 in the bicarbonate arm) had catheter dysfunction (p = 0.386). Sixty-four patients (28%) with jugular catheters were discharged with patent catheters and continued their dialysis in other facilities., Conclusion: Sodium bicarbonate is as effective as classic unfractionated heparin in preventing catheter lumen thrombosis with a comparable incidence of catheter-related complications. Furthermore, it is a cost-effective option that can be used confidently, especially when heparin is contraindicated., Trial Registration: ClinicalTrials.gov Identifier: NCT04772209 (26.02.2021)., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Metabolic acidosis (MA) is frequently associated with chronic kidney disease (CKD) progression. Our aim was to compare the effect of oral sodium citrate (SC) with that of oral sodium bicarbonate (SB) on renal function and serum bicarbonate correction, as well as to evaluate their safety profile in patients with MA of CKD., Methods: We conducted a prospective, single-center, randomized 1:1, parallel, controlled, unblinded clinical trial of 124 patients with MA and CKD stages 3b and 4. The primary outcome was the mean change in estimated glomerular filtration rate (eGFR). The secondary outcomes were mean change in serum bicarbonate level, eGFR decrease by 30%, eGFR decrease by 50%, dialysis, death or prolonged hospitalization, and a combined endpoint., Results: No significant difference was found between the groups in terms of mean eGFR change [adjusted mean difference = -0.99 mL/min/1.73 m2 (95% CI: -2.51 to 0.93, P = .20)]. We observed a mean serum bicarbonate change of 6.15 mmol/L [(95% CI: 5.55-6.74), P < .001] in the SC group and of 6.19 mmol/L [(95% CI: 5.54-6.83), P < .001] in the SB group, but no significant difference between the 2 groups [adjusted mean difference = 0.31 mmol/L (-0.22 to 0.85), P = .25]. Cox proportional hazard analysis showed similar risks regarding eGFR decrease by 30% (P = .77), eGFR decrease by 50% (P = .50), dialysis (P = .85), death or prolonged hospitalization (P = .29), and combined endpoint (P = .57). Study drug discontinuation due to adverse events was significantly more common in the SB group (17.7% vs 4.8%, P = .02)., Conclusions: SC and SB have a similar effect on kidney function decline, both improve serum bicarbonate level, but SB is associated with higher rates of medication discontinuation due to adverse events., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Sodium bicarbonate (NaHCO3) is commonly utilized as a therapeutic to treat metabolic acidosis in people with chronic kidney disease (CKD). While increased dietary sodium chloride (NaCl) is known to promote volume retention and increase blood pressure, the effects of NaHCO3 loading on blood pressure and volume retention in CKD remain unclear. In the present study, we compared the effects of NaCl and NaHCO3 loading on volume retention, blood pressure, and kidney injury in both 2/3 and 5/6 nephrectomy remnant kidney rats, a well-established rodent model of CKD. We tested the hypothesis that NaCl loading promotes greater volume retention and increases in blood pressure than equimolar NaHCO3. Blood pressure was measured 24 h daily using radio telemetry. NaCl and NaHCO3 were administered in drinking water ad libitum or infused via indwelling catheters. Rats were housed in metabolic cages to determine volume retention. Our data indicate that both NaHCO3 and NaCl promote hypertension and volume retention in remnant kidney rats, with salt-sensitivity increasing with greater renal mass reduction. Importantly, while NaHCO3 intake was less pro-hypertensive than equimolar NaCl intake, NaHCO3 was not benign. NaHCO3 loading significantly elevated blood pressure and promoted volume retention in rats with CKD when compared with control rats receiving tap water. Our findings provide important insight into the effects of sodium loading with NaHCO3 in CKD and indicate that NaHCO3 loading in patients with CKD is unlikely to be benign., (© 2024 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Background: Gingivitis is driven by plaque accumulation and, if left untreated, can progress to irreversible periodontitis. For many, the mechanical action of toothbrushing does not achieve adequate plaque control. The aim of this study was to investigate whether twice-daily use of a toothpaste containing 0.2% high molecular weight (HMW) sodium hyaluronate with 67% sodium bicarbonate and 0.221% sodium fluoride (experimental toothpaste) could improve gingival health compared with a regular fluoride toothpaste (negative control). The study also assessed whether the experimental toothpaste could provide additive gingival health benefit over a toothpaste containing only 67% sodium bicarbonate and 0.221% sodium fluoride (positive control)., Methods: This was a single-center, examiner-blinded, randomized, clinical study in healthy adults with mild-to-moderate gingivitis. At baseline, after abstaining from toothbrushing for 12 h, prospective participants underwent oral soft tissue (OST) and oral hard tissue examination followed by assessments for gingival inflammation (Modified Gingival Index [MGI]), gingival bleeding (Bleeding Index [BI]), and supra-gingival plaque (Turesky Plaque Index [TPI]). Eligible participants were stratified by gender and baseline number of bleeding sites (low: <45; high: ≥45 bleeding sites). Following randomization, participants underwent prophylactic dental treatment. Participants received a full OST examination, MGI, BI and TPI assessments after 3 days, 1, 2 and 6 weeks of product use., Results: In total, 110 participants were screened for study entry and all were randomized to receive one of three toothpastes (experimental: sodium hyaluronate, sodium bicarbonate, sodium fluoride; positive control: sodium bicarbonate, sodium fluoride; negative control: regular fluoride toothpaste). For all measures, significant improvements were observed in participants receiving either sodium bicarbonate-containing toothpaste (experimental or positive control) compared with the regular fluoride toothpaste (negative control) at week 6. No significant difference was observed in any assessment or visit comparing the experimental toothpaste with the positive control., Conclusions: Both the experimental and the positive control toothpastes demonstrated clinically relevant improvements in gingival health compared with a regular fluoride toothpaste (negative control). However, no additional gingival health improvement was observed for the experimental toothpaste compared with the positive control, therefore, no additional gingival health benefit can be attributed to the inclusion of sodium hyaluronate in this formulation., Trial Registration: ClinicalTrials.gov Identifier: NCT04737538 (04/02/2021)., (© 2024. The Author(s).)

