CsA Group Research Articles

Cyclosporine plus avatrombopag versus cyclosporine monotherapy for first-line treatment of elderly patients with transfusion-dependent non-severe aplastic anemia: a single center retrospective study

Background Elderly patients with transfusion-dependent non-severe aplastic anemia (TD-NSAA) face limited treatment options owing to transplantation incompatibility and safety concerns. Methods Data from older patients (≥60 years) newly diagnosed with TD-NSAA and had been treated with either avatrombopag (AVA) + cyclosporine (CsA) or CsA monotherapy at our center were retrospectively collected. Results In total, 52 patients were enrolled, with 26 receiving AVA + CsA and 26 receiving CsA monotherapy. The overall response (OR) rate was higher in the AVA + CsA group than in the CsA group at the 1st, 2nd, 3rd, 6th months, and at the end of the follow-up (all p < 0.05). The complete response (CR) rate was higher in the AVA + CsA group than in the CsA group at the 6th month and at the end of follow-up (p = 0.017 and 0.039). Patients receiving AVA + CsA had a shorter time to achieve the first response (p = 0.008) and CR (p = 0.010) than those receiving CsA monotherapy. Furthermore, patients receiving AVA + CsA exhibited a higher rate of platelet transfusion independence at the 3rd (p = 0.041), 6th (p = 0.008) months, and likewise at the end of the follow-up (p = 0.097). Conclusions The addition of AVA to CsA can significantly improve the OR or CR rate and platelet levels with acceptable side effects in elderly patients, which implies that the combination is a viable alternative for elderly patients with TD-NSAA.

Mass spectrometry of water-soluble vitamins to establish a risk model for predicting recurrent spontaneous abortion

The adverse pregnancy outcomes, including recurrent spontaneous abortion (RSA), are strongly correlated with water-soluble vitamins, but how to predict RSA occurrence using them remains unsatisfactory. This study aims to investigate the possibility of predicting RSA based on the baseline levels of water-soluble vitamins tested by ultra-liquid chromatography-tandem mass spectrometry. A total of 918 pregnant women was consecutively enrolled in this cross-sectional study. According to the miscarriage numbers, they were divided into normal first pregnancy (NFP, n = 608), once spontaneous abortion (OSA, n = 167), and continuous spontaneous abortion (CSA, n = 143) groups. The Cox proportional-hazards regression model was employed to establish a risk model for predicting RSA. The RSA occurrence was 6.54% in overall pregnant women, with a prevalence of 12.57% in the OSA group and 27.27% in the CSA group. Significant differences were observed in baseline deficiencies of vitamin B3, B5, B6, and B9 among NFP, OSA, and CSA groups (χ2 = 12.191 ~ 37.561, all P < 0.001). Among these vitamins, B9 (HR = 0.89 and 0.88, all P < 0.001) and B6 (HR = 0.83 and 0.78, all P < 0.05) were identified as independent factors in both the OSA and CSA groups; whereas B5 was identified as an additional independent factor only in the CSA group (HR = 0.93, P = 0.005). The Cox proportional-hazards model established using these three vitamins exhibited poor or satisfactory predictive performance in the OSA (Sen = 95.2%, Spe = 39.0%) and CSA (Sen = 92.3%, Spe = 60.6%) groups, respectively. However, B5, B6, and B9 compensatory levels were not associated with RSA occurrence (all P > 0.05). Our study presents a highly sensitive model based on mass spectrometry assay of baseline levels in B vitamins to predict the RSA occurrence as possible.

