Utilization of the evidence from studies with no events in meta-analyses of adverse events: An empirical investigation (Chinese translation) / 中国胸心血管外科临床杂志

@#Objective    Zero-events studies frequently occur in systematic reviews of adverse events, which consist of an important source of evidence. We aimed to examine how evidence of zero-events studies was utilized in the meta-analyses of systematic reviews of adverse events. Methods    We conducted a survey of systematic reviews published in two periods: January 1, 2015 to January 1, 2020 and January 1, 2008, to April 25, 2011. Databases were searched for systematic reviews that conducted at least one meta-analysis of any healthcare intervention and used adverse events as the exclusive outcome. An adverse event was defined as any untoward medical occurrence in a patient or subject in healthcare practice. We summarized the frequency of occurrence of zero-events studies in eligible systematic reviews and how these studies were dealt with in the meta-analyses of these systematic reviews. Results    We included 640 eligible systematic reviews. There were 406 (63.45%) systematic reviews involving zero-events studies in their meta-analyses, among which 389 (95.11%) involved single-arm-zero-events studies and 223 (54.93%) involved double-arm-zero-events studies. The majority (98.71%) of these systematic reviews incorporated single-arm-zero-events studies into the meta-analyses. On the other hand, the majority (76.23%) of them excluded double-arm-zero-events studies from the meta-analyses, of which the majority (87.06%) did not discuss the potential impact of excluding such studies. Systematic reviews published at present (2015-2020) tended to incorporate zero-events studies in meta-analyses than those published in the past (2008-2011), but the difference was not significant [proportion difference=–0.09, 95%CI (–0.21, 0.03), P=0.12]. Conclusion    Systematic review authors routinely treated studies with zero-events in both arms as "non-informative" carriers and excluded them from their reviews. Whether studies with no events are "informative" or not, largely depends on the methods and assumptions applied, thus sensitivity analyses using different methods should be considered in future meta-analyses.

The prognostic significance of dynamic monitoring of minimal residual disease (MRD) status in patients with newly-diagnosed multiple myeloma / 中华血液学杂志

Objective: To evaluate the prognostic value of kinetic changes in minimal residual disease (MRD) status, as well as its relationship with risk stratification, therapeutic response and treatment in patients with newly-diagnosed multiple myeloma (MM) . Methods: A total of 135 patients with newly-diagnosed MM were screened, and 105 patients who achieved VGPR or more as the best responses were included into this study. The MRD status was determined by multiparameter flow cytometry (MFC) at multiple intervals after two cycles of treatment until clinical relapse, death, or last follow-up. The statistical methods included Kaplan-Meier analysis, Cox regression, etc. Results: ①In all 135 patients, 57.8% (78/135) patients achieved MRD negativity (MRD(-)) after treatment. In 105 patients who achieved VGPR and thus included in this study, the MRD(-) rate was 72.4% (76/105) , with a median interval of 3 months from starting treatment to achievement of MRD(-) status. ②The 2-year PFS rate of patients with MRD(-) status was significantly higher than that of MRD(+) status (62.2% vs 41.3%, P=0.001) , while MRD persistence (MRD(+)) was an independent factor for poor prognosis (multivariate analysis for PFS: P=0.044, HR=3.039, 95%CI 1.029-8.974) . ③Loss of MRD(-) status (i.e., MRD reappearance) showed inferior outcomes compared with MRD sustained negative ones, the PFS was 18 months versus not reach (P<0.001) and the OS was not reach for both (P=0.002) . ④The 2-year PFS and OS rates of patients with duration of MRD(-)status≥12 months were significantly higher than those of the control group (PFS: 77.7% vs 36.7%, P<0.001; OS: 96.4% vs 57.9%, P<0.001 respectively) . Duration of MRD(-) status was associated with a marked reduction in risk of relapse or death (univariate analysis for PFS: P<0.001, HR=0.865, 95%CI 0.815-0.918; for OS: P=0.001, HR=0.850, 95%CI 0.741-0.915 respectively) . ⑤Moreover, even in patients carrying high-risk cytogenetic abnormalities (CA) or ineligible for ASCT, MRD negativity remained its prognostic value to predict PFS (high-risk CA medianPFS: not reach vs 19 months, P=0.006; ineligible for ASCT medianPFS: not reach vs 25 months, P=0.052 respectively) . ⑥Last, treatment with the bortezomib-based regimens contributed to prolonged MRD(-) duration (median MRD(-) duratio: 25 months vs 10 months, P=0.034) . Conclusion: Our findings supported MRD(+) status as an independent poor prognostic factor in MM patients, which implicated that duration of MRD(-) status also played a significant role in evaluation of prognosis, while loss of MRD(-)status might serve as an early biomarker for relapse. Therefore, monitoring of MRD kinetics might more precisely predict prognosis, as well as guide treatment decision, especially for when to start retreatment in relapsed patients.

