Current treatment paradigm and survival outcomes among patients with newly diagnosed multiple myeloma in China:a retrospective multicenter study

Objective:Evidence on the prognostic value of autologous stem cell transplantation(ASCT)and minimal residual disease(MRD)dynamics of patients with newly diagnosed multiple myeloma(NDMM)in China is limited.Our objective in the current study was to understand the current care paradigm and outcomes of these patients.Methods:This longitudinal cohort study used historical data from three top-tier hematologic disease care hospitals that contributed to the National Longitudinal Cohort of Hematological Diseases-Multiple Myeloma.Treatment regimens[proteasome inhibitor(PI)-,immunomodulatory drug(IMiD)-,PI+IMiD-based,and conventional],post-induction response,ASCT and MRD status,and survival outcomes[progression-free survival(PFS)and overall survival(OS)]were evaluated.Results:In total,454 patients with NDMM were included(median age,57 years;59.0%males)with a median follow-up of 58.7 months.The overall response rate was 91.0%,83.9%,90.6%,and 60.9%for PI-,IMiD-,PI+IMiD-based,and conventional regimens,respectively.Patients with ASCT during first-line therapy(26.2%)had a longer PFS and OS than patients who did not receive ASCT[median PFS,42.9 vs.21.2 months,P<0.001;median OS,not reached(NR)vs.65.8 months,P<0.001].The median OS was NR,71.5,and 56.6 months among patients with sustained MRD negativity,loss of MRD negativity,and persistent MRD,respectively(P<0.001).Multivariate analysis revealed that the lactic dehydrogenase level,International Staging System stage,extra-medullary disease,and upfront ASCT were independent factors in predicting OS among NDMM patients.Conclusions:Our study showed that novel agent-based regimens,first-line ASCT,and sustained MRD negativity were associated with a superior outcome for patients with NDMM in China(Identifier:NCT04645199).

Efficacy and Safety of the Chinese Herbal Compound TJAOA101 in Treating Diminished Ovarian Reserve: A Protocol for Multicenter, Prospective, and Pre-Post Study

Objective Diminished ovarian reserve(DOR)can lead to early menopause,poor fecundity,and an increased risk of disorders such as osteoporosis,cardiovascular disease,and cognitive impairment,seriously affecting the physical and mental health of women.There is still no safe and effective strategy or method to combat DOR.We have developed a novel Chinese herbal formula,Tongji anti-ovarian aging 101(TJAOA101),to treat DOR.However,its safety and efficacy need to be further validated.Methods In this prospective and pre-post clinical trial,100 eligible patients aged 18–45 diagnosed with DOR will be recruited.All participants receive TJAOA101 twice a day for 3 months.Then,comparisons before and after treatment will be analyzed,and the outcomes,including anti-mullerian hormone(AMH)and follicle-stimulating hormone(FSH)levels and the antral follicle count(AFC),the recovery rate of menopause,and the Kupperman index(KMI),will be assessed at baseline,every month during medication(the intervention period),and 1,3 months after medication(the follow-up period).Assessments for adverse events will be performed during the intervention and follow-up periods.Conclusion A multicenter,prospective study will be conducted to further confirm the safety and efficacy of TJAOA101 in treating DOR and to provide new therapeutic strategies for improving the quality of life in DOR patients.

Efficacy and safety of endoscopic submucosal dissection for gastric tube cancer:A multicenter retrospective study

BACKGROUND Recent improvements in the prognosis of patients with esophageal cancer have led to the increased occurrence of gastric tube cancer(GTC)in the reconstructed gastric tube.However,there are few reports on the treatment results of endoscopic submucosal dissection(ESD)for GTC.AIM To evaluate the efficacy and safety of ESD for GTC after esophagectomy in a multicenter trial.METHODS We retrospectively investigated 48 GTC lesions in 38 consecutive patients with GTC in the reconstructed gastric tube after esophagectomy who had undergone ESD between January 2005 and December 2019 at 8 institutions participating in the Okayama Gut Study group.The clinical indications of ESD for early gastric cancer were similarly applied for GTC after esophagectomy.ESD specimens were evaluated in 2-mm slices according to the Japanese Classification of Gastric Carcinoma with curability assessments divided into curative and non-curative resection based on the Gastric Cancer Treatment Guidelines.Patient characteristics,treatment results,clinical course,and treatment outcomes were analyzed.RESULTS The median age of patients was 71.5 years(range,57-84years),and there were 34 men and 4 women.The median observation period after ESD was 884 d(range,8-4040 d).The median procedure time was 81 min(range,29-334 min),the en bloc resection rate was 91.7%(44/48),and the curative resection rate was 79%(38/48).Complications during ESD were seen in 4%(2/48)of case,and those after ESD were seen in 10%(5/48)of case.The survival rate at 5 years was 59.5%.During the observation period after ESD,10 patients died of other diseases.Although there were differences in the procedure time between institutions,a multivariate analysis showed that tumor size was the only factor associated with prolonged procedure time.CONCLUSION ESD for GTC after esophagectomy was shown to be safe and effective.

