A comparative safety review of histone deacetylase inhibitors for the treatment of myeloma

Introduction: Dysregulation of histone deacetylase (HDAC) activity is an epigenetic hallmark of multiple myeloma (MM), leading to aberrant gene expression and cellular signaling in myeloma cell growth, survival and resistance to therapy. Hyper-methylation at diagnosis is a frequent observation, which eventually may convert to hypo-methylation during advanced phases.

Areas covered: A literature search on ‘HDAC inhibitors’ and ‘multiple myeloma’ was carried out using PubMed and Google Scholar in the preparation of this overview on clinical efficacy and safety data.

Expert opinion: First-generation non-selective HDAC inhibitors have demonstrated minimal single-agent activity in refractory MM. Subsequently, combination therapy has proven an improvement in progression-free survival (PFS) but not response rates. The main concerns are associated with toxicities. Ongoing studies on new and more selective agents, i.e. Romidepsin or Ricolinostat, are promising in terms of better efficacy and less toxicity.     

单侧外固定治疗重度Pilon骨折的临床疗效探究

目的探讨单侧外固定治疗重度Pilon骨折的临床疗效。方法回顾性分析2017年6月-2018年12月南京中大医院江北院区骨科收治的重度Pilon骨折患者100例,男性54例,女性46例;年龄18~65岁,平均35.5岁;Ruedi-AllgowerⅡ型39例,Ⅲ型61例。按照不同固定方法分为常规固定组和单侧外固定组,各50例,比较两组患者住院时间、完全负重下地时间、骨折愈合时间,评价治疗前及治疗后3个月踝关节活动度、踝关节功能恢复情况、疼痛程度,并统计患者的治疗效果及并发症发生情况。结果单侧外固定组住院时间、完全负重下地时间、骨折愈合时间分别为(16.50±1.50)d、(132.56±10.25)d、(14.16±0.69)周,均短于常规固定组(19.25±2.35)d、(198.65±16.58)d、(17.58±1.50)周(t/P=6.975/0.001、23.970/0.001、14.650/0.001)。治疗后3个月,单侧外固定组踝关节Mazur评分为(85.67±6.59)分,显著高于常规固定组(62.78±3.45)分,VAS评分为(2.23±0.36)分,低于常规固定组(4.59±0.89)分(t/P=21.760/0.001、17.380/0.001);单侧外固定组患者踝关节活动度分别为(17.29±0.16)°、(28.36±1.23)°、(19.68±0.16)°、(16.89±2.12)°,均高于常规固定组(10.62±1.25)°、(21.57±2.58)°、(14.36±1.62)°、(14.25±0.57)°(t/P=37.430/0.001、16.800/0.001、23.110/0.001、8.503/0.001)。单侧外固定组治疗优良率为90.00%,显著高于常规固定组74.00%(χ^2/P=4.336/0.037)。单侧外固定组总并发症发生率为4.00%,显著低于常规固定组的18.00%(χ^2/P=5.005/0.025)。结论单侧外固定支架治疗重度Pilon骨折可有效减轻患者疼痛症状,提高患者踝关节活动度,恢复患者功能,治疗效果显著,安全性较高。     

老年人桡骨远端C型骨折的手术治疗与非手术治疗的疗效对比

目的：探讨老年人桡骨远端C型骨折的手术治疗与非手术治疗的疗效差异，评价两种方法的优缺点。方法回顾性分析2009-12—2011-12收治的老年桡骨远端C型骨折68例，按照治疗方法分为A组(手术组)及B组(非手术组)，统计分析两组患者的临床资料。结果 A组33例， B组35例，平均随访21.5个月。两组患者的年龄、骨折类型均无差异(P＞0.05)；术后影像学指标A组优于B组，骨折愈合时间B组优于A组，治疗成本A组大于B组(P＜0.05)；Cooney评分早期A组优于B组，1年后两组无差异，两组的并发症无差异(P＞0.05)。结论老年人桡骨远端C型骨折手术治疗较非手术治疗可获得更好的复位及早期功能，但远期功能恢复无差异。     

Survival and Outcomes of Newly Diagnosed Multiple Myeloma Patients Stratified by Transplant Status 2007-2018: Retrospective Analysis from the Canadian Myeloma Research Group Database

