Gaps and opportunities in the treatment of relapsed-refractory multiple myeloma: Consensus recommendations of the NCI Multiple Myeloma Steering Committee

A wide variety of new therapeutic options for Multiple Myeloma (MM) have recently become available, extending progression-free and overall survival for patients in meaningful ways. However, these treatments are not curative, and patients eventually relapse, necessitating decisions on the appropriate choice of treatment(s) for the next phase of the disease. Additionally, an important subset of MM patients will prove to be refractory to the majority of the available treatments, requiring selection of effective therapies from the remaining options. Immunomodulatory agents (IMiDs), proteasome inhibitors, monoclonal antibodies, and alkylating agents are the major classes of MM therapies, with several options in each class. Patients who are refractory to one agent in a class may be responsive to a related compound or to a drug from a different class. However, rules for selection of alternative treatments in these situations are somewhat empirical and later phase clinical trials to inform those choices are ongoing. To address these issues the NCI Multiple Myeloma Steering Committee formed a relapsed/refractory working group to review optimal treatment choices, timing, and sequencing and provide recommendations. Additional issues considered include the role of salvage autologous stem cell transplantation, risk stratification, targeted approaches for genetic subsets of MM, appropriate clinical trial endpoints, and promising investigational agents. This report summarizes the deliberations of the working group and suggests potential avenues of research to improve the precision, timing, and durability of treatments for Myeloma.Subject terms: Combination drug therapy, Cancer therapeutic resistance, Targeted therapies     

Refeeding Syndrome: A Critical Reality in Patients with Chronic Disease

Malnutrition is one of the most frequent metabolic challenges in the population of chronically ill patients. This results in increased administration of nutritional therapy in inpatient settings, which poses the risk of side effects, in particular, the development of refeeding syndrome. If not managed accordingly, it leads to a significant rise in morbidity and mortality. However, despite its importance, evidence-based recommendations on the management of refeeding syndrome are largely lacking, and only a few randomized controlled trials have been conducted. In light of this, the aim of this review is to raise awareness of refeeding syndrome in chronically ill patients by critically reviewing recent literature and providing a short overview as well as diagnosis and treatment algorithms of this underreported metabolic condition. In summary, recent findings suggest undergoing risk assessment and stratification for every patient receiving nutritional therapy. According to this, adaptation of energy and fluid support during the replenishment phase should be implemented in the nutritional therapy for patients at high risk. Additionally, continuous monitoring should take place, and appropriate actions should be initiated when necessary.     

Global,regional and national burden of disease attributable to 19 selected occupational risk factors for 183 countries, 2000–2016: A systematic analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury

ObjectivesWe provide a brief introduction to the objectives, data, methods and results of the World Health Organization (WHO)/International Labor Organization (ILO) Joint Estimates of the Work-related Burden of Disease and Injury (WHO/ILO Joint Estimates), which estimated the burden attributable to 19 selected occupational risk factors.MethodsThe WHO/ILO Joint Estimates were produced within the global Comparative Risk Assessment framework, which attributes the burden of one specific health outcome (ie, disease/injury) to a specific occupational risk factor. For 39 established occupational risk factor-health outcome pairs, estimates are produced using population attributable fractions (PAF) from recent burden of disease estimates. For two additional pairs, PAF are calculated from new databases of exposure and risk ratios produced in WHO/ILO systematic reviews. Attributable disease burdens were estimated by applying the PAF to total disease burdens.ResultsGlobally in 2016, it is estimated that 1.88 [95% uncertainty range (UR) 1.84–1.92] million deaths and 89.72 (95% UR 88.61–90.83) million disability-adjusted life years were attributable to the 19 selected occupational risk factors and their health outcomes. A disproportionately large work-related burden of disease is observed in the WHO African Region (for disability-adjusted life years), South-East Asia Region, and Western Pacific Region (for deaths), males and older age groups.ConclusionsThe WHO/ILO Joint Estimates can be used for global monitoring of exposure to occupational risk factors and work-related burden of disease and to identify, plan, cost, implement and evaluate policies, programs and actions to prevent exposure to occupational risk factors and their associated burden.     

A diagnostic dilemma: lupus nephritis or renal polyarteritis nodosa?

Lupus nephritis and renal polyarteritis nodosa (PAN) are two distinct disorders that rarely overlap. Herein, we describe a patient who was initially diagnosed with lupus nephritis based on her clinical presentation, proteinuria, hematuria, positive anti-nuclear antibody, and a kidney biopsy. A month later, the patient presented with left flank pain and weakness. A CT scan of the abdomen and pelvis showed a perinephric hematoma and the renal arteriogram revealed numerous microaneurysms within the kidney consistent with renal PAN. This case elucidates the diagnostic and management dilemmas that confront physicians taking care of patients with overlapping features of lupus nephritis and renal PAN and also points to the possible role of lupus nephritis in pathogenesis of renal PAN.     

Solid lipid microparticles containing loratadine prepared using a Micromixer

Solid lipid microparticles were investigated as a taste-masking approach for a lipophilic weak base in a suspension. The idea was that the drug concentration in the aqueous phase of a suspension might be reduced by its partitioning into the solid lipid particles. Loratadine, as a model drug, was used to prepare Precirol® ATO 5 microparticles by a Micromixer. The effects of three process variables: drug loading, PVA concentration and water/lipid ratio on the microparticle size, encapsulation efficiency, surface appearance, in-vitro release and drug partitioning in a suspension were studied. Loratadine release was slow in simulated saliva and very fast at the pH of stomach. In suspension of loratadine lipid microparticles, drug was released into the aqueous phase to the same concentration as in a drug suspension. Therefore, the usefulness of these microparticles for taste-masking in liquids is limited. However, they might be useful for taste-masking in solid dosage forms.     

Systematic review of minimally invasive ablation treatment for locally advanced pancreatic cancer

Unresectable locally advanced pancreatic cancer with or without metastatic disease is associated with a very poor prognosis. Ablation techniques are based on direct application of chemical, thermal, or electrical energy to a tumor, which leads to cellular necrosis. Initial studies about ablation therapies of the pancreas were associated with significant morbidity and mortality, which limited widespread adoption. Modifications to the various applications, in particular combining the techniques with high-quality imaging and intra-operative approach has enabled real-time treatment monitoring and significant improvements in safety. Inoperable cases of pancreatic cancer have been treated by various ablation techniques in the last few years with promising results. The purpose of this review is to present the current status of local ablative therapies in the treatment of pancreatic advanced tumor.     

Development of microsatellite markers from 454 transcriptome derived sequences for the scallop Pecten maximus

Twelve microsatellite markers were developed for the scallop Pecten maximus. The markers were tested in three geographically diverse populations and all markers were polymorphic in all three populations. The mean number of alleles per locus ranged from 2 to 10.67 and the observed and expected heterozygosity ranged from 0.05 to 0.67 and 0.05 to 0.81 respectively. Some loci showed evidence of null alleles and an excess of homozygotes in some populations but 9 loci conformed to Hardy–Weinberg expectations. These new loci can be combined with previously published microsatellites to create a powerful suite of markers for genetic analyses.