Regional citrate anticoagulation with continuous renal replacement therapy as a cause of hypercalcemia.

CLINICAL RELEVANCE: Awareness of the causes of hypercalcemia is essential for timely diagnosis of calcium disorders and optimal treatment. Citrate is commonly used as an anticoagulant during continuous renal replacement therapy (CRRT). Accumulation of citrate in the systemic circulation during CRRT may induce several metabolic disturbances, including total hypercalcemia and ionized hypocalcemia. The aim of the present study is to increase awareness of citrate accumulation and toxicity as a cause of hypercalcemia by relating three cases and reviewing the pathophysiology and clinical implications. OBSERVATIONS: We utilized electronic health records to examine the clinical cases and outlined key studies to review the consequences of citrate toxicity and general approaches to management. CONCLUSIONS: Citrate toxicity is associated with high mortality. A safe threshold for tolerating hypercalcemia during citrate anticoagulation is not clearly defined, and whether citrate toxicity independently increases mortality has not been resolved. Greater attention to citrate toxicity as a cause of hypercalcemia may lead to earlier detection, help to optimize the management of systemic calcium levels, and foster interest in future clinical studies.

Early experience of using regional citrate anticoagulation for continuous renal replacement therapy in critically ill patients in a resource-limited setting.

AIM: Despite the superiority of regional citrate anticoagulation (RCA) in continuous renal replacement therapy (CRRT), its application is limited in resource-limited settings. We aim to explore the cost and safety of RCA for CRRT in critically ill patients, compared to usual care. METHODS: This prospective observational study included patients requiring CRRT in a tertiary intensive care unit (ICU) from February 2022 to January 2023. They were classified to either the RCA or usual care groups based on the anticoagulation technique chosen by the treating physician, considering contraindications. The CRRT prescription follows the institutional protocol. All relevant data were obtained from the ICU CRRT-RCA charts and electronic medical records. A cost analysis was performed. RESULTS: A total of 54 patients (27 per group) were included, with no demographic differences. Sequential Organ Failure Assessment score and lactate levels were significantly higher in the usual care group. The number of filters used were comparable (p = .108). The median filter duration in the RCA group was numerically longer (35.00 [15.50-56.00] vs. 23.00 [17.00-29.00] h), but not statistically significant (p = .253). The duration of mechanical ventilation, vasopressor requirement, and mortality were similar, but the RCA group had a significantly longer ICU stay. The rate of adverse events was similar, with four severe metabolic alkalosis cases in the RCA group. The RCA group had higher total cost per patient per day (USD 611 vs. 408; p = .013). CONCLUSION: In this resource-limited setting, RCA for CRRT appeared safe and had clinically longer filter lifespan compared with usual care, albeit the increased cost.

Toothpaste containing TiF4 and chitosan against erosive tooth wear in situ.

OBJECTIVE: This study compared the protective effect of an experimental TiF4/Chitosan toothpaste with a commercial toothpaste on the prevention of erosive tooth wear (ETW) in situ. METHODS: Fifteen subjects took part in this crossover and double-blind study, in which they wore a palatal appliance containing 4 bovine enamel and 4 dentin in 3 phases (5 days each). Half of the samples were subjected to erosive challenges (90 s in 0.1 % citric acid, pH 2.5, 4 times/day), and the other half to erosive plus abrasive challenges (15 s plus 45 s of contact, 2 times/day). The phases corresponded to the application of the different toothpastes: 1) TiF4 (1400 ppm F-) plus Chitosan, 2) Elmex®, Erosion Protection (1400 ppm F-, Chitosan), and 3) Placebo (negative control). Tooth wear was measured using contact profilometry (µm) and submitted to two-way RM ANOVA/Tukey test (p < 0.05). RESULTS: No significant differences were detected between the experimental and commercial toothpastes, regardless of the challenge on both tissues. Both significantly reduce ETW compared to negative control (p < 0.0006). Tooth wear was increased by brushing only on eroded enamel (p < 0.01), but not on dentin (p = 0.6085). TiF4/Chitosan [erosion 2.98 ± 1.12 µm vs. erosion and abrasion 3.12 ± 1.33 µm] and Elmex® toothpastes [erosion 2.35 ± 0.93 µm vs. erosion and abrasion 2.98 ± 1.0 µm] minimized the impact of brushing compared to placebo on enamel [erosion 4.62 ± 1.48 µm vs. erosion and abrasion 5.15 ± 1.50 µm]. CONCLUSIONS: TiF4 plus chitosan toothpastes showed to be effective in minimizing the ETW as the commercial toothpaste is in situ. CLINICAL RELEVANCE: The experimental toothpaste has similar effect against ETW compared to the commercial toothpaste. Considering the increased ETW prevalence worldwide, this result supports clinical trials and a possible application of this experimental anti-erosive toothpaste in the future.