Upper gastrointestinal endoscopic findings in celiac disease at diagnosis:A multicenter international retrospective study

BACKGROUND Gastroduodenal endoscopy and biopsy following positive specific serology is considered the gold standard to diagnose celiac disease(CeD)in adults.Whether upper endoscopy helps detect comorbid conditions is unknown.AIM To investigate the prevalence of non-celiac endoscopic findings in patients in whom endoscopy was performed to confirm CeD diagnosis.METHODS This is an observational,descriptive,multicenter,retrospective study that reports endoscopic findings obtained in adult patients enrolled in local registries from four tertiary centers.We collected data reported on first endoscopy,indicated for investigation of CeD.Diagnosis of CeD was performed by histology(≥Marsh 2type mucosal damage)and specific serology.Two European and one North American center included biopsy-confirmed CeD following positive serology.A fourth center(South America)included symptomatic patients undergoing endoscopy,irrespective of CeD serology.The latter cohort included a non-CeD control group.RESULTS A total of 1328 patients(80%female;35 years median age)were enrolled,of whom 95.6%had positive specific serology.In 135 patients,endoscopy revealed 163 abnormalities unrelated to CeD(prevalence:10.1%).Erosive reflux esophagitis(6.4%),gastric erosions(2.0%),and suspicion of esophageal metaplasia(1.2%)were the most common findings.Biopsy-confirmed Barrett’s esophagus was infrequent(0.2%).No endoscopic cancer was detected.Older patients(≥51 years of age)had a higher prevalence of endoscopic findings than those≤50(P<0.01).Within the South American cohort,CeD was associated with a lower rate(8.2%)of comorbid endoscopic findings compared with controls(29.1%;P<0.001).In the adjusted multivariate analysis of this cohort,having CeD was associated with a 72%reduction in the risk of any endoscopic abnormality(P<0.0001),and having alarm symptoms was associated with a 37%reduction in the risk of finding at least one endoscopic lesion(P<0.02).CONCLUSION In this large multicenter study,young adults with positive CeD serology had few comorbid endoscopic findings.Although patients over 51 years had a high prevalence of non-CeD gastroduodenal mucosal damage,no malignancy or premalignant lesions were found.

Clinical and economic impact of infliximab one-hour infusion protocol in patients with inflammatory bowel diseases:A multicenter study

AIM To assess the impact of short infliximab(IFX) infusion on hospital resource utilization and costs.METHODS All inflammatory bowel diseases(IBD) patients who received IFX 1 h infusion from March 2007 to September 2014 in eight centers from Southern Italy were included in the analysis. Demographic, clinical and infusion related data were collected. The potential benefits related to the short infusion protocol were assessed both in terms of time saving and increased infusion unit capacity. In addition, indirect patient-related cost savings were evaluated.RESULTS One hundred and twenty-five patients were recruited(64 with ulcerative colitis and 61 with Crohn's disease). Median duration of disease was of 53 mo and mean age of pts at diagnosis was of 34 years(SD: ± 13). Adverse infusion reactions were reported in less than 4% both before and after short infusion. The total number of infusions across the selected centers was of 2501(30.5% short infusions). In the analyzed cohort, 1143 h were saved(762 in the infusion and 381 in observation phases) through the rapid IFX infusion protocol. This time saving(-15% compared to the standard protocol in infusion phase) represents, from the hospital perspective, an opportunity to optimize infusion unit capacity by allocating the saved time in alternative cost-effective treatments. This is the case of opportunity cost that represents the value of forgone benefit which could be obtained from a resource in its next-best alternative use. Hence, an extra hour of infusion in the case of standard 2-h IFX represents a loss in opportunity to provide other cost effective services. The analysis showed that the short infusion increased the infusion units capacity up to 50% on days when the IFX infusions were scheduled(infusion phase). Furthermore, the analysis showed that the short IFX infusion protocol leads to time savings also in the post-infusion phase(observation) leading to a time saving of 10% on average among the analyzed centers. Finally, the short infusion protocol has been demonstrated to lead to indirect cost savings of €138/patient(average-€17.300 on the whole cohort).CONCLUSION A short IFX infusion protocol can be considered time and cost saving in comparison to the standard infusion protocol both from the hospital's perspective, as it contributes to increase infusion units capacity, and the patients' perspective, as it reduces indirect costs and the impact of treatment on everyday life and work productivity.

