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.     

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.     

Acute total hip arthroplasty for older patients with acetabular fractures: A meta-analysis

ObjectiveMultiple treatment options for acetabular fractures in geriatric patients exist. However, no large-scale studies have reported the outcomes of acute total hip arthroplasty (THA) in this patient population. We systematically evaluated all available evidence to characterize clinical outcomes, complications, and revisions of acute THA for acetabular fractures in geriatric patients.MethodsMeta-analysis of 21 studies of 430 acetabular fractures with mean follow-up of 44 months (range, 17−97 months). Two independent researchers searched and evaluated the databases of Ovid, Embase, and United States National Library of Medicine using a Boolean search string up to December 2019. Population demographics and complications, including presence of heterotopic ossification (HO), dislocation, infection, revision rate, neurological deficits, and venous thromboembolic event (VTE), were recorded and analyzed.ResultsWeighted mean Harris Hip Score was 83.3 points, and 20% of the patients had reported complications. The most common complication was HO, with a rate of 19.5%. Brooker grade III and IV HO rates were lower at 6.8%. Hip dislocation occurred at a rate of 6.1%, 4.1% of patients developed VTE, deep infection occurred in 3.8%, and neurological complications occurred in 1.9%. Although the revision rate was described in most studies, we were unable to perform a survival analysis because the time to each revision was described in only a few studies. The revision rate was 4.3%.ConclusionsAcute THA is a viable option for treatment of acetabular fracture and can result in acceptable clinical outcomes and survivorship rates in older patients but with an associated complication rate of approximately 20%. Considering the limited treatment options, THA might be a viable alternative for appropriately selected patients.     

前后挤压型骶骨Ⅱ区骨折与骶丛神经损伤的关系

目的 探讨前后挤压致骶骨Ⅱ区骨折造成骶丛神经损伤的机制。方法 经甲醛短期（1年内）浸泡固定的国人尸体6具，12侧。解剖保护骶丛神经，制成前后挤压型暴力致骶Ⅱ区骨折模型，定量测量不同骨折移位时骶丛神经被拉长的距离。另外，利用X线片观察骶从神经受压情况。结果 随耻骨联合分离逐渐增大，骶丛神经张应变呈直线相关逐渐加大，以S1，S4为最显著，且可造成神经的刺伤，多见于L5和S1，X线未发现骶丛神经受压表现。结论 前后挤压型暴力致骶骨Ⅱ区骨折神经损伤以牵拉伤为丰，以S1，S4为主，且与骨折移位程度成正相关关系。神经的刺伤，多见于骨折移位较大的L5和S1。     

Patient-proxy response comparability on measures of patient health and functional status

The present study evaluates the response comparability between 361 elderly hip fracture patients admitted from the community to seven Baltimore area hospitals between 1984 and 1986 and interviewer selected proxies on items pertaining to patients' pre-fracture health and functional status. Agreement across items ranges from very poor to good and varies with respect to the health or functional area assessed. Proxies tend to overestimate patient disability relative to the patients themselves, especially with regard to capacity to perform instrumental activities of daily living. Although proxies who report the greatest contact with patients respond most comparably to the patients, when they do disagree, proxies with the greatest patient contact tend to overestimate patient disability. The authors suggest that attention to item construction and phrasing may improve response comparability.     

A comparison of conventional and fast spin-echo sequences for the measurement of lesion load in multiple sclerosis using a semi-automated contour technique

Changes on serial assessments of brain MRI lesion load are used for monitoring therapeutic efficacy in patients with multiple sclerosis (MS). We assessed the accuracy and reliability of conventional spin-echo (CSE) and fast spin-echo (FSE) sequences for measurement of lesion volume using a semiautomated contour technique. Cranial CSE and FSE examinations of 18 patients with secondary progressive MS were studied. The mean lesion load was slightly higher with the CSE sequence (p = 0.002). Intraobserver variability was significantly higher for FSE than for CSE, according to both the coefficient of variation between two measurements (mean 2.48 % and 1.35 % respectively, p < 0.05) and back-transformed 95 % limits of agreement (1.005–1.060 for FSE; 0.988–1.019 for CSE). Although FSE sequences are quicker and the total lesion volume measurements are similar to those obtained with CSE, the poorer reproducibility raises doubts about the use of FSE to replace CSE in clinical trials. Received: 26 March 1996 Accepted: 4 April 1996     

Nasal fractures in children

Summary A group of thirty children with nasal fractures was evaluated retrospectively by means of a questionnaire and hospital records. Age at the time of injury ranged from age 3 to 12 (mean = 8.6) years and mean follow-up period was 9 years. Eight patients reported some degree of nasal obstruction post reduction, but only one patient required submucous resection and two patients underwent septorhinoplasty for appearance. No patients reported class III malocclusion, or required orthodontic treatment or maxillofacial corrective surgery for maxillary hypoplasia. We concluded that a childhood nasal fracture treated by closed reduction does not have deleterious effects on facial or nasal growth.This work was supported in part by the Brigham Surgical Group Foundation, Inc., Boston, Massachusetts, USA     

HLA-DPB1 gene polymorphism and multiple sclerosis: a large case-control study in the southwest of France

The polymorphism at the HLA-DPB1 locus has been characterized in a large number of patients with multiple sclerosis (n = 112) and in healthy controls (n = 115). Both patients and controls lived in the southwest of France (in the Pyrénées Atlantiques) and had similar ethnic background. The typing procedure involved the selective amplification of the second exon of the DPB1 locus by polymerase chain reaction, followed by hybridization of the amplified DNA with 14 sequence-specific oligonucleotide probes. Individual alleles were identified by the pattern of hybridization of the different probes. The distribution of the DPB1 alleles was not significantly different in multiple sclerosis patients and controls (p = 0.11). This does not corroborate the reported association of multiple sclerosis with the primed lymphocyte typing (PLT)-defined DPw4 specificity and is not in favour of a role played by polymorphic residues of the DP molecule in susceptibility to multiple sclerosis.