Sodium Thiosulfate for Protection from Cisplatin-Induced Hearing Loss.

BACKGROUND: Cisplatin chemotherapy and surgery are effective treatments for children with standard-risk hepatoblastoma but may cause considerable and irreversible hearing loss. This trial compared cisplatin with cisplatin plus delayed administration of sodium thiosulfate, aiming to reduce the incidence and severity of cisplatin-related ototoxic effects without jeopardizing overall and event-free survival. METHODS: We randomly assigned children older than 1 month and younger than 18 years of age who had standard-risk hepatoblastoma (≤3 involved liver sectors, no metastatic disease, and an alpha-fetoprotein level of >100 ng per milliliter) to receive cisplatin alone (at a dose of 80 mg per square meter of body-surface area, administered over a period of 6 hours) or cisplatin plus sodium thiosulfate (at a dose of 20 g per square meter, administered intravenously over a 15-minute period, 6 hours after the discontinuation of cisplatin) for four preoperative and two postoperative courses. The primary end point was the absolute hearing threshold, as measured by pure-tone audiometry, at a minimum age of 3.5 years. Hearing loss was assessed according to the Brock grade (on a scale from 0 to 4, with higher grades indicating greater hearing loss). The main secondary end points were overall survival and event-free survival at 3 years. RESULTS: A total of 109 children were randomly assigned to receive cisplatin plus sodium thiosulfate (57 children) or cisplatin alone (52) and could be evaluated. Sodium thiosulfate was associated with few high-grade toxic effects. The absolute hearing threshold was assessed in 101 children. Hearing loss of grade 1 or higher occurred in 18 of 55 children (33%) in the cisplatin-sodium thiosulfate group, as compared with 29 of 46 (63%) in the cisplatin-alone group, indicating a 48% lower incidence of hearing loss in the cisplatin-sodium thiosulfate group (relative risk, 0.52; 95% confidence interval [CI], 0.33 to 0.81; P=0.002). At a median of 52 months of follow-up, the 3-year rates of event-free survival were 82% (95% CI, 69 to 90) in the cisplatin-sodium thiosulfate group and 79% (95% CI, 65 to 88) in the cisplatin-alone group, and the 3-year rates of overall survival were 98% (95% CI, 88 to 100) and 92% (95% CI, 81 to 97), respectively. CONCLUSIONS: The addition of sodium thiosulfate, administered 6 hours after cisplatin chemotherapy, resulted in a lower incidence of cisplatin-induced hearing loss among children with standard-risk hepatoblastoma, without jeopardizing overall or event-free survival. (Funded by Cancer Research UK and others; SIOPEL 6 ClinicalTrials.gov number, NCT00652132 ; EudraCT number, 2007-002402-21 .).

Phase 1 study to evaluate safety, tolerability and pharmacokinetics of a novel intra-tympanic administered thiosulfate to prevent cisplatin-induced hearing loss in cancer patients.

Cisplatin is a widely used chemotherapy for the treatment of certain solid tumors. Ototoxicity and subsequent permanent hearing loss remain a serious dose-limiting side effect associated with cisplatin treatment. To date, no therapies have been approved to prevent or treat cisplatin-induced hearing loss (CIHL). Sodium thiosulfate effectively inactivates cisplatin through covalent binding and may provide protection against cisplatin-induced ototoxicity. DB-020 is being developed as a novel formulation of sodium thiosulfate pentahydrate in 1% sodium hyaluronate for intratympanic injection (IT), enabling the delivery of high concentrations of thiosulfate into the cochlea prior to cisplatin administration. In the DB-020-002 phase 1a single-ascending dose study, healthy volunteers were enrolled into 5 cohorts to receive different doses of DB-020 via IT injection. Cohorts 1-4 received unilateral injections while Cohort 5 received bilateral injections. Plasma thiosulfate pharmacokinetics was measured, and safety and audiometric data were collected throughout the study. This study has demonstrated that intratympanic administration of DB-020 results in nominal systemic increases in thiosulfate levels, hence it should not compromise cisplatin anti-tumor efficacy. Furthermore, DB-020 was safe and well tolerated with most adverse events reported as transient, of mild-to-moderate severity and related to the IT administration procedure. These results support the design and execution of the ongoing proof-of-concept study, DB-020-002, to assess otoprotection using DB-020 in cancer patients receiving cisplatin without negatively impacting cisplatin anti-tumor efficacy.

