Abstract

This meta-analysis evaluated the efficacy and safety of infliximab as initial therapy for patients with Kawasaki disease (KD) and intravenous immunoglobulin (IVIG) resistant KD.Studies of infliximab in KD, published between January 2004 and December 2019, were curated from PubMed, MEDLINE, and Cochrane Library. Data were analyzed using STATA Version 12.0. Of the 8 studies considered, 4 evaluated the effect of infliximab combined with IVIG as primary therapy in KD, and the remaining investigated the effect of infliximab in IVIG resistant patients. Infliximab was more effective than the control group, with the total summary odds ratio (OR) of 0.34 (95% confidence interval (CI): 0.19-0.62). The treatment resistance of the infliximab group was lower than the IVIG group (0.36 [95% CI: 0.14-0.92]) when infliximab was combined with IVIG as the initial treatment. However, infliximab treatment for IVIG resistant KD was more effective than the IVIG group (0.28 [95% CI: 0.12-0.66]). There was no significant increase in the incidence of coronary artery lesions. The total summary OR for the incidence of coronary artery lesions and infliximab treatment was 0.88 (95% CI: 0.48-1.62). There was no statistically significant difference in adverse events (AEs) when compared between the groups (0.71 [95% CI: 0.44-1.16]).Infliximab combined with IVIG reduced treatment resistance in KD patients vs. conventional IVIG therapy. Infliximab improved clinical course in IVIG resistant KD patients. Infliximab treatment did not reduce the incidence of coronary artery lesions and did not show any significant increase in the incidence of AEs. PROSPERO REGISTRATION NUMBER CRD42020218554.

Abstract

Objective: This study aimed to identify the clinical features of Kawasaki disease shock syndrome (KDSS) in children. Methods: The case-control studies of KDSS and KD children up until April 30, 2021 were searched in multiple databases. The qualified research were retrieved by manually reviewing the references. Review Manager 5.3 software was used for statistical analysis. Results: The results showed that there was no significant difference in the incidence of male and female in children with KDSS. Children with KDSS compared with non-shocked KD, there were significant difference in age, duration of fever, white blood cell (WBC) count, percentage of neutrophils (NEUT%), platelet count (PLT), c-reactive protein level (CRP), alanine transaminase concentration (ALT), aspartate transaminase concentration (AST), albumin concentration (ALB), sodium concentration (Na), ejection fraction, and length of hospitalization as well as the incidence of coronary artery dilation, coronary artery aneurysm, left ventricular dysfunction, mitral regurgitation, pericardial effusion, initial diagnosis of KD, intravenous immunoglobulin (IVIG) resistance and receiving second dose of IVIG, vasoactive drugs, hormones, and albumin. In contrast, there was no difference in the hemoglobin concentration, erythrocyte sedimentation rate, and the incidence of conjunctival injection, oropharyngeal change, polymorphous rash, extremity change, and incomplete KD. Conclusion: Current evidence suggested that the children with KDSS had more severe indicators of inflammation and more cardiac abnormalities. These patients were resistant to immunoglobulin treatment and required extra anti-inflammatory treatment. Systematic Review Registration: PROSPERO registration number CRD42021241207.