Effect of Polyphenols on the Ultrastructure of the Dentin Pellicle and Subsequent Erosion.

INTRODUCTION: Erosive tooth wear is a highly prevalent dental condition that is modified by the ever-present salivary pellicle. The aim of the present in situ study was to investigate the effect of polyphenols on the ultrastructure of the pellicle formed on dentin in situ and a subsequent erosive challenge. METHODS: The pellicle was formed on bovine dentin specimens for 3 min or 2 h in 3 subjects. After subjects rinsed with sterile water (negative control), 1% tannic acid, 1% hop extract, or tin/fluoride solution containing 800 ppm tin and 500 ppm fluoride (positive control), specimens were removed from the oral cavity. The erosive challenge was performed on half of the specimens with 1% citric acid, and all specimens were analyzed by transmission electron microscopy. Incorporation of tannic acid in the pellicle was investigated by fluorescence spectroscopy. RESULTS: Compared to the negative control, ultrastructural analyses reveal a thicker and electron-denser pellicle after application of polyphenols, in which, according to spectroscopy, tannic acid is also incorporated. Application of citric acid resulted in demineralization of dentin, but to a lesser degree when the pellicle was pretreated with a tin/fluoride solution. The pellicle was more acid-resistant than the negative control when modified with polyphenols or tin/fluoride solution. CONCLUSION: Polyphenols can have a substantial impact on the ultrastructure and acid resistance of the dentin pellicle, while the tin/fluoride solution showed explicit protection against erosive demineralization.

Citrate anticoagulation in plasma exchange followed by continuous renal replacement therapy in critically ill children.

OBJECTIVE: To investigate the effectiveness and safety of regional citrate-anticoagulated (RCA) plasma exchange (PE) and whether citrate-related metabolic disorders can be improved by sequential RCA continuous renal replacement therapy (CRRT). METHODS: This retrospective, single-center observational study included 79 critically ill children requiring PE followed by CRRT (June 2018 to June 2021) at the Pediatric Intensive Care Unit of Hunan Children's Hospital, China. Patients were divided into the RCA-PE (n = 30) and systemic heparin anticoagulation (SHA-PE) (n = 49) groups. Filter level comparison post-PE assessed RCA-PE efficacy, and metabolic changes occurring pre- and post-PE and CRRT were used to evaluate the effect of CRRT on RCA-based anticoagulation safety. RESULTS: The RCA-PE group had a better overall filter performance than the SHA-PE group. Two hours after PE, pH and HCO3- levels increased more significantly for the RCA-PE than the SHA-PE group. The RCA-PE incidence of metabolic alkalosis was 48.3%, higher by 4.2% (p < 0.001) compared to the SHA-PE group. In the RCA-PE group, pH and HCO3- decreased significantly 4 h after CRRT; the metabolic alkalosis caused by RCA-PE decreased to 13.8% (p = 0.005). No significant difference in pH, HCO3-, and metabolic alkalosis incidence was observed between the two groups 4 h after CRRT. CONCLUSIONS: The overall filtration performance of RCA-PE is superior to that of SHA-PE followed by CRRT. The metabolic complications associated with RCA-PE are mainly metabolic alkalosis that can be improved by using CRRT after RCA-PE and this is a better alternative for anticoagulation during PE in critically ill children.

Longterm abrasive and erosive effect of whitening toothpaste on dentin surface.