Safety and Tolerability of Sodium Thiosulfate in Patients with an Acute Coronary Syndrome Undergoing Coronary Angiography: A Dose-Escalation Safety Pilot Study (SAFE-ACS).

BACKGROUND: In animal studies, hydrogen sulfide (H2S) has been shown to protect the heart from ischemia-reperfusion injury. This study evaluates the safety and tolerability of the H2S donor sodium thiosulfate (STS) in patients with acute coronary syndrome (ACS). METHODS: Eighteen patients, undergoing coronary angiography for ACS, received STS intravenously immediately after arrival at the catheterization laboratory according to a "3 + 3 dose-escalation design" with fixed dosing endpoint (0, 2.5, 5, 10, 12.5, and 15 grams). This first dose STS was combined with verapamil and nitroglycerin required for transradial procedures. A second dose STS was administered 6 hours later. Primary endpoint was dose-limiting toxicity, defined as significant hemodynamic instability or death up to 24 hours or before discharge from the coronary care unit. Secondary outcomes included the occurrence of anaphylaxis, nausea, vomiting, and systolic blood pressure (SBP) course. RESULTS: Sixteen patients received two dosages of STS and two patients one dosage. None of the patients reached the primary endpoint, nor experienced a serious adverse event. We observed a clinically well-tolerated decline in SBP 1 hour after administration of the first STS dose and concomitant verapamil/nitroglycerin. SBP for all patients together reduced 16.8 (8.1-25.5) mmHg (P = 0.0008). No significant decline in SBP occurred after the second dose. Mild nausea was observed in one patient. CONCLUSION: This is the first report on sodium thiosulfate administration in patients with acute coronary syndromes. Our data suggest that sodium thiosulfate was well tolerated in this setting. The potential benefit of this intervention has to be examined in larger studies.

Therapeutic effect of intravenous sodium thiosulfate for uremic pruritus in hemodialysis patients.

OBJECTIVES: This study aimed to compare the efficacy of intravenous sodium thiosulfate (IV STS) with that of loratadine in the treatment of uremic pruritus in hemodialysis (HD) patients. METHODS: This retrospective study included 44 HD patients with pruritus aged over 18 years between June 2018 and January 2020 at the Aerospace Center Hospital of China. Twenty-four HD patients received 3.2 g IV STS treatment three times per week at the end of each HD session for 8 weeks. Twenty HD patients received loratadine (10 mg/day) for 8 weeks. Pruritus intensity was measured using a visual analog scale (VAS) and the detailed pruritus score (DPS) at three time points. The safety of STS was evaluated according to adverse event symptoms and biological variable changes. RESULTS: There was no significant difference between the STS and loratadine groups in age, sex, characteristics of pruritus, or other clinical variables before treatment. After 8 weeks of treatment, the VAS score (7.07 ± 2.56 and 2.67 ± 2.01) and DPS (30.72 ± 4.81 and 8.04 ± 2.86) decreased significantly in the STS group (p < 0.05). The mean decrease in VAS score (6.89 ± 1.98 and 6.34 ± 2.35) and DPS (28.90 ± 3.24 and 26.92 ± 2.41) in the loratadine group was not statistically significant (p > 0.05). There were no morbidities or mortalities associated with the use of either drug. All biological variables remained stable after therapy. CONCLUSIONS: STS can improve uremic pruritus in HD patients. However, literature on the subject remains lacking. Close monitoring for adverse effects is advised.

Thiosulfate promotes hair growth in mouse model.

