Effect of frailty on the risk of all-cause mortality —a 12-year follow-up study of community residents aged 45 years and above in Shanghai / 上海预防医学

ObjectiveTo analyze the effect of frailty status on the risk of mortality in a community-based population aged 45 years and above in Shanghai with different characteristics， and to provide further basis for population-based interventions for frailty and prevention of adverse outcomes. MethodsData were derived from baseline data from the Shanghai prospective study on AGEing and adult health （2009-2010） and cohort follow-up of causes of death up to October 30， 2021. Frailty index （FI） scores were constructed from 40 variables. Those with frailty index FI≥0.2 were judged to be in a frail state， and a multifactorial Cox regression model was used to calculate the hazard ratio （HR） to evaluate the effect of frailty status on the risk of death in different age groups by gender. Socioeconomic characteristics （age， residence， marital status， education and family economic level， etc.） and health-related behaviors （smoking， alcohol consumption， fruit and vegetable intake， social participation， etc.） were included as control variables. ResultsThe study included 7 978 subjects， 777 （9.7%） of whom were in a frail state. After （11.3±1.8） years of follow-up， 1 043 （13.1%） individuals were dead， including 214 （27.5%） who were frail. The results of the multifactorial Cox regression analysis showed that the effect of frailty on the risk of death in each subgroup was in descending order of men in the middle-aged group （45‒ years） （HR=2.92， 95%CI： 1.38-6.19）， women in the low-aged elderly group （60‒ years） （HR=1.68， 95% CI： 1.08-2.60）， and women in the old-aged elderly group （≥75 years and older） （HR=1.59， 95%CI： 1.22‒2.06）. ConclusionFrailty is associated with the risk of death， and we should focus on the frailty status of men aged 45~59 years and women aged 60 years and above. Early screening and assessment of frailty status and taking appropriate preventive interventions may reduce the occurrence of adverse outcomes and premature death.

Outcomes of 33 patients with anaplastic large cell lymphoma treated after hematopoietic stem cell transplantation / 中华血液学杂志

Objective@#To explore the efficacy and prognostic factors of hematopoietic stem cell transplantation (HSCT) for the treatment of patients with anaplastic large cell lymphoma (ALCL) .@*Methods@#The clinical records of 33 ALCL patients after HSCT were collected and analyzed retrospectively to evaluate the rates of overall survival (OS) and recurrence after autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT) and the factors influencing prognosis.@*Results@#The median-age of this cohort of 33 ALCL cases at diagnosis was 31 (12-57) years old with a male/female ratio of 23/10, 24 cases (72.7%) were ALK+ and 9 ones (27.3%) ALK-. Of them, 25 patients (19 ALK+ and 6 ALK-) underwent auto-HSCT and 8 cases (5 ALK+ and 3ALK-) allo-HSCT with a median follow-up of 18.7 (4.0-150.0) months. Disease states before HSCT were as follows: only 6 patients achieved CR status and received auto-HSCT, 16 patients achieved PR (14 cases by auto-HSCT and 2 ones allo-HSCT) , the rest 11 cases were refractory/relapse (5 cases by auto-HSCT and 6 ones allo-HSCT) . There were 7 cases died of disease progression (5 after auto-HSCT and 2 allo-HSCT) and 5 cases treatment-related mortality (TRM) (2 after auto-HSCT and 3 allo-HSCT) , TRM of two groups were 8.0% and 37.5%, respectively. Both the median progression-free survival (PFS) and OS were 15 months after auto-HSCT, the median PFS and OS after allo-HSCT were 3.7 (1.0-90.0) and 4.6 (1.0-90.0) months, respectively. There was no statistically significant difference in terms of survival curves between the two groups (OS and PFS, P=0.247 and P=0.317) . The 2-year OS rates in auto-HSCT and allo-HSCT groups were 72% and 50%, respectively. The 5-year OS rates in auto-HSCT and allo-HSCT groups were 36% and 25%, respectively.@*Conclusion@#ALCL treated by chemotherapy produced high rates of overall and complete responses. Chemotherapy followed by auto-HSCT remained to be good choice for patients with poor prognostic factors. High-risk patients should be considered more beneficial from allo-HSCT.

