Perinatal and familial risk factors for soft tissue sarcomas in childhood through young adulthood: A population-based assessment in 4 million live births

Perinatal factors have been associated with soft tissue sarcomas (STS) in case-control studies. However, (i) the contributions of factors including fetal growth remain unknown, ( ii ) these factors have not been examined in cohort studies and (iii) few assessments have evaluated risk in specific STS subtypes. We sought to identify the role of perinatal and familial factors on the risk of STS in a large population-based birth cohort. We identified 4,023,436 individuals in the Swedish Birth Registry born during 1973–2012. Subjects were linked to the Swedish Cancer Registry, where incident STS cases were identified. We evaluated perinatal and familial factors obtained from Statistics Sweden, including fetal growth, gestational age, and presence of a congenital malformation. Poisson regression was used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for associations between perinatal factors and STS overall, as well as by common subtypes. There were 673 individuals diagnosed with STS in 77.5 million person-years of follow-up. Having a congenital malformation was associated with STS (IRR = 1.70, 95% CI: 1.23–2.35). This association was stronger (IRR = 2.90, 95% CI: 1.25–6.71) in recent years (2000–2012). Low fetal growth was also associated with STS during the same time period (IRR = 1.86, 95% CI: 1.05–3.29). Being born preterm was associated with rhabdomyosarcoma (IRR = 1.74, 95% CI: 1.08–2.79). In our cohort study, those with congenital malformations and other adverse birth outcomes were more likely to develop a STS compared to their unaffected contemporaries. These associations may point to disrupted developmental pathways and genetic factors influencing the risk of STS.     

Characteristics and risk factors of bortezomib induced peripheral neuropathy: A systematic review of phase III trials

Bortezomib-induced peripheral neuropathy (BIPN) is a common toxicity associated with the treatment of multiple myeloma (MM), typically requiring dose reduction, delay, or cessation of treatment protocol. This systematic review aimed to investigate risk factors, trends, and variability associated with the development of BIPN. Searches were undertaken using Medline, PubMed, Cochrane Central Register of Controlled Trials, Embase, Scopus, and Web of Science. Additional studies were identified by investigating authors' bibliographic references cited by original and review articles. Articles that reported on neuropathy in phase III randomised control trials involving bortezomib in any treatment arm for the treatment of MM were included in this review. A total of 43 full text articles met criteria, which examined 23 phase III trials (N = 8218). Overall incidence of neuropathy ranged from 8.4% to 80.5% (median = 37.8%) and severe neuropathy (grade 3-4) ranged from 1% to 33.2% (median = 8%). Similar reports of neuropathy of any grade and severe neuropathy were observed between the newly diagnosed and relapsed cohort. Bortezomib regimens with reduced dose intensity were associated with reduced neuropathy incidence. Increased cumulative dosing levels, intravenous compared with subcutaneous administration and combination therapy with thalidomide were associated with higher rates of BIPN. This analysis revealed that BIPN is a significant toxicity. More sensitive measures are required to capture the incidence and severity of BIPN. Better understanding of risk factors and reversibility profiles will minimise the number of cancer survivors living with residual treatment side effects.     

Assessment of music experience after cochlear implantation: A review of current tools and their utilization

ObjectiveTo provide an overview of the current available music assessment tools after cochlear implantation (CI); to report on the utilization of music assessments in the literature; to propose potential future directions in music assessment after CI.MethodsA thorough search was performed in PubMed, Embase, and The Cochrane Library through October 31, 2020. MeSH search terms, keywords, and phrases included “cochlear implant,” “cochlear prosthesis,” “auditory prosthesis,” “music,” “music assessment,” “music questionnaire,” “music perception,” “music enjoyment, and “music experience.” Potentially relevant studies were reviewed for inclusion, with particular focus on assessments developed specifically for the cochlear implant population and intended for widespread use.Results/conclusionsSix hundred and forty-three studies were screened for relevance to assessment of music experience among cochlear implantees. Eighty-one studies ultimately met criteria for inclusion. There are multiple validated tools for assessment of music experience after cochlear implantation, each of which provide slightly differing insights into the patients’ subjective and/or objective post-activation experience. However, no single assessment tool has been adopted into widespread use and thus, much of the literature pertaining to this topic evaluates outcomes non-uniformly, including single-use assessments designed specifically for the study at hand. The lack of a widely accepted universal tool for assessment of music limits our collective understanding the contributory and mitigating factors applicable to current music experience of cochlear implantees, and limits our ability to uniformly evaluate the success of new implant technologies or music training paradigms.     

Pivarubicin Is More Effective Than Doxorubicin Against Triple-Negative Breast Cancer In Vivo

Triple-negative breast cancer (TNBC) is unresponsive to antiestrogen and anti-HER2 therapies, requiring the use of cytotoxic drug combinations of anthracyclines, taxanes, cyclophosphamide, and platinum compounds. Multidrug therapies achieve pathological cure rates of only 20–40%, a consequence of drug resistance and cumulative dose limitations necessitated by the reversible cardiotoxic effects of drug therapy. Safer and more effective treatments for TNBC are required to achieve durable therapeutic responses. This study describes the mechanistic analyses of the novel anthracycline, pivarubicin, and its in vivo efficacy against human primary TNBC. Pivarubicin directly activates PKCd, triggers rapid mitochondrial-dependent apoptosis, and circumvents resistance conferred by overexpression of P-glycoprotein, Bcl-2, Bcl-X_L, and Bcr-Abl. As a consequence, pivarubicin is more cytotoxic than doxorubicin against MDA-MB-231, and SUM159 TNBC cell lines grown in both monolayer culture and tumorspheres. Comparative in vivo efficacy of pivarubicin and doxorubicin was performed in an orthotopic NSG mouse model implanted with MDA-MB-231 human TNBC cells and treated with the maximum tolerated doses (MTDs) of pivarubicin and doxorubicin. Tumor growth was monitored by digital caliper measurements and determination of endpoint tumor weight and volume. Endpoint cardiotoxicity was assessed histologically by identifying microvacuolization in ventricular cardiomyocytes. Primary tumors treated with multiple rounds of doxorubicin at MTD failed to inhibit tumor growth compared with vehicletreated tumors. However, administration of a single MTD of pivarubicin produced significant inhibition of tumor growth and tumor regression relative to tumor volume prior to initiation of treatment. Histological analysis of hearts excised from drug- and vehicle-treated mice revealed that pivarubicin produced no evidence of myocardial damage at a therapeutic dose. These results support the development of pivarubicin as a safer and more effective replacement for doxorubicin against TNBC as well as other malignancies for which doxorubicin therapy is indicated.