Screening of Class 1 and Class 2 Integrons in Clinical Isolates of Pseudomonas aeruginosa Collected from Seven Hospitals in Turkey:A Multicenter Study

Pseudomonas aeruginosa is one of the leading nosocomial pathogens worldwide, and their infections are difficult to treat due to acquired resistance to many antibiotics. This study aimed to detect class 1 and 2 integrons and antibiotic susceptibility of clinical isolates of P. aeruginosa. Two hundred and five P. aeruginosa strains were collected from the seven general state hospitals in Turkey. They were characterized by antimicrobial susceptibility testing, screened for class 1 and class 2 integrons, and evaluated for the association between antibiotic resistance phenotypes and the presence of integrons. intI gene was amplified in 10 isolates (4.87%) by PCR and in seven isolates of them (70%) were found different gene cassettes. The aadA gene integrated into the class 1 integrons was most frequently found and it was followed by aac genes and blaOXA family genes. Sequence analysis of variable regions of the class 1 integrons showed five gene cassette arrays;aadA1(99%), aac(3)-Id(82%)-orf-aac(3”)-Ia(99%), aac(3)-Ie(83%)-blaoxa10(100%)- aadA1 (100%), aadA6(99%, 100%), aac(6’)-I(97%)-orf-aadA2(99%). No class 2 integron was detected. This study is the first multicenter study for class 1 integrons and it indicates the low rate of presence of class 1 gene cassette in P. aeruginosa.

Long term follow-up and outcome of liver transplantation from hepatitis B surface antigen positive donors

Liver transplant for hepatitis B virus(HBV) currently yields excellent outcomes: it allows to rescue patients with an HBV-related advanced liver disease, resulting in a demographical modification of the waiting list for liver transplant. In an age of patient-tailored treatments, in liver transplantation as well the aim is to offer the best suitable graft to the patient who can benefit from it, also expanding the criteria for organ acceptance and allocation. With the intent of developing strategies to increase the donor pool, we set-up a multicenter study involving 3 Liver Transplant Centers in Italy: patients undergoing liver transplantation between March 03, 2004, and May 21, 2010, were retrospectively evaluated. 1408 patients underwent liver transplantation during the study period, 28(2%) received the graft from hepatitis B surface antigen positive(HBs Ag)-positive deceased donors. The average follow-up after liver transplantation was 63.7 mo [range: 0.1-119.4; SD ± 35.8]. None Primary nonfunction, re-liver transplantation, early or late hepatic artery thrombosis occurred. The 1-, 3-and 5-year graft and patient survival resulted of 85.7%, 82.1%, 78.4%. Our results suggest that the use of HBs Agpositive donors liver grafts is feasible, since HBV can be controlled without affecting graft stability. However, the selection of grafts and the postoperative antiviral therapy should be managed appropriately.

A multicenter study of the clinicopathological characteristics and a risk prediction model of early-stage breast cancer with hormone receptor-positive/human epidermal growth factor receptor 2-low expression