Data Analysis on Protocol Deviation in Blind Review of Drug Clinical Trials of a CRO Company from 2010 to 2019 / 中国药房

OBJECTIVE：To study the effects of protocol deviation on the results of clinical trials ，and to provide reference for rising the quality management of drug clinical trials. METHODS ：Blind data review forms for clinical trials of a contract research organzation （CRO） company in Guangzhou from 2010 to 2019 were collected to analyze general characteristics of protocol deviation，the situation of protocol deviation before and after the “722 announcement”（Announcement on Carrying Out Self-inspection and Verification of Drug Clinical Trial Data issued by CFDA on July 22，2015）as well as the effects of protocol deviation on full analysis set （FAS）population division. The suggestions were put forward. RESULTS ：A total of 45 trials were included，involving 454 centers，14 304 disease cases and 5 562 cases of protocol deviation. The most common types of protocol deviations were over-window ，violation of criteria of the inclusion and exclusion ，and drop-out ，which accounted for 36.88％， 20.71％ and 18.43％ respectively. There was no statistical significance in protocol deviation degree of clinical trials with different stages or drug types （P＞0.05）；there was significant difference in the degree of protocol deviations in clinical trials with different stages before and after the “722 announcement”（P＜0.05）；the incidence of deviations from over-window ，violation of cirteria of the inclusion and exclusion ，and medication compliance had increased after the “722 announcement”；82.07％ of cases with protocol deviations could enter FAS ，and the population who included in FAS but did not enter per protocol set （PPS）accounted for 53.99％ of the total deviation ，of which deviations from drop-out and combined medication accounted for 19.51％ and 4.29％ respectively. All cases with deviation from medication compliance did not enter PPS. CONCLUSIONS ：Drop-out，violation of criteria of the inclusion and exclusion ，and over-window are the main factors that cause clinical trial protocol deviations. The “722 announcement”played a certain role on improving the quality management awareness of the personnel in drug clinical trial. Appropriate statistical methods should be selected to control bias ，and to strengthen the quality management of drug clinical trials and reduce protocol deviations ，by paying attention to trial design， staff training ， institutional management and 85223869。

Effects of gross motor skills on physical activity in preschoolers aged 3-6 years / 中国学校卫生

Objective@#To investigate the effect of gross motor skills on physical activity of children aged 3-6 years, and to provide basis for children’s health behavior intervention.@*Methods@#A total of 332 young children in Shanghai Xiangyin kindergarten were selected as survey objects. The development of gross movements of young children was measured by TGMD-2. Caregivers reported children’s physical activity using the International Physical Activity Questionnaire (IPAQ-SF).@*Results@#The development level of gross movements of children aged 3-6 in Shanghai was relatively low(54.76±13.86). The physical activity of children was mainly light-intensity physical activity, and the daily moderate-to-vigorous intensity physical activity time was (58.62±52.73) minutes every day. Locomotor skills had the greatest effect on children’s VPA (β=0.19) and TPA(β=0.12), with a contribution rate of 3.3% and 1.1%, respectively; Object control skills has the greatest effect on children’s MVPA (β=0.17) and MPA (β=0.12) had the largest effect(P<0.05), with contribution rates of 2.5% and 1.2%, respectively. The relationship between gross motor skills and physical activity had nothing to do with gender and age.@*Conclusion@#Children’s gross motor skills in the 3-6 year-old population should be improved and may be an effective way to promote physical activity.