The present study describes the hair growth-promoting effects of sodium thiosulfate (STS), a widely used compound, in mice. STS accelerated hair growth in the "telogen model", suggesting that it stimulates telogen hair follicles to reenter the anagen phase of hair growth. In the same model, STS potentiated hair growth in an additive manner with minoxidil (MXD), a drug used for the treatment of androgenic alopecia. Furthermore, in the "anagen model", STS promoted hair growth, probably by promoting hair follicle proliferation. Since STS elevated the skin surface temperature, its hair growth-promoting activity may be partly due to vasorelaxation, similar to MXD. In addition, STS is known to generate a gaseous mediator, H2S, which has vasorelaxation and anti-inflammatory/anti-oxidative stress activities. Therefore, STS and/or provisionally its metabolite, H2S, may aid the hair growth process. Collectively, these results suggest that salts of thiosulfate may represent a novel and beneficial remedy for hair loss.

Systematic review of sodium thiosulfate in treating calciphylaxis in chronic kidney disease patients.

AIM: Calciphylaxis is a severe complication of advanced chronic kidney disease (CKD). Sodium thiosulphate (STS), an antioxidant and calcium chelating agent, has been used for the treatment of calciphylaxis. However, its efficacy and safety have not been systematically analysed and evaluated. METHODS: MEDLINE, EMBASE, and the Cochrane Library database were systematically searched for case report or cases series on use of STS for calciphylaxis published between July 1974 and October 2016. We extracted data on clinical characteristics, laboratory tests result and medication use. The effective treatment was defined as improvement in skin lesion cicatrisation or pain relief without death. Non-responding effects were defined as stable skin lesions without remission or exacerbation of the disease in patients who remained alive. All-cause mortality after STS treatment was defined as death due to exacerbations of calciphylaxis or other complications of advanced CKD. We compared the baseline parameters of the patients as well as the efficacy and mortality of the STS therapy between case report and multi-case reports. Statistical analyses were performed using SPSS 19. RESULTS: A total of 83 papers were screened, 45 of them (n = 358) met the inclusion criteria, including 36 case reports (n = 64) and nine multi-case reports (n = 294). The mean age of the patients with calciphylaxis was 58 ± 14 years (range 26-91 years). They were female predominant, accounting for 74.1%. Among the patients with calciphylaxis, 96.1% patients were on dialysis with median dialysis vintage of 44.5 months (range 24-84 months). STS was effective in 70.1% of patients, 37.6% patients died. The proportion of patients with sepsis was higher among those who received intravenous STS. There was no significant difference in efficacy between the different STS administration methods (P = 0.19). CONCLUSION: Although the study was unable to assess the efficacy of sodium thiosulphate alone in the treatment of calciphylaxis, it still reveals a promising role of STS as an effective therapy for calciphylaxis. Further prospective studies to define the optimal therapy for calciphylaxis are needed.

Effects of sodium thiosulfate versus observation on development of cisplatin-induced hearing loss in children with cancer (ACCL0431): a multicentre, randomised, controlled, open-label, phase 3 trial.