Abstract

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are a new class of oral medicines being developed for the treatment of anemia in chronic kidney disease (CKD) patients. This study aimed to compare the efficacy and safety of HIF-PHI vs epoetin and darbepoetin in CKD patients with anemia not undergoing dialysis. The PubMed, Embase, Cochrane Library, Web of Science, and http://clinicaltrials.gov/ clinicaltrials.gov databases were searched from inception to October 2019 for randomized controlled trials investigating different agents (six HIF-PHIs, epoetin, darbepoetin, and placebo) for treating CKD patients with anemia that did not undergo dialysis. The outcomes included a change in hemoglobin (Hb) levels and all-cause mortality. A total of 19 studies were included. Compared with the placebo, except for vadadustat (mean differences: 1.12, 95% confidence interval [CI]: 0.11-2.35), the other drugs significantly increased Hb levels, with mean differences of 2.46 (95% CI: 0.933.99) for desidustat, 1.81 (0.872.75) for enarodustat, 1.68 (0.642.72) for molidustat, 1.66 (0.892.44) for epoetin, 1.63 (0.692.56) for darbepoetin, 1.61 (0.992.22) for roxadustat, and 1.55 (0.742.36) for daprodustat. No differences were found in the Hb level elevations among these eight drugs. Compared with the placebo, there also was no significant association between the drugs and all-cause mortality (molidustat of RR, 0.39 [95% CI, 0.062.59]; roxadustat, 0.40 (0.062.84); enarodustat, 0.33 (0.0116.25); desidustat, 0.34 (0.0117.00); epoetin, 0.50 (0.181.42); daprodustat, 0.54 (0.093.31); darbepoetin, 1.03 (0.651.65); and vadadustat, 1.43 (0.1513.27)). No differences were observed in the all-cause mortality among the drugs. In conclusion, these HIF-PHIs are effective and relatively tolerant for treating anemia patients with CKD not undergoing dialysis. Further research should consider the limitations of our study to evaluate the value of these HIF-PHIs in clinical settings.

Abstract

Objective: Daprodustat is a novel oral agent in treating anemia of chronic kidney disease (CKD), and several clinical trials have been conducted to compare daprodustat with recombinant human erythropoietin (rhEPO) or placebo. Our systematic review aimed to investigate the efficacy and safety of daprodustat for anemia treatment in both dialysis-dependent (DD) and non-dialysis-dependent (NDD) patients. Methods: Six databases were searched for randomized controlled trials (RCTs) reporting daprodustat vs. rhEPO or placebo for anemia patients in CKD. The outcome indicators were focused on hemoglobin (Hb), ferritin, transferrin saturation (TSAT), total iron-binding capacity (TIBC), vascular endothelial growth factor (VEGF), and serious adverse events (SAEs). Results: Eight eligible studies with 1,516 participants were included. For both NDD and DD patients, changes in Hb levels from baseline were significantly higher in daprodustat group than that in the placebo (mean difference (MD) = 1.73, [95% confidence interval (CI), 0.34 to 3.12], p = 0.01; MD = 1.88, [95% CI, 0.68 to 3.09], p = 0.002; respectively), and there was no significant difference between daprodustat and rhEPO group (MD = 0.05, [95% CI, -0.49 to 0.59], p = 0.86; MD = 0.12, [95% CI, -0.28 to 0.52], p = 0.55; respectively). The indexes of iron metabolism were improved significantly in the daprodustat group compared to placebo- or rhEPO-treated patients, while there was no similar change in terms of TSAT for DD patients. Furthermore, no trend of increasing plasma VEGF was observed in daprodustat-treated subjects. As for safety, there was no significant difference in the incidence of SAEs between daprodustat and placebo treatment, while the incidence of SAEs in the daprodustat group was significantly lower than that in the rhEPO group. Conclusion: Daprodustat was efficacious and well tolerated for anemia in both NDD and DD patients in the short term based on current RCTs. And daprodustat may become an effective alternative for treatment of anemia with CKD. Since the application of daprodustat is still under exploration, future researches should consider the limitations of our study to evaluate the value of daprodustat.