Epidemiological analysis of cytogenetic abnormalities in patients with newly-diagnosed multiple myeloma: a multi-center retrospective study / 中华血液学杂志

Objective@#To analyze the frequency and composition of risk-related cytogenetic abnormalities (CAs) in patients with newly-diagnosed multiple myeloma (NDMM) .@*Methods@#The frequency and composition of risk-related CAs from a cohort of 1 015 Chinese patients with NDMM were determined by interphase fluorescence in situ hybridization (iFISH) , individually or in combination.@*Results@#Of the cohort of 1 015 Chinese patients with NDMM, the frequencies of IgH arrangement, del (13q) /13q14, 1q gain and del (17p) were 54.0%, 46.4%, 46.1% (35.8% and 12. 7% for 3 or more than 3 copies) and 9.9%, respectively. Among 454 patients who had the baseline information for all risk-related CAs [except t (14;20) , which was not covered by the FISH panels performed routinely at all five centers], the frequencies of t (4;14) , t (11;14) or t (14;20) were 14.1%, 11.2% and 4.8%, respectively; of them, 44.3% patients carried 2 or more CAs (28.0%, 13.4% and 2.9% for 2, 3 or ≥4 CAs) ; 83.3%, 95.0% or 68.6% patients with 1q gain, del (17p) or IgH rearrangement had 1 or more additional CA (s) , with del (13q) /13q14 as the most frequently accompanied CA; 57.7% patients carried at least 1 HRCA; the incidences of double-hit (DH) MM (DHMM) (=2 HRCAs) and triple-hit (TH) (THMM) (≥3 HRCAs) were 14.3% and 2.9%, respectively.@*Conclusions@#Our results provided an up-to-date profile of CAs in Chinese NDMM patients, which revealed that approximately 58% patients might carry at least 1 HRCA, and 17% could experience so-called DHMM or THMM who presumably had the worst outcome.

Clinical outcomes of hematopoietic stem cell transplantation for angioimmunoblastic T-cell lymphoma / 中华血液学杂志

Objective@#To evaluate clinical outcomes of autologous (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for angioimmunoblastic T-cell lymphoma (AITL) .@*Methods@#From June 2007 to June 2017, clinical data of AITL patients who underwent HSCT in eight hospitals were assessed retrospectively.@*Results@#Of 19 patients, 13 male and 6 female with a median age of 50 (32-60) years old, 12 auto-HSCT and 7 allo-HSCT recipients were enrolled in this study, all donors were HLA-identical siblings. Two of allo-HSCT recipients were relapsed auto-HSCT ones. There were 5 patients (5/12) in complete response (CR) status and 7 (7/12) in partial remission (PR) status before transplantation in auto-HSCT group, and 2 (2/7) in PR status and 3 (3/7) in progression disease (PD) status before transplantation in allo-HSCT group. The median follow-up for the surviving patients was 46.5 months (range, 1-100 months) for the whole series, two patients lost in auto-HSCT group. Three patients developed acute graft-versus-host disease (aGVHD) and 5 chronic graft-versus-host disease (cGVHD) after allo-HSCT. Three patients died of primary disease and 1bleeding in auto-HSCT group. One patient died of primary disease and 2 transplantation-related mortality in allo-HSCT group. The 3-year cumulative overall survival (OS) were 56% (95%CI 32%-100%) and 57% (95%CI 30%-100%) for auto-HSCT and allo-HSCT, respectively (P=0.979) . The 3-year cumulative progression-free survival (PFS) were 34% (95%CI 14%-85%) and 57% (95%CI 30%-100%) for auto-HSCT and allo-HSCT, respectively (P=0.451) .@*Conclusion@#Both auto-HSCT and allo-HSCT were optimal choices for AITL. In clinical practice, which HSCT was better for AITL patients should be based on comprehensive factors including sensitivity to chemotherapy, risk stratification and disease status at transplantation.