Treatment outcomes between cyclosporin and chemotherapy in adult subcutaneous panniculitis-like T-cell lymphoma: a report from nation-wide Thai lymphoma study group registry.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of T-cell lymphomas with a characteristic feature of subcutaneous nodules associated with hemophagocytic lymphohistiocytosis (HLH). Treatment options for SPTCL are mainly chemotherapy (CMT) or immunosuppressive agents with selection currently dependent on physician decisions. Outcomes between the 2 treatment remedies have not yet been comprehensively compared. This study aimed to compare complete remission (CR) rates between SPTCL patients receiving cyclosporin (CSA)-based regimen (CSA +/- steroid) and CMT. The 5-year overall survival (OS) and 5-year progression free survival (PFS) were also analyzed. Clinical data from patients with SPTCL were drawn from the Thai Lymphoma Study Group registry who were newly diagnosed between 2007 and 2023. A total of 93 patients were selected with 45 cases having received CSA-based regimen and 48 cases having received CMT. There were more patients with limited stage at skin in the CSA group (63.8% vs. 36.2%, p = 0.003), while more patients with hepato- and/or splenomegaly were found in the CMT group (56.2% vs. 24.5%; p = 0.002). Germline HAVCR2 mutations were detected in 26/33 (78.8%) cases. The CR rate was significantly higher in patients treated with CSA (87% vs. 58.3%; OR = 6.5 [95%CI, 2.7-15.3]; p = 0.002). At a median follow-up of 87.8 months (range 0-185), the 5-year OS (98% vs. 87%, p = 0.19) and PFS (72.4% vs. 69.2%, p = 0.19) showed a trend favoring patients treated with CSA. Based on our study, CSA-based regimens are the preferred first-line treatment remedy for newly diagnosed SPTCL, especially in patients with limited cutaneous involvement.

Acute and chronic ocular outcomes in SJS/TEN patients treated with oral ciclosporin vs intravenous immunoglobulin.

To evaluate differences in ocular complications of Stevens Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN) patients receiving either systemic IVIG or Ciclosporin (CsA) as initial treatments. Retrospective review of consecutive patients admitted for SJS/TEN at the Singapore General Hospital (SGH) from 2011 to 2017 who received either IVIG or Ciclosporin at the onset of the disease and had ophthalmological follow-up of at least 6 months were included. Acute ocular severity of SJS/TEN was graded using the Gregory grading score; chronic ocular complications were graded using the Sotozono system. A total of 18 subjects were included for analysis, with eight in the IVIG group and 10 in the CsA group. There were no significant differences in acute Gregory severity grading between the two groups. The CsA group had a trend towards worse overall chronic Sotozono grading scores compared to the IVIG group (median [IQR]: 2 [0-3] vs. 1 [0-6.5], p = 0.27), with a higher incidence of acute severe cornea involvement (60% vs. 25%, p = 0.93) and chronic corneal and eyelid involvement in the former than the latter. SJS/TEN patients with worse acute ocular involvement were more likely to have TEN and perianal mucosal involvement (50% vs. 0, p = 0.01). Compared to those who received IVIG, SJS/TEN patients who received CsA at the acute disease stage, seemed to have worse acute corneal and chronic corneal and eyelid complications. Larger studies are needed to confirm this finding.

Structural integrity assessment of CANDU pressure tubes using Sobol indices for global sensitivity analysis

CANDU11CANDU is a registered trademark of Atomic Energy of Canada Limited. reactors are a channel-type design where up to 480 zirconium alloy pressure tubes (PTs) act as the reactor pressure boundary. Fitness-for-service standards such as CSA N285.8 (CSA Group, 2015) have been established to prescribe the requirements of pressure tube evaluations to maintain their integrity throughout their lifetime. Probabilistic leak-before-break (LBB) assessments can be used in evaluations to demonstrate that the likelihood of a flaw growing past the stability point while undetected (or before a safe shutdown can be achieved) is below regulatory limits. The assessments typically require a ranking of model parameters based on their influence. The ranking process traditionally uses expert judgment and local sensitivity analysis methods. There has been recent interest in implementing global methods for LBB assessments as they can manage large numbers of variables and extensive sampling spaces. However, their adoption is hindered by the computational cost of the models involved.The current study proposes a method for performing global sensitivity parameter rankings during probabilistic LBB assessments. The study is the continuation of the CANDU nuclear power plant (NPP) pressure tube (PT) case study in El Bouzidi et al., (2024) where a probabilistic approach was implemented in RAVEN (Rabiti and Alfonsi, 2019) to estimate whether the probability of unstable crack growth in PTs is within acceptable limits. This follow-up work proposes surrogate modeling using a high-dimensional model representation to derive Sobol indices and establish a parameter influence ranking. The methodology is demonstrated in a Monte Carlo simulation campaign of a pressure tube inlet rolled joint. The implemented approach successfully identified and quantified critical parameters of the model while efficiently ranking and quantifying the interactions between input variables.