Background:In light of the significant clinical benefits of antibody-drug conjugates in clinical trials,the human epidermal growth factor receptor 2(HER2)-low category in breast cancers has gained increasing attention.Therefore,we studied the clinicopathological characteristics of Chinese patients with hormone receptor(HR)-positive/HER2-low early-stage breast cancer and developed a recurrence risk prediction model.Methods:Female patients with HR-positive/HER2-low early-stage breast cancer treated in 29 hospitals of the Chinese Society of Breast Surgery(CSBrS)from Jan 2015 to Dec 2016 were enrolled.Their clinicopathological data and prognostic information were collected,and machine learning methods were used to analyze the prognostic factors.Results:In total,25,096 patients were diagnosed with breast cancer in 29 hospitals of CSBrS from Jan 2015 to Dec 2016,and clinicopathological data for 6486 patients with HER2-low early-stage breast cancer were collected.Among them,5629 patients(86.79%)were HR-positive.The median follow-up time was 57 months(4,76 months);the 5-year disease-free survival(DFS)rate was 92.7%,and the 5-year overall survival(OS)rate was 97.7%.In total,412 cases(7.31%)of metastasis were observed,and 124(2.20%)patients died.Multivariate Cox regression analysis revealed that T stage,N stage,lymphovascular thrombosis,Ki-67 index,and prognostic stage were associated with recurrence and metastasis(P<0.05).A recurrence risk prediction model was established using the random forest method and exhibited a sensitivity of 81.1%,specificity of 71.7%,positive predictive value of 74.1%,and negative predictive value of 79.2%.Conclusion:Most of patients with HER2-low early-stage breast cancer were HR-positive,and patients had favorable outcome;tumor N stage,lymphovascular thrombosis,Ki-67 index,and tumor prognostic stage were prognostic factors.The HR-positive/HER2-low early-stage breast cancer recurrence prediction model established based on the random forest method has a good reference value for predicting 5-year recurrence events.Registritation:ChiCTR.org.cn,ChiCTR2100046766.

A Multicenter Study of Viral Aetiology of Community-Acquired Pneumonia in Hospitalized Children in Chinese Mainland

Community-acquired pneumonia(CAP) is one of the leading causes of morbidity and mortality in children worldwide.In this study,we aimed to describe the aetiology of viral infection of pediatric CAP in Chinese mainland.During November2014 to June 2016,the prospective study was conducted in 13 hospitals.The hospitalized children under 18 years old who met the criteria for CAP were enrolled.The throat swabs or nasopharyngeal aspirates(NPAs) were collected which were then screened 18 respiratory viruses using multiplex PCR assay.Viral pathogens were present in 56.6%(1539/2721) of the enrolled cases,with the detection rate of single virus in 39.8% of the cases and multiple viruses in 16.8% of the cases.The most frequently detected virus was respiratory syncytial virus(RSV)(15.2%,414/2721).The highest detection rate of virus was in <6-month-age group(70.7%,292/413).RSV,human metapneumovirus(HMPV),human parainfluenza viruses(HPIVs) and influenza B virus(Flu B) showed the similar prevalence patterns both in north and south China,but HPIVs,Flu A,human bocavirus(HBoV),human adenovirus(HAdV) and human coronaviruses(HCoVs) showed the distinct circulating patterns in north and south China.Human enterovirus/human rhinovirus(HEV/HRV)(27.6%,27/98),HBoV(18.4%,18/98),RSV(16.3%,16/98) and HMPV(14.3%,14/98) were the most commonly detected viruses in severe pneumonia cases with single virus infection.In conclusion,viral pathogens are frequently detected in pediatric CAP cases and may therefore play a vital role in the aetiology of CAP.RSV was the most important virus in hospitalized children with CAP in Chinese mainland.

Geriatric Assessment to Predict Survival and Risk of Serious Adverse Events in Elderly Newly Diagnosed Multiple Myeloma Patients： A Multicenter Study in China

Background： Elderly multiple myeloma （MM） patients often tend to suffer a variety of diseases, so the treatment of choice is very difficult for the elderly myeloma patients. The overall survival （OS） time and side effects with elderly patients are unclear in China. The study tried to find out the role of geriatric assessment in the Chinese elderly MM. Methods： We retrospectively analyzed the data of 628 newly diagnosed patients from six hospitals from June 2011 to June 2013. A geriatric assessment had been performed to assess comorbidities, cognitive, and physical status for these patients. The primary endpoint was to evaluate different physical states of elderly patients with OS time and treatment-related side effects. Results： An additive scoring system （range： 0-5）, based on age, Katz＇s Activity of Daily Living （ADL） and Lawton＇s Instrumental Activity of Daily Living （IADL） 〈5 and Charlson Comorbidity Index （CC1） was developed to identify three groups： fit （score = 0）; intermediate-fitness （score = 1 ）; and fi＇ail （score ≥2）. The 3-year OS was 63% in fit patients, 63% in intermediate-fimess patients, and 49% in frail patients ≥3 hematologic adverse events （AEs） were documented in 45 （35.4%） fit, 34 （34%） intermediate-fitness, and 121 （30.2%） frail patients. The risk of a grade ≥3 hematologic AEs was not significantly increase in intermediate-fitness （hazard ratios [HR]： 0.99, 95% confidence interval [CI]： 0.54 1.47, P = 1.000） and in frail patients （tfR： 1.16, 95% CI： 0.70-1.93, P- 0.558） compared with fit ones. Conclusions： MM occurs earlier in life and being advanced when the diagnosis is made in the mainland of China. The overall survival in fi＇ailty with International Staging System （ISS） ll/lll was the worst in all patients.

