Correlation between urine cytology results on the day after overnight continuous saline irrigation following transurethral resection of bladder tumor and bladder tumor recurrence.

PURPOSE: To investigate the relationship between urine cytology results after overnight continuous saline irrigation (OCSI) following transurethral resection of bladder tumor (TURBT) and bladder tumor recurrence in non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: A retrospective study was conducted on patients diagnosed with NMIBC between 2016 and 2020 after undergoing TURBT at our hospital. All patients received OCSI following TURBT and had urine cytology test at postoperative 1 day. Urine cytology was classified into three groups: Negative, low-grade urothelial neoplasm (LGUN)+atypical urothelial cells (AUC), and suspicious for high-grade urothelial carcinoma (SHGUC)+high-grade urothelial carcinoma (HGUC). Recurrence-free survival (RFS) in each group was compared using the Kaplan-Meier method. Univariable and multivariable Cox regression analyses were performed to evaluate independent prognostic factors. RESULTS: A total of 172 patients were included in this study. Based on urine cytology group (after OCSI), RFS did not reach the median value in the Negative group. In the LGUN+AUC group, the median RFS was 615.00 days. In the SHGUC+HGUC group, the median RFS was 377.00 days. In survival analysis, the Negative group had a longer RFS than the SHGUC+HGUC group (p=0.013). However, Cox regression analysis showed that SHGUC+HGUC was not an independent prognostic factor for recurrence. CONCLUSIONS: Urine cytology results after OCSI following TURBT in NMIBC were associated with bladder tumor recurrence. Specifically, SHGUC or HGUC in urine cytology after OCSI showed earlier recurrence than negative cases. However, further research is needed to accurately determine whether it is an independent prognostic factor.

Intratracheal instillation of budesonide suspension versus normal saline on oxidative stress in neonates with meconium aspiration syndrome.

BACKGROUND: Presently, the efficacy of neonatal resuscitation techniques via interventions such as oral, nasal, and endotracheal suction for preventing meconium aspiration syndrome (MAS) after delivery has not been satisfactory. OBJECTIVE: This study aimed to investigate the role of intratracheal instillation of budesonide on oxidative stress in MAS. METHODS: Sixty-two neonates with MAS admitted to Huai'an Maternity and Child Healthcare Hospital from January 2018 to June 2020 were divided into a study group (intratracheal instillation of 2 ml budesonide suspension; n = 31) and a control group (intratracheal instillation of 2 ml normal saline; n = 31). Collect data from two groups of patients and evaluate clinical outcomes, including oxygenation index (OI), as well as serum total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI) and 8-Isoprostane before treatment and 72h after admission. RESULTS: We found no statistical differences in mortality, complication rate, total oxygen inhalation time, OI before treatment and 72h after admission between the two groups of neonates with MAS, while the duration of invasive respiratory support in the study group was significantly shorter than in the control group. Also, serum TAC, TOS, OSI and 8-isoprostane levels were not statistically different before treatment between the two groups. After 72h of admission, OSI and 8-Isoprostane in neonates with MAS in the study group were much lower than those in the control group. TOS, OSI, 8-Isoprostane in the control group and 8-Isoprostane in the study group were significantly higher than those before treatment. As for TAC and TOS, no significant differences were observed between the two groups. CONCLUSION: Intratracheal instillation of budesonide was shown to alleviate oxidative stress and shorten invasive ventilation time in neonates with MAS.

Effect of Heated Saline Solution on Pain Intensity, Wound Bed Temperature, and Comfort during Chronic Wound Dressing Changes: Crossover Randomized Clinical Trial.