Effect of 1q21 amplification on bortezomib therapeutic response and prognosis of newly diagnosed multiple myeloma patients / 中华血液学杂志

Objective: To investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients. Methods: A total of 180 newly diagnosed MM were included for analyses of clinical characteristics, cytogenetics, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), retrospectively. Gene expression profiling (GEP) was analyzed using publicly available R2 platform. Results: ① In 180 patients, 1q was found in 51.1% cases. Of them, 174 patients had complete follow-up data, including 88 cases with 1q and 86 without 1q (non-1q). ②Incidence of 1q was positively associated with percentage of IGH rearrangement (72.2%, P=0.017) and 1p deletion (1p) (27.8%, P=0.040). ③ The median PFS was 15.0 and 20.3 months for the 1q group and non-1q group, and the median OS was 29.4 and 44.0 months, respectively. Both PFS and OS of 1q group was significantly shorter than those of the non-1q group (P=0.029 and 0.038, respectively). Multivariate analysis further revealed that 1q was an independent prognostic factor for both PFS (HR=1.910, 95% CI 1.105-3.303, P=0.020) and OS (HR=2.353, 95% CI 1.090-5.078, P=0.029). ④ In 91 evaluable cases with 1q, very good partial remission (VGPR) rate was higher after treatment with Btz than those without Btz (62.1% vs 40.0%, P=0.032). Of note, the patients with 1q who received auto-HSCT after induction with Btz had significantly longer PFS than those without auto-HSCT (19 months vs 13 months, P=0.048). ⑤GEP analysis revealed that 1q21 amplification predominantly up-regulated expression of >50% genes within 1q21 region, and also altered expression of 28% genes in chromosome 1 and 10% genes in whole genome, particularly related to DNA repair and cell cycle. Conclusions: 1q is an independent adverse prognostic factor in patients with newly diagnosed MM. It is often associated with 1p deletion and IGH rearrangement. Patients with 1q respond well to Btz-based regimen, but they fail to gain long-term benefit from this treatment itself. However, auto-HSCT following Btz induction might improve survival of patients with 1q, suggesting a potential strategy to treat this high-risk subset of MM. GEP analysis warrants further attention in understanding the mechanisms underlying the high-risk of 1q.

Comparison of the effect between endoscopic thyroidectomy and open thyroidectomy in treatment of benign thyroid diseases / 新乡医学院学报