Clinical outcome of allogeneic hematopoietic stem cell transplantation with FLAG sequential busulfan/cyclophosphamide conditioning regimen for refractory/relapsed acute myeloid leukemia / 中华内科杂志

Objective@#To investigate the therapeutic effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with FLAG sequential busulfan/cyclophosphamide(Bu/Cy) conditioning regimen for refractory/relapsed acute myeloid leukemia.@*Methods@#From February 2012 to June 2017, 21 patients with refractory/relapsed acute myeloid leukemia underwent allo-HSCT with FLAG sequential Bu/Cy conditioning regimen. Transplantation-related complications and clinical outcome were retrospectively analyzed.@*Results@#After conditioning, no hepatic veno-occlusive disease (VOD) and grade Ⅲ hemorrhagic cystitis occurred. 76.2% (16/21) patients had fever with 4 septicemia. One patient died of septic shock before engraftment. Twenty patients achieved neutrophil engraftment with a median time of 13 days (range, 10 to 21 days). Seventeen patients achieved platelet engraftment with a median time of 18 days (range, 9 to 25 days). The cumulative incidence of acute graft-versus-host disease (aGVHD) was 39.5%, and 3 patients developed grade Ⅲ-Ⅳ aGVHD. Of 19 patients who survived more than 100 days after transplantation, 4 had local chronic graft-versus-host disease (cGVHD). Of 21 patients, the median survival time was 15 months (range, 0.5 to 67 months) post-transplantation. Transplantation-related mortality rate was 28.7%. Leukemia relapse occurred in 4 patients with a median time of 4 months (range, 3 to 8 months) after transplantation. The cumulative relapse rate at 1 year was 21.4%. The 1-year and 3-year overall survival (OS) rates were 60.7% and 54.9% respectively. Log-rank analysis revealed that bone marrow blasts ≥ 20% or extramedullary leukemia before transplantation, poor platelet engraftment and grade Ⅲ-Ⅳ aGVHD were significantly related to shortened OS (P<0.05).@*Conclusions@#Allo-HSCT with FLAG sequential Bu/Cy conditioning regimen in patients with refractory/relapsed myeloid leukemia has acceptable transplantation-related risk and relapse rate. The 1-year and 3-year OS rates are comparable with those in remission patients.

Combination of busulfan with increased-dose of fludarabine as conditioning regimen for MDS and MDS-AML patients with allo-HSCT / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS) and secondary acute myelogenous leukemia (MDS-AML) using conditioning regimen with busulfan (Bu) and increased-dose of fludarabine (ID-Flu).</p><p><b>METHODS</b>A total of 49 patients with MDS or MDS-AML were treated by allo-HSCT, the clinical data was analyzed retrospectively.</p><p><b>RESULTS</b>All patients achieved hematopoietic reconstitution. Neutrophil engraftment was at 10 - 22 days (median 13 days), and platelet engraftment was at 8 - 66 days (median 16 days). The cumulative incidences of Ⅱ-Ⅳ degree acute graft-versus-host disease (GVHD), hemorrhagic cystitis (HC), and hepatic venous occlusive disease (VOD) were 28.6%, 14.3% and 2.0%, respectively. The transplant-related mortality (TRM) was only 4.1% at 100d and 8.2% at 1-92 months of followed-up (median 14 months) period. Overall survival (OS) and disease free survival (DFS) was 75.5%, 73.5%, respectively. Kaplan-Meier curve showed that 3-year OS and 3-year DFS was (71.1 ± 7.8)%, (66.7 ± 8.3)%, respectively, with a relapse incidence (RI) 16.3%. OS for MDS and MDS-AML was 81.5% and 68.2%, and RI in two settings was 3.7%, 31.8%, respectively. OS for MDS-AML at complete remission (CR) and non-CR subgroup was 83.3% and 50.0%, respectively, while cumulative RR was 16.7% and 50.0%, respectively. OS and RI except for non-CR subgroup were 82.1% and 7.7%. Univariate analysis showed that pre-HSCT disease status had correlation with OS (P=0.031), but age, decitabine in conditioning regimen, stem cell source, HLA matching, patient-donor gender, dose of mononuclear cells and GVHD had no correlation with OS.</p><p><b>CONCLUSION</b>Bu/ID-Flu conditioning regimen for MDS and MDS-AML has high efficiency, fewer complications, lower toxicity and TRM. The OS and DFS were higher and RI was lower except for refractory MDS-AML patients. The regimen is valuable for clinical application.</p>