OBJECTIVE: To evaluate the use of heated saline solution during wound cleaning on the intensity of pain related to the procedure, the temperature of the wound bed, and the comfort of patients with chronic wounds. Further, to investigate patient preference in relation to the temperature of the solution used for cleaning. METHODS: Crossover, single-blind, clinical trial with 32 people with chronic wounds. Providers cleaned the wounds with room temperature and heated saline solution. Participants were randomized into group 1 A/B (heated solution first, room temperature second) or group 2 B/A (room temperature solution first, heated solution second), with a 10-minute washout period. Investigators evaluated pain intensity, wound bed temperature, and patient-reported comfort and preference. RESULTS: The heated solution was preferred (P = .04) and more often referred to as comfortable (P = .04) by the participants. There was no difference in pain intensity before and after cleaning with room temperature (2.03; P = .155) and heated saline (2.25; P = .44). The heated solution increased the temperature of the wound bed by 0.5 °C. CONCLUSIONS: Although heating saline solution could be an important comfort measure during dressing changes, quantitatively, the temperature of the solution did not significantly change the temperature of the wound bed nor the intensity of pain patients experienced.

Short-term effects of small volume saline infusion on acid base equilibrium in critically ill patients.

BACKGROUND: Short-term acid-base effects of 0.9% saline solution infusion are not well described. Aim of this study was to assess the effects of a fluid challenge with 0.9% saline in critically ill patients according to the Stewart's approach, which allows a precise determination of acid base equilibrium. METHODS: In 40 mechanically ventilated critically ill patients, acid-base variables according to Stewart's approach were measured before and after 30 minutes from the infusion of 0.5L of 0.9% saline. Patients were divided in saline responder (fractional sodium excretion increase <0.5) and non-responders, and in patients with (estimated glomerular filtration rate >63 mL/min) and without renal impairment. RESULTS: After saline infusion, plasma sodium concentration did not change (138 [135-141] vs. 138 [135-140] mEq/L, P=0.646), while chloride concentration significantly increased (102 [100-106] vs. 104 [191-106] mEq/L, P=0.003), reducing strong ion difference (37.0 [34.9-38.0] vs. 35.4 [32.7-37.5] mEq/L, P=0.004) without any impact on pH, due to the concomitant albumin dilution. In saline non-responders, the increase of plasma chloride concentration caused a reduction in strong ion difference, while in saline responders both plasma chloride concentration and strong ion difference remained similar. Patients with and without renal impairment presented a similar acid-base response. CONCLUSIONS: The infusion of 0.9% saline reduced strong ion difference by increasing plasma chloride concentration, with no effect on pH due to concomitant albumin dilution. Saline non-responders, characterized by the ability to excrete the sodium excess, were more likely to suffer the acidifying effects of saline infusion, while renal function did not affect the acid-base response to saline infusion.

A novel approach to saline/contrast delivery in excimer laser coronary atherectomy (ELCA) to enhance efficacy: MAXCon ELCA technique.

The advent of excimer laser coronary atherectomy (ELCA) nearly four decades ago heralded a novel way to treat complex lesions, both coronary and peripheral, which were previously untraversable and thus untreatable. These complex lesions include heavily calcified lesions, ostial lesions, bifurcation lesions, chronic total occlusions, in-stent restenosis (including stent underexpansion), and degenerative saphenous vein grafts. We discuss the technology of ELCA, its indications, applications, and complications, and suggest the "MAXCon ELCA" technique for better outcomes without increased risk. Lastly, we present a case of MAXCon ELCA effectively treating a complex lesion.

Evaluation of a Protocol Change Promoting Lactated Ringers Over Normal Saline in the Treatment of Diabetic Ketoacidosis.

BACKGROUND: Current guidelines recommend normal saline (NS) for fluid resuscitation in the management of patients presenting with diabetic ketoacidosis (DKA). However, previous prospective studies have demonstrated improvement in patient-specific outcomes, including time to DKA resolution, when balanced crystalloid fluids are used. METHODS: We conducted a single institution, retrospective cohort study of adult patients admitted with DKA before and after a protocol change within our institution, which shifted the default resuscitative and maintenance fluid in our DKA management protocol from NS to lactated Ringer's solution (LR). The primary outcome was time from DKA clinical presentation until DKA resolution. The secondary outcome was time to discontinuation of DKA protocol insulin drip. RESULTS: Of 246 patients meeting inclusion criteria, 119 were in the NS group (preprotocol change, where NS was the default resuscitative fluid) and 127 to the LR group (postprotocol change, where LR was the default resuscitative fluid). Time to DKA resolution was significantly decreased in the LR group (mean = 17.1 hours; standard deviation [SD] = 11.0) relative to the NS group (mean = 20.6 hours; SD = 12.2; P = .02). Duration of DKA protocol insulin drip was shorter in the LR group (mean = 16.0 hours; SD = 8.7) compared with the NS group (mean = 21.4 hours; SD = 12.5; P < .001). CONCLUSIONS: In this retrospective cohort study, protocolized DKA intravenous fluid management with LR resulted in shorter time to resolution of DKA and reduced duration of DKA protocol insulin drip.

