超高CD34+采集的动员方案序贯二次自体造血干细胞移植治疗难治性 霍奇金淋巴瘤

目的:探讨超高CD34+采集的动员方案后序贯二次自体造血干细胞移植治疗难治性霍奇金淋巴瘤的疗效和安全性。方法:对1例经过多疗程一线、二线、新药、免疫等均难治的霍奇金淋巴瘤患者，予以IA+C方案化疗+G-CSF动员干细胞后采集出超高水平CD34+细胞，之后行自体造血干细胞移植，移植后获得完全缓解，再予序贯第二次自体造血干细胞移植进行巩固治疗。结果:总计输注单个核细胞数13.67×108/kg，CD34+细胞48.68×106/kg，第一次自体造血干细胞移植术后第7天造血功能恢复，复查全身PET-CT提示获得完全缓解，第二次自体造血干细胞移植术后第8天造血功能恢复，两次自体造血干细胞移植相关并发症均在可控范围内。结论:超高CD34+细胞采集的IA+C方案化疗+G-CSF动员可以让患者有机会进行多次自体造血干细胞移植，是临床动员的创新方案。对于难治性霍奇金淋巴瘤，序贯二次自体造血干细胞移植可达到更深层次缓解，且安全性较高，延长患者无疾病生存期及总生存期，为难治性霍奇金淋巴瘤治疗提供更多临床依据。     

Daratumumab,Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Patients With Previously Treated Multiple Myeloma: Three-year Follow-up of CASTOR

BackgroundIn the phase III CASTOR study in relapsed or refractory multiple myeloma, daratumumab, bortezomib, and dexamethasone (D-Vd) demonstrated significant clinical benefit versus Vd alone. Outcomes after 40.0 months of median follow-up are discussed.Patients and MethodsEligible patients had received ≥ 1 line of treatment and were administered bortezomib (1.3 mg/m²) and dexamethasone (20 mg) for 8 cycles with or without daratumumab (16 mg/kg) until disease progression.ResultsOf 498 patients in the intent-to-treat (ITT) population (D-Vd, n = 251; Vd, n = 247), 47% had 1 prior line of treatment (1PL; D-Vd, n = 122; Vd, n = 113). Median progression-free survival (PFS) was significantly prolonged with D-Vd versus Vd in the ITT population (16.7 vs. 7.1 months; hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.25-0.40; P < .0001) and the 1PL subgroup (27.0 vs. 7.9 months; HR, 0.22; 95% CI, 0.15-0.32; P < .0001). In lenalidomide-refractory patients, the median PFS was 7.8 versus 4.9 months (HR, 0.44; 95% CI, 0.28-0.68; P = .0002) for D-Vd (n = 60) versus Vd (n = 81). Minimal residual disease (MRD)–negativity rates (10⁻⁵) were greater with D-Vd versus Vd (ITT: 14% vs. 2%; 1PL: 20% vs. 3%; both P < .0001). PFS2 was significantly prolonged with D-Vd versus Vd (ITT: HR, 0.48; 95% CI, 0.38-0.61; 1PL: HR, 0.35; 95% CI, 0.24-0.51; P < .0001). No new safety concerns were observed.ConclusionAfter 3 years, D-Vd maintained significant benefits in patients with relapsed or refractory multiple myeloma with a consistent safety profile. D-Vd provided the greatest benefit at first relapse and increased MRD-negativity rates.     

Molecular profiling of Chinese R-CHOP treated DLBCL patients: Identifying a high-risk subgroup

