Citations

Abstract The congenital heart care community faces a myriad of public health issues that act as barriers toward optimum patient outcomes. In this article, we attempt to define advocacy and policy initiatives meant to spotlight and potentially address these challenges. Issues are organized into the following 3 key facets of our community: patient population, health care delivery, and workforce. We discuss the social determinants of health and health care disparities that affect patients in the community that require the attention of policy makers. Furthermore, we highlight the many needs of the growing adults with congenital heart disease and those with comorbidities, highlighting concerns regarding the inequities in access to cardiac care and the need for multidisciplinary care. We also recognize the problems of transparency in outcomes reporting and the promising application of telehealth. Finally, we highlight the training of providers, measures of productivity, diversity in the workforce, and the importance of patient–family centered organizations in advocating for patients. Although all of these issues remain relevant to many subspecialties in medicine, this article attempts to illustrate the unique needs of this population and highlight ways in which to work together to address important opportunities for change in the cardiac care community and beyond. This article provides a framework for policy and advocacy efforts for the next decade.

The Clinical and Laboratory Standards Institute (CLSI) Subcommittee on Antimicrobial Susceptibility Testing (AST) develops and publishes standards and guidelines for AST methods and results interpretation in an annual update to the Performance Standards for Antimicrobial Susceptibility Testing (M100). This minireview will discuss changes to M100 for the 31st edition, including new and revised breakpoints and testing recommendations.

Invasive infections with emerging yeasts such asGeotrichum,Saprochaete/Magnusiomyces, Trichosporon, and other species are associated with high morbidity and mortality rates. Due to the rarity and heterogeneity of these yeasts, medical mycology has lacked guidance in critical areas affecting patient management.

AbstractBackground and purposePerry disease (or Perry syndrome) is an autosomal dominant neurodegenerative disorder characterized by parkinsonism, neuropsychiatric symptoms, central hypoventilation, weight loss and distinct TDP‐43 pathology. It is caused by mutations of the DCTN1 gene encoding an essential component of axonal transport. The objectives were to provide the current state of knowledge on clinical, pathological and genetic aspects of Perry disease, as well as practical suggestions for the management of the disease.MethodsData on new patients from New Zealand, Poland and Colombia were collected, including autopsy report. Also all of the published papers since the original work by Perry in 1975 were gathered and analyzed.ResultsParkinsonism was symmetrical, progressed rapidly and was poorly responsive to L‐Dopa; nonetheless, a trial with high doses of L‐Dopa is warranted. Depression was severe, associated with suicidal ideations, and benefited from antidepressants and L‐Dopa. Respiratory symptoms were the leading cause of death, and artificial ventilation or a diaphragm pacemaker prolonged survival. Weight loss occurred in most patients and was of multifactorial etiology. Autonomic dysfunction was frequent but underdiagnosed. There was a clinical overlap with other neurodegenerative disorders. An autopsy showed distinctive pallidonigral degeneration with TDP‐43 pathology. Genetic testing provided evidence of a common founder for two families. There was striking phenotypic variability in DCTN1‐related disorders. It is hypothesized that oligogenic or polygenic inheritance is at play.ConclusionsPerry disease and other DCTN1‐related diseases are increasingly diagnosed worldwide. Relatively effective symptomatic treatments are available. Further studies are needed to pave the way toward curative/gene therapy.

AbstractObjectiveTau hyperphosphorylation at threonine 217 (pT217) in cerebrospinal fluid (CSF) has recently been linked to early amyloidosis and could serve as a highly sensitive biomarker for Alzheimer’s disease (AD). However, it remains unclear whether other tauopathies induce pT217 modifications. To determine if pT217 modification is specific to AD, CSF pT217 was measured in AD and other tauopathies.MethodsUsing immunoprecipitation and mass spectrometry methods, we compared CSF T217 phosphorylation occupancy (pT217/T217) and amyloid‐beta (Aβ) 42/40 ratio in cognitively normal individuals and those with symptomatic AD, progressive supranuclear palsy, corticobasal syndrome, and sporadic and familial frontotemporal dementia.ResultsIndividuals with AD had high CSF pT217/T217 and low Aβ42/40. In contrast, cognitively normal individuals and the majority of those with 4R tauopathies had low CSF pT217/T217 and normal Aβ 42/40. We identified a subgroup of individuals with increased CSF pT217/T217 and normal Aβ 42/40 ratio, most of whom were MAPT R406W mutation carriers. Diagnostic accuracies of CSF Aβ 42/40 and CSF pT217/T217, alone and in combination were compared. We show that CSF pT217/T217 × CSF Aβ 42/40 is a sensitive composite biomarker that can separate MAPT R406W carriers from cognitively normal individuals and those with other tauopathies.InterpretationMAPT R406W is a tau mutation that leads to 3R+4R tauopathy similar to AD, but without amyloid neuropathology. These findings suggest that change in CSF pT217/T217 ratio is not specific to AD and might reflect common downstream tau pathophysiology common to 3R+4R tauopathies.

Abstract Background: Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. Methods: We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values<5x10-8 as genome-wide significant, and p-values<1x10-5 as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants.Results: None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values<1x105. The strongest evidence was found for rs4674019 (p-value=2.27x10-7), which showed genome-wide significant interaction (p-value=3.8x10-8) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen-progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. Conclusions: In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT–breast cancer risk association.

Personalized treatment of genetically stratified subgroups has the potential to improve outcomes in many malignant tumors. This study distills clinically meaningful prognostic/predictive genomic marker for cervical adenocarcinoma using signature genomic aberrations and single-point nonsynonymous mutation-specific droplet digital PCR (ddPCR). Mutations in PIK3CA E542K, E545K, or H1047R were detected in 41.7% of tumors. PIK3CA mutation detected in the patient’s circulating DNA collected before treatment or during follow-up was significantly associated with decreased progression-free survival or overall survival. PIK3CA mutation in the circulating DNA during follow-up after treatment predicted recurrence with 100% sensitivity and 64.29% specificity. It is the first indication of the predictive power of PIK3CA mutations in cervical adenocarcinoma. The work contributes to the development of liquid biopsies for follow up surveillance and a possibility of tailoring management of this particular women’s cancer.