Skin wounds are susceptible to microbial infections which commonly lead to the delayed wound healing. Rapid clearance of pathogens from the wound is of great significance and importance for efficient healing of the infected wounds. Herein, we report a multifunctional hybrid dressing, which simply combines sodium bicarbonate (NaHCO 3 ) and hyaluronic acid (HA) for the synergistic wound healing. Addition of NaHCO 3 allows the hybrid dressing to have the great antibacterial and antioxidant activity, while maintaining the intrinsic skin repair function of HA. As a result, NaHCO 3 /HA hybrid dressing showed the great antibacterial activity against both Gram-positive (S. aureus) and Gram-negative (E. coli) pathogens, the ability to improve the fibroblasts proliferation and migration, the cell-protection capacity under H 2 O 2 -induced oxidative stress, and most importantly, the great healing efficacy for the mice wound infected by S. aureus. We further found that the epidermal regeneration, the collagen deposition and the angiogenesis were enhanced by NaHCO 3 /HA hybrid dressing. All these effects were NaHCO 3 concentration-dependent. Since the NaHCO 3 /HA hybrid dressing is drug-free, easily fabricated, biocompatible, and efficient for wound healing, it may have great potentials for clinical management of infected wounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Current international guidelines recommend administrating calcium chloride and sodium bicarbonate to patients with hyperkalemia-induced cardiac arrest, despite limited evidence. The aim of this study was to evaluate the efficacy of calcium chloride and sodium bicarbonate on return of spontaneous circulation (ROSC) in a pig model of hyperkalemia-induced cardiac arrest., Design: A randomized, blinded, placebo-controlled experimental pig study. Hyperkalemia was induced by continuous infusion of potassium chloride over 45 minutes followed by a bolus. After a no flow period of 7 minutes, pigs first received 2 minutes of basic cardiopulmonary resuscitation and subsequently advanced life support. The first intervention dose was administered after the fifth rhythm analysis, followed by a defibrillation attempt at the sixth rhythm analysis. A second dose of the intervention was administered after the seventh rhythm analysis if ROSC was not achieved. In case of successful resuscitation, pigs received intensive care for 1 hour before termination of the study., Setting: University hospital laboratory., Subjects: Fifty-four female Landrace/Yorkshire/Duroc pigs (38-42 kg)., Interventions: The study used a 2 × 2 factorial design, with calcium chloride (0.1 mmol/kg) and sodium bicarbonate (1 mmol/kg) as the interventions., Measurements and Main Results: Fifty-two pigs were included in the study. Sodium bicarbonate significantly increased the number of animals achieving ROSC (24/26 [92%] vs. 13/26 [50%]; odds ratio [OR], 12.0; 95% CI, 2.3-61.5; p = 0.003) and reduced time to ROSC (hazard ratio [HR] 3.6; 95% CI, 1.8-7.5; p < 0.001). There was no effect of calcium chloride on the number of animals achieving ROSC (19/26 [73%] vs. 18/26 [69%]; OR, 1.2; 95% CI, 0.4-4.0; p = 0.76) or time to ROSC (HR, 1.5; 95% CI, 0.8-2.9; p = 0.23)., Conclusions: Administration of sodium bicarbonate significantly increased the number of animals achieving ROSC and decreased time to ROSC. There was no effect of calcium chloride on the number of animals achieving ROSC or time to ROSC., Competing Interests: Dr. Granfeldt’s institution received funding from NMD Pharma; he received funding from Noorik Pharmaceuticals; and he was supported by a grant from the Health Research Foundation of Central Denmark Region. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: A systematic review and meta-analysis have been conducted to evaluate the efficacy of alkalinization for COVID-19 patients based on current evidence to determine the impact of alkalinization on COVID-19 outcomes., Methods: We searched MEDLINE (Pubmed), Web of Science, Cochrane Library, and Clinicaltrials.gov for studies evaluating the efficacy of alkalinization up to 30 April 2023. Based on the PRISMA 2020 statement criteria a systematic review and meta-analysis of studies were performed., Results: The results of our meta-analysis showed a significant reduction in mortality rate in the alkalinization group compared to controls (RR 0.73, 95% CI: 0.56-0.95; I2  =  0%). However, our subgroup analysis showed no significant improvement in RCT-only studies (RR 0.78, 95% CI: 0.59-1.05; I2  =  0%), the recovery rate was significantly higher in the alkalinization group (RR 2.13, 95% CI: 1.39-3.26; I2  =  0%), duration of recovery also has improved in alkalinization group (SMD 0.76, 95% CI: 0.33-1.18; I2  =  0%). The results of our meta-analysis showed a significant reduction in the duration of hospitalization in the alkalinization group compared to controls with very low certainty of evidence (SMD -0.66, 95% CI: -0.97 to -0.35; I2  =  36%)., Conclusion: With low certainty of evidence, alkalinization (by sodium bicarbonate) can be an efficient and safe adjuvant treatment for COVID-19 patients. Future randomized controlled trials are needed to strengthen the available evidence., Competing Interests: Declaration of Conflicting InterestsThe authors declare that they have no known competing interests.