Diffuse large B-cell lymphoma (DLBCL) is a clinically aggressive and heterogenous disease. Although most patients can be cured by immunochemotherapy, 30% to 40% patient will ultimately develop relapsed or refractory disease. Here, we investigated the molecular landscapes of patients with diverse responses to R-CHOP. We performed capture-based targeted sequencing on baseline samples of 105 DLBCL patients using a panel consisting of 112 lymphoma-related genes. Subsequently, 81 treatment-naïve patients with measurable disease and followed for over 1 year were included for survival analysis. Collectively, the most commonly seen mutations included IGH fusion (69%), PIM1(33%), MYD88 (29%), BCL2 (29%), TP53 (29%), CD79B (25%) and KMT2D (24%). Patients with TP53 mutations were more likely to have primary refractory disease (87.0% vs 50.0%, P = .009). For those with TP53 disruptive mutations, 91.7% patients were in the primary refractory group. Interestingly, BCL-2 somatic hypermutation was only seen in patients without primary refractory disease (P = .014). In multivariate analysis, BCL-2 amplification (hazard ratio [HR] = 2.94, P = .022), B2M mutation (HR = 2.99, P = .017) and TP53 mutation (HR = 3.19, P < .001) were independently associated with shorter time to progression (TTP). Furthermore, TP53 mutations was correlated with worse overall survival (P = .049). Next, we investigated mutation landscape in patients with wild-type (WT) TP53 (n = 58) and found that patients harboring MYD88 L265P had significantly inferior TTP than those with WT or non-265P (P = .046). Our study reveals the mutation spectrum of treatment-naive Chinese DLBCL patients. It also confirms the clinical significance of TP53 mutations and indicates the prognostic value of MYD88 L265P in TP53 WT patients.     

参麦注射液联合米力农治疗难治性心力衰竭疗效观察

目的探讨参麦注射液联合米力农治疗难治性心力衰竭的临床效果。方法选择难治性心力衰竭患者92例,依据随机数字的方法分为对照组46例和观察组46例,患者入院后均常规治疗,对照组给予米利农治疗,观察组在对照组治疗方法基础上给予参麦注射液。对两组治疗前后的心型脂肪酸结合蛋白(H-FABP),血浆心肌肌钙蛋白Ⅰ(cTnⅠ),氨基末端B型钠尿肽原(NT-proBNP),心率(HR),左心室射血分数(LVEF),每搏输出量(SV)进行对比。对两组的临床治疗效果进行对比。对两组治疗过程中的不良反应对比。结果经过治疗后,对照组的H-FABP从(17.23±3.51)ng/L降低到(15.11±3.12)ng/L,NT-proBNP从(8.13±2.32)μg/L降低到(6.51±1.45)μg/L,cTnⅠ从(31.25±5.01)ng/L降低到(23.81±4.25)ng/L,观察组的H-FABP从(16.97±3.78)ng/L降低到(9.91±3.01)ng/L,NT-proBNP从(8.21±1.98)μg/L降低到(4.13±1.34)μg/L,cTnⅠ从(32.07±5.23)ng/L降低到(18.81±5.12)ng/L,观察组的变化幅度大于对照组,数据差异均具有统计学意义(t=8.135,8.176,5.096,P<0.05),经过治疗后,对照组的HR从(135.26±10.51)次/min降低到(103.81±9.81)次/min,LVEF从(32.41±5.41)%升高到(38.31±4.87)%,SV从(37.91±2.71)mL升高到(43.23±3.47)mL,观察组的HR从(134.81±11.28)次/min降低到(95.31±9.97)次/min,LVEF从(31.87±5.37)%升高到(43.21±4.25)%,SV从(38.11±3.13)mL升高到(50.91±3.68)mL,观察组的变化幅度大于对照组,数据差异均具有统计学意义(t=4.122,-5.142,-10.298,P<0.05),观察组的治疗效果优于对照组,数据差异具有统计学意义(z=-4.994,P<0.05),两组的恶心[4.35%(2/46)VS. 2.17%(1/46)],血压低[6.52%(3/46)VS. 4.35%(2/46)],头晕[8.70%(4/46)VS. 13.04%(6/46)],乏力[15.22%(7/46)VS. 8.70%(4/46)],呕吐[4.35%(2/46)VS. 6.52%(3/46)],室性早搏[2.17%(1/46)VS. 4.35%(2/46)],发生率数据差异均不具有统计学意义(χ^2=0.000,0.000,0.449,0.929,0.000,0.000,P>0.05)。结论利用参麦注射液联合米力农治疗难治性心力衰竭,可以改善心肌功能,提升治疗效果,安全性良好。     