Intraoperative Normal Saline Administration and Acute Kidney Injury in Patients Undergoing Liver Transplantation.

BACKGROUND: Normal saline is still used in patients undergoing living donor liver transplantation (LDLT) with normonatremia. We investigated whether the normal saline administered during LDLT is associated with the increased risk of acute kidney injury (AKI) compared with the balanced crystalloids. METHODS: We reviewed 1011 cases undergoing LDLT. The primary exposure variable was normal saline administered intraoperatively compared with the balanced crystalloid. To compare the risk of AKI after adjusting for potential confounders of baseline characteristics and surgical parameters, a propensity score matching analysis was performed. As a sensitivity analysis, ordinal logistic regression analysis was performed for AKI using inverse probability of treatment weighting (IPTW). RESULTS: The incidence of AKI was significantly higher in the saline group (n = 88/174, 50.6%) than in the balanced group (n = 67/174, 38.5%) after matching (P = .010). The incidence of stage 2 or 3 AKI was also significantly higher in the saline group (n = 26/174, 14.9%) than in the balanced group (n = 43/174, 24.7%) after matching (P = .022). The length of hospital stay was significantly longer in the saline group than in the balanced group after matching. Ordinal logistic regression analysis using IPTW showed that the saline group showed a significant association of saline administration with the risk of AKI (odds ratio 1.23, 95% CI 1.05-1.28, P = .013). CONCLUSION: Our propensity score analysis using propensity score matching and IPTW showed that normal saline administration during LDLT is associated with a high risk of postoperative AKI and longer hospital stays. However, our results should be interpreted carefully due to the relatively long period of data collection.

The Effect of Cold Saline Irrigation of Dissection Planes in Rhinoplasty on Postoperative Edema and Ecchymosis.

BACKGROUND: Periorbital edema and ecchymosis are frequently encountered after rhinoplasty and may be distressing to patients. Cold therapy is frequently employed in rhinoplasty to reduce postoperative edema and ecchymosis. PURPOSE: The aim of this study was to evaluate the effect of cold saline irrigation (CSI) of dissection planes in rhinoplasty on postoperative edema and ecchymosis. STUDY DESIGN, SETTING, SAMPLE: The investigators designed a retrospective cohort study. The data of patients who underwent rhinoplasty in our clinic between January 2021 and January 2023 were scanned. Patients who underwent primary open rhinoplasty from the same surgeon and standard rhinoplasty steps were applied in the same way and order were included in the study. Patients who had systemic diseases and previous nose surgery, and patients whose photographs could not be accessed from the photograph archive were excluded. PREDICTOR VARIABLE: According to whether CSI was applied to the dissection plans during rhinoplasty, the patients were divided into the CSI group and the control group (without CSI). MAIN OUTCOME VARIABLES: Patients' grades of periorbital edema and ecchymosis were the main outcome variables. The differences of outcome variables were compared between the 2 groups. COVARIATES: Demographics (age, sex), and surgical detail (duration of surgery) were collected as covariates. ANALYSES: The numerical variables were compared between the two groups using the student's t-test and Mann-Whitney U test, whereas the categorical variables were compared using Pearson's χ2 and Fisher's exact tests. P < .05 was considered statistically significant. RESULTS: Among the 167 patients who met the inclusion criteria, 60 patients were randomly selected, 30 patients in each group. No statistically significant difference was found between the two groups in terms of age (P = .45) and sex (P = .27). The mean ecchymosis grade was statistically significant lower in the CSI group than in the control group for all evaluation times (P < .05). Similarly, the mean edema grade was statistically significant lower in the CSI group than in the control group for all evaluation times, with the exception of the 10th and 15th day (P < .05). CONCLUSION AND RELEVANCE: CSI of the dissection planes in rhinoplasty reduced the development of periorbital edema and ecchymosis. This procedure is straightforward, inexpensive, and effective.