Abstract

Objective: To examine the blood protective effect of autologous platelet-rich plasma separation for cardiac valve replacement under cardiopulmonary bypass. Methods: Sixty patients who underwent cardiac valve replacement under cardiopulmonary bypass from August 2018 to May 2019 in Shanghai Chest Hospital, Shanghai Jiao Tong University were randomly divided into control and treatment groups(each 30 cases). There were 33 males and 27 females, aged (52.0±8.4) years (range: 35 to 65 years). Autologous platelet separation was performed in the treatment group after anaesthesia administration and was completed before systemic heparinisation. Platelet separation was not performed in the control group. The thromboelastogram, blood routine, blood coagulation, perioperative fluid infusion, allogeneic blood transfusion, postoperative pleural fluid volume and postoperative fibrinogen were recorded before the operation, and 1 hour and 24 hours post operation. The two groups' data was compared by t test, Kruskal-Wallis test, Mann-Whitney U test or χ(2) test. Repeated measurement analysis of variance was used to compare platelet and coagulation indexes at different times. Results: The perioperative red blood cell transfusion of 0, 1~2, 3~4,>4 units with 6, 11, 1, 12 cases in treatment group and 14, 8, 6, 2 cases in control group (Z=-2.516, P=0.012). The postoperative fibrinogen of 0, 1, 2 units with 19, 2, 9 cases in treat group and 26, 2, 2 cases in control group (Z=-2.190, P=0.029). There was no significant difference in the cost of blood transfusion between the two groups during admission ((1 732±1 275) yuan vs. (1 176±941) yuan; t=-1.570, P=0.125). Conclusion: The use of autologous platelet-rich plasma separation can reduce the amount of allogeneic blood transfusion during valvular surgery under cardiopulmonary bypass.

Abstract

BACKGROUND Tranexamic acid (TXA) has been widely used during on-pump coronary artery bypass graft (CABG) surgery owing to its antifibrinolytic effect. However, the efficacy and safety of TXA in off-pump CABG surgery remains unconfirmed, especially intravenous (IV) administration. OBJECTIVE The aim of this study was to evaluate the effectiveness and safety of IV administration of TXA in off-pump CABG settings. METHODS AND RESULTS A comprehensive literature search was performed to identify randomized controlled trials (RCTs) that compared IV use of TXA with placebo in the reduction of postoperative 24-hour blood transfusion, as well as postoperative death and thrombotic events. The combined estimations were compiled with a fixed-effects model or, if heterogeneity existed, a random-effects model. Funnel plots and Egger's test were used to assess potential publication bias. Subgroup analyses were used to explore possible sources of heterogeneity. In total, 12 RCTs met the inclusion criteria. IV administration of TXA significantly reduced the risk of packed red blood cell (PRBC) transfusion [risk ratio (RR) = 0.61, 95% confidence interval (CI) 0.503 to 0.756, P < .001, I2 = 0.0%) during the 24 hours after surgery. However, there was no statistical significance in platelet (RR = 0.613, 95% CI 0.112 to 3.348, P = .572, I2 = 0.0%) or total fresh frozen plasma (FFP) (RR = 0.511, 95% CI 0.246 to 1.063, P = .073, I2 = 0.0%) transfusion. Also, no significant difference was found in major adverse events (death or thrombotic complications) (RR = 0.917, 95% CI 0.532 to 1.581, P = .756, I2 = 0.0%) between the 2 groups. Interestingly, further subgroup analysis demonstrated that IV TXA decreased the risk of prothrombin time (PT)- and international normalized ratio (INR)-guided FFP transfusion (RR = 0.462, 95% CI 0.296 to 0.721, P = .001, I2 = 0.0%). CONCLUSION IV TXA was effective in reducing allogeneic blood component transfusion (PRBCs and PT- or INR-guided FFP transfusion), without increasing the incidence of postoperative death or thrombotic complications in off-pump CAB surgery.