PURPOSE: To evaluate the amount of dentin loss following immersion in or toothbrushing with whitening toothpaste (WT) containing hydrogen peroxide (HP) and citric acid (CA). Additionally, the amount of dentin loss after brushing with a WT alone or in combination with a conventional toothpaste was assessed, and the effects of HP and CA solutions on the dentin surface were investigated. METHODS: Bovine dentin specimens (n= 350) were randomly assigned to seven solutions of various compositions as toothpaste: The specimens assigned to each solution were then further divided into five treatment groups (n=10 each) : Group A = 1-hour immersion in each solution (ES); Group B = 10,000 brushing in ES; Group C = 1-hour immersion in ES + 10,000 brushing in ES; Group D = 1-hour immersion in ES + 10,000 brushing in reference slurry (RS); Group E = 10,000 brushing in ES + 10,000 brushing in RS. The amount and pattern of dentin loss were determined, and the surfaces were observed using noncontact profilometry. RESULTS: The WT (pH 5.0) caused lower dentin loss than RS after a single brushing cycle; however, the extent of dentin loss after 1 hour of immersion in the WT was significantly greater than that in the RS. Among the specimens treated with WT, a significant difference in dentin loss was observed between Group C and Groups D and E (P< 0.05) but not between Groups D and E. The surfaces exposed to CAS1, CAPB, and WT exhibited U-shaped patterns of dentin loss after brushing or immersion, whereas a wedge-shaped pattern was observed in those that underwent brushing with the RS. CLINICAL SIGNIFICANCE: The effects (dentin abrasion) of a whitening toothpaste containing hydrogen peroxide and citric acid when used in combination with a conventional toothpaste were similar to those seen with the continuous use of a conventional toothpaste alone.

Effects of a commercial whitening toothpaste containing hydrogen peroxide and citric acid on dentin abrasion and erosion.

BACKGROUND: Hydrogen peroxide (HP) and citric acid (CA), key contributors to toothpaste acidity, can lead to dental loss. This study aimed to compare the amount of abrasion or loss of dentin based on pH, buffering, and concentration of HP and CA in commercial and experimental toothpastes after toothbrushing or immersion. METHODS: Bovine dentin specimens were randomly assigned to nine solutions. The prepared solutions included two commercial toothpastes (whitening toothpaste [WT] with HP and CA; conventional toothpaste [CT] without HP and CA), reference slurry (RS), two CA solutions (1.92%, CAS1; 0.001%, CAS2), basic solution (7.16% sodium phosphate dibasic [SPDS]), CA phosphate buffer solution (3.58% SPDS and 0.96% CA [CAPB]), HP solution (4%, HPS), and distilled water (DW). Dentin specimens were performed in two treatments: one with only abrasion (10,000 brushings) and one with only immersion (1 h). After treatments, the amount of dentin loss and surface images were measured and observed using noncontact profilometry. Data were analyzed using an one-way analysis of variance and the Tukey test as a post hoc analysis (p < 0.05). RESULTS: WT with pH 5.0 had lower dentin abrasion than CT and RS after brushing but had higher dentin loss than both after immersion. The dentin surfaces of CAS1, CAPB, and WT were damaged after immersion, whereas HPS, CAS2, CT, SPDS, RS, and DW remained intact after soaking. CAS2 and HPS, which had a pH of 5.0 like WT, did not significantly differ from those of DW after brushing. CONCLUSIONS: WT containing HP and CA did not cause significant dentin abrasion but may cause additional dentin loss even without brushing. After brushing or immersion, the CA concentration may affect the dentin surface more than the HP concentration included in WT. The amount of abrasion or loss of dentin after brushing or soaking can vary based on the composition, concentration, and buffer in the solution, even if the pH of the solution is similar to pH 5.0.

Evaluation of the efficacy and associated complications of regional citrate anticoagulation in neonates: experience from a fourth level neonatal intensive care unit.