A 120-Minute Saline Infusion Test for the Confirmation of Primary Aldosteronism: A Pilot Study.

BACKGROUND: The saline infusion test (SIT) to confirm primary aldosteronism requires infusing 2 L of normal saline over 240 minutes. Previous studies raised concerns regarding increased blood pressure and worsening hypokalemia during SIT. We aimed to evaluate the diagnostic applicability of a SIT that requires 1 L of saline infusion over 120 minutes. METHODS: A cross-sectional study, including all patients in a large medical center who underwent SIT from 1 January 2015 to 30 April 2023. Blood samples were drawn for baseline renin and aldosterone (t = 0) after 2 hours (t = 120 min) and after 4 hours (t = 240 min) of saline infusion. We used ROC analysis to evaluate the sensitivity and specificity of various aldosterone cut-off values at t = 120 to confirm primary aldosteronism. RESULTS: The final analysis included 62 patients. A ROC analysis yielded 97% specificity and 90% sensitivity for a plasma aldosterone concentration (PAC) of 397 pmol/L (14 ng/dL) at t = 120 to confirm primary aldosteronism, and an area under the curve of 0.97 (95% CI [0.93, 1.00], P < 0.001). Almost half (44%) of the patients did not suppress PAC below 397 pmol/L (14 ng/dL) at t = 120. Of them, only one (4%) patient suppressed PAC below 276 pmol/L (10 ng/dL) at t = 240. Mean systolic blood pressure increased from 140.1 ±â€…21.3 mm Hg at t = 0 to 147.6 ±â€…14.5 mm Hg at t = 240 (P = 0.011). CONCLUSIONS: A PAC of 397 pmol/L (14 ng/dL) at t = 120 has high sensitivity and specificity for primary aldosteronism confirmation.

Pneumothorax Incidence with Normal Saline Instillation for Sealing the Needle Track After Computed Tomography-Guided Percutaneous Lung Biopsy.

PURPOSE: To determine whether instillation of normal saline solution for sealing the needle track reduces incidence of pneumothorax and chest tube placement after computed tomography-guided percutaneous lung biopsy. MATERIALS AND METHODS: A total of 242 computed tomography-guided percutaneous lung biopsies performed at a single institution were retrospectively reviewed, including 93 biopsies in which the needle track was sealed by instillation of 3-5 ml of normal saline solution during needle withdrawal (water seal group) and 149 biopsies without sealing (control group). Patient and lesion characteristics, procedure-specific variables, pneumothorax and chest tube placement rates were recorded. RESULTS: Baseline characteristics were comparable in both groups. There was a statistically significant decrease in the pneumothorax rate (19.4% [18/93] vs. 40.9% [61/149]; p < 0.001) and a numerically lower chest tube placement rate without significant reduction (4.3% [4/93] vs. 10.7% [16/149]; p = 0.126) with using normal saline instillation for sealing the needle track versus not using sealant material. Using a multiple logistic regression analysis, using normal saline instillation to seal the needle track, having a senior radiologist as operator of the procedure and putting patients in prone position were significantly associated with a decreased risk of pneumothorax. The presence of emphysema along the needle track was significantly associated with an increased risk of pneumothorax. No complication was observed due to normal saline injection. CONCLUSION: Normal saline solution instillation for sealing the needle track after computed tomography-guided percutaneous lung biopsy is a simple, low-cost and safe technique resulted in significantly decreased pneumothorax occurrence and a numerically lower chest tube placement rate, and might help to reduce both hospitalization risks and costs for the healthcare system. Level of evidence 3 Non-controlled retrospective cohort study.