Objective To compare the clinical effect of endoscopic thyroidectomy and open thyroidectomy in the treat-ment of benign thyroid diseases. Methods A total of 120 patients with benign thyroid diseases were selected from March 2015 to June 2017 in the Third Affiliated Hospital of Xinxiang Medical University. The patients were divided into endoscopic opera-tion group(n = 62)and open operation group(n = 58)according to the treatment methods. The patients in the open operation group were treated with conventional open thyroidectomy,and the patients in the endoscopic operation group were treated with endoscopic thyroidectomy. The operation time,intraoperative bleeding volume,postoperative drainage volume and hospitalization time were recorded in the two groups;and the intraoperative and postoperative complications were observed. The pain of the pa-tients in the two groups was evaluated by visual analogue scale(VAS)at the time points of 6,12 and 24 hours after operation. The cosmetic satisfaction of the patients in the two groups was evaluated by numerical scoring system(NSS)at the time points of 1 and 3 months after operation. Results The operation time and hospitalization time in the endoscopic operation group were significantly shorter than those in the open operation group(P < 0. 05),and the intraoperative bleeding volume and postopera-tive drainage volume in the endoscopic operation group were significantly lower than those in the open operation group(P <0. 05). The VAS score of pain in the endoscopic operation group was significantly lower than that in the open operation group at the time points of 6,12 and 24 hours after operation(P < 0. 05). The NSS score in the endoscopic operation group was sig-nificantly higher than that in the open operation group at the time points of 1 and 3 months after operation(P < 0. 05). The in-cidence of complications in the endoscopic operation group and the open operation group was 12. 90％(8 / 62)and 39. 66％(23 / 58)respectively,the incidence of complications in the endoscopic operation group was significantly lower than that in the open operation group(χ2 = 11. 210,P < 0. 05). Conclusion Endoscopic thyroidectomy is reliable in the treatment of benign thyroid diseases. It has the advantages of small trauma,short operation time,quick recovery,light postoperative pain,small sur-gical scar and fewer complications and so on.

Effect of Low Frequency Repetitive Transcranial Magnetic Stimulation at Uninjured Side on Memory and Quality of Life in Patients with Traumatic Brain Injury / 中国康复理论与实践

@#Objective To observe the effect of low frequency repetitive transcranial magnetic stimulation at uninjured side on memory and quality of life in patients with traumatic brain injury. Methods From September, 2013 to June, 2015, 60 cases of memory impairment af-ter traumatic brain injury were randomly divided into control group (n=30) and observation group (n=30). The control group was given neu-rosurgical conventional treatment;the observation group was given low frequency repetitive transcranial magnetic stimulation in addition, for four weeks. The scores of Rivermead Behavior Memory Test (RBMT) and the World Health Organization Quality of Life-BREF (WHO-QOL-BREF) were observed before and after treatment in both groups. Results After treatment, there was no significant difference in the RBMT score in the control group (t=1.233, P=0.223);the RBMT score increased in the observation group (t=2.186, P=0.033);and there was no significant difference between two groups (t=1.133, P=0.262). After treatment, the WHOQOL-BREF score increased in physical health in the control group (t=5.606, P<0.001), while it increased in the physical, psychological health, and environment in the observation group (t>2.879, P<0.01), which were higher in the observation group than in the control group (t>2.095, P<0.05). There was no significant differ-ence in the social relationship between two groups (t=0.508, P=0.614). Conclusion Low frequency repetitive transcranial magnetic stimula-tion at uninjured side could improve the memory ability and quality of life for patients with traumatic brain injury.

Effect of Low Frequency Repetitive Transcranial Magnetic Stimulation at Uninjured Side on Memory and Quality of Life in Patients with Traumatic Brain Injury / 中国康复理论与实践

@#Objective To observe the effect of low frequency repetitive transcranial magnetic stimulation at uninjured side on memory and quality of life in patients with traumatic brain injury. Methods From September, 2013 to June, 2015, 60 cases of memory impairment af-ter traumatic brain injury were randomly divided into control group (n=30) and observation group (n=30). The control group was given neu-rosurgical conventional treatment;the observation group was given low frequency repetitive transcranial magnetic stimulation in addition, for four weeks. The scores of Rivermead Behavior Memory Test (RBMT) and the World Health Organization Quality of Life-BREF (WHO-QOL-BREF) were observed before and after treatment in both groups. Results After treatment, there was no significant difference in the RBMT score in the control group (t=1.233, P=0.223);the RBMT score increased in the observation group (t=2.186, P=0.033);and there was no significant difference between two groups (t=1.133, P=0.262). After treatment, the WHOQOL-BREF score increased in physical health in the control group (t=5.606, P<0.001), while it increased in the physical, psychological health, and environment in the observation group (t>2.879, P<0.01), which were higher in the observation group than in the control group (t>2.095, P<0.05). There was no significant differ-ence in the social relationship between two groups (t=0.508, P=0.614). Conclusion Low frequency repetitive transcranial magnetic stimula-tion at uninjured side could improve the memory ability and quality of life for patients with traumatic brain injury.