Outcomes in refractory diffuse large B-cell lymphoma:results fromamulticenter real-world study in China

Background:Diffuse large B-cell lymphoma(DLBCL)patients refractory to rituximab-based immunochemotherapy have a dismal prognosis.However,the definition of refractory DLBCL remains inconsistent and no large cohort study data is available from Asian countries.To validate the definition and outcomes of refractory DLBCL in China,we conducted a multicenter,retrospective cohort study.Methods:The REtrospective AnaLysis of Treatment REspoNse of refractory DLBCL(REAL-TREND)study was performed using real-world data from 8 centers in China.DLBCL patients with curative intent were included in the REAL-TREND dataset.Overall survival(OS)was estimated using the Kaplan-Meier method and compared by the log-rank test.Due to heterogeneity in response rates among different centers,the response rates of refractory patients were pooled using random-effect models.Multivariate survival analysis was performed using the Cox regression model.Results:A total of 2778 DLBCL patients diagnosed between January,2010 and December,2015 were enrolled to this study.After validating previous definitions,the SCHOLAR-1 study was most suitable to define refractory DLBCL.The estimated 5-year cumulative incidence of refractory patients was 20%(95% confidence Interval[CI]=18%-22%).After the determination of refractory disease,overall response rate and complete remission rate were 30%(95%CI=22%-38%)and 9%(95%CI=4%-15%),respectively.Patients with either no response to immunochemotherapy or relapse within 12 months after stem-cell transplantation had inferior survival with a median OS of 5.9 months(95%CI=5.5-7.1 months)and 2-year OS rate of 16%(95%CI=12%-20%).International prognostic index score 4-5(hazard ratio[HR]=2.22;95%CI=1.47-3.35),central nervous systemrelapse(HR=1.43;95%CI=1.04-1.97),and best response status(HR=2.68;95%CI=1.42-5.03 for partial remission.HR=5.97,95%CI=3.21-11.11 for stable disease/progressive disease)were independent unfavorable prognostic factors.Conclusions:This is the first large-scale Asian cohort study focusing on outcomes of refractory DLBCL.The definition of the SCHOLAR-1 study identifies patients with homogenously inferior survival,thus is appropriate to select refractory DLBCL.Due to poor clinical outcomes in the rituximab era,patients with refractory DLBCL may be potential candidates for novel treatment modalities.

Clinical characteristics and survival of 5283 esophageal cancer patients: A multicenter study from eighteen hospitals across six regions in China

Objective:This study aimed to investigate the potential determining epidemiological and clinical risk factors affecting the survival of esophageal cancer(EC)patients across multiple hospitals in China.Methods:This was a multicenter study comprising of newly diagnosed EC cases from Beijing,Hebei,Henan,Hubei,Zhejiang,and Guangdong Province of China.Their baseline characteristics and treatment methods data were collected from their medical records.The EpiData software was used for data quality control.The Kaplan-Meier method was used to estimate their overall survival(OS),and the Cox’s proportional hazard regression model was used to estimate hazard ratios(HR)and 95%confidence interval(CI).Results:The 3-and 5-year OS rates of the 5283 investigated EC patients were 49.98%and 39.07%,respectively.Their median survival was 36.00 months.The median survival time of females was longer than that of males(females vs.males:45.00 vs.33.00,P<0.001).The 5-year OS rate of patients who never-smoked was higher than that of smokers(never-smokers vs smokers:40.73%vs.37.84%,P=0.001).There was no significant difference in the 5-year OS rate between drinkers and never-drinkers(drinkers vs never-drinkers:34.22%vs.29.65%,P=0.330).In multivariate analysis,pathological stage(stage II:HR=1.80,95%CI=1.40-2.31;stage III:HR=2.62,95%CI=2.06-3.34;stage IV:HR=3.90,95%CI=2.98-5.09),poor differentiation/undifferentiated(HR=1.34,95%CI=1.11-1.63),not married status(HR=2.45,95%CI=1.49-4.04),production and service personnel(HR=1.36,95%CI=1.01-1.83)and farming/fishing(HR=1.40,95%CI=1.12-1.76)were independent prognostic risk factors for poor EC survival.Tumors in the thoracic or abdominal part of the esophagus,female and family history of any cancer were independent factors predictive of a good EC OS.Conclusion:Gender,marital status,occupation,family history of any cancer,tumor topographical site,differentiation status,and pathological stage were associated with the survival rate of EC.This study reveals important clinical characteristics of esophageal cancer patients in China and provides helpful information for their clinical management and surveillance.