Continuous kidney replacement therapy (CKRT) use has increased in recent years, but anticoagulation is a challenge for neonates. Regional citrate anticoagulation (RCA) is rarely preferred in neonates because of citrate accumulation (CA) and metabolic complications. We aimed to demonstrate the efficacy and safety of RCA in neonates. We retrospectively analyzed the medical records of 11 neonates treated with RCA-CKRT between 2018 and 2023. The initial dose of RCA was 2.1-3 mmol/l, and then, its dose was increased according to the level of ionized calcium (iCa+2) in the circuit and patients. The total/iCa+2 ratio after-treatment > 2.5 was indicated as CA. We evaluated to citrate dose, CA, circuit lifespan, and dialysis effectivity. The median gestational age was 39 (36.4-41.5) weeks, the median body weight (BW) was 3200 (2400-4000) grams, and the mean postnatal age was 4 (2-24) days. The most common indication for CKRT was hyperammonemia (73%). All neonates had metabolic acidosis and hypocalcemia during CKRT. Other common metabolic complications were hypophosphatemia (90%), hypokalemia (81%), and hypomagnesemia (63%). High dialysate rates with a median of 5765 ml/h/1.73 m2 allowed for a rapid decrease in ammonia levels to normal. Four patients (36.3%) had CA, and seven (63.7%) did not (non-citrate accumulation, NCA). Mean BW, median postnatal age, biochemical parameters, coagulation tests, and ammonia levels were similar between the CA and NCA groups. Low pH, low HCO3, high lactate, and SNAPPE-II scores could be associated with a higher T/iCa ratio. CONCLUSION:  RCA was an efficient and safe anticoagulation for neonates requiring CKRT. Metabolic complications may occur, but they could be managed with adequate supplementation. WHAT IS KNOWN: • Continuous kidney replacement therapy (CKRT) has become popular in recent years due to its successful treatment of fluid overload, electrolyte imbalance, metabolic acidosis, multi-organ failure, and hyperleucinemia/hyperammonemia associated with inborn errors of metabolism. • The need for anticoagulation is the major difficulty in neonatal CKRT. In adult and pediatric patients, regional citrate anticoagulation has been shown to be effective. WHAT IS NEW: • RCA is an effective and safe anticoagulation method for neonates who require CKRT. • Electrolyte imbalances and metabolic acidosis could be managed with adequate supplementation and appropriate treatment parameters such as citrate dose, blood flow rate, and dialysate flow rate.

Efficacy and Safety of Citric Acid and Heparin Anticoagulation in Patients with Septic Acute Kidney Injury Undergoing Continuous Renal Replacement Therapy: A Meta-Analysis.

Objective: This meta-analysis compares the clinical efficacy and safety of citrate anticoagulation with heparin anticoagulation in continuous renal replacement therapy for acute kidney injury in sepsis. Methods: The experimental group underwent local anticoagulation with citrate, whereas the control group received systemic anticoagulation with heparin. Relevant data from randomized controlled trials (RCTs) meeting the inclusion criteria were independently extracted through computer searches of the China Journal Full Text Database (CNKI), Wanfang, and Vipul databases. Additionally, references to included literature were searched to expand the dataset. Extracted RCTs that met inclusion criteria underwent independent quality evaluation and cross-checking using the Cochrane systematic review method. Subsequently, a meta-analysis was conducted using Stata 12.0 software. Results: The analysis included seven studies involving a total of 652 patients. After treatment, renal function improvement was significantly more significant in the citrate group, while creatinine and urea nitrogen levels showed a more significant decrease in the heparin group, with statistically significant differences (WMD = -51.30, 95% CI = -68.54 ~ -34.06, P = .000 and WMD = 3.68, 95% CI = -4.52 ~ -2.85, P = .000). The filter lifespan in the citrate group was significantly longer than in the heparin group, with a statistically significant difference (WMD = 6.93, 95% CI = 6.30 ~ 7.55, P = .000). Adverse bleeding reactions were significantly less common in the citrate group compared to the heparin group, with a statistically significant difference (RR = 0.14, 95% CI = 0.06 ~ 0.32, P = .000). Conclusions: The results of this meta-analysis indicate that citrate anticoagulation is more effective than heparin anticoagulation in continuous renal replacement therapy for patients with acute kidney injury in sepsis. Citrate anticoagulation contributes to improved renal function and extended filter usage and reduces the incidence of adverse bleeding reactions.

Effect of a high-citrate beverage on urine chemistry in patients with calcium kidney stones.