Critical shoulder angle and acromial index do not influence functional outcomes after repair of massive rotator cuff tears

ObjectivesCritical shoulder angle (CSA) and acromial index (AI) are two radiographic signs that can influence the risk of rotator cuff tears and the outcomes of repair. The purpose of this study was to determine the influence of CSA and AI on massive cuff tears and on the functional outcomes after repair. The hypothesis was that CSA and AI would be higher in posterosuperior compared to anterosuperior tears. MethodsCSA and AI were retrospectively measured on radiographs of patients who underwent repair of two rotator cuff tendons. Functional outcomes were evaluated using the American Shoulder and Elbow Surgeons (ASES) score and Simple Shoulder Test (SST) at least six months postoperatively. Patients were divided according to the tendons repaired into anterosuperior group and posterosuperior group. Radiographic measurements and functional outcomes were compared. Patients in the posterosuperior group were subdivided into low or high CSA (cut-off value ​= ​39), and into low or high AI (cut-off value ​= ​0.75). All available preoperative magnetic resonance images were reviewed and graded according to Goutallier classification. Multivariate analysis was used to determine the influence of CSA, AI and Goutallier grade on functional outcomes. ResultsEighty six patients were included. Both CSA and AI were statistically significantly higher in the posterosuperior group (p ​= ​0.0143 and 0.0052, respectively). After a mean follow-up of 33 months, ASES and SST were significantly better in patients with Goutallier grades 0–1 than grades>1 (multivariate p ​= ​0.03 and 0.009, respectively). No statistically significant differences were found between low and high CSA and AI groups in terms of functional outcomes of the posterosuperior group after repair (multivariate p ​= ​0.9). ConclusionHigher CSA and AI seem to increase the risk of posterosuperior more than anterosuperior rotator cuff tears. Neither of these radiographic parameters influenced the functional outcomes of massive posterosuperior tears after repair. Level of evidenceLevel III.

Tacrolimus versus cyclosporine a combined with post-transplantation cyclophosphamide for AML In first complete remission: a study from the acute leukemia working party (EBMT)

Choice of calcineurin inhibitor may impact the outcome of patients undergoing T-cell replete hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PT-Cy) and mycophenolate mofetil (MMF) for prophylaxis of graft-versus-host disease (GVHD). We retrospectively analyzed 2427 patients with acute myeloid leukemia (AML) in first remission transplanted from a haploidentical (n = 1844) or unrelated donor (UD, n = 583) using cyclosporine A (CSA, 63%) or tacrolimus (TAC, 37%) and PT-Cy/MMF. In univariate analysis, CSA and TAC groups did not differ in 2-year leukemia-free or overall survival, cumulative incidence (CI) of relapse or non-relapse mortality. CI of severe grade III-IV acute GVHD was lower with TAC (6.6% vs. 9.1%, p = 0.02), without difference in grade II-IV acute GVHD or grade III-IV acute GVHD/severe chronic GVHD, relapse-free survival (GRFS). In multivariate analysis, TAC was associated with a lower risk of severe grade III-IV acute GVHD solely with haploidentical donors (HR 0.64 [95% CI, 0.42–0.98], p = 0.04), but not UD (HR 0.49 [95% CI, 0.2–1.21], p = 0.12). There was no significant difference for chronic GVHD. In conclusion, PT-Cy/MMF-based GVHD prophylaxis resulted in favorable OS and GRFS, irrespective of the CNI added. In haploidentical HCT, TAC seemed to prevent severe acute GVHD more effectively than CSA without impact on other outcome parameters.

A novel approach to induce early remission in high-risk primary membranous nephropathy.

This prospective single-arm trial with historic controls evaluated the efficacy and safety of treatment based on a combination of rituximab, intravenous cyclophosphamide, and corticosteroids (RCP) administered at lower cumulative doses for the induction of early remission in primary membranous nephropathy (PMN). We prospectively enrolled 30 high-risk PMN patients with persistent nephrotic syndrome (NS) and elevated antibodies to the phospholipase A2 receptor who underwent RCP therapy. We compared the effectiveness of RCP with that of historic controls who received rituximab-based therapy (RTX, n=15) or cyclosporine+corticosteroids (CSA, n=42). The primary outcomes were complete remission (CR) and overall remission (OR) by month 12 and the time to remission. In the RCP group, the OR and CR rates by 12 months (97% and 60%) were higher than those in the RTX group (60% and 7%, P≤0.009) and the CSA group (50% and 24%, P≤0.003). The median time to OR (2.8 (1.6-3.9) months) was shorter compared to RTX (7.1 (3.4-17.5) months, P=0.008) and CSA (7.3 (6.0-13.6) months, P<0.001). In adjusted Cox regression, hazard ratios for OR and CR attainment for RCP versus other treatments were 5.2 (95% CI: 2.8-9.6) and 4.8 (95% CI: 2.2-10.3), respectively. Propensity score-matched group analyses confirmed these results. One serious adverse event occurred in the RCP group in the follow-up of 56 patient-years. RCP therapy is considered effective and safe for inducing early remission in high-risk PMN patients.

Evaluation of adjuvant role of topical cyclosporine 1% in acute Stevens-Johnson syndrome: a randomised control trial

PurposeTo evaluate the role of topical cyclosporine A 1% (CsA) as an adjuvant therapy in patients with acute Stevens-Johnson syndrome (SJS).MethodsThis is a randomised controlled trial in which 44 patients...

#2427 A multi-targeted treatment approach to induce early remission in high-risk primary membranous nephropathy

Abstract Background and Aims A considerable proportion of primary membranous nephropathy (PMN) patients do not achieve early clinical remission with current immunosuppression regimens. The goal of the study was to evaluate efficacy and safety of the multi-targeted treatment regimen including rituximab, cyclophosphamide, and corticosteroids (all administered at low cumulative doses) (RCP) in PMN with antibodies to the phospholipase A2 receptor (anti-PLA2R). Method The study enrolled 30 high- or very-high risk PMN patients with persistent nephrotic syndrome (NS) and elevated anti-PLA2R in a prospective single-arm study of RCP treatment. The experimental protocol consisted of a single intravenous infusion of RTX (375 mg/m2) and methylprednisolone (500 mg), followed by oral prednisolone (1 mg/kg) tapered rapidly at 10 mg per week and discontinued at week 49. An additional RTX infusion at the same dose was given during weeks 8-12, 20-24, and 32-36 if complete remission was not achieved and peripheral CD19+ cell exceeded 5 cells/μl. Four intravenous infusions of CYC were administered at a dose of 7.5 mg/kg every other week, in weeks 1, 3, 5, and 7. The effectiveness of RCP was compared to that of historic controls who received either rituximab-based therapy (RTX, n = 15) or cyclosporine+corticosteroids (CSA, n = 42). The primary outcomes measured were complete clinical remission (CR), overall remission (OR, which combines complete and partial remission) at month 12 after treatment initiation, and the time to clinical remission. Cox regression models were used to analyse the effect of RCP therapy on the probability of remission. Furthermore, we conducted comparative time-to-remission analyses in the RCP group and controls after propensity score (PS) matching. Results The RCP group exhibited higher OR and CR rates at 12 months (97% and 60%) compared to the RTX group (60% and 7%, P≤0.009) and the CSA group (50% and 24%, P≤0.003) (Fig. 1A,B). The median time to OR was shorter in the RCP group (2.8 (1.6–3.9) months) than in the RTX group (7.1 (3.4–17.5) months, P = 0.008) and the CSA group (7.3 (6.0–13.6) months, P &amp;lt; 0.001) (Fig. 1A). In the adjusted Cox regression, the hazard ratios for OR and CR attainment for RCP compared to other treatments were 5.2 (95% CI: 2.8–9.6) and 4.8 (95% CI: 2.2–10.3), respectively. These results were confirmed by comparative analyses of propensity score-matched groups. Only one serious adverse event (SAE) occurred in the RCP group during the 56 patient-year follow-up. Conclusion RCP therapy is considered effective and safe for inducing early remission in high-risk PMN patients.

Ginkgo biloba supplement modulates mTOR/ERK1/2 activities to mediate cardio-protection in cyclosporin-A-induced cardiotoxicity in Wistar rats

BackgroundCyclosporine-A (Cs-A), an immunosuppressant drug indicated for organ transplant patients has been associated with toxicities arising from activation of pathological signalling. Meanwhile Ginkgo biloba supplement (GBS) is an antioxidant-enhancing herbal product widely used for treating neurological and vascular dysfunctions. ObjectivesThis study investigated the ameliorative effect of GBS on cyclosporine-A induced cardiotoxicity in Wistar rats. MethodsThe study included 20 Wistar rats (n = 5) and they were treated as follows: group 1 received distilled water (10 mL/kg), group 2 received Cs-A (25 mg/kg), group 3 received GBS (50 mg/kg) and group 4 received Cs-A (25 mg/kg) and GBS (50 mg/kg). All treatment were done intraperitoneal for 14 days and thereafter, animals were euthanised and heart tissues were harvested for biochemical assays as well as immunohistochemical studies. Blood was also collected for serum biochemical studies. ResultsOur results revealed that GBS reduces Cs-A induced increase of AST, ALT, ALP, LDH, and GGT levels in serum relative to Cs-A group. Also, increased oxido-nitrergic markers like MDA, NO, together with elevated concentrations of cholesterol, triglycerides, LDL, creatine kinase-MB, troponin-I, as well as pro-inflammatory cytokines (IL-6, and TNF-α) and heart weight index were reduced by GBS. The Cs-A induced suppression of low-density lipoprotein, antioxidant (GSH, SOD, CAT), Na-K ATPase activities and antiapoptotic element, Bcl-2 were increased by GBS. Additionally, signalling pathways including ERK1/2, and mTOR as well as ventricular thickness were significantly alleviated by GBS treatment. ConclusionThe findings suggest that GBS ameliorated Cs-A-induced cardiotoxicity by activating mTOR/ERK1/2 signalling pathways.

Induced pluripotent stem cell-derived vascular smooth muscle cells as an in vitro model of coronary spastic angina

Abstract Background Coronary spastic angina (CSA), also known as Prinzmetal’s variant angina, is a form of angina caused by coronary artery spasm. CSA is characterized by enhanced basal tone of coronary artery smooth muscle and hyperreactivity to vasoconstrictor stimuli. The vascular smooth muscle hyperreactivity is likely due to a post-receptorial cellular abnormality in the regulation of myofibril contraction, suggesting the possibility of multiple stimuli acting on various cellular receptors. However, its detailed mechanism is still unclear. To investigate it, various experiments using coronary artery smooth muscle cells obtained from the CSA patients is preferable, but it is impossible to do it clinically and ethically. Purpose The purpose of this study was to establish induced pluripotent stem cell (iPSC)-derived vascular smooth muscle cells (VSMCs) and to characterize this VSMC model for CSA research. Methods Three CSA patients with ST-segment elevation, which is a characteristic of variant angina, were recruited for this study. The isolated skin fibroblasts or peripheral blood mononuclear cells were reprogrammed into iPSCs through electroporation of episomal plasmids encoding the reprogramming genes OCT3/4, SOX2, KLF4, L-MYC, LIN28, and mouse p53DD. We differentiated mesodermal using Glycogen synthase kinase 3 inhibition and Bone morphogenetic protein 4 treatment from iPSCs and resulted in the differentiation of VSMCs by platelet-derived growth factor-BB and Activin A. The differentiation of VSMCs was confirmed by VSMC-specific gene expression in qRT–PCR and fluorescence-activated cell sorting (FACS). We examined biological features and intracellular calcium response to acetylcholine (ACh) in VSMCs obtained from 3 CSA patients and 3 healthy controls. Intracellular free Ca2+ concentration ([Ca2+]i; nM) was measured by fura-2. Results CSA iPSCs were confirmed to have normal karyotypes and pluripotency to differentiate. FACS showed that VSMCs differentiated from iPSCs exhibited smooth muscle cell marker expressions including alpha-smooth muscle actin and SM22-alpha. qRT–PCR showed that VSMCs from iPSCs had expressions of ACTA2 and TAGLN gene similar to the human coronary artery smooth muscle cells. Differentiation induction rate of VSMCs differentiated from iPSCs between CSA and control did not show significant difference. [Ca2+]i at baseline did not differ significantly between them (143 nM in CSA versus 120 nM in control, p=0.63, n=3), but peak increase in [Ca2+]i from baseline after ACh stimulation was significantly increased in CSA group compared with control (372 nM versus 177 nM, p&amp;lt;0.05, n=3). Conclusions iPSC-derived VSMCs obtained from CSA patients showed an enhanced intracellular calcium response to ACh, which is likely responsible for CSA phenotype. Our iPSC-derived VSMC model can be useful for elucidating the mechanism of coronary spasm and developing therapeutic strategy such as drug efficacy.

Standard Practice

Manufacturers need to ready themselves – and their product lines – for the new edition of the IEC 62368-1 safety standard, says CSA Group.

Alternative treatment modality for severe aplastic anemia in a resource-limited setting: a single-institution prospective cohort study from Upper Egypt

This study compared the efficacy and safety of CsA monotherapy with eltrombopag (E-PAG) + CsA combined treatment in children with severe aplastic anemia (SAA). The study including 30 children had SAA. Ten were a retrospective cohort treated with CsA monotherapy. The other 20 were prospective cohort received E-PAG + CsA. All patients were evaluated for partial (PR) and complete (CR) hematological response at 3, 6, and 12 months. overall response (OR), overall survival rates (OS), and treatment safety. OR for the E-PAG patients was 40% after 3 months of therapy. At 6 months, this had increased to 75% with significantly higher CR rate (40%) than in the CsA group (p = 0.0001). After a year of treatment, the CR for the E-PAG + CsA regimen had increased to 50% and the OR to 85%, compared to 20% in the CsA group (p = 0.0001). The OS at 12 months was 100% in the E-PAG+ CsA group compared to 80% in the CsA cohort. At 24 months, the OS in the E-PAG + CsA group was 90%. In conclusion, E-PAG+ CsA was found to be a safe and effective alternative treatment for children with SAA particularly in countries with limited resources.

Efficacy of chemotherapy combined with surgical resection for gastric cancer with synchronous ovarian metastasis: A propensity score matching analysis.

Ovarian metastasis from gastric cancer (GC) is characterized by aggressive biological behavior and poor outcome. Currently, there is no standard treatment mode for such patients. Thus, we evaluated the efficacy of conversion therapy in patients with synchronous ovarian metastasis from GC in this study. About 219 GC patients with ovarian metastasis in 2011-2020 were enrolled. Two groups were established based on the different treatment: the conversion therapy group (chemotherapy combined with surgical resection, CS group) and the non-conversion therapy group (NCS group). Propensity score matching (PSM) was used to analyze the efficacy of different treatment modes on the prognosis of these patients. Ninety-two patients were included according to PSM results, with 46 patients each in CS and NCS groups. The median overall survival (OS) in the CS group was notably better than that in the NCS group (p < 0.001). Twenty-six patients (56.52%) in the CS group achieved R0 resection, and they had a better prognosis (p = 0.003). Compared with patients who underwent simultaneous gastrectomy and ovarian metastasectomy (CSb group), those who underwent ovarian metastasectomy before systemic chemotherapy (CSa group) had a higher R0 resection rate (p = 0.016) and longer survival time (p = 0.002). A total of 38 patients (41.30%) across both groups received hyperthermic intraperitoneal chemotherapy (HIPEC), and these patients had a better survival (p = 0.043). The conversion therapy is safe and effective for patients with synchronous ovarian metastasis from GC and can improve their prognosis. However, our results need to be confirmed by more randomized controlled clinical studies.

Effect of continuous spinal anesthesia on the hemodynamics of labor analgesia in hypertensive pregnant women: a comparative, randomized clinical trial

BackgroundTo observe the changes in hemodynamic, stress and inflammatory responses during labor and their labor outcomes after continuous spinal anesthesia labor analgesia for hypertensive pregnant women, and to evaluate whether the continuous spinal anesthesia had any advantages compared to continuous epidural analgesia for hypertensive pregnant women and their newborns.MethodsA total of 160 hypertensive pregnant women were selected and randomly divided into continuous spinal anesthesia analgesia group (CSA group) and continuous epidural analgesia group (EA group). Participant age, height, weight and gestational week were recorded; MAP, VAS score, CO and SVR were recorded after the onset of regular uterine contractions (T0), 10 min after analgesia (T1), 30 min (T2), 60 min (T3), when the uterine opening was complete (T4) and when the fetus was delivered (T5); the duration of the first stage of labor and the second stage of labor were recorded; the number of cases of treatment with oxytocin and antihypertensive therapy, mode of delivery, eclampsia and postpartum hemorrhage were counted; pregnant women Bromage scores were recorded at T2. We also recorded neonatal weight, Apgar scores at 1, 5 and 10 min after birth; arterial blood gas analysis of the umbilical cord was performed in newborns; finally, TNF-α, IL-6, and cortisol in pregnant women venous blood were measured at T0, T5, and 24 h after delivery (T7). The number of successful compressions and the total drug dosage administered by the analgesic pump were recorded for both groups.ResultsThe first stage of labor in CSA was longer than EA (P < 0.05); the MAP, VAS and SVR value in CSA were lower than EA group at T1, T3 and T4 (P < 0.05); in contrast, the CO in CSA at T3 and T4 was higher than in EA (P < 0.05). The oxytocin was more often used whereas the antihypertensive drugs were less used in CSA as compared to EA. The level of TNF-α, IL-6, Cor in the CSA at T5 was lower than the EA group (P < 0.05), and the level of TNF-α in the CSA group at T7 was lower than the EA group (P < 0.05).ConclusionFor pregnant women with hypertension during pregnancy, continuous spinal anesthesia labor analgesia has no significant effect on the final mode of delivery, but shows precise analgesic effect and stabilizes circulatory system, it is recommended to perform continuous spinal anesthesia early in labor for hypertensive pregnant women, which can effectively reduce the stress reaction.Trial registrationChiCTR-INR-17012659.Date of registration: 13/09/2017.

Comparison of the effectiveness of cyclosporine and tacrolimus in preventing acute rejection and their effects on kidney functions.

The aim of this study is to compare the effects of cyclosporine (CsA) and tacrolimus (TAC) on preventing acute rejection and analyze the side-effect profiles of both agents, particularly on kidney functions. In our study, 71 patients who underwent heart transplantation were included. For maintenance immunosuppression, 28 of these patients were treated with mycophenolate mofetil (MMF), steroid, and steroid CsA, and 43 of them were treated with MMF steroid and TAC. Endomyocardial biopsy results of the patients in the first month and the first year were compared. In the follow-ups, creatinine values and other parameters were recorded. Endomyocardial biopsy (EMB) performed at 1 month showed no rejection in 12 patients (42.9%) in the CsA group, grade 1R rejection in 15 patients (53.6%), and grade 2R rejection in one patient (3.6%). In the TAC group, rejection was not detected in 25 patients (58.1%), while grade 1R rejection was diagnosed in 17 patients (39.5%) and grade 2R rejection in 1 patient (2.3%) (p=0.4). In EMBs performed in the first year, 14 patients (51.9%) in the CsA group did not have rejection, 12 patients (44.4%) had grade 1R rejection, and one patient (3.7%) had grade 2R rejection. In the TAC group, grade 0R rejection was diagnosed in 23 patients (60.5%), grade 1R rejection in 15 patients (39.5%), and grade 2R rejection was not detected. Postoperative first-week creatinine values, which were found to be higher in the CsA group, were significant compared to the TAC group (p=0.028). TAC and CsA are drugs that help prevent acute rejection after heart transplantation and can be used safely in heart transplant recipients. Neither drug is superior to the other in preventing rejection. TAC may be preferred to CsA as it has fewer negative effects on kidney functions in the early postoperative period.

Impact of Topical Cyclosporine-A or Topical Chloroquine on Post-LASIK Ocular Surface Stability- A Randomized Controlled Trial

Purpose To compare effect of topical cyclosporine-A 0.05% (CsA) and chloroquine phosphate 0.03% (CHQ) as an adjunct to standard therapy in maintaining post-laser assisted in situ keratomileusis (LASIK) ocular surface stability Methods Randomized controlled trial on 100 eyes undergoing femtosecond-LASIK randomized into three groups- 33 eyes in Group I (Standard Treatment group), 34 eyes in Group II (CsA group) and 33 eyes in Group III (CHQ group). Standard treatment included topical moxifloxacin, topical prednisolone and carboxymethyl cellulose. Group II received topical CsA 0.05% twice daily for three months and group III received topical CHQ 0.03% twice daily for three months in addition to standard treatment. Primary outcome measure was change in ocular surface disease index (OSDI) at 6 months. Secondary outcome measures were tear break up time (TBUT), Schirmer-I score, tear film osmolarity, tear film MMP-9 and visual acuity. Follow up was performed at postoperative 1, 3 and 6 months. Results At 6 months, OSDI score, MMP-9, tear osmolarity, TBUT and Schirmer score were significantly better in both CsA and CHQ groups as compared with controls (p < 0.001). OSDI, Tear osmolarity, TBUT, MMP-9 levels were comparable in CsA and CHQ group (p > 0.05). In CsA group, tear film MMP-9 levels at 6 months were comparable to preoperative baseline (p = 0.09). There was no significant change in the Schirmer score from baseline in the CsA group; in addition, the Schirmer score was significantly better than the CHQ group at 6 months (p = 0.02). Visual acuity was comparable in all three groups. Adverse effects including burning sensation, stinging, pain and redness were reported by ten patients (CsA group- 3, CHQ group-7; p = 0.28). Conclusion Both CsA and CHQ are useful adjuncts to standard therapy in maintaining ocular surface stability after refractive surgery. Cyclosporine A has more potent and sustained anti-inflammatory effect with less ocular irritative effects.

Effects of Quercetin-3-O-β-D-Glucuronide on Platelet Apoptosis and Activation in Mice with Immune-Mediated Bone Marrow Failure via PI3K/AKT Pathway

To investigate the effect of quercetin-3-O-β-D-glucuronide(QG) on platelet apoptosis and activation in mice with immune-mediated bone marrow failure via PI3K/AKT pathway. An immune-mediated bone marrow failure mice model was established and forty C57BL/6 mice were randomly assigned into 4 groups: normal group, model group,cyclosporine (CsA) group and QG group, with 10 mice in each group.The mice in CsA group were intragastrically administered with 0.027 g/kg CsA daily and the mice in QG group were intragastrically administered with 0.2 g/kg QG daily, while the mice in the normal group and model group were intragastrically administered with normal saline, respectively. After three days of modeling, the mice were euthanized, and the blood was collected through the tail vein. Part of the blood was used for blood routine examination, and the other part was used to prepare washed platelets. Some of the prepared washed platelets were used to detect the expressions of BAX, BAD, caspase-9, phosphatidylserine (PS), platelet activated complex-1 (PAC-1) and P-selectin by flow cytometry; some of washed platelets was used to determine the protein contents of PI3K, p-PI3k, AKT and p-AKT by Western blot; the other part of the washed platelets was used to measure the expressions of PI3K mRNA and AKT mRNA by real-time quantitative PCR (RT-qPCR). In the model group, the absolute platelet count of the mice was significantly decreased, and the levels of BAX, BAD, caspase-9, PS, PAC-1, and P-selectin in the washed platelets were significantly increased, compared to the normal group (P<0.05). At the same time, the expression levels of PI3K, p-PI3K, AKT, p-AKT proteins and PI3K mRNA, AKT mRNA in model group were significantly reduced, compared to the normal group (P<0.05). In the CsA group and QG group, the expression levels of BAX, BAD, caspase-9, PS, PAC-1, and P-selectin in the washed platelets were significantly reduced (P<0.05), while the levels of PI3K, p-PI3K, AKT, p-AKT and PI3K mRNA, AKT mRNA were significantly increased, compared to the model group (P<0.05). QG can reduce platelet apoptosis in mice with immune-mediated bone marrow failure, and activation of some platelets is involved, which may be related to the regulation of PI3K/AKT pathway.

Pomegranate attenuates kidney injury in cyclosporine-induced nephrotoxicity in rats by suppressing oxidative stress

Abstract To investigate the effect of pomegranate juice (PJ) on the cyclosporine (CsA)-induced nephrotoxicity in rats, 80 rats were divided into four groups. The first group was regarded a negative control group, and the others were as follows: group 2 (CsA group) received CsA in a dose of 25 mg/kg/day orally, group 3 (treated group) received CsA in a dose of 25 mg/kg/day plus 2.5 mL/day of PJ, and group 4 (PJ group) received 2.5 mL of PJ daily. By the end of the 21st day, plasma creatinine, blood urea nitrogen (BUN), creatinine clearance, urinary KIM-1, and NGAL were determined. Histopathological investigation and the determination of malondialdehyde and antioxidant enzymes were analyzed in kidney tissues. The results show that plasma creatinine, BUN, creatinine clearance, and kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin were significantly altered in the CsA group. The supplement of PJ attenuated the alteration in these parameters. The treatment with PJ also prohibits the CsA-induced alteration in the histopathology, lipid peroxidation, and antioxidant enzymes. We can conclude that PJ protects against CsA-induced nephrotoxicity due to its antioxidant effects.