Multicenter Clinical Study on the Treatment of Children's Tic Disorder with Qufeng Zhidong Recipe(祛风止动方)

Objective:To assess the effect and adverse reaction of Qufeng Zhidong Recipe(袪风止动方, QZR)in treating children's tic disorder(TD).Methods:With multicenter randomized parallel open-controlled method adopted,the patients enrolled were assigned to two groups,41 cases in the Chinese medicine (CM)group and 40 in the Western medicine(WM)group.They were treated by QZR and haloperidol plus trihexyphenidyl respectively for 12 weeks as one course.In total,two courses of treatment were given.The curative effect and adve...

Rapid screening for Klinefelter syndrome with a simple high-resolution melting assay： a multicenter study

Klinefelter syndrome （KS） is the set of symptoms that result from the presence of an extra X chromosome in males. Postnatal population-based KS screening will enable timely diagnosis of this common chromosomal disease, providing the opportunity for early intervention and therapy at the time point when they are most effective and may prevent later symptoms or complications. Therefore, through this study, we introduced a simple high-resolution melting （HRM） assay for KS screening and evaluated its clinical sensitivity and specificity in three medical centers using 1373 clinical blood samples. The HRM assay utilized a single primer pair to simultaneously amplify specific regions in zinc finger protein, X-linked （ZFX） and zinc finger protein, Y-linked （ZFY）. In cases of KS, the ratios of ZFX/ZFYare altered compared to those in normal males. As a result, the specific melting profiles differ and can be differentiated during data analysis. This HRM assay displayed high analytical specificity over a wide range of template DNA amounts （5 ng-50 ng） and reproducibility, high resolution for detecting KS mosaicism, and high clinical sensitivity （100%） and specificity （98.1%）. Moreover, the HRM assay was rapid （2 h per run）, inexpensive （0.2 USD per sample）, easy to perform and automatic, and compatible with both whole blood samples and dried blood spots. Therefore, this HRM assay is an ideal postnatal population-based KS screening tool that can be used for different age groups.

A multicenter retrospective cohort study of ketogenic diet therapy in 481 children with infantile spasms

Background:Ketogenic diet(KD)therapy is one of the main treatments for drug-resistant epilepsy.However,the KD therapy has been applied in only a small number of infantile spasm cases.In this large multicenter study,we investigated the efficacy of KD therapy in the treatment of infantile spasms.Methods:In this retrospective,multicenter cohort study,clinical data from main epilepsy centers were analyzed.Patients were classified into different groups according to age,type of drug and whether glucocorticoid was used before initiation of KD.Results:From October 2014 to March 2020,481 patients(308 males and 173 females)with infantile spasms were treated with the KD therapy.The age of the patients ranged from 2 months to 20 years,with a mean age of 1 year and 10 months.The number of anti-seizure medications(ASMs)used before KD initiation ranged 0-6,with a median of 3.In different time from initiation(1,3,6,and 12 months),the rates of seizure freedom after KD were 6.9,11.6;16.0 and 16.8%,respectively(x^(2)=27.1772,P<0.0001).There was a significant difference in the rate of seizure freedom between 3 months and 1 month(x^(2)=6.5498,P=0.0105)groups,and 6 months and 3 months(x^(2)=3.8478,P=0.0498)groups,but not between 12 months and 6 months(x^(2)=0.1212,P=0.7278)groups.The rates of effectiveness were 44.7;62.8,49.1 and 32.0%(x^(2)=93.2674,P<0.0001),respectively.The retention rates were 94.0,82.5,55.7 and 33.1%(x^(2)=483.7551,P<0.0001),correspondingly.The rate of effectiveness and the retention rate of KD were significantly different among the 1,3,6 and 12 months.KD treatment was the first choice in 25 patients(5.2%),55 patients(11.4%)started KD after the failure of the first ASM,158 patients(32.8%)started KD after the failure of the second ASM,157 patients(32.6%)started KD after the failure of the third drug,and 86 patients(17.9%)started KD after the failure of the fourth and more.The KD effect was not related to the number of ASMs used before KD startup(P>0.05).Two hundred and eighteen patients(45.3%)failed to respond to corticotropin or glucocorticoid before initiation.There was no significant difference in the effectiveness rate at different time points between the group of KD therapy after glucocorticoid failure and the group after non-hormone failure (x^(2)=0.8613,P=0.8348).The rate of adverse events of KD in 1,3,6,and 12 months after KD initiation were 22.3,21.7,16.8 and 6.9%,respectively.The adverse events mainly occurred during the first 3 months of KD,and the main adverse events were gastrointestinal disturbance and constipation.Conclusions:The efficacy of the KD treatment for infantile spasms was not affected by age,medication,and glucocorticoid use before initiation.KD is one of the effective treatments for infantile spasms.