A well-accepted strategy to prevent kidney stones is to increase urine volume by increasing oral intake of fluids, especially water, to lower supersaturation of the relevant, relatively insoluble salts, and thereby lower the risk of precipitation. Randomized controlled trials have shown that this strategy works. It is inexpensive, safe, and intuitively attractive to patients. However, although any beverage can increase urine volume, and citrus juices can increase urine citrate content and pH, no beverage other than water has been clearly shown by randomized controlled trial to prevent kidney stones. We designed an innovative, palatable, low-calorie, high alkali citrate beverage to prevent kidney stones, called Moonstone. One packet of Moonstone powder, mixed in 500 ml of water, contains 24.5 meq of alkali citrate. We administered one packet twice a day to ten calcium stone formers. Moonstone resulted in an increase in mean 24-h urine citrate and urine pH, and a decrease in supersaturation of calcium oxalate in calcium stone formers compared to an equal volume of water. These changes, comparable to those seen in a prior study of a similar amount of (potassium-magnesium) citrate, will likely be associated with a clinically meaningful reduction in kidney stone burden in patients with calcium stones. The effect to increase urine pH would also be expected to benefit patients with uric acid and cystine stones, groups that we hope to study in a subsequent study. The study preparation was well tolerated and was selected as a preferred preventative strategy by about half the participants. Moonstone is an alternative, over-the-counter therapy for kidney stone prevention.

Factors affecting continuous renal replacement therapy duration in critically ill patients: A retrospective study.

INTRODUCTION: This study aimed to analyze the factors affecting continuous renal replacement therapy (CRRT) duration in critically ill patients and provide a reference for clinical treatment. MATERIAL AND METHODS: We divided patients into regional citrate anti-coagulation (RCA) and low-molecular-weight-heparin (LMWH) groups according to the anti-coagulation method and collected the relevant data, to analyze the factors associated with CRRT time. RESULTS: Compared with the LMWH group, the RCA group had a longer mean treatment time (55.36 ± 22.57 vs. 37.65 ± 27.09 h, p < 0.001), lower transmembrane pressure, and lower filter pressure, regardless of vascular access site. Multivariable linear regression analysis showed a significant correlation between anti-coagulation patterns, filter pressure at CRRT discontinuation, nurses' level of intensive care unit experience, pre-machine fibrinogen level, and CRRT time. CONCLUSION: Anti-coagulation is the most important factor affecting CRRT duration. Filter pressure, nurses' level of intensive care unit experience, and fibrinogen level also affecting CRRT duration.

Heparin anticoagulation versus regional citrate anticoagulation for membrane therapeutic plasma exchange in patients with increased bleeding risk.

Background Heparin anticoagulation (HA) is commonly employed for membrane therapeutic plasma exchange (mTPE). However, for patients with increased bleeding risk, there were controversial opinions on the use of HA versus regional citrate anticoagulation (RCA) for mTPE. Our present study aimed to evaluate the efficacy and safety of HA vs. RCA for mTPE in patients with increased bleeding risk.Methods Patients with increased bleeding risk who underwent mTPE between 2014 and 2021 in our center were screened. Observations of anticoagulation efficacy and safety were used as the study endpoints.Results A total of 108 patients with 368 mTPE sessions were included. Of the included patients, 38 and 70 received HA and RCA mTPE, respectively. There was no significant difference in the clotting of extracorporeal circuits between the HA and RCA groups (4.1% vs. 4.4%, p = 0.605). More bleeding episodes were observed in the HA group compared to the RCA group (16.4% vs. 4.4% mTPE sessions, p < 0.001). The frequency of postoperative transfusion within 24 h (11% vs. 3.4%, p = 0.007) was significantly different in the HA and RCA group. Anticoagulation strategy (HA vs. RCA; OR 5.659, 95%CI 2.266-14.129; p < 0.001), and mean arterial pressure (prior treatment, OR 1.052, 95%CI 1.019-1.086; p = 0.002) were independent risk factors of bleeding episodes. At the end of mTPE treatment, the incidence of metabolic alkalosis (16.7% vs. 54.1%, p = 0.027) and hypocalcemia (41.7% vs. 89.2%, p = 0.001) was significantly different in the HA (n = 5, 12 sessions) and RCA (n = 22, 74 sessions) groups, respectively.Conclusion RCA is as effective as HA for mTPE. However, for patients with increased bleeding risk, RCA is associated with a lower risk of bleeding, compared with HA. With careful monitoring and timely adjustment, RCA most likely is a safe and effective anticoagulation option for mTPE in patients with increased bleeding risk.