苇茎汤合麻杏石甘汤加减联合半量激素治疗儿童毒热闭肺证难治性肺炎支原体肺炎

目的:观察苇茎汤合麻杏石甘汤加减联合半量激素治疗儿童毒热闭肺型难治性肺炎支原体肺炎的临床疗效。方法:120例患儿随机分为对照组和观察组,各60例。在基础治疗基础上,对照组给予连花清瘟颗粒+甲强尼龙(每次10 mg·kg-1,2次/日),观察组给予苇茎汤合麻杏石甘汤加减+甲强尼龙(每次10 mg·kg-1,1次/日),疗程均为14 d。观察两组治疗前后肺功能指标[最大通气量(MVV),呼气达峰时间(TPTEF),第1秒用力呼气容积(FEV1),呼气达峰容积(VPTEF)],血浆心肌酶谱[肌酸激酶(CK),肌酸激酶同工酶(CKMB),乳酸脱氢酶(LDH),胫丁酸脱氢酶(HBDH)],免疫功能[免疫球蛋白G(IgG),免疫球蛋白M(IgM),红细胞免疫复合物(RBC-ICR),红细胞C3b受体(RBC-C3bR)],炎性因子[肿瘤坏死因子-α(TNF-α),γ-干扰素(IFN-γ),白细胞介素-13(IL-13),白细胞介素-17A(IL-17A)],临床疗效和不良反应。结果:研究期间脱落4例。观察组总有效率96.6%(57/59),高于对照组的84.2%(48/57)(P<0.05)。与对照组治疗后比较,观察组MVV,TPTEF,FEV1,VPTEF,RBC-C3bR,IL-13升高(P<0.05);CK,CKMB,LDH,HBDH,IgG,IgM,RBC-ICR,TNF-α,IFN-γ和IL-17A降低(P<0.05)。观察组不良反应发生率低于对照组(P<0.05)。结论:苇茎汤合麻杏石甘汤加减联合半量激素可明显改善毒热闭肺型难治性肺炎支原体肺炎患儿的肺功能,心肌酶谱,免疫功能和炎性因子水平,不良反应发生率低。     

从气从痰论治顽固性胃食管反流病

胃食管反流病多因饮食不节、七情失和、素体禀赋虚弱等原因,导致脾胃受损,土壅木郁,肝胃不和,胃失和降,胃气上逆,出现反酸、烧心、嗳气、胃胀等症状。其发生与肝、脾、胃密切相关,气机逆乱,胃失和降是其基本病机。由于本病病程较长,病情易反复发作,易成为顽固性胃食管反流病。而顽固性胃食管反流病多为本虚标实之证,本虚是指因疾病反复发作所导致的脾胃虚弱,标实是指由于脾胃虚弱、脾失健运、土壅木郁、气机不畅所导致的痰湿、气滞、热郁、血瘀等实邪。最后结局是痰气郁(瘀)交阻,脾胃升降失司,胃气上逆,从而引起反酸烧心反复发作,缠绵难愈。纵观核心病机,乃"气郁"、"痰阻"导致的胃失和降、胃气上逆。治疗顽固性胃食管反流病时宜"从气而治""从痰而治"。     

Refractory Ascites After Liver Transplantation: An Analysis of 1058 Liver Transplant Patients at a Single Center

A retrospective study of 1058 liver transplant recipients was performed to determine: (i) the incidence, etiology, timing, clinical features and treatment of refractory ascites (RA), (ii) risk factors for RA development, (iii) predictors of RA disappearance, (iv) predictors of survival following RA and (v) the impact of RA on patient survival. Sixty-two patients (5.9%) developed RA and its disappearance occurred in 27/62 cases. Patients having hepatitis C virus (HCV) had a significantly higher hazard rate of developing RA (p < 0.00001). No other baseline characteristic was associated with RA. Cox stepwise regression analysis of the hazard rate of RA disappearance found two significant factors: HCV recurrence as the reason for developing RA implied a poorer outcome (p = 0.006), whereas an unknown reason implied a favorable outcome (p = 0.02). In addition, survival following RA was significantly poorer among patients having bacterial peritonitis or HCV recurrence. Finally, the mortality rate was significantly (nearly 8.6 times) higher in patients following RA development while it was ongoing (p < 0.00001); however, if the RA disappeared, then the additional risk of death also disappeared. This study illustrates the importance of developing an optimal treatment strategy to (i) effectively treat RA if it develops and (ii) prevent hepatitis C recurrence.