Tolerance and acceptance of hepatic venous pressure gradient measurement in cirrhosis(CHESS1904):An international multicenter study

Aim:To determine the tolerance and acceptance of hepatic venous pressure gradient(HVPG)measurements in patients with liver cirrhosis.Methods:This prospective international multicenter study included 271 patients with cirrhosis who were scheduled to undergo HVPG measurement between October 2019 and June 2020.Data related to the tolerance and acceptance of HVPG measurements were collected using descriptive questionnaires.Results:HVPG measurements were technically successful in all 271 patients,with 141(52.0%)undergoing HVPG measurement alone.The complication rate was 0.4%.Postoperative pain was significantly lower than preoperative expected pain(p<0.001)and intraoperative pain(p<0.001),and intraoperative pain was also significantly lower than preoperative expected pain(p=0.036).No,mild,moderate,severe,and intolerable discomfort scores were reported by 36.9%,44.6%,11.1%,6.3%,and 0.4%of these patients,respectively,during HVPG measurement and by 54.6%32.5%,11.4%,1.5%,and 0%,respectively,after HVPG measurement.Of these patients,39.5%had little understanding and 10%had no understanding of the value of HVPG measurement,with 35.1%and 4.1%regarding HVPG measurements as being of little or no help,respectively.Most patients reported that they would definitely(15.5%),probably(46.9%),or possibly(29.9%)choose to undergo additional HVPG measurements again,and 62.7%regarded the cost of the procedure as acceptable.Conclusion:HVPG measurement was safe and well‐tolerated in patients with cirrhosis,but patient education and communication are warranted to improve the acceptance of this procedure.

Multicenter clinical study on the efficacy and safety of inhalable insulin aerosol in the treatment of type 2 diabetes

Background A new inhalable insulin aerosol （Inh-lns） was developed in China. The aim of this multicenter clinical study was to evaluate the efficacy and safety of this new Inh-lns as a treatment of type 2 diabetes. Regular porcine insulin （RI） was used as a control. Methods This study is a prospective, randomized, open-label, parallel-group multicenter clinical trial in which 253 qualified patients with type 2 diabetes received the insulin Glargine daily at bedtime plus either a pre-meal Inh-lns or a pre-meal subcutaneous RI for 12 weeks. HbAlc, fasting plasma glucose （FPG）, the 1-hour-postprandial blood glucose （1hPBG） and the 2-hour-postprandial blood glucose （2hPBG） were measured. Events were monitored for adverse effects. Results After 12 weeks, the HbAlc decreased significantly from baseline in both treatment groups, with no significant difference between the two regimens. In the Inh-lns group, FPG, both lhPBG and 2hPBG significantly declined from baseline after the 8th- and 12th-weeks of treatment. The reduced values of FPG or 1hPBG between the two groups showed a more significant hypoglycemic effect with the Inh-lns than the RI. After 12 weeks, the pulmonary carbon monoxide diffusing capacity （DLco） was significantly lower in Inh-lns group than in the RI. The main side effects of Inh-lns were coughing, excessive sputum, and hypoglycemia. Conclusions Inh-lns was effective in decreasing HbAlc like the RI. It was better in lowering the FPG and the lhPBG than the RI. Its main side effects were coughing, excessive sputum, and hypoglycemia. Also, Inh-lns slightly impaired DLco.