Abstract

Background: Tranexamic acid (TXA) has been widely used during craniofacial and orthognathic surgery (OS). However, results of the literature are inconsistent due to specific type of surgery and a small sample of studies. The purpose of this study was to evaluate the role of TXA in bimaxillary OS. Methods: We performed a comprehensive literature search of PubMed, Cochrane Central Register of Controlled Trials, and EMBASE to identify randomized controlled trials (RCTs) that compared effect of TXA on bimaxillary OS with placebo. Outcomes of interests included intraoperative blood loss, allogenic transfusion, operation time, and volume of irrigation fluid. Random effects models were chosen considering that heterogeneity between studies was anticipated, and I (2) statistics were used to test for the presence of heterogeneity. Results: Totally 6 RCTs were identified. Tranexamic acid resulted in significantly reduced intraoperative blood loss (weighted mean difference [WMD] = -264.82 mL; 95% CI: -380.60 to -149.04 mL) and decreased amounts of irrigation fluid (WMD = -229.23 mL; 95% CI: -399.63 to -58.83 mL). However, TXA had no remarkable impact on risk of allogenic blood transfusion (pooled risk ratio = 0.50; 95% CI: 0.20-1.23), operation time (WMD = -8.71 min; 95% CI: -20.98 to 3.57 min), and length of hospital stay (WMD = -0.24 day; 95% CI: -0.62 to 0.14 day). No TXA-associated severe adverse reactions or complications were observed. Conclusions: Currently available meta-analysis reveals that TXA is effective in decreasing intraoperative blood loss; however, it does not reduce the risk of allogenic blood transfusion in bimaxillary OS.

Abstract

OBJECTIVE To explore the clinical value of early fluid resuscitation guided by passive leg-raising test (PLR) combined with transthoracic echocardiography (TTE) in patients with septic shock. METHODS A prospective randomized controlled trial (RCT) was conducted. Seventy-four patients with septic shock admitted to China-Japan Friendship Hospital from January 2017 to October 2018 were enrolled. The patients were randomly divided into control group and experimental group with 37 patients in each group. Both groups of patients were treated with broad-spectrum antibiotics empirically, while received fluid resuscitation via the subclavian vein catheter. The patients of control group were given rapid fluid replacement, and those of experimental group received fluid replacement according to result of PLR combined with TTE. The stroke volume (SV) was measured by TTE before and after PLR, volumetric response of patients was judged by stroke volume variation (SVV). If the SVV ≥ 15%, it was considered that there was a volume responsiveness, and fluid loading was given. If SVV < 15%, it was considered that there was no volume shortage, and the restrictive fluid replacement was given. The goal of fluid resuscitation in both groups were to simultaneously meet the central venous pressure (CVP) of 8-12 mmHg (1 mmHg = 0.133 kPa), mean arterial pressure (MAP) ≥ 65 mmHg, urine volume ≥ 0.5 mLxkg(-1)xh(-1), and central venous blood oxygen saturation (ScvO2) ≥ 0.70 within 6 hours. Vasoactive drugs were used when the patients could not achieve the treatment goals. The MAP, lactic acid (Lac), oxygenation index (PaO2/FiO2) and ScvO2 of the patients were determined at 6 hours of treatment, and serum C-reactive protein (CRP) and chest CT were reviewed at 48 hours of treatment, and compared with those before treatment. The total hospital stay and the mortality were recorded. RESULTS There was no significant difference in gender, age, body weight and etiological structure between the two groups, which indicated that the baseline data were generally balanced. There was no statistical difference in MAP, Lac, PaO2/FiO2, ScvO2 and CRP before infusion between the two groups. After 6 hours of treatment, the MAP, Lac, PaO2/FiO2 and ScvO2 of the two groups were all better than those before infusion. Except for the difference in MAP between the experimental group and the control group (mmHg: 78.76+/-5.22 vs. 76.35+/-6.66, P > 0.05), the other three parameters in the experimental group were significantly better than those in the control group [Lac (mmol/L): 2.52+/-1.15 vs. 3.89+/-1.42, PaO2/FiO2 (mmHg): 338.14+/-27.47 vs. 303.35+/-22.52, ScvO2: 0.70+/-0.04 vs. 0.63+/-0.05, all P < 0.01]. After 48 hours of treatment, CRP levels of both groups were lower than those before infusion, and the experimental group was better than the control group (mg/L: 110.12+/-39.80 vs. 137.98+/-31.23, P < 0.01). Chest CT showed that the incidence of pulmonary edema in the experimental group was significantly lower than that in the control group [13.5% (5/37) vs. 37.8% (14/37), P < 0.01]. The hospital stay of the experimental group was shorter than that of the control group (days: 21.47+/-5.58 vs. 28.33+/-4.93, P < 0.01), but no significant difference in mortality was found between the two groups [18.9% (7/37) vs. 18.9% (7/37), P > 0.05]. CONCLUSIONS Compared with the traditional rapid fluid replacement, early fluid resuscitation treatment strategies guided by the PLR combined with TTE, could better improve perfusion and oxygenation level of tissues and organs, avoid pulmonary edema caused by rapid fluid replacement, shorten the hospital stay in patients with septic shock, but had no significant effect on hospital mortality.