A simplified protocol of regional citrate anticoagulation with phosphate-containing solutions in infants and children treated with continuous kidney replacement therapy.

BACKGROUND: Regional citrate anticoagulation (RCA) is the preferred modality of anticoagulation used in continuous kidney replacement therapy (CKRT) in adults and less extensively in children. Potential metabolic complications limit widespread use in infants, neonates, and in children with liver failure. METHODS: We report our experience with a simplified protocol in 50 critically ill children, infants, and neonates, some of them with liver failure, with commercially available solutions containing phosphorous and higher concentration of potassium and magnesium. RESULTS: RCA allowed attainment of a mean filter lifetime of 54.5 ± 18.2 h, 42.5% of circuits lasted more than 70 h, and scheduled change was the most frequent cause of CKRT interruption. Patient Ca++ and circuit Ca++ were maintained in the target range with mean values of 1.15 ± 0.13 mmol/l and 0.38 ± 0.07 mmol/l, respectively. No session had to be stopped because of metabolic complications. The most frequent complications were hyponatremia, hypomagnesemia, and metabolic acidosis mostly related to primary disease and critical illness. No session had to be stopped because of citrate accumulation (CA). Transitory CA occurred in 6 patients and was managed without requiring RCA interruption. No patients with liver failure presented CA episodes. CONCLUSIONS: In our experience, RCA with commercially available solutions was easily applied and managed in critically ill children, even in patients with low weight or with liver failure. Solutions containing phosphate and higher concentrations of magnesium and potassium allowed reduction of metabolic derangement during CKRT. Prolonged filter life was ensured with no detrimental effects on patients and reduced staff workload. A higher resolution version of the Graphical abstract is available as Supplementary information.

Simplified regional citrate anticoagulation protocol for CVVH, CVVHDF and SLED focused on the prevention of KRT-related hypophosphatemia while optimizing acid-base balance.

BACKGROUND: Hypophosphatemia is a common electrolyte disorder in critically ill patients undergoing prolonged kidney replacement therapy (KRT). We evaluated the efficacy and safety of a simplified regional citrate anticoagulation (RCA) protocol for continuous venovenous hemofiltration (CVVH), continuous venovenous hemodiafiltration (CVVHDF) and sustained low-efficiency dialysis filtration (SLED-f). We aimed at preventing KRT-related hypophosphatemia while optimizing acid-base equilibrium. METHODS: KRT was performed by the Prismax system (Baxter) and polyacrylonitrile AN69 filters (ST 150, 1.5 m2, Baxter), combining a 18 mmol/L pre-dilution citrate solution (Regiocit 18/0, Baxter) with a phosphate-containing solution (HPO42- 1.0 mmol/L, HCO3- 22.0 mmol/L; Biphozyl, Baxter). When needed, phosphate loss was replaced with sodium glycerophosphate pentahydrate (Glycophos™ 20 mmol/20 mL, Fresenius Kabi Norge AS, Halden, Norway). Serum citrate measurements were scheduled during each treatment. We analyzed data from three consecutive daily 8-h SLED-f sessions, as well as single 72-h CVVH or 72-h CVVHDF sessions. We used analysis of variance (ANOVA) for repeated measures to evaluate differences in variables means (i.e. serum phosphate, citrate). Because some patients received phosphate supplementation, we performed analysis of covariance (ANCOVA) for repeated measures modelling phosphate supplementation as a covariate. RESULTS: Forty-seven patients with acute kidney injury (AKI) or end stage kidney disease (ESKD) requiring KRT were included [11 CVVH, 11 CVVHDF and 25 SLED-f sessions; mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score 25 ± 7.0]. Interruptions for irreversible filter clotting were negligible. The overall incidence of hypophosphatemia (s-P levels <2.5 mg/dL) was 6.6%, and s-P levels were kept in the normality range irrespective of baseline values and the KRT modality. The acid-base balance was preserved, with no episode of citrate accumulation. CONCLUSIONS: Our data obtained with a new simplified RCA protocol suggest that it is effective and safe for CVVH, CVVHDF and SLED, allowing to prevent KRT-related hypophosphatemia and maintain the acid-base balance without citrate accumulation. TRIAL REGISTRATION: NCT03976440 (registered 6 June 2019).