The value of sequential application of hydrogen peroxide, povidone-iodine and physiological saline in reducing postoperative infections after total knee arthroplasty: A prospective, randomized, controlled study.

BACKGROUND: Currently, in the field of total joint arthroplasty (TJA), there are no studies that have demonstrated the value of the sequential application of hydrogen peroxide, povidone-iodine, and physiological saline during the surgical procedure in decreasing postoperative infections in total knee arthroplasty (TKA), and in decreasing the incidence of periprosthetic joint infections (PJI) in particular. This study aimed to assess the efficacy of the sequential application of hydrogen peroxide, povidone-iodine, and physiological saline in reducing postoperative infections in TKA. METHODS: The study prospectively included 4743 patients, with Group A (2371, 49.9%) receiving sequential intraoperative application of hydrogen peroxide, povidone-iodine, and physiological saline irrigation of the incision, and Group B (2372, 50.1%) receiving intraoperative application of physiological saline irrigation of the incision only, to collect the patients' baseline data and clinical characteristics, and to statistically assess the incidence of superficial infections and the PJI during the follow up period to evaluate the clinical value of the study. RESULTS: The baseline levels of patients in Groups A and B were comparable. There were 132 (2.8%) lost visits during the study period. The incidence of superficial infections within 30 days after surgery was 0.22% in Group A and 1.17% in Group B, the difference between the two groups was statistically significant (P = 0.007). The incidence of PJI was 0.17% in Group A and 1.26% in Group B, the difference between the two groups was statistically significant (P = 0.0121). CONCLUSION: Sequential application of hydrogen peroxide, povidone-iodine, and physiological saline to irrigate incision in TKA can significantly reduce the incidence of postoperative superficial infections and PJI. The scientific and rational application of this therapy intraoperatively greatly reduces the incidence of PJI and postoperative superficial infections, which is of great benefit to the patient's prognosis.

Post-mastectomy Breast Reconstruction With Gas vs Saline Tissue Expanders: Does the Fill Type Matter?

The most common reconstruction technique following mastectomy is a 2-stage technique that involves tissue expansion followed by definitive implant-based reconstruction (IBR). Tissue expanders (TEs) have classically used saline for initial fill; however, TEs with an initial gas fill (GTE)-including the CO2-based AeroForm (AirXpanders, San Francisco, CA) TE and TEs initially filled with atmospheric air-have been increasingly used in the past decade. We aimed to compare the outcomes in breast reconstruction for tissue expanders initially filled with saline vs gas. PubMed was queried for studies comparing gas- and saline-filled tissue expanders (STEs) used in IBR. A meta-analysis was performed on major postoperative outcomes and the required expansion and definitive reconstruction time. Eleven studies were selected and included in the analysis. No significant differences existed between tissue expansion with GTEs vs STEs for 11 of the 13 postoperative outcomes investigated. Out of the complications investigated, only the risk of infection/cellulitis/abscess formation was significantly lower in the GTE cohort (odds ratio 0.62; 95% CI, 0.47 to 0.82; P = .0009). The time to definitive reconstruction was also significantly lower in the GTE cohort (mean difference [MD], 45.85 days; 95% CI, -57.80 to -33.90; P < .00001). The total time to full expansion approached significance in the GTE cohort (MD, -20.33 days; 95% CI, -41.71 to 1.04; P = .06). A cost analysis considering TE cost and infection risk determined that GTE use saved a predicted $2055.34 in overall healthcare costs. Surgical outcomes for both fill types were predominantly similar; however, GTEs were associated with a significantly decreased risk of postoperative infection compared to saline-filled TEs. GTEs could also reduce healthcare expenditures and require less time until definitive reconstruction after placement.

Effect Of Elastomeric Separator On Microbial Count In Gingival Crevicular Fluid.

BACKGROUND: The separators are a preliminary step for band insertion, but there is a potential risk of bacteraemia during their placement, particularly in susceptible patients. The objective of the study is to determine the effect of separators on the bacterial count in gingival crevicular fluid (GCF) and to assess the efficacy of chlorhexidine mouth rinse and saline irrigation in the reduction of the bacterial count. METHODS: This randomized controlled trial was conducted on 51 participants who were divided into three equal g roups randomly (brushing only/control, saline irrigation, and 2% chlorhexidine mouthwash rinse). The inclusion criteria were age between 18-25 years, good oral hygiene, gingival and plaque index <1, no previous orthodontic treatment, and healthy individuals. The bacterial count was obtained from GCF samples after two hours, on the third day, and on the seventh day. Kruskal Wallis test was used to compare the bacterial count among the three groups, and post hoc analysis was done using Dunn's test. Friedman test was applied to see the difference at three-time points in each group. RESULTS: In both saline and chlorhexidine groups the mean bacterial count decreased significantly from baseline to 3rd day and 7th day after separator placement (p<0.001). For the third day, a significant difference was found in control versus saline and control versus chlorhexidine. No significant difference was found between saline and chlorhexidine on the third day. Similar results were found on the 7 thday. For controls, the bacterial count increased with time and for both saline and chlorhexidine groups the bacterial count decreased. The highest decrease in the bacterial count was found for the chlorhexidine group. CONCLUSIONS: After the placement of separators, there was an increase in the bacterial count in GCF. Notably, chlorhexidine was found to be more effective than saline irrigation in reducing the bacterial count.

Qualitative Histologic Assessment vs. Geomorphometric Analysis of Nerve Fiber Shape after the Intraneural Application of Liposomal Bupivacaine / Evaluación Histológica Cualitativa Versus Análisis Geomorfométrico de la Forma de la Fibra Nerviosa Después de la Aplicación Intraneural de Bupivacaína Liposomal

SUMMARY: The preserved form of all components of the nerve fiber is a prerequisite for the proper conduction of the nerve impulse. various factors can change the shape of nerve fibers. In everyday practice, qualitative histological analysis is the gold standard for detecting changes in shape. Geometric morphometry is an innovative method that objectively enables the assessment of changes in nerve fibers' shape after local anesthetics action. A total of sixty sciatic nerves were used as material, which was intraneural injected with saline solution in the control group (n=30), and a solution of 1.33 % liposomal bupivacaine (n=30) in the test group. After the animals were sacrificed, nerve samples were taken and histological preparations were made. The preparations were first described and examined using a qualitative histological method, after which digital images were made. The images were entered into the MorphoJ program and processed using the method of geometric morphometry. Qualitative histological examination revealed no differences in nerve fibers after intraneurally applied physiological solution and liposomal bupivacaine. Using the method of geometric morphometry, a statistically significant change in the shape of axons was found after intraneurally applied saline solution and liposomal bupivacaine (p=0.0059). No significant differences in histological changes were found after the qualitative histological analysis of nerve fiber cross-section preparations. A statistically significant change in the shape of nerve fiber axons was observed after geometric morphometric analysis of digital images after intraneural application of saline and liposomal bupivacaine.

La forma conservada de todos los componentes de la fibra nerviosa es un requisito previo para la conducción correcta del impulso nervioso. Varios factores pueden cambiar la forma de las fibras nerviosas. En la práctica diaria, el análisis histológico cualitativo es el estándar de oro para detectar cambios de forma. La morfometría geométrica es un método innovador que permite evaluar objetivamente los cambios en la forma de las fibras nerviosas después de la acción de los anestésicos locales. Se utilizó como material un total de sesenta nervios ciáticos, que se inyectaron intraneuralmente con solución salina en el grupo control (n=30), y una solución de bupivacaína liposomal al 1,33 % (n=30) en el grupo de prueba. Después de sacrificados los animales, se tomaron muestras de nervios y se realizaron preparaciones histológicas. Primero se describieron y examinaron las preparaciones utilizando un método histológico cualitativo, después de lo cual se tomaron imágenes digitales. Las imágenes fueron ingresadas al programa MorphoJ y procesadas mediante el método de morfometría geométrica. El examen histológico cualitativo no reveló diferencias en las fibras nerviosas después de la aplicación intraneural de solución fisiológica y bupivacaína liposomal. Usando el método de morfometría geométrica, se encontró un cambio estadísticamente significativo en la forma de los axones después de la aplicación intraneural de solución salina y bupivacaína liposomal (p = 0,0059). No se encontraron diferencias significativas en los cambios histológicos después del análisis histológico cualitativo de las preparaciones de secciones transversales de fibras nerviosas. Se observó un cambio estadísticamente significativo en la forma de los axones de las fibras nerviosas después del análisis de morfometría geométrica de imágenes digitales después de la aplicación intraneural de solución salina y bupivacaína liposomal.

The toxicity assessment of neorudin in cynomolgus monkeys.

In this study, the toxicity effects on circulatory system and respiratory system, and the acute toxicity test of recombinant neorudin (EPR-hirudin, EH) in cynomolgus monkeys were evaluated to provide reference information for clinical studies. Eighteen cynomolgus monkeys were randomly divided into three groups for single intravenous administration of 3, 30 mg/kg EH and normal saline, respectively. The changes of respiratory frequency, respiratory intensity, blood pressure and electrocardiogram before and after administration were recorded. In acute toxicity test, six cynomolgus monkeys were intravenously received EH at a single dose of 171, 257, 385, 578, 867 and 1300 mg/kg respectively. The vital signs, hematology, serum biochemistry, coagulation indexes and electrocardiogram indexes of the animals were determined before administration and on the 7th and 14th day after administration. As the results showed that there were no significant abnormal changes in respiratory frequency, respiratory intensity, blood pressure or electrocardiogram in cynomolgus monkeys after receiving EH at 3 mg/kg and 30 mg/kg, and there was no statistical difference between the treated groups and normal saline group. In the acute toxicity test, no significant abnormalities were observed in vital signs, hematology, serum biochemistry, coagulation indexes and electrocardiogram indexes of six cynomolgus monkeys at day 7 and 14 after EH administration. Furthermore, autopsies of all cynomolgus monkeys showed no abnormalities. The results of toxicokinetics showed that AUClast of the drug increased in proportion to the EH dose in the range of 171-578 mg/kg, and increased in over proportion to the EH dose in the range of 578-1300 mg/kg. The variation of Cmax was basically consistent with AUClast. In a sum, A single intravenous injection of 3 and 30 mg/kg of EH did not affect the circulatory system and respiratory system in cynomolgus monkeys and the maximum tolerated dose of EH in cynomolgus monkey is over 1300 mg/kg (equivalent to 619-1300 times of the proposed clinical equivalent dose).

Is the combination of linagliptin and allopurinol better prophylaxis against post-contrast acute kidney injury? A multicenter prospective randomized controlled study.

BACKGROUND: Patients with diabetic kidney disease (DKD) are at increased risk to develop post-contrast acute kidney injury (AKI). Diabetic patients under dipeptidyl peptidase 4 inhibitors (DPP4Is) experience a lower propensity to develop AKI. We speculated that linagliptin as a single agent or in combination with allopurinol may reduce the incidence of post-contrast AKI in stage 3-5 chronic kidney disease (CKD) patients with underlying DKD. METHODS: Out of 951 DKD patients eligible for this study, 800 accepted to sign informed consent. They were randomly allocated to 4 equal groups that received their prophylaxis for 2 days before and after radiocontrast. The first control group received N-acetyl cysteine and saline, the 2nd received allopurinol, the 3rd group received linagliptin, and the 4th received both allopurinol and linagliptin. Post-procedure follow-up for kidney functions was conducted for 2 weeks in all patients. RESULTS: 20, 19, 14, and 8 patients developed post-contrast AKI in groups 1 through 4, respectively. Neither linagliptin nor allopurinol was superior to N-acetyl cysteine and saline alone. However, the combination of the two agents provided statistically significant renal protection: post-contrast AKI in group 4 was significantly lower than in groups 1 and 2 (p < 0.02 and <0.03, respectively). None of the post-contrast AKI cases required dialysis. CONCLUSION: Linagliptin and allopurinol in combination may offer protection against post-contrast AKI in DKD exposed to radiocontrast. Further studies are needed to support this view. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT03470454.