BACKGROUND: Sodium thiosulfate is an antioxidant shown in preclinical studies in animals to prevent cisplatin-induced hearing loss with timed administration after cisplatin without compromising the antitumour efficacy of cisplatin. The primary aim of this study was to assess sodium thiosulfate for prevention of cisplatin-induced hearing loss in children and adolescents. METHODS: ACCL0431 was a multicentre, randomised, open-label, phase 3 trial that enrolled participants at 38 participating Children's Oncology Group hospitals in the USA and Canada. Eligible participants aged 1-18 years with newly diagnosed cancer and normal audiometry were randomly assigned (1:1) to receive sodium thiosulfate or observation (control group) in addition to their planned cisplatin-containing chemotherapy regimen, using permuted blocks of four. Randomisation was initially stratified by age and duration of cisplatin infusion. Stratification by previous cranial irradiation was added later as a protocol amendment. The allocation sequence was computer-generated centrally and concealed to all personnel. Participants received sodium thiosulfate 16 g/m2 intravenously 6 h after each cisplatin dose or observation. The primary endpoint was incidence of hearing loss 4 weeks after final cisplatin dose. Hearing was measured using standard audiometry and reviewed centrally by audiologists masked to allocation using American Speech-Language-Hearing Association criteria but treatment was not masked for participants or clinicians. Analysis of the primary endpoint was by modified intention to treat, which included all randomly assigned patients irrespective of treatment received but restricted to those assessable for hearing loss. Enrolment is complete and this report represents the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00716976. FINDINGS: Between June 23, 2008, and Sept 28, 2012, 125 eligible participants were randomly assigned to either sodium thiosulfate (n=61) or observation (n=64). Of these, 104 participants were assessable for the primary endpoint (sodium thiosulfate, n=49; control, n=55). Hearing loss was identified in 14 (28·6%; 95% CI 16·6-43·3) participants in the sodium thiosulfate group compared with 31 (56·4%; 42·3-69·7) in the control group (p=0·00022). Adjusted for stratification variables, the likelihood of hearing loss was significantly lower in the sodium thiosulfate group compared with the control group (odds ratio 0·31, 95% CI 0·13-0·73; p=0·0036). The most common grade 3-4 haematological adverse events reported, irrespective of attribution, were neutropenia (117 [66%] of 177 participant cycles in the sodium thiosulfate group vs 145 [65%] of 223 in the control group), whereas the most common non-haematological adverse event was hypokalaemia (25 [17%] of 147 vs 22 [12%] of 187). Of 194 serious adverse events reported in 26 participants who had received sodium thiosulfate, none were deemed probably or definitely related to sodium thiosulfate; the most common serious adverse event was decreased neutrophil count: 26 episodes in 14 participants. INTERPRETATION: Sodium thiosulfate protects against cisplatin-induced hearing loss in children and is not associated with serious adverse events attributed to its use. Further research is needed to define the appropriate role for sodium thiosulfate among emerging otoprotection strategies. FUNDING: US National Cancer Institute.

Thiocyanate Accumulation in Critically Ill Patients Receiving Nitroprusside Infusions.

PURPOSE: This study evaluated thiocyanate concentrations and factors associated with thiocyanate accumulation in intensive care unit patients receiving nitroprusside with and without sodium thiosulfate coadministration. MATERIALS AND METHODS: This retrospective study evaluated critically ill adults who received nitroprusside infusions and had at least one thiocyanate concentration. Patients with thiocyanate accumulation (concentrations ≥30 µg/mL) were compared to patients without accumulation. Factors associated with accumulation were determined by Spearman correlation and multivariate regression. RESULTS: Thiocyanate concentrations (n = 192) were obtained from 87 patients. Fourteen of the 87 (16%) patients experienced thiocyanate accumulation with a mean (SD) thiocyanate concentration of 44 ± 11 µg/mL. Patients with accumulation had received greater cumulative nitroprusside doses (28 vs 8.2 mg/kg, P < .01), greater cumulative sodium thiosulfate doses (16.8 vs 10.1 mg/kg, P < .01), and longer infusion durations (10.9 vs 6.0 days, P < .01), compared to patients without accumulation. Sodium thiosulfate coadministration resulted in greater thiocyanate concentrations (22.8 ± 16.7 vs 16.8 ± 14.9 µg/mL, P = .01), despite utilization of lower cumulative nitroprusside doses (10.2 vs 14.6 mg/kg, P = .03). Cumulative nitroprusside dose ( r2 .44, P < .001) and cumulative sodium thiosulfate dose ( r2 .32, P < .001) demonstrated a significant correlation with measured thiocyanate concentrations. Thiocyanate accumulation was independently associated with cumulative nitroprusside dose in mg/kg (regression coefficient 0.75, 95% CI 0.63-0.89; P < .01). No clinically significant adverse effects of cyanide or thiocyanate toxicity were observed. CONCLUSIONS: Cumulative nitroprusside dose was independently associated with thiocyanate accumulation. Despite elevated thiocyanate levels in 16% of patients, there was no clinical evidence of cyanide or thiocyanate toxicity. Routine monitoring of thiocyanate concentrations appears most warranted in patients receiving higher cumulative doses of nitroprusside.

Sodium thiosulphate treatment of uraemic tumoral calcinosis.