A nomogram prediction of citrate reaction during mononuclear cell collection in solid tumor patients.

PURPOSE: Citrate reaction is one of the main adverse events in peripheral blood mononuclear cell (MNC) collection. The aim of this study was to elucidate the risk factors for citrate reaction in patients with advanced solid tumor collection and to construct a nomogram to predict the risk. METHODS: One hundred forty-eight patients with advanced solid tumor who underwent peripheral blood MNC collection in our hospital between January 2021 to December 2021 were selected. The general data, creatinine level before collection, Ca2+ concentration before collection, absolute value of monocyte lymphocytes before collection, circulating blood volume, anticoagulant dosage, and blood collection duration were included in Logistic regression analysis to identify the risk factors of citrate reaction. According to the results of the multivariate logistic model, nomogram was established and receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of the model. RESULTS: Among the 148 solid tumor patients, 35 patients (23.6%) of the 148 patients developed citrate reaction. Multivariate analysis showed that the risk factors for citrate reaction in the process of collection included sex (odds ratio [OR] = 6.718; 95% confidence interval [95% CI]: 2.191-20.594, P = .001), age (OR = 0.957; 95% CI: 0.921-0.996, P = .03), and processed circulating blood volume (OR = 1.001; 95% CI: 1.000-1.002, P = .01). Logistic regression can analyze independent risk factors and establish risk prediction model. The predictive performance of the model is good, and the area under ROC curve is 0.799. CONCLUSIONS: The MNC collection process is safe. The incidence of citrate reaction in the collection of peripheral blood MNCs from patients with advanced solid tumor is related to the age, gender, and processed circulating blood volume of patients. The nomogram can be used to assess a patient's risk of citrate reaction.

Modification of oestrogen signalling pathways influences cough induced by citric acid but not capsaicin in the animal model of both sexes.

To clarify the role of oestrogen signalling and the role of oestrogen receptor alpha (ERα) in the cough pathways we performed a study in which coughing was observed in both sexes animal models after the treatment by selective ERα degrader fulvestrant (ICI 182-780) and inhibitor of oestrogen synthesis danazol. Degradation of ERα with the normal plasma oestrogen levels induced by fulvestrant, significantly augments the cough response of female but not male guinea pigs. These changes were observed in citric acid-induced cough. Female guinea pigs responded with an increased count of cough expulsions per challenge time and we also detected shorter cough latency. The capsaicin-induced cough did not change. A similar response was observed after danazol treatment, which decreased the plasma oestrogen level. Our results indicate that the transient receptor potential vanilloid-1 (TRPV1) channel-mediated cough is resistant to the hypoestrous state, while the citric acid-mediated cough is oestrogen-dependent and hypersensitive during the hypoestrous state.

Comparison of optimal bowel cleansing effects of 1L polyethylene glycol with ascorbic acid versus sodium picosulfate with magnesium citrate: A randomized controlled study.