Effect of Gengnianchun Recipe on bone mineral density, bone biomechanical parameters and serum lipid level in ovariectomized rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effect of Gengnianchun Recipe (GNC) on bone mineral density (BMD), bone biomechanical parameters and serum lipid level in the bilaterally ovariectomized (OVX) rats and to explore the prophylactic and therapeutic action of GNC on ovariectomy induced osteoporosis and hyperlipidemia.</p><p><b>METHODS</b>OVX SD rats, 10 - 12 months old, were divided into different groups and fed with GNC 2 g/d, GNC 1 g/d and Nilestriol 0.125 mg/week, respectively for 4 months to observe the change of BMD and bone biomechanical parameters of the lumbar vertebrae, and the serum levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), and to compare the effect of the two drugs on the morphology of the uterus.</p><p><b>RESULTS</b>There was marked reduction in BMD and biomechanical parameters in lumbar vertebrae (P < 0.01) and increase of serum TC and LDL-C levels (P < 0.01) in rats after OVX. GNC or Nilestriol significantly improved the decreased BMD and biomechanical parameters of the lumbar vertebrae (P < 0.05 or P < 0.01), and reduced the serum TC and LDL-C levels (P < 0.01). In the Nilestriol group, the wet weight of uterus got increased obviously (P < 0.01), the number of uterine glands increased, uterine columnar epithelium thickened, and the mitotic figures in the epithelial stroma and myointimal cells augmented. But no such effect in wet weight and morphology of uterus was found in the GNC group.</p><p><b>CONCLUSION</b>GNC could increase the BMD and biomechanical parameters of the lumbar vertebrae, reduce the serum TC and LDL-C levels, yet produce no adverse reaction in stimulating proliferation and hypertrophy of uterus.</p>

Improvement of massive human islet isolation techniques and the evaluation of isolated human islets / 中华外科杂志

<p><b>OBJECTIVE</b>To obtain massive human pancreatic islets with modified techniques and evaluation of the islets for the clinical allo-transplantation to treat type I and II diabetes.</p><p><b>METHODS</b>28 consecutive adult human pancreata were isolated with modified automated techniques. Islets were purified using continuous density gradient. The islet yield was counted with international standard known as islet equivalent (IEQ). The function of the isolated islets was evaluated by measuring DNA/insulin ratio, static glucose stimulating test in vitro and transplanting the islets into diabetic nude mice in vivo followed by abdominal glucose tolerance test and C peptide measurement.</p><p><b>RESULTS</b>The yield of 28 consecutive human pancreata isolations ranged from 5 000 to 1 030 000 IEQs/pancreas with the average of 291 635 IEQs/pancreas. The first 13 isolations yielded 49 123 IEQs/pancreas, 846 IEQs/g and, purity 87% in average. The remained 15 isolations after the modifications yielded 501 813 IEQs/pancreas, 7 003 IEQs/g and purity 89% in average. The results of in vitro SGS showed good response to the different glucose concentration. 34 diabetic nude mice were transplanted under the renal capsule with the freshly isolated islets. 29 out of 34 diabetic mice obtained normoglycemia within 12 hours and the glucose tolerance tests were near normal. Serum C peptide level of transplanted mice is close to that of the control group.</p><p><b>CONCLUSIONS</b>Massive human islets can be isolated with the modified techniques. Quality assessment of these islets both in vitro and in vivo has indicated that these high quality human islets could be used for the clinical allogeneic islet transplantation.</p>