Aim: Radiation-induced oral mucositis (RIOM) is the most frequent side effect in head and neck cancer (HNC) patients treated with curative radiotherapy (RT). A standardized strategy for preventing and treating RIOM has not been defined. Aim of this study was to perform a real-life survey on RIOM management among Italian RT centers., Methods: A 40-question survey was administered to 25 radiation oncologists working in 25 different RT centers across Italy., Results: A total of 1554 HNC patients have been treated in the participating centers in 2021, the majority (median across the centers 91%) with curative intent. Median treatment time was 41 days, with a mean percentage of interruption due to toxicity of 14.5%. Eighty percent of responders provide written oral cavity hygiene recommendations. Regarding RIOM prevention, sodium bicarbonate mouthwashes, oral mucosa barrier agents, and hyaluronic acid-based mouthwashes were the most frequent topic agents used. Regarding RIOM treatment, 14 (56%) centers relied on literature evidence, while internal guidelines were available in 13 centers (44%). Grade (G)1 mucositis is mostly treated with sodium bicarbonate mouthwashes, oral mucosa barrier agents, and steroids, while hyaluronic acid-based agents, local anesthetics, and benzydamine were the most used in mucositis G2/G3. Steroids, painkillers, and anti-inflammatory drugs were the most frequent systemic agents used independently from the RIOM severity., Conclusion: Great variety of strategies exist among Italian centers in RIOM management for HNC patients. Whether different strategies could impact patients' compliance and overall treatment time of the radiation course is still unclear and needs further investigation., (© 2023. The Author(s).)

Background: Sodium bicarbonate (SB) infusion is commonly used to correct metabolic acidosis, but its clinical efficacy remains controversial. This study aims to investigate whether acid-base balance parameters should be a consideration for administering SB treatment., Methods: Children with metabolic acidosis (pH < 7.35 and bicarbonate < 22 mmol/L) who were treated with or without 50 mg/ml SB injection were grouped and extracted from a retrospective cohort database of the Pediatric Intensive Care Unit. The interaction between acid-base balance parameters and SB treatment on mortality was analyzed through mortality curves and cross-effect models. Logistic regression was conducted to estimate the risk of death following SB treatment in the overall children as well as in subgroups, and potential confounding factors were adjusted for. After employing propensity score matching to account for confounding factors, further analysis was performed to evaluate the effectiveness of SB treatment within each chloride subgroup., Results: A total of 5865 children with metabolic acidosis were enrolled, of which 2462 (42.0%) received SB treatment. In the overall population, it was found that SB treatment did not reduce hospital mortality or 28-day mortality. Interactions between acid-base balance parameters (chloride and anion gap) and SB treatment on mortality were observed. Subgroup analysis clarified that when chloride levels were below 107 mmol/L, children treated with SB had higher in-hospital mortality (29.8% vs 14.9%) and 28-day mortality (26.5% vs 13.4%), with adjusted ORs of 2.065 (95% CI, 1.435-2.97) and 1.947 (95% CI, 1.332-2.846), respectively. In contrast, when chloride levels were greater than or equal to 113 mmol/L, children treated with SB had a shorter stay in the PICU (median: 1.1 days vs 5.1 days, adjusted p = 0.004) and lower in-hospital mortality (4.3% vs 10.3%) and 28-day mortality (4.0% vs 8.4%), with adjusted ORs of 0.515 (95% CI, 0.337-0.788) and 0.614 (95% CI, 0.391-0.965), respectively. After controlling for confounding factors through matching, the impact of SB treatment on the risk of death in each chloride subgroup was consistent with the aforementioned results. However, treatment with SB did not significantly increase the risk of death in newborns or children with moderate to severe metabolic acidosis when chloride levels were below 107 mmol/L (p > 0.05)., Conclusions: The use of sodium bicarbonate for treating metabolic acidosis has been found to increase mortality in children with low chloride levels but decrease mortality in those with high chloride levels in this study. Further prospective multi-center clinical studies and basic research are needed to validate these findings., (© 2023. The Author(s).)

Objectives: To identify the best population, design of the intervention, and to assess between-group biochemical separation, in preparation for a future phase III trial., Design: Investigator-initiated, parallel-group, pilot randomized double-blind trial., Setting: Eight ICUs in Australia, New Zealand, and Japan, with participants recruited from April 2021 to August 2022., Patients: Thirty patients greater than or equal to 18 years, within 48 hours of admission to the ICU, receiving a vasopressor, and with metabolic acidosis (pH < 7.30, base excess [BE] < -4 mEq/L, and Pa co2 < 45 mm Hg)., Interventions: Sodium bicarbonate or placebo (5% dextrose)., Measurements and Main Result: The primary feasibility aim was to assess eligibility, recruitment rate, protocol compliance, and acid-base group separation. The primary clinical outcome was the number of hours alive and free of vasopressors on day 7. The recruitment rate and the enrollment-to-screening ratio were 1.9 patients per month and 0.13 patients, respectively. Time until BE correction (median difference, -45.86 [95% CI, -63.11 to -28.61] hr; p < 0.001) and pH correction (median difference, -10.69 [95% CI, -19.16 to -2.22] hr; p = 0.020) were shorter in the sodium bicarbonate group, and mean bicarbonate levels in the first 24 hours were higher (median difference, 6.50 [95% CI, 4.18 to 8.82] mmol/L; p < 0.001). Seven days after randomization, patients in the sodium bicarbonate and placebo group had a median of 132.2 (85.6-139.1) and 97.1 (69.3-132.4) hours alive and free of vasopressor, respectively (median difference, 35.07 [95% CI, -9.14 to 79.28]; p = 0.131). Recurrence of metabolic acidosis in the first 7 days of follow-up was lower in the sodium bicarbonate group (3 [20.0%] vs. 15 [100.0%]; p < 0.001). No adverse events were reported., Conclusions: The findings confirm the feasibility of a larger phase III sodium bicarbonate trial; eligibility criteria may require modification to facilitate recruitment., Competing Interests: Dr. Higgins’ institution received funding from the National Health and Medical Research Council (NHMRC) investigator grant. Dr. Young disclosed government work. Dr. Maeda disclosed work for hire. Dr. French disclosed the off-label product use of Sodium bicarbonate in critical illness. Dr. Cooper’s institution received funding from the NHMRC of Australia and Eustralis Pharmaceuticals Pty Ltd (Pressura Neuro). Dr. Udy disclosed that he received trial consumables from Integra Lifesciences. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objective: To investigate the efficacy and safety of intravesical instillation of heparin/alkalized lidocaine (lidocaine mixed with sodium bicarbonate) combined with hydrodistension and transurethral fulguration in the treatment of female interstitial cystitis (IC)., Methods: Female patients who attended the Department of Urology at the First Hospital of China Medical University between January 2012 and December 2020 and met the diagnostic criteria proposed in the guidelines of the American Urological Association with a new diagnosis of IC were selected for retrospective analysis. Cystoscopy and biopsy of suspicious lesions were performed at the time of diagnosis. All the patients were treated with an intravesical instillation regimen of 2% lidocaine 10 mL + 5% sodium bicarbonate 5 mL + heparin 25 000 IU for a continuous period of 12 months, with or without water dilatation and transurethral electrocautery according to the patient's preference, categorized as hydrodistension and transurethral fulguration (HD/TF) group and non-HD/TF group. The patients were evaluated before and 1, 6, and 12 months after treatment for O'Leary-Sant interstitial cystitis patient symptom index scores (ICSI), interstitial cystitis patient problem index scores (ICPI), visual analog scale (VAS) of suprapubic pain, and functional bladder capacity (FBC) changes., Results: A total of 79 patients were collected in this study. Four (5.1%) of these patients underwent cystectomy due to pathological diagnosis of cancer or treatment failure. The remaining patients were followed up 1, 6 and 12 months after treatment. Repeated-measures ANOVA showed a significant decrease in ICPI, ICSI and VAS and an increase in FBC after treatment compared with before treatment ( P < 0.05). FBC continued to decrease during the 1, 6 and 12 months' post-treatment follow-ups, with statistically significant differences; ICSI continued to decrease during the 1 and 6 months post-treatment follow-ups, with statistically significant differences, while the difference between ICSI at 6 months post-treatment and at 12 months' post-treatment was not statistically significant. In the HD/TF group, ICPI continued to decrease in the follow-up from 1 and 6 months after treatment, and the difference was statistically significant, while the difference between ICPI 6 months after treatment and 12 months after treatment was not statistically significant. There was no statistically significant difference between the remaining indicators 1, 6 and 12 months after treatment. ICPI, ICSI, VAS and FBC improved earlier and the changes in VAS and FBC were more significant in the HD/TF group compared with the non-HD/TF group ( P < 0.05)., Conclusion: Heparin/alkalized lidocaine combination of intravesical instillation with hydrodistension and transurethral fulguration for IC is an effective treatment option. Heparin/alkalized lidocaine combination of intravesical instillation may be the first choice of treatment, which can significantly reduce the economic burden of patients and medical insurance system. If patients can accept it, transurethral fulguration with hydrodistension may be considered.

Hyperkalemia is a common electrolyte abnormality frequently complicated with chronic kidney disease. By injecting potassium chloride (KCl) solutions intravenously into bullfrogs, we reproduced typical electrocardiogram (ECG) abnormalities of hyperkalemia in the frog hearts, such as the peaked T waves and the widening of QRS complexes. Simultaneous recordings of cardiac action potentials showed morphological changes that synchronized with those of ECG. After 100 mM KCl injection, the widened QRS complexes continued for a while and gradually restored to their baseline widths. However, pre-treatment with sodium bicarbonate or salbutamol, which directly or indirectly stimulates Na + /K + -ATPase activity, significantly facilitated the recovery from the widened QRS duration, indicating the transcellular movement of potassium ions from the extracellular fluid into the intracellular stores.

Although immunotherapy has a broad clinical application prospect, it is still hindered by low immune responses and immunosuppressive tumor microenvironment. Herein, a simple and drug-free inorganic nanomaterial, alkalescent sodium bicarbonate nanoparticles (NaHCO 3 NPs), is prepared via a fast microemulsion method for amplified cancer immunotherapy. The obtained alkalescent NaHCO 3 regulates lactic acid metabolism through acid-base neutralization so as to reverse the mildly acidic immunosuppressive tumor environment. Additionally, it can further release high amounts of Na + ions inside tumor cells and induce a surge in intracellular osmolarity, and thus activate the pyroptosis pathway and immunogenic cell death (ICD), release damage-associated molecular patterns (DAMPs) and inflammatory factors, and improve immune responses. Collectively, NaHCO 3 NPs observably inhibit primary/distal tumor growth and tumor metastasis through acid neutralization remitted immunosuppression and pyroptosis induced immune activation, showing an enhanced antitumor immunity efficiency. This work provides a new paradigm for lactic acid metabolism and pyroptosis mediated tumor treatment, which has a potential for application in clinical tumor immunotherapy., (© 2023 Wiley-VCH GmbH.)

Background: Low urine pH, which may be mediated by metabolic syndrome (MetS), is common in gout. Tart cherries are shown to improve MetS symptoms and possess anti-inflammatory properties. However, the efficacy of tart cherry supplements on urine pH has yet to be studied., Objectives: This study aimed to investigate the efficacy and safety of tart cherry supplementary citrate (TaCCi) mixture on urine pH, serum urate (sUA), C-reactive protein (CRP), and gout flares in gout patients initiating urate-lowering therapy (ULT), in comparison to citrate mixture and sodium bicarbonate., Methods: A prospective, randomized (1:1:1), open-label, parallel-controlled trial was conducted among 282 men with gout and fasting urine pH ≤ 6, who were initiating ULT with febuxostat (initially 20 mg daily, escalating to 40 mg daily if serum urate ≥ 360 μmol/L). Participants were randomized to groups taking either sodium bicarbonate, citrate mixture, or TaCCi mixture. All participants were followed every 4 weeks until week 12. Urine pH and sUA were co-primary outcomes, with various biochemical and clinical secondary endpoints., Results: Urine pH increased to a similar extent in all three groups. SUA levels declined in all three groups as well, with no significant differences observed between the groups. At week 12, the TaCCi mixture group exhibited a greater reduction in the urine albumin/creatinine ratio (UACR) compared to the other two groups (p < 0.05). Participants taking TaCCi mixture or citrate mixture experienced fewer gout flares than those in the sodium bicarbonate group over the study period (p < 0.05). Additionally, the TaCCi mixture group had a lower CRP level at week 12 relative to the other two groups (p < 0.01). Adverse events were similar across all three groups., Conclusion: The TaCCi mixture had similar efficacy and safety on urine alkalization and sUA-lowering as the citrate mixture and sodium bicarbonate in patients with gout. However, the TaCCi mixture resulted in greater improvements in UACR and CRP, which suggests that tart cherry supplements may provide additional benefits for renal protection and reduce inflammation in gout, particularly when starting ULT., Trial Registration: This project was registered in ChiCTR ( www.chictr.org.cn ), with the registration number: ChiCTR2100050749., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: When both severe metabolic acidemia (pH equal or less than 7.20; PaCO2 equal or less than 45 mm Hg and bicarbonate concentration equal or less than of 20 mmol/L) and moderate-to-severe acute kidney injury are observed, day 28 mortality is approximately 55%-60%. A multiple centre randomised clinical trial (BICARICU-1) has suggested that sodium bicarbonate infusion titrated to maintain the pH equal or more than 7.30 is associated with a higher survival rate (secondary endpoint) in a prespecified stratum of patients with both severe metabolic acidemia and acute kidney injury patients. Whether sodium bicarbonate infusion may improve survival at day 90 (primary outcome) in these severe acute kidney injury patients is currently unknown., Methods and Analysis: The sodium bicarbonate for the treatment of severe metabolic acidosis with moderate or severe acute kidney injury in the critically ill: a randomised clinical trial (BICARICU-2) trial is an investigator-initiated, multiple centre, stratified, parallel-group, unblinded trial with a computer-generated allocation sequence and an electronic system-based randomisation. After randomisation, the intervention group will receive 4.2% sodium bicarbonate infusion to target a plasma pH equal or more than 7.30 while the control group will not receive sodium bicarbonate. The primary outcome is the day 90 mortality. Main secondary outcomes are organ support dependences., Ethics and Dissemination: The trial has been approved by the appropriate ethics committee (CPP Nord Ouest, Rouen, France, 25 April 2019, number: 19.03.15.72446). Informed consent is required. If sodium bicarbonate improves day 90 mortality, it will become part of the routine care., Trial Registration Number: NCT04010630., Competing Interests: Competing interests: SJ reports receiving consulting fees from Drager, Medtronic, Mindray, Baxter, Fisher & Paykel and Fresenius-Xenios. No potential conflict of interest relevant to this article was reported for other authors., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The use of sodium bicarbonate to treat metabolic acidosis is intuitive, yet data suggest that not all patients benefit from this therapy., Objective: In this narrative review, we describe the physiology behind commonly encountered nontoxicologic causes of metabolic acidosis, highlight potential harm from the indiscriminate administration of sodium bicarbonate in certain scenarios, and provide evidence-based recommendations to assist emergency physicians in the rational use of sodium bicarbonate., Discussion: Sodium bicarbonate can be administered as a hypertonic push, as a resuscitation fluid, or as an infusion. Lactic acidosis and cardiac arrest are two common scenarios where there is limited benefit to routine use of sodium bicarbonate, although certain circumstances, such as patients with concomitant acute kidney injury and lactic acidosis may benefit from sodium bicarbonate. Patients with cardiac arrest secondary to sodium channel blockade or hyperkalemia also benefit from sodium bicarbonate therapy. Recent data suggest that the use of sodium bicarbonate in diabetic ketoacidosis does not confer improved patient outcomes and may cause harm in pediatric patients. Available evidence suggests that alkalinization of urine in rhabdomyolysis does not improve patient-centered outcomes. Finally, patients with a nongap acidosis benefit from sodium bicarbonate supplementation., Conclusions: Empiric use of sodium bicarbonate in patients with nontoxicologic causes of metabolic acidosis is not warranted and likely does not improve patient-centered outcomes, except in select scenarios. Emergency physicians should reserve use of this medication to conditions with clear benefit to patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Heparin purge solution is recommended to be used in Impella devices to prevent biomaterial buildup and subsequent device dysfunction. The use of sodium bicarbonate purge solution in an Impella device is described in two patients with heparin-induced thrombocytopenia (HIT). The first case details a patient with severe mitral regurgitation and cardiogenic shock who had an Impella CP placed who developed HIT. Heparin purge solution was replaced by sodium bicarbonate purge solution in addition to systemic direct thrombin inhibitor (DTI) initiation. There was no significant change in Impella purge pressure or flow over the 13 days of Impella use. The second case describes a patient who developed an acute myocardial infarction and subsequent cardiogenic shock for which an Impella CP was placed who also developed HIT. Heparin purge solution was replaced by sodium bicarbonate purge solution. There was no significant change in purge pressure, flow, or motor current spikes over 11 days of use. In conclusion, we describe the successful use of a novel sodium bicarbonate purge solution utilized in patients with HIT for Impella management alone and in combination with systemic direct thrombin inhibitor therapy. This resulted in no protein deposition in the device gaps or device dysfunction.

Significance Statement: Lower serum bicarbonate levels, even within the normal range, are strongly linked to risks of cardiovascular disease in CKD, possibly by modifying vascular function. In this randomized, controlled trial, treatment with sodium bicarbonate (NaHCO 3 ) did not improve vascular endothelial function or reduce arterial stiffness in participants with CKD stage 3b-4 with normal serum bicarbonate levels. In addition, NaHCO 3 treatment did not reduce left ventricular mass index. NaHCO 3 did increase plasma bicarbonate levels and urinary citrate excretion and reduce urinary ammonium excretion, indicating that the intervention was indeed effective. NaHCO 3 therapy was safe with no significant changes in BP, weight, or edema. These results do not support the use of NaHCO 3 for vascular dysfunction in participants with CKD., Background: Lower serum bicarbonate levels, even within the normal range, are strongly linked to risks of cardiovascular disease in CKD, possibly by modifying vascular function. Prospective interventional trials with sodium bicarbonate (NaHCO 3 ) are lacking., Methods: We conducted a randomized, double-blind, placebo-controlled trial examining the effect of NaHCO 3 on vascular function in 109 patients with CKD stage 3b-4 (eGFR 15-44 ml/min per 1.73 m 2 ) with normal serum bicarbonate levels (22-27 mEq/L). Participants were randomized 1:1 to NaHCO 3 or placebo at a dose of 0.5 mEq/lean body weight-kg per day for 12 months. The coprimary end points were change in brachial artery flow-mediated dilation (FMD) and change in aortic pulse wave velocity over 12 months., Results: Ninety patients completed this study. After 12 months, plasma bicarbonate levels increased significantly in the NaHCO 3 group compared with placebo (mean [SD] difference between groups 1.35±2.1, P = 0.003). NaHCO 3 treatment did not result in a significant improvement in aortic pulse wave velocity from baseline. NaHCO 3 did result in a significant increase in flow-mediated dilation after 1 month; however, this effect disappeared at 6 and 12 months. NaHCO 3 resulted in a significant increase in 24-hour urine citrate and pH and a significant decrease in 24-hour urine ammonia. There was no significant change in left ventricular mass index, ejection fraction, or eGFR with NaHCO 3 . NaHCO 3 treatment was safe and well-tolerated with no significant changes in BP, antihypertensive medication, weight, plasma calcium, or potassium levels., Conclusion: Our results do not support the use of NaHCO 3 for vascular dysfunction in participants with CKD and normal serum bicarbonate levels., (Copyright © 2023 by the American Society of Nephrology.)

A common occurrence in the neonatal intensive care unit (NICU) is metabolic acidosis. Sodium bicarbonate (SB) has been widely used, but there is insufficient evidence on how SB affects neonates in NICUs with metabolic acidosis. The worsening of intracellular acidosis, the impairment of myocardial function, fluctuations in cerebral blood flow, and intracranial hemorrhage are some of the unfavorable effects of SB treatment in neonates that have been documented in the literature. This study aimed to explore neonatologists' practices for using intravenous SB (ISB) in NICUs. A multi-country survey was carried out in 2022 using an online questionnaire sent to neonatologists in various countries in order to gather information about the use of ISB in NICUs. A previously validated questionnaire was adapted and used in this study. The response rate was 67%. The findings show that 91.2% of neonatologists were using SB to correct metabolic acidosis in the NICU; 71.4% did not have written guidelines for using sodium bicarbonate. The majority of them (78.9%) reported that dosage is included in their guidelines for the use of ISB. The findings of this study emphasize the critical importance of providing guidelines in using ISB for managing metabolic acidosis in NICU to standardize procedures and reduce the use of potentially unsuitable and unsafe treatments, as it has been shown that 71.4% of neonatologists worldwide use sodium bicarbonate without guidelines., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Management of patients with salicylate toxicity frequently requires urine alkalinization to enhance excretion of salicylate. One strategy for determining when to stop urine alkalinization is to wait for two consecutive serum salicylate concentrations to be less than 300 mg/L (2.17 mmol/L) and declining. When alkalinization of the urine ceases, a rebound in serum salicylate concentration can occur from tissue redistribution or delayed gastrointestinal absorption. Whether this can lead to rebound toxicity is not well understood., Methods: This was a single-center, retrospective review of cases with a primary ingestion of acetylsalicylic acid reported to the local poison center over a five-year period. Cases were excluded if the product was not listed as the primary ingestion or if there was no serum salicylate concentration documented after discontinuation of intravenous sodium bicarbonate infusion. The primary outcome was the incidence of serum salicylate rebound to a concentration greater than 300 mg/L (2.17 mmol/L) after discontinuation of intravenous sodium bicarbonate infusion., Results: A total of 377 cases were included. Of these, eight (2.1%) had a serum salicylate concentration increase (rebound) after stopping the sodium bicarbonate infusion. All these cases were acute ingestions. Five of the eight cases had rebound serum salicylate concentrations that were greater than 300 mg/L (2.17 mmol/L). Of these five patients, only one reported recurrent symptoms (tinnitus). Prior to stopping urinary alkalinization, the last or the last two serum salicylate concentrations were less than 300 mg/L (2.17 mmol/L) in three and two cases, respectively., Conclusions: In patients with salicylate toxicity, the incidence of rebound in serum salicylate concentration after cessation of urine alkalinization, is low. Even if serum salicylate rebounds to supratherapeutic concentrations, symptoms are often absent or mild. Routine repeat serum salicylate concentrations after urine alkalinization is stopped may be unnecessary unless symptoms recrudesce.

Objective: The primary endpoint of the present study was to assess the potential therapeutic effects of three different mouthwashes for alleviation and treatment of oral complications (OCs). The secondary endpoint was to assess patients' perceptions and daily functional activities after therapy of OCs in patients with colon cancer receiving 5-fluorouracil (5-FU)-based chemotherapy regimens., Methods: A prospective, randomised controlled study carried out on 90 patients with colon cancer eligible for 5-FU-based chemotherapy regimens at the oncology centre, Istanbul, Turkey. Patients were randomly randomised into three groups (30 patients in each group) and received a single mouthwash. The first group (group A) received benzydamine at a dose of 15 mL; the second group (group B) received sodium bicarbonate at a dose of 1.2-2.4 g in 240 mL of water; and the third group (group C) received glutamine suspension 10 g. Patients were assessed for the occurrence of oral complications based on the WHO scale for oral mucosa evaluation and National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Oral pain was assessed using a visual analogue scale alongside assessment of patients' perceptions and daily functional activities based on the Rotterdam Symptom Checklist., Results: A total of 119 oral complications were reported, including mouth dryness (n=56, 47.1%), oral mucositis (n=31, 26.1%) and oral pain (n=32, 26.8%). At the end of the study, patients of group A and group B significantly suffered from mouth dryness (p=0.0001), oral mucositis (p=0.029) and oral pain (p=0.039) compared with patients in group C. Although there was no significant change, group C patients showed a slight improvement in psychological discomfort, activity levels and quality of life at the end of the study., Conclusion: The present study showed that benzydamine and sodium bicarbonate mouthwashes were significantly less effective for the alleviation and treatment of oral complications compared with glutamine among patients with colon cancer receiving 5-FU-based chemotherapy regimens., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: New agents are introduced each day to be used in the prevention and treatment of mucositis in cancer treatment. One of those agents is the Ankaferd hemostat. Ankaferd hemostat has pleiotropic effects and anti-infective characteristics in tissue healing., Methods: The study was designed as a randomized controlled experimental study. The sample of the study comprised a total of 66 patients (33 patients in the Ankaferd hemostat group and 33 patients in the sodium bicarbonate group) with colorectal cancer who received FOLFOX combination chemotherapy treatment in the first cycle of chemotherapy to prevent mucositis. Participants who met the criteria were randomly assigned to the groups. Before the patient received chemotherapy, ECOG performance score and Oral Mucositis Grading Scale were applied on the 7th day and 15th day. The Ankaferd hemostat group brushed teeth at least twice a day for 2 min and gargled with Ankaferd hemostat twice for 2 min for 2 weeks. The sodium bicarbonate group brushed teeth at least 2 min a day and gargled with sodium bicarbonate 4 times for 2 min for 2 weeks. The Consolidated Standards of Reporting Trials diagram was used to illustrate the randomization of patients., Results: When the Ankaferd hemostat group is compared with the sodium bicarbonate group, there is a significant difference in favor of the Ankaferd hemostat group in the mucositis grade on the 7th day and 15th day after chemotherapy (p < 0.05). In the binary logistic regression analysis, among the factors affecting the formation of mucositis on the 7th day, only neutrophil and thyroid-stimulating hormone (TSH) were included in the model, while only the TSH variable is statistically significant., Conclusions: It was determined that Ankaferd hemostat is effective in preventing oral mucositis due to chemotherapy in adult patients diagnosed with colorectal cancer. In addition, it has been suggested to conduct new studies on the effectiveness of Ankaferd hemostat in the prevention of mucositis in different groups., Trial Registration: The study was registered at ClinicalTrials.gov (ID: NCT05438771, Date: 25.06.2022)., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Bupropion cardiotoxicity widens QRS complexes by inhibiting cardiac gap junctions. Sodium bicarbonate is the standard treatment for QRS widening from sodium channel blockade, but its effect on QRS widening in bupropion cardiotoxicity is not well-studied., Methods: This is a retrospective cohort study of bupropion overdoses from 10 hospitals between January 2010 and June 2022. Patients with documented administration of sodium bicarbonate and QRS duration > 100 milliseconds on pre-bicarbonate electrocardiogram were included. Patients with no electrocardiogram within four hours of treatment or with baseline pre-overdose wide QRS and < 10 milliseconds widening from baseline were excluded. The primary outcome was a change in QRS duration between the pre-bicarbonate electrocardiogram and the first electrocardiogram after initial bicarbonate administration. Secondary outcomes included prevalence of post-bicarbonate QRS < 100 milliseconds, change in electrocardiogram intervals after total bicarbonate administration, and change in metabolic parameters and hemodynamics. Wilcoxon signed-rank testing was performed on the primary outcome. Linear regression modeling was performed to test for an association between change in QRS and bicarbonate dosing., Results: Thirteen patients were included for final analysis. The median age was 32 years, and 54% were male. Six patients developed seizures; one developed ventricular tachycardia, and four received vasopressors. The median QRS and QTc pre-bicarbonate were 116 and 495 milliseconds, respectively. The median change in QRS duration was -2.0 milliseconds, which was not statistically significant ( P  = 0.42). The median bicarbonate dose administered before the first post-bicarbonate electrocardiogram was 100 milliequivalents. We did not identify an association between QRS change and bicarbonate dosing ( P  = 0.9, R-squared = 0.001). No patient had a QRS duration < 100 milliseconds after the initial bicarbonate dose. There was minimal change in QTc, electrolytes, heart rate, or blood pressure; alkalemia post-bicarbonate was achieved in eight patients., Conclusion: Sodium bicarbonate did not significantly decrease QRS duration in this small retrospective cohort of bupropion overdoses.

Aim: To assess the anti-plaque effect of a high concentration sodium bicarbonate dentifrice on plaque formation, and gingivitis, as compared to a control toothpaste, irrespective of individual brushing technique and plaque quality., Methods: The experimental gingivitis model, with a split-mouth design was used to assess the anti-plaque effect of a high concentration sodium bicarbonate dentifrice on plaque formation. By producing individual fitted trays, the toothpaste was applied in the test quadrant and a control dentifrice in the contralateral. The participants used the individual fitted trays for 1 min every morning and evening, for 21 days. In this period, the participants was only allowed to brush the teeth in the opposite jaw, as usual. Twenty healthy individuals successfully completed the study., Results: At 21 days, there was no statistically significant difference between test quadrant and control quadrant with regard to plaque indices, gingival index and number of bleeding sites., Conclusion: This study demonstrated that the high concentration sodium bicarbonate dentifrice used did not produce statistically significant anti-plaque effect compared to the control dentifrice, in terms of Plaque- and Gingival Indices, number of bleeding sites or by Quigely and Hein, the Turesky modification Plaque Index, irrespective of brushing technique and individual plaque quality., Trial Registration: Regional Committee for Medical Research and Ethics, South-East Norway in 2021 (REK.2021/370116)., Clinical Trial Registration: NCT05441371 (First registered 09/06/2022, First posted 01/07/2022) ( http://www., Clinicaltrials: gov ). (Retrospectively registered)., (© 2023. The Author(s).)

BACKGROUND Sodium bicarbonate Ringer's solution (BRS) is the latest generation of balanced crystal solutions. BRS does not increase the liver burden, but its impact in liver transplantation is unclear. The aim of this study was to investigate the effect of BRS as a fluid therapy on intraoperative blood gas analysis and postoperative recovery time in orthotopic liver transplantation (LT) patients. MATERIAL AND METHODS The study included 101 patients who received classical in situ liver transplantation at the Second Affiliated Hospital of Guangxi Medical University from November 2019 to January 2022. The patients were divided into 2 groups according to the intraoperative fluid infusion: the BRS group and the sodium lactate Ringer's solution group (LRS group). Intraoperative blood gas analysis, including pH, base excess (BE), bicarbonate, and lactic acid levels of radial artery blood, were collected after induction (T0), 30 min before opening (T1), 30 min after no liver period (T2), 30 min after opening (T3), and at the end of the operation (T4). Postoperative ICU catheter time, ICU stay time, and total hospitalization days were also recorded and compared between the 2 groups. RESULTS Lactic acid levels were decreased significantly at T3 in the BRS group (P<0.05). ICU catheter time, ICU hospitalization days, and total hospitalization days were significantly shorter in the BRS group (P<0.05). CONCLUSIONS BRS can decrease the lactic acid level at 30 min after opening, reducing the postoperative recovery time. BRS is more effective than LRS in liver transplantation.

Background: Individuals with CKD are at a higher risk of cardiovascular morbidity and mortality. Acidosis is positively correlated with CKD progression and elevated systolic BP. Sodium bicarbonate is an efficacious treatment of acidosis, although this may also increase systolic BP. In this systematic review and meta-analysis, we summarize the evidence evaluating systolic BP and antihypertensive medication change (which may indicate systolic BP change) in response to sodium bicarbonate therapy in individuals with CKD., Methods: Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Cochrane Central Register of Controlled Trials, and World Health Organization (WHO) trials registry databases were searched for randomized control trials where sodium bicarbonate was compared with placebo/usual care in CKD stage G1-5 non-dialysis-dependent populations. Random effects meta-analyses were used to evaluate changes in systolic BP and BP-modifying drugs after sodium bicarbonate intervention., Results: Fourteen randomized control trials (2110 individuals, median follow-up 27 [interquartile range 97] weeks, mean age 60 [SD 10] years, mean systolic BP 136 [SD 17] mm Hg, mean eGFR 38 [SD 10] ml/min, mean serum bicarbonate 22 [SD 4] mmol/L) were eligible for inclusion. Meta-analysis suggested that sodium bicarbonate did not influence systolic BP in individuals with CKD stage G1-5. Results were consistent when stratifying by dose of sodium bicarbonate or duration of intervention. Similarly, there was no significant increase in the use of antihypertensive medication or diuretics in individuals taking sodium bicarbonate, whereas there was a greater decrease in antihypertensive medication use in individuals taking sodium bicarbonate compared with controls., Conclusions: Our results suggest, with moderate certainty, that sodium bicarbonate supplementation does not adversely affect systolic BP in CKD or negatively influence antihypertensive medication requirements., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of American Society of Nephrology.)

Background: Recent studies have shown that the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is reduced under alkaline conditions. The purpose of this study is to assess the effect of nasal irrigation and oral rinse with sodium bicarbonate solution on virus clearance among COVID-19 patients., Materials and Methods: COVID-19 patients were recruited and randomly divided into two group, i.e., the experimental group and the control group. The experimental group received regular care plus nasal irrigation and oral rinse with 5% sodium bicarbonate solution, while the control group only received regular care. Nasopharyngeal and oropharyngeal swab samples were collected daily for reverse transcription-polymerase chain reaction (RT-PCR) assays. The negative conversion time and hospitalization time of the patients were recorded, and the results were statistically analyzed., Results: A total of 55 COVID-19 patients with mild or moderate symptoms were included in our study. There was no significant difference in gender, age and health status between the two groups. The average negative conversion time was 1.63 days after treatment with sodium bicarbonate, and the average hospitalization time of the control group and the experimental group were 12.53 and 7.7 days, respectively., Conclusions: Nasal irrigation and oral rinse with 5% sodium bicarbonate solution is effective in virus clearance for COVID-19 patients., Competing Interests: XW is employed by company Nanning Jiuzhouyuan Biotechnology Co Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Zhang, Zhang, Mao, Yan, Long, Chen, Li, Wang, Huang, Zhu, Teng and Wang.)