Neoadjuvant therapy for early human epidermal growth factor receptor 2 positive breast cancer in China: A multicenter real-world study (CSBrS-015)

Background:Pertuzumab has been approved for application in China by the National Medical Products Administration,and both national and international guidelines make recommendations for the use of neoadjuvant treatment with trastuzumab or trastuzumab+pertuzumab plus chemotherapy regimens for patients with indications.The goal of this study was to investigate the short-term clinical efficacy of the neoadjuvant therapies trastuzumab and trastuzumab+pertuzumab for patients with early human epidermal growth factor receptor 2(HER2)-positive breast cancer in China.Methods:A real-world study was conducted using the clinicopathological data of patients with early HER2-positive breast cancer who were admitted to the member hospitals of the Chinese Society of Breast Surgery,Chinese Surgical Society of Chinese Medical Association between March 2019 and December 2020.This study analyzed the efficacy and tolerance of trastuzumab+chemotherapy and trastuzumab+pertuzumab+chemotherapy in patients with early HER2-positive breast cancer.The Response Evaluation Criteria in Solid Tumors 1.1 was adopted to evaluate clinical efficacy.The pathological efficacy was evaluated using the MillerPayne grade.The Common Terminology Criteria for Adverse Events(version 5.0)was adopted to evaluate adverse events(AEs).The propensity scores were subjected to propensity score matching using the R language(1:1 matching with a maximum allowable difference of 0.05 between the two groups).Efficacy was compared using the chi-square test,and correlation analysis was performed using linear regression.Results:A total of 1032 patients with early HER2-positive breast cancer met the enrollment criteria and were included in this study.Among these patients,472 received neoadjuvant trastuzumab+chemotherapy(the trastuzumab group),and 560 received neoadjuvant trastuzumab+pertuzumab+chemotherapy(the trastuzumab+pertuzumab group).The overall pathologic complete response(pCR)rate was 47.2%(487/1032),while the pCR rates of the trastuzumab and trastuzumab+pertuzumab groups were 34.5%(163/472)and 57.9%(324/560),respectively,and the difference was significant(P<0.001).The incidence of grade 4 AEs was 24/321(7.5%)in the trastuzumab+pertuzumab group,and there were no cases in which the left ventricular ejection fraction decreased by more than 10%.Conclusions:Patients in the trastuzumab+pertuzumab group had a higher pCR rate than those in the trastuzumab group,and the toxic side effects were tolerable.

A PROSPECTIVE STUDY TO EVALUATE THE SAFETY AND EFFICACY USING REMOVING BLOOD STASIS HERBALS FOR PATIENTS WITH INTRACRANIAL HEMORRHAGE OF HYPERACUTE STAGE AND RELATIVE FACTORS OF HEMATOMA ENLARGEMENT(A MULTICENTER PROSPECTIVE RANDOMIZED DOUBLE-BLIND PLACEBO

The aim was to investigate whether using a removing blood stasis method in hyperacute intracranial hemorrhage stage can lead to hematoma enlargement and its clinical efficacy.A multicenter retrospective randomized double-blind placebo-controlled clinical study.We recruited patients aged 18 years or older and presenting at less than 6 h from symptom onset in 8 research centers.All the patients

Male reproductive function before and after theadjustment of the COVID-19 prevention policy:amulticenter study in China

At the end of 2022,the adjustment of the coronavirus disease 2019(COVID-19)pandemic control policy in China resulted in alarge-scale increase in public infection.To compare the fertility parameters of male patients before and after the adjustments ofthe COVID-19 pandemic control policy in China,we collected data on patients’medical histories and laboratory examinations ontheir first visits between June 2022 and March 2023 in five different hospitals.Data were divided into five groups according tothe timeline of the policy adjustment.The data we collected from male patients included semen quality and serum reproductivehormone levels,and intergroup comparisons were made using the Mann–Whitney U and Chi-square tests.In total,16784 casesunderwent regular semen analysis,11180 had sperm morphology assessments,and 7200 had reproductive hormone analyses.Thedata showed declining trends in semen volume,sperm motility,and the progressive sperm motility rate after the policy adjustment.Subgroup comparison revealed an initial decrease and gradual recovery in progressive motility rate.Sperm morphology analysisshowed increased neck and tail abnormalities after the policy adjustment.No significant change in hormone levels was observed.Following the adjustment of the COVID-19 prevention policy in China,a decline in sperm motility and morphology was observed.This trend may gradually recover over 2 months.After the policy adjustment,reproductive hormone levels were relatively stablethroughout,except for an increase in luteinizing hormone(LH).These changes in semen parameters suggest that the policyadjustment had a short-to medium-term impact on male reproductive function.