Abstract

Aim of the present work was to investigate the clinical efficacy of Kuntai capsule in the treatment of postmenopausal women with endometriosis, Breast pain and Vaginal Bleeding. 120 elderly female outpatients over 50 years old with Breast pain were randomly divided into control group (60 cases) and observation group (60 cases). All patients were given diclofenac sodium enteric-coated tablets 25mg, 3 times a day. The observation group was given additional Kuntai capsules at a dose of 4 capsules per time, 3 times a day. Serum estradiol (E2), follicle stimulating hormone (FSH), and luteinizing hormone (LH) were detected in all patients before and at 12 weeks after treatment. Modified Kupperman score (K score) for evaluating menopausal symptoms. The post therapeutic serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) level and endometrial thickness decreased significantly (p<0.05). After treatment, KMI scores of kunati group was significantly decreased compared with baseline (<0.01) and there was no significant difference between groups (p>0.05). After treatment, hot flush and insomnia scores were both improved significantly. After therapy, serum E2 level obviously higher than the control groups, while FSH and LH levels were obviously lower (p<0.05). The incidence of vaginal bleeding, breast distending pain in group was obviously higher in control group than Kuntai group. Thus, Kuntai capsule improved the ovarian function of patients, raised the level of estrogen in vivo and alleviates the clinical manifestations of Breast pain.

Abstract

The purpose of this study was to identify the clinical features and laboratory factors that are predictive of intravenous immunoglobulin (IVIG)-resistant Kawasaki disease. Multiple databases were searched for relevant studies on IVIG-resistant Kawasaki disease published from January 2002 to April 2017. Eligible studies were retrieved by manual review of the references. Stata 12 was used for the meta-analysis. Weighted mean differences and odds ratios with 95% confidence intervals were calculated for several indices. Twenty-eight studies involving 26,260 patients comprising 4442 IVIG-resistant Kawasaki disease patients and 21,818 IVIG-sensitive Kawasaki disease patients were included. The meta-analysis showed that the erythrocyte sedimentation rate (ESR) in the IVIG-resistant group was significantly higher than that in the IVIG-sensitive group, and that platelet count and hemoglobin levels were significantly lower in the IVIG-resistant group. The patients with oral mucosa alterations, cervical lymphadenopathy, swelling of the extremities, polymorphous rash, and initial administration of IVIG ≤ 4.0 days after the onset of symptoms were more likely to be IVIG resistant. CONCLUSION The initial administration of IVIG ≤ 4.0 days after the onset of symptoms increased ESR and decreased hemoglobin and platelet counts, oral mucosa alterations, cervical lymphadenopathy, swelling of the extremities, and polymorphous rash and are the risk factors for IVIG-resistant Kawasaki disease. What is Known: * Recent reports on this topic are about aspartate aminotransferase (AST), alanine aminotransferase (ALT), gammaglutamyl transferase, total bilirubin, white blood cells, platelets, erythrocyte sedimentation rate (ESR), polymorphonuclear leukocytes (PMN), C-reactive protein (CRP), pro-brain natriuretic peptide (BNP), albumin, and sodium as the risk factors in the IVIG-resistant Kawasaki disease; however, no studies have been published on clinical features as predictors of IVIG resistance. What is New: * This meta-analysis identified the clinical features, the initial administration of IVIG ≤ 4.0 days after the onset of symptoms, and much more comprehensive laboratory indicators, such as hemoglobin, as predictors of IVIG-resistant Kawasaki disease.