Citations

Cutaneous reactions to red tattoo pigment rarely manifest as pseudolymphomatous reactions. We describe an exceedingly rare case of red tattoo‐related T‐cell predominant pseudolymphoma microscopically mimicking mycosis fungoides. Careful clinicopathological correlation was required to obtain the correct diagnosis and aid in an effective treatment course.

The purpose of this guideline is to provide information for the interpretation of clinical dihydropyrimidine dehydrogenase ( DPYD ) genotype tests so that the results can be used to guide dosing of fluoropyrimidines (5‐fluorouracil and capecitabine). Detailed guidelines for the use of fluoropyrimidines, their clinical pharmacology, as well as analyses of cost‐effectiveness are beyond the scope of this document. The Clinical Pharmacogenetics Implementation Consortium (CPIC ® ) guidelines consider the situation of patients for which genotype data are already available (updates available at https://cpicpgx.org/guidelines/guideline‐for‐fluoropyrimidines‐and‐dpyd/ ).

AbstractIntroductionWe sought to assess the individual and combined contribution of limbic and neocortical α‐synuclein, tau, and amyloid β (Aβ) to duration of illness in dementia with Lewy bodies (DLB).MethodsQuantitative digital pathology of limbic and neocortical α‐synuclein, tau, and Aβ was assessed in 49 patients with clinically probable DLB. Regression modeling examined the unique and shared contribution of each pathology to the variance of illness duration.ResultsPatients with diffuse Lewy body disease had more severe pathology of each type and a shorter duration of illness than individuals with transitional Lewy body disease. The three pathologies accounted for 25% of the total variance of duration of illness, with 19% accounted for by α‐synuclein alone or in combination with tau and Aβ. When the diffuse Lewy body disease group was examined separately, α‐synuclein deposition significantly exceeded that of tau and Aβ. In this model, 20% of 24% total variance in the model for duration of illness was accounted for independently by α‐synuclein.DiscussionIn DLB, α‐synuclein is an important predictor of disease duration, both independently and synergistically with tau and Aβ.

Current compression garments are often made from a spandex-type elastic material with static levels of compression and can become uncomfortable and difficult to don/doff [1]. This limits their usability, especially for unhealthy or aging populations. The only current alternative to elastic compression stockings are inflatable compression sleeves that are controllable, but highly immobile and must be tethered to an inflation source [2]. Neither design offers a solution that is simultaneously low profile, mobile, and controllable. Here we present the design and development of compression garments with embedded shape-changing materials that can produce controllable compression without the need for a bulky inflation system. This active materials approach enables dynamic control over the degree, timing and location of compression, and allows for graded, synchronized, pulsed, and peristaltic compression patterns, which provide the medical benefit of moving fluid in the body [2]. Such a design combines the best features of both elastic and inflatable compression garments: a slim, low-profile form factor that is easy to don/doff and provides dynamic control. Shape memory alloy (SMA) coil actuators, as described by Holschuh et al., [3] have the ability to apply compressive forces to the body when paired with passive textiles and wrapped circumferentially around the body. These actuators are engineered to contract when heated, creating controllable forces and displacements that are modulated through an applied current. SMA compression garments (SMA-CG) have important applications, from consumer uses to clinical interventions, including: augmenting venous return for conditions of orthostatic intolerance (e.g., postural orthostatic tachycardia syndrome (POTS)); cardiac rehabilitation in heart failure patients; lymphedema venous insufficiency; reducing deep vein thrombosis (DVT) risk; sports performance; and countermeasures for flight or space flight. While the potential uses for this technology are broad, the basic design is similar across many conditions. Key research areas include: 1) identifying and addressing design considerations relevant to prototype development of SMA-CG; 2) determining the compression thresholds needed to dynamically oppose orthostatic changes; and 3) evaluating the effectiveness of the prototypes for augmented venous return by synchronizing compression during cardiac diastole. Here, we focus on the first question: design of SMA-CG prototypes.

Abstract Introduction Comparative transcriptome analyses in Alzheimer's disease (AD) and other neurodegenerative proteinopathies can uncover both shared and distinct disease pathways. Methods We analyzed 940 brain transcriptomes including patients with AD, progressive supranuclear palsy (PSP; a primary tauopathy), and control subjects. Results We identified transcriptional coexpression networks implicated in myelination, which were lower in PSP temporal cortex (TCX) compared with AD. Some of these associations were retained even after adjustments for brain cell population changes. These TCX myelination network structures were preserved in cerebellum but they were not differentially expressed in cerebellum between AD and PSP. Myelination networks were downregulated in both AD and PSP, when compared with control TCX samples. Discussion Downregulation of myelination networks may underlie both PSP and AD pathophysiology, but may be more pronounced in PSP. These data also highlight conservation of transcriptional networks across brain regions and the influence of cell type changes on these networks.

Cutaneous reactions from targeted biologics are increasingly common. We describe a case of a cutaneous lichenoid drug eruption from the RANK inhibitor denosumab and a previously unreported lymphohistiocytic reaction pattern. The clinical and histopathological details of this case will aid in recognition, diagnosis, and treatment of drug rashes from denosumab.

Abstract: Calciphylaxis is a rare, painful, and life-threatening condition with a high mortality rate. Although the etiology of calciphylaxis is not well understood, it has been proposed that calcium deposition within and around subcutaneous vessels restricts blood flow chronically, thereby predisposing the patient to acute pannicular and dermal thrombosis. Given increasing recognition of the role of hypercoagulability in calciphylaxis, this retrospective cohort study sought to evaluate the presence of thromboses and dermal angioplasia in calciