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BackgroundProgressive supranuclear palsy is a neurodegenerative tauopathy manifesting clinically as a progressive akinetic-rigid syndrome. In this study, we sought to identify genetic variants influencing PSP susceptibility through a genome-wide association analysis of a cohort of well-characterized patients who had participated in the Neuroprotection and Natural History in Parkinson Plus Syndromes and Blood Brain Barrier in Parkinson Plus Syndromes studies.MethodsWe genotyped single-nucleotide polymorphisms in 283 PSP cases from the United Kingdom, Germany, and France and compared these with genotypes from 4472 controls. Copy number variants were identified from genotyping data.ResultsWe observed associations on chromosome 17 within or close to the MAPT gene and explored the genetic architecture at this locus. We confirmed the previously reported association of rs1768208 in the MOBP gene (P = 3.29 × 10-13 ) and rs1411478 in STX6 (P = 3.45 × 10-10 ). The population-attributable risk from the MAPT, MOBP, and STX6 single-nucleotide polymorphisms was found to be 0.37, 0.26, and 0.08, respectively. In addition, we found 2 instances of copy number variants spanning the MAPT gene in patients with PSP. These copy number variants include tau but few other genes within the chromosome 17 haplotype region, providing additional support for the direct pathogenicity of MAPT in PSP.ConclusionsClinicians should also be aware of MAPT duplication as a possible genetic cause of PSP, especially in patients presenting with young age at onset. © 2019 International Parkinson and Movement Disorder Society.

Objectives Measurable residual disease flow cytometry (MRD-FC) and molecular studies are the most sensitive methods for detecting residual malignant populations after therapy for TP53 -mutated acute myeloid leukemia and myelodysplastic neoplasms (TP53+ AML/MDS). However, their sensitivity is limited in suboptimal aspirates or when the immunophenotype of the neoplastic blasts overlaps with erythroids or normal maturing myeloid cells. In this study, we set out to determine if p53 immunohistochemistry (IHC) correlates with MRD-FC and next-generation sequencing (NGS) in the posttherapy setting and to determine the utility of p53 IHC to detect residual disease in the setting of negative or equivocal MRD-FC. Methods We retrospectively identified 28 pre- and posttherapy bone marrow biopsy specimens from 9 patients with TP53+ AML/MDS and a p53 overexpressor phenotype by IHC (strong 3+ staining at initial diagnosis). Next-generation sequencing and/or MRD-FC results were collected for each specimen. Results Using a threshold of more than ten 2-3+ cells in any one 400× field, p53 IHC detected residual disease with a sensitivity of 94% and a specificity of 89%. The threshold used in this study showed a high degree of concordance among 6 blinded pathologists (Fleiss κ = 0.97). Conclusions Our study suggests that p53 IHC can be used as a rapid tool (within 24 hours) to aid in the detection of residual disease that may complement MRD-FC or NGS in cases in which the flow cytometry immunophenotype is equivocal and/or the bone marrow aspirate is suboptimal. [ABSTRACT FROM AUTHOR]

Trichodysplasia spinulosa polyomavirus (TSPyV) is an alphapolyomavirus whose primary clinical manifestation in a posttransplant setting is folliculocentric papular cutaneous eruptions, typically involving the face (1). Identification of TSPyV nucleic acids [...]

Context.--Mutational signatures have been described in the literature and a few centers have implemented pipelines for clinical reporting. Objective.--To describe the performance of a mutational signature caller with clinical samples sequenced on a targeted next-generation sequencing panel with a small genomic footprint. Design.--One thousand six hundred eighty-two clinical samples were analyzed for the presence of mutational signatures using deconstructSigs on variant calls with at least 20 variant reads. Results.--Signature 10 (associated with POLe mutation) achieved separation of cases and controls in hypermutated samples. Signatures 4 (associated with tobacco smoking) and 7 (associated with ultraviolet radiation) as an indicator of pulmonary or cutaneous primary sites showed moderate sensitivity and high specificity at optimal cutpoints. Mutational signatures in malignancies with unknown primaries were somewhat consistent with the clinically suspected primary site, with an apparent dose-response relationship between the number of variants analyzed and the ability of mutational signature analysis to correctly suggest a primary site. Conclusions.--Mutational signatures represent an opportunity for orthogonal testing of primary site, which may be particularly useful in supporting cutaneous or pulmonary sites in poorly differentiated neoplasms. Tobacco smoking, ultraviolet radiation, and POLe mutational signatures are the most appropriate signatures for implementation. Even relatively small numbers of variants appear capable of supporting a clinically suspected primary. (Arch Pathol Lab Med. 2021;145:1424-1431; doi: 10.5858/arpa.2020-0536-OA), Mutational signatures have been described in the literature (1) and reflect the presence of mutagenic exposures present during a tumor's evolution. Various types of mutational signatures have been described, including [...]

Background: Viral infection is an oncogenic factor in many hematolymphoid malignancies. We sought to determine the diagnostic yield of aligning off‐target reads incidentally obtained during targeted hematolymphoid next‐generation sequencing to a large database of viral genomes to screen for viral sequences within tumor specimens. Methods: Alignment of off‐target reads to viral genomes was performed using magicBLAST. Localization of Merkel cell polyomavirus (MCPyV) RNA was confirmed by RNAScope in situ hybridization. Integration analysis was performed using Virus‐Clip. Results: Four cases of post‐cardiac‐transplant folliculotropic mycosis fungoides (fMF) and one case of peripheral T‐cell lymphoma (PTCL) were positive in off‐target reads for MCPyV DNA. Two of the four cases of posttransplant fMF and the case of PTCL showed localization of MCPyV RNA to malignant lymphocytes, whereas the remaining two cases of posttransplant fMF showed MCPyV RNA in keratinocytes. Conclusions: Our findings raise the question of whether MCPyV may play a role in rare cases of T‐lymphoproliferative disorders, particularly in the skin and in the heavily immunosuppressed posttransplant setting. [ABSTRACT FROM AUTHOR]

Objective: Describe the relationship among rurality, socioeconomic status (SES), and patient/tumor characteristics in patients presenting with head and neck cancer. Study Design: Retrospective single-institution study. Setting: Academic tertiary-level medical center. Methods: Patients with head and neck cancer presenting between 2011 and 2015 were included. Stage at presentation, insurance status, and demographic characteristics were collected. Rurality was measured through Rural-Urban Continuum Codes. SES was measured by SES index scores of the Agency for Healthcare Research and Quality, which incorporate multiple components of SES. Associations among rurality, SES, and patient/tumor characteristics were assessed with univariate and multivariable statistics. All P values were calculated via 2-sided hypotheses. The threshold for statistical significance was set at P <.05. Statistical analyses were conducted with Stata/SE 14 (StataCorp). Results: The study included 266 patients diagnosed with head and neck cancer between 2011 and 2015. Rural residence was associated with lower SES (P <.001). T and N stages were associated with rurality (P =.036 and.050, respectively). Higher educational status was associated with oropharyngeal cancer (P =.005). Conclusions: Rurality and SES have distinct impacts on patients with head and neck cancer. Specifically, rurality is associated with tumor stage among patients with head and neck cancer. Knowledge of disparities among patients with rural residency may help target interventions to facilitate earlier diagnosis. [ABSTRACT FROM AUTHOR]

Background There is a lack of population-based, multi-institutional analyses of factors associated with morbidity and mortality following pituitary tumor excision. Methods The American College of Surgeons National Surgical Quality Improvement Project files were used to compile information on patients that had undergone transnasal microscopic pituitary tumor resection from 2006 to 2012. Patient demographics, comorbidities, operative characteristics, and morbidity and mortality in the 30 days following surgery were included. Multivariate logistic regression was used for categorical variables and multivariate linear regression was used for continuous variables to evaluate factors leading to adverse events. Results A total of 658 patients were included, of which 58 (8.81%) experienced a complication, reoperation or death in the 30 days following surgery. The most common complications were reoperation (3.37%), followed by unplanned reintubation (1.99%), urinary tract infection (1.68%), and transfusion (1.68%). Predictors of any complication, reoperation, or death include preoperative sepsis (odds ratio [OR] = 7.596) and lower preoperative serum albumin (OR = 6.667). Younger age predicted surgical complications (OR = 1.105). Predictors of medical complications include higher body mass index (OR = 1.112), chronic steroid use (OR = 6.568), preoperative sepsis (OR = 15.297), and lower preoperative serum hematocrit (OR = 1.225). Predictors of increased total length of hospital stay were older age (β = 0.146), higher body mass index (β = 0.188), chronic steroid use (β = 0.142), preoperative sepsis (β = 0.489), and lower preoperative serum albumin (β = −0.213). Conclusion Although adverse events following pituitary tumor excision are low, awareness of factors associated with morbidity and mortality in the early postoperative period may allow for improved patient monitoring and outcomes. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis Recognition of the potentially severe sequelae arising from inadequate facial protection has facilitated sustained efforts to increase the use of protective visors in recent decades. Our objective was to characterize nationwide trends among patients presenting to emergency departments (ED) for facial injuries sustained while playing ice hockey. Methods The National Electronic Injury Surveillance System was searched for hockey-related facial injuries, with analysis for incidence; age and gender; and specific injury diagnoses, mechanisms, and facial locations. Results There were an estimated 93,444 ED visits for hockey-related facial injuries from 2003 to 2012. The number of annual ED visits declined by 43.8% from 2003 to 2012. A total of 90.6% of patients were male; and the peak age of injury was 17 years. Lacerations were the most common form of facial injury (81.5% of patients) across all age groups. Contusions/abrasions and fractures followed in frequency, with fractures increasing with advancing age. Conclusions The overall incidence of ED visits due to facial injuries from ice hockey has significantly decreased over the last decade, concurrent with increased societal use of facial protective equipment. Nonetheless, facial hockey injuries facilitate a significant number of ED visits among both adults and children; thus, the knowledge of demographic-specific trends described in this analysis is relevant for physicians involved in the management of facial trauma. These findings reinforce the need to educate individuals who play hockey about the importance of appropriate facial protection. Level of Evidence 4. Laryngoscope, 125:589-593, 2015 [ABSTRACT FROM AUTHOR]

Presents the poem "Dorothy," by Lauren Lawrence. First Line: The straw man is rutted; Last Line: To find your way home.

Presents the poem "Articulations," by Lauren Lawrence. First Line: Your words articulated their limbs; Last Line: Where you need to go.