Various low-volume bowel cleansing formulations that improve compliance have been approved and are being used in clinical practice. This study aimed to compare the effectiveness of 1 L polyethylene glycol (PEG) with ascorbic acid with that of sodium picosulfate (PICO) with magnesium citrate. This was a multicenter, randomized controlled, non-inferiority study. Patients were randomized into a 1 L PEG with ascorbic acid group and a PICO with magnesium citrate group according to the bowel cleansing agent used. Colonoscopy was performed as a single-blind study wherein the endoscopist had no information about any bowel preparation agent. The efficacy of bowel cleansing was assessed using the Harefield Cleansing Scale (HCS), and adverse events, preferences, and satisfaction were evaluated using a patient-reported questionnaire before colonoscopy. A total of 254 participants were randomly assigned to two groups: 115 in the 1 L PEG with ascorbic acid group and 113 in the PICO with magnesium citrate group. Overall bowel cleansing success was not statistically different between the two groups (97.4 vs. 97.3%), confirming that 1 L PEG with ascorbic acid was not inferior to PICO with magnesium citrate (lower confidence limit, -4.15%; p = 1.00). High-quality bowel cleansing was achieved in 87% of the 1 L PEG with ascorbic acid group and 77% of the PICO with magnesium citrate group (Lower confidence limit, 1.29%, p = 0.05). In terms of patient satisfaction, PICO with magnesium citrate was better, but compliance and side effects were similar in both groups. The 1 L PEG with ascorbic acid showed similar efficacy and adverse events as PICO with magnesium citrate. Although 1 L PEG with ascorbic acid is very effective in bowel preparation despite its small volume, it is necessary to increase satisfaction such as taste and feeling.

Mitochondrial citrate accumulation drives alveolar epithelial cell necroptosis in lipopolysaccharide-induced acute lung injury.

Necroptosis is the major cause of death in alveolar epithelial cells (AECs) during acute lung injury (ALI). Here, we report a previously unrecognized mechanism for necroptosis. We found an accumulation of mitochondrial citrate (citratemt) in lipopolysaccharide (LPS)-treated AECs because of the downregulation of Idh3α and citrate carrier (CIC, also known as Slc25a1). shRNA- or inhibitor-mediated inhibition of Idh3α and Slc25a1 induced citratemt accumulation and necroptosis in vitro. Mice with AEC-specific Idh3α and Slc25a1 deficiency exhibited exacerbated lung injury and AEC necroptosis. Interestingly, the overexpression of Idh3α and Slc25a1 decreased citratemt levels and rescued AECs from necroptosis. Mechanistically, citratemt accumulation induced mitochondrial fission and excessive mitophagy in AECs. Furthermore, citratemt directly interacted with FUN14 domain-containing protein 1 (FUNDC1) and promoted the interaction of FUNDC1 with dynamin-related protein 1 (DRP1), leading to excessive mitophagy-mediated necroptosis and thereby initiating and promoting ALI. Importantly, necroptosis induced by citratemt accumulation was inhibited in FUNDC1-knockout AECs. We show that citratemt accumulation is a novel target for protection against ALI involving necroptosis.

Application of regional citrate anticoagulation in patients at high risk of bleeding during intermittent hemodialysis: a prospective multicenter randomized controlled trial.

OBJECTIVES: Safe and effective anticoagulation is essential for hemodialysis patients who are at high risk of bleeding. The purpose of this trial is to evaluate the effectiveness and safety of two-stage regional citrate anticoagulation (RCA) combined with sequential anticoagulation and standard calcium-containing dialysate in intermittent hemodialysis (IHD) treatment. METHODS: Patients at high risk of bleeding who underwent IHD from September 2019 to May 2021 were prospectively enrolled in 13 blood purification centers of nephrology departments, and were randomly divided into RCA group and saline flushing group. In the RCA group, 0.04 g/mL sodium citrate was infused from the start of the dialysis line during blood draining and at the venous expansion chamber. The sodium citrate was stopped after 3 h of dialysis, which was changed to sequential dialysis without anticoagulant. The hazard ratios for coagulation were according to baseline. RESULTS: A total of 159 patients and 208 sessions were enrolled, including RCA group (80 patients, 110 sessions) and saline flushing group (79 patients, 98 sessions). The incidence of severe coagulation events of extracorporeal circulation in the RCA group was significantly lower than that in the saline flushing group (3.64% vs. 20.41%, P<0.001). The survival time of the filter pipeline in the RCA group was significantly longer than that in the saline flushing group ((238.34±9.33) min vs. (221.73±34.10) min, P<0.001). The urea clearance index (Kt/V) in the RCA group was similar to that in the saline flushing group with no statistically significant difference (1.12±0.34 vs. 1.08±0.34, P=0.41). CONCLUSIONS: Compared with saline flushing, the two-stage RCA combined with a sequential anticoagulation strategy significantly reduced extracorporeal circulation clotting events and prolonged the dialysis time without serious adverse events.