Clinical investigation of reduced-dose voriconazole on primary prevention in invasive fungal disease after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and tolerability of intravenous voriconazole on primary prevention in invasive fungal disease (IFD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>At the time of conditioning regimen, patients without IFD was intravenously administered with voriconazole at a dose of 100 mg two times per day until neutrophils greater than 0.5×10⁹/L. Patients treated with oral fluconazole, 200 mg per day, were control group. The incidence and risk factors of IFD and side effects of medicines were evaluated.</p><p><b>RESULTS</b>Of the total 227 patients, 33 (14.54%) had IFD within 3 months after allo-HSCT. There was significant difference on overall survival between patients with or without IFD by Kaplan-Meier survival curve (P=0.029). Of the 83 cases with intravenous voriconazole, 7 cases occurred IFD (8.43%). In contrast, the incidence of IFD in control group was 18.06% (26 out of 144). There was remarkable difference between the two groups (P=0.048). But there was no significant difference on risk factors of IFD between the two groups. In addition, the incidence of liver function abnormalities between the two groups was no difference. The ratio of auditory hallucination and visual impairment induced by voriconazole was not high.</p><p><b>CONCLUSION</b>Intravenous voriconazole on primary prevention for IFD after allo-HSCT is much better than oral fluconazole with well tolerability and satisfactory efficacy.</p>

Bortezomib-based chemotherapy for patients with multiple myeloma: a single center experience / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of bortezomib-based chemotherapy for 80 patients with multiple myeloma (MM).</p><p><b>METHODS</b>A total of 80 cases with a median age of 57 (range: 25-78) years were enrolled in the study. Bortezomib-based regimens included VD (bortezomib and dexamethasone) and PAD (bortezomib, doxorubicin and dexamethasone). 16 of the 80 patients received autologous or allo-hematopoietic stem cell transplantation (HSCT).</p><p><b>RESULTS</b>The overall response (OR) rate was 80%, including a complete response (CR) of 46.3%. After a median follow-up of 25 months, the 1-year and 2-year overall survival (OS) was 81.4% and 72.9%, and the 2-year progression-free survival (PFS) was 76% and 62.5%, respectively. The 2-year OS and PFS were 100% and 73.9 % in patients with HSCT, while both were 66% (P=0.029) and 58.7% (P=0.447) in patients without HSCT. In univariate analysis, Durie-Salmon group, ISS stage, CR and very good partial response (VGPR), and HSCT were prognostic factors for OS. Gender and extramedullary plasmacytomas were important prognostic factors for PFS. Multivariate analysis by Cox regression revealed that CR and VGPR, Durie-Salmon group A, and HSCT were prognostic factors for better OS; while male and patients without extramedullary plasmacytomas were prognostic factors for longer PFS.</p><p><b>CONCLUSION</b>MM patients could benefit from bortezomib-based chemotherapy with satisfactory efficacy and safety. HSCT could improve the OS for young MM patients.</p>