BackgroundConsiderable progress has been made in therapeutic options for multiple myeloma (MM). Understanding the current landscape of MM treatment options and associated outcomes in the real world is important in providing key insights into clinical and knowledge gaps which could be targeted for further optimization.MethodsThe Canadian Myeloma Research Group Database (CMRG-DB) is a prospectively maintained disease-specific database with >7000 patients. The objective of this study was to describe the trends in the treatment landscape and outcomes including early mortality, time to next treatment, and overall survival (OS) in each line of treatment stratified by autologous stem cell transplant (ASCT) receipt among newly-diagnosed MM patients in Canada between 2007 and 2018.ResultsA total of 5154 patients were identified among which 3030 patients (58.8%) received an upfront ASCT and 2124 (41.2%) did not. At diagnosis, the median age was 64 years and 58.6% were males. Bortezomib and lenalidomide were most frequently used (>50%) in first and second-line treatment respectively among both the ASCT and non-ASCT cohort. The median OS was 122.0 months (95% Cl 115.0-135.0 months) and 54.3 months (95% CI 50.8-58.8 months) for the ASCT and non-ASCT cohort respectively with an incremental decrease in OS in each subsequent line of treatment.ConclusionWe present the largest study to date in the Canadian landscape showing the characteristics, therapy usage, and outcomes among MM patients. This information will be critical in benchmarking current outcomes and provide key insight into areas of unmet needs and gaps for improvement of MM patients nationally.     

Acceptance of multiple injectable vaccines in a single immunization visit in The Gambia pre and post introduction of inactivated polio vaccine

BackgroundAs the World Health Organization (WHO) currently recommends that children be protected against 11 different pathogens, it is becoming increasingly necessary to administer multiple injectable vaccines during a single immunization visit. In this study we assess Gambian healthcare providers’ and infant caregivers’ attitudes and practices related to the administration of multiple injectable vaccines to a child at a single immunization visit before and after the 2015 introduction of inactivated polio vaccine (IPV). IPV introduction increased the number of injectable vaccines recommended for the 4-month immunization visit from two to three in The Gambia.MethodsWe conducted a cross-sectional questionnaire-based survey before and after the introduction of IPV at 4 months of age in a representative sample of all health facilities providing immunizations in The Gambia. Healthcare providers who administer vaccines at the selected health facilities and caregivers who brought infants for their 4 month immunization visit were surveyed.FindingsPrior to IPV introduction, 9.9% of healthcare providers and 35.7% of infant caregivers expressed concern about a child receiving more than 2 injections in a single visit. Nevertheless, 98.8% and 90.9% of infants received all required vaccinations for the visit before and after IPV introduction, respectively. The only reason why vaccines were not received was vaccine stock-outs. Infant caregivers generally agreed that vaccinators could be trusted to provide accurate information regarding the number of vaccines that a child needed.ConclusionHealthcare providers and infant caregivers in this resource limited setting accepted an increase in the number of injectable vaccines administered at a single visit even though some expressed concerns about the increase.     

经皮椎弓根技术治疗胸腰椎骨折的临床探讨

目的:探讨微创经皮椎弓根螺钉内固定手术治疗胸腰椎骨折的可行性及其疗效。方法:20例胸腰椎骨折病例,男13例,女7例;年龄28~65岁,平均48·2岁。其中16例损伤平面以下无神经功能损害、无双下肢和大小便障碍;4例有不同程度的脊髓损伤,按Frankel分级:C级1例,D级3例。在C形臂X线的定位下确定需要固定的椎弓根根部,做4个1·5cm长的切口,固定与复位均在4个小切口内完成。结果:所有病例均获随访,时间9~18个月,平均15个月。术后患者椎体高度均有不同程度恢复,椎体后凸畸形获得不同程度矫正。手术时间约1·5h,出血量约80ml。结论:微创经皮椎弓根螺钉内固定手术操作简便、安全可靠,具有创伤小、出血少、疼痛轻、恢复快、住院时间短等优点。     

AO钢板内固定治疗跟骨骨折

目的 探讨复杂跟骨骨折治疗方法及AO钢板内固定价值.方法 应用AO钢板治疗累及距下关节的跟骨骨折24例,术中注意关节面复位和Bohler角的恢复.结果 24例病人经12～24个月随访,按照Fernandez评定标准:24例跟骨SandersⅡ-Ⅳ型骨折病人有18足评为优良.结论 距下关节面的复位和Bohler角的恢复,牢固的内固定和术后足够长时间的负重限制是成功的关键.     

下肢复杂骨折交锁髓内钉治疗粉碎骨折螺钉辅助固定的意义

[目的]探索在交锁髓内钉治疗下肢复杂骨折中粉碎骨折块辅助固定的意义。[方法]下肢复杂骨折78例根据AO分型均为C型骨折，通过交锁髓内钉内固定，辅以拉力螺钉固定。[结果]术后摄片骨折及骨折块达解剖或功能复位，随诊6～24个月，优良率为94．88％（74／78例）。[结论]四肢复杂骨折治疗中，粉碎骨折块的螺钉辅助固定能够加强交锁髓内钉的稳定性，减少断钉、断棒现象，有利于骨折愈合。