OBJECTIVE: The objective of this study was to describe the efficacy of sodium thiosulphate (STS) in tumoral calcinosis (TC). METHODS: The methodology involved the reporting of four retrospective case reports of TC complicating end-stage renal disease (ESRD). RESULTS: We investigated STS treatment in four patients (two men; ages 46-70 years) with TC. ESRD was secondary to nephronophthisis (n = 1), membranoproliferative glomerulonephritis (n = 1), diabetic nephropathy (n = 1), and thrombotic microangiopathy (n = 1). TC developed 3-28 years after dialysis began and resulted in articular pain (n = 4) and stiffness (n = 1). It involved shoulders and hips and was diffuse in one patient. Several treatments were tried without success. STS 12.5-25 g was given intravenously after each dialysis session for 11-14 months. Pain and stiffness rapidly disappeared and TC showed partial or total regression. Side effects during infusion included increased blood pressure (n = 1), nausea (n = 1) and vomiting (n = 1). TC did not recur after treatment discontinuation with follow-up of 1.5-12 years. CONCLUSION: STS showed promising efficacy in this short series of TC. Further studies are warranted.

Evaluation of ototoxicity in patients treated with hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin and sodium thiosulfate.

OBJECTIVES: Ototoxic hearing loss associated with intravenous or intra-arterial administration of cisplatin is well documented. However, there is limited data regarding the ototoxic effect of cisplatin when perfused into the abdominal cavity using hyperthermic intraperitoneal chemotherapy (HIPEC). The purpose of this study is to assess and describe ototoxicity in patients treated with HIPEC with cisplatin and sodium thiosulfate for peritoneal surface malignancies. DESIGN: We performed a retrospective chart review (2007-2012) of patients treated for advanced peritoneal malignancies at a tertiary care center using HIPEC with cisplatin and sodium thiosulfate infusion. Thirteen patients (12 males, 1 female) met study criteria. Audiometric thresholds were compared before and after treatment. A 20 dB loss at any single frequency, 10 dB decrease at any two adjacent frequencies, or loss of response at three consecutive test frequencies defined a significant ototoxic change (). RESULTS: Despite minimal hearing change in six patients, none of the 13 patients in our study exhibited a significant ototoxic change in hearing sensitivity post HIPEC with cisplatin at any test interval in any test frequency. CONCLUSIONS: Our findings represent the first objective assessment of ototoxic effect after HIPEC with cisplatin and sodium thiosulfate infusion. Our results suggest that peritoneal perfusion of cisplatin with intravenous perfusion of sodium thiosulfate is not associated with ototoxic changes in hearing sensitivity. Further investigation of the administration and systemic mechanism of absorption of sodium thiosulfate as a potential protection against cisplatin ototoxicity is needed to confirm these findings.

Pediatric cyanide poisoning by fire smoke inhalation: a European expert consensus. Toxicology Surveillance System of the Intoxications Working Group of the Spanish Society of Paediatric Emergencies.

Most fire-related deaths are attributable to smoke inhalation rather than burns. The inhalation of fire smoke, which contains not only carbon monoxide but also a complex mixture of gases, seems to be the major cause of morbidity and mortality in fire victims, mainly in enclosed spaces. Cyanide gas exposure is quite common during smoke inhalation, and cyanide is present in the blood of fire victims in most cases and may play an important role in death by smoke inhalation. Cyanide poisoning may, however, be difficult to diagnose and treat. In these children, hydrogen cyanide seems to be a major source of concern, and the rapid administration of the antidote, hydroxocobalamin, may be critical for these children.European experts recently met to formulate an algorithm for prehospital and hospital management of adult patients with acute cyanide poisoning. Subsequently, a group of European pediatric experts met to evaluate and adopt that algorithm for use in the pediatric population.

Unexpectedly severe metabolic acidosis associated with sodium thiosulfate therapy in a patient with calcific uremic arteriolopathy.

Calcific uremic arteriolopathy, formerly known as calciphylaxis is a devastating condition that primarily affects patients with end-stage renal disease. The lesions can progress to massive ulcerations of the subcutaneous tissue that are associated with a high degree of morbidity and mortality, usually related to sepsis. Although the pathophysiology of this condition is poorly understood, it appears to be related to a derangement in calcium-phosphate metabolism. Thus, treatments have focused on the treatment of hyperparathyroidism albeit with poor results. More recently, sodium thiosulfate (STS) has emerged as a promising therapy following multiple case reports of marked disease regression following its use. As STS is a strong acid, metabolic acidosis has been described following its administration, although relatively mild in degree. We report a case of a patient with calciphylaxis who repeatedly developed a severe anion gap metabolic acidosis following each dose of STS requiring a significant reduction in the dose.

Clinical Efficacy and Safety of Sodium Thiosulfate in the Treatment of Uremic Pruritus: A Meta-Analysis of Randomized Controlled Trials.

Uremic pruritus is a distressful complication of chronic kidney disease and results in impaired quality of life and higher mortality rates. Intravenous sodium thiosulfate has been reported to alleviate pruritus in hemodialysis patients. We performed a systematic review and meta-analysis to estimate the efficacy of intravenous sodium thiosulfate in patients with uremic pruritus. A systematic search of electronic databases up to June 2021 was conducted for randomized controlled trials that evaluated the clinical effects of sodium thiosulfate in the management of patients with uremic pruritus. Two reviewers selected eligible articles and evaluated the risk of bias; the results of pruritus assessment and uremic pruritus-related laboratory parameters in selected studies were analyzed. There are four trials published between 2018 and 2021, which include 222 participants. The sodium thiosulfate group displayed significant decrease in the pruritus score (standardized mean difference = -3.52, 95% confidence interval = -5.63 to -1.41, p = 0.001), without a significant increase in the adverse effects (risk ratio = 2.44, 95% confidence interval = 0.37 to 15.99, p = 0.35) compared to the control group. Administration of sodium thiosulfate is found to be a safe and efficacious complementary therapy in improving uremic pruritus in patients with chronic kidney disease.

Sodium thiosulfate delays the progression of coronary artery calcification in haemodialysis patients.

BACKGROUND: Coronary artery calcification (CAC) is prevalent among haemodialysis patients and predicts cardiovascular mortality. In addition to modifying traditional cardiovascular risk factors, therapy aimed at lowering serum phosphate and calcium-phosphate product has been advocated. Sodium thiosulfate, through its chelating property, removes calcium from precipitated minerals decreasing calcification burden in calcific uraemic arteriolopathy and soft tissue calcification. The effect of sodium thiosulfate on CAC in haemodialysis patients has never been studied. METHODS: Eighty-seven stable chronic haemodialysis patients underwent multi-row spiral computed tomography and bone mineral density (BMD) measurement. Patients with a CAC score >or=300 were included to receive intravenous sodium thiosulfate infusion twice weekly post-haemodialysis for 4 months. CAC and BMD were re-evaluated at the end of the treatment course. RESULTS: Progression of CAC occurred in 25% and 63% of the patients in the treatment and control group, respectively (P = 0.03). CAC score was unchanged in the treatment group but increased significantly in the control group. BMD of the total hip declined significantly in the treatment group. In multivariate analysis adjusted for factors that influenced CAC progression, therapy with sodium thiosulfate was an independent protective factor (odds ratio = 0.05, P = 0.04). Major side effects were persistent anorexia and metabolic acidosis. CONCLUSIONS: The effect of sodium thiosulfate in delaying the progression of CAC is encouraging and will require a larger study. Determination of the safe therapeutic window is necessary in order to avoid bone demineralization.

Sodium-Thiosulfate Induced Life-Threatening Metabolic Acidosis Limiting Treatment of Calciphylaxis.

BACKGROUND Calcific uremic arteriolopathy (CUA) is a rare and incredibly painful cutaneous disorder secondary to microvascular involvement in which calcium dysregulation leads to stenosis of medium sized arterial blood vessels along with endothelial dysregulation and thrombosis. Ultimately, these patients are at high risk for non-healing wounds with risk of death from sepsis and multi-organ failure. It is a poorly understood condition with limited therapies that do not offer mortality benefit. Prevalence is about 4% in hemodialysis patients. Sodium thiosulfate (STS) can be used in hemodialysis patients but therapy is often limited by the development of high anion gap metabolic acidosis. CASE REPORT A 53-year-old male who had end stage renal disease and who was on hemodialysis and taking warfarin for bio-prosthetic mitral valve replacement and atrial fibrillation presented with non-healing right lower extremity cellulitis which had failed outpatient treatment. A skin biopsy of the lesion was consistent with CUA. The patient failed to improve on calcitriol and cinacalcet and was started on intravenous STS. Subsequently, he developed life threatening metabolic acidosis requiring a bicarbonate drip. He died 12 weeks after his initial diagnosis of CUA. CONCLUSIONS This article seeks to describe how the treatment of CUA; a rare disease with high mortality, is limited by the development of metabolic acidosis when using STS therapy. There is an 80% mortality rate within 6 months from CUA with major adverse effect of a high anion gap metabolic acidosis. Further research is needed in the field of establishing optimal dosing and frequency.

Impact of Pronase, Sodium Thiosulfate, and Methylene Blue Combinations on Development and Survival of Sodium Hypochlorite Surface-Disinfected Zebrafish (Danio rerio) Embryos.

Embryo surface disinfection is utilized in aquaculture to decrease the risk of pathogen introduction into established colonies. Zebrafish embryos are commonly disinfected with unbuffered sodium hypochlorite at 25-50 ppm for 10 min with or without concurrent treatment with chemicals, including pronase (Pron), sodium thiosulfate, and/or methylene blue; however, the impact of these chemicals on embryo survival and development has not been evaluated. In this study, AB and casper embryos were exposed to disinfection protocols that used Pron, sodium thiosulfate, and/or methylene blue (given alone, in various combinations, or all three combined) with 50 and 100 ppm sodium hypochlorite performed 6 and 24 h postfertilization (HPF). All groups were evaluated for survival, hatching, and malformations at 5 days postfertilization. Maximal survival (69%-97%) and hatching rates (66%-94%) were generally observed with sodium hypochlorite disinfection followed by exposure to both Pron and sodium thiosulfate and maintenance in standard embryo medium without methylene blue. Methylene blue had variable effects on survival and hatching. Higher survival and hatching rates were seen in AB embryos disinfected at 6 HPF and casper embryos disinfected at 24 HPF. Susceptibility to sodium hypochlorite toxicity differed by strain, emphasizing the need to test disinfection protocols on small embryo cohorts.

Effect of Sodium Thiosulfate on Arterial Stiffness in End-Stage Renal Disease Patients Undergoing Chronic Hemodialysis (Sodium Thiosulfate-Hemodialysis Study): A Randomized Controlled Trial.

BACKGROUND: Arterial stiffness (AS) and vascular calcification are significantly related to a high cardiovascular mortality risk in hemodialysis (HD) patients. Intravenous sodium thiosulfate (IV STS) can prevent and delay the vascular calcification progression in uremic states; however, the STS effect on AS has not been assessed. This study aimed to evaluate the STS efficacy on vascular calcification and AS in HD patients. METHODS: Fifty HD patients with abnormal AS, as measured via the cardio-ankle vascular index (CAVI ≥8), were prospectively randomized to open-label 12.5 g IV STS during the last HD hour twice weekly for 6 months (n = 24) or the usual care (control group; n = 26). Patients and treating physicians were not blinded. The CAVI, coronary artery calcification (CAC) score, hemodynamics, and biochemical parameters were measured at the baseline and at 3 and 6 months. RESULTS: All the baseline parameters were comparable. The IV STS significantly reduced the CAVI when compared to the control group (mean CAVI difference = -0.53; 95% CI -1.00 to -0.06; p = 0.03). A significant CAVI improvement was seen in those patients without diabetes mellitus. The natural logarithm of the CAC volume score was significantly increased in the control group. The high sensitivity C-reactive protein level was slightly lowered in the IV STS group (not significant). CONCLUSION: The intradialytic STS treatment significantly reduced the AS, as measured by the CAVI, and stabilized the vascular calcification in the HD patients. STS may be a novel therapeutic strategy for delaying and treating the structural and functional vascular wall abnormalities in HD patients.