Effect of CAG induction therapy in patients with acute myeloid leukemia / 中国综合临床

Objective To assess the effect of low-dose cytarabine and aclarubicin in combination with gran-ulocyte colony-stimulating factor (G-CSF) protocol (CAG) in patients with acute myeloid leukemia (AML),and to understand the potential factors affecting the outcome of CAG induction therapy, therefore to find the optimum pa-tients for CAG therapy. Methods Twenty-one AML patients were enrolled in the current study. All patients were treated with CAG regimen including cytarabine (10 mg/m~2, subcutaneously, every 12 h, days 1 - 14), lacinomycin (5～7 mg/m~2,intravenously,every day, days 1 -8) ,and G-CSF (200 μg/m~2,subcutaneously, every day,12 h be-fore Ara-C was given) priming. Results The overall complete remission (CR) rate of the 21 AML patients was 66.7% (14/21). The CR rates was 87.5% (7/8) in patients older than 60 yrs,60.0% (9/15) in the refractory or relapsed patients,83.3% (5/6) in the MDS transformed AML patients. The CR rates for patients with hyperprolif-erative BM and median to poor proliferative BM were 33.3% and 91.7% ,respectively(P =0.009). The median o-verall survival (OS) time of the 21 AML patients was 450 days. Two-year survival rate estimated by Kaplan-Meier Method was 30.6%. The overall median disease free survival (DFS) was 165 days. The median OS time for those refractory or relapsed was 435 days. The median OS time for those with poor cytogenetic state or standard or good cytogenetic state was 140 days and 620 days, respectively (P = 0.001). The median OS time for patients with hyperproliferative BM and median to poor proliferative BM was 321 days and 620 days, respectively (P = 0.05). The median recovery time of granulocytes above 1.0×10~9/L was 8 days. The median duration of fever was 3.5 days. The rate of infections exceeding WHO grade Ⅱ was 42.9%. No early death occurred. Conclusions The CAG induction therapy may have a higher CR rate in patients with refractory or relapsed AML, elderly AML and secondary AML from MDS transformation, and extend the median overall survival time in refractory or relapsed patients. CAG therapy can not improve the outcome of patients whose BM was in high grade proliferation state or whose cytogenetic state was poor. CAG therapy can shorten the duration of agranulocytosis and decrease the inci-dence of serious infection. Therefore, CAG therapy is worth recommending to patients who can not endure the rou-tine intensive chemotherapy.

CT characteristics of thoracoabdominal localized Castleman disease / 中华放射学杂志

Objective To assess the CT characteristics of thoracoabdominal localized Castleman disease (LCD) in 55 cases and correlate with histopathologic features. Methods Fifty-five patients with LCD proved histopathologically in thorax ( n = 25 ) and abdomen ( n = 30 ) were collected during past 20 years. The unenhanced and contrast-enhanced CT were performed in all patients. Two radiologists reviewed CT images and the CT findings were analyzed simultaneously. Results In 54 patients with hyaline-vascular type ( n = 50 ) and mixed type ( n = 4 ) localized CD, the lesion typically presented as solitary mass (90. 7% , 49 cases), with irregular or lobular or infiltrative margin ( 83.3% , 45 cases),central calcification (38. 9%, 21 cases), marked enhancement (100% , 54 cases), focal non-necrosis low attenuation areas (72. 2%, 39 cases), lymphadenopathy (70.4%, 38 cases) and dilated feeding vessels adjacent to the mass (96.3%, 52 cases). One lesion with plasma cell type localized CD presented as a mass with irregular margin, mild enhancement and central necrosis. Four morphologic patterns wereclassified on CT, including solitary mass with well-circumscribed margin (n =4), irregular or lobular margin ( n = 30), infiltrative or halo-like margin ( n = 16 ), and multiple coalescent maasses ( n = 5 ). Conclusion CT features of thoracoabdominal localized CD are closely related to the location and pathological type. LCD with hyaline-vascular and mixed type has typical CT characteristics, while LCD with plasma cell type has no typical CT findings.

Renal Tuberculosis CT Diagnosis and Mis-diagnostic Analysis / 实用放射学杂志

Objective To evaluate the CT values in diagnosis of renal tuberculosis. Methods 26 cases were collected , the CT findings of renal tuberculosis were analysed and compared with the data of operation-pathology and clinical followed up. Results Of 26 cases, 22 cases diagnosed by CT as renal tuberculosis of one side were confirmed by operation-pathology but one (pseudaneurysm). Bilateral renal tuberculosis and renal cysts were diagnosed in 2 cases respectively by CT, while these 4 cases were confirmed as tuberculosis by other auxiliary checking methods and followed-up. The multiple tuberculoses cavities appeared as a petal-shape low-density area and other untypical signs on CT. The single cavity only showed as a low-density area should be distinguished with cystonephrosis. At early renal tuberculosis, a great quantity of effusion beneath the perinephrium was the only sign on CT.Conclusion CT scan has a special value for diagnosis renal tuberculosis. Typical renal tuberculosis can be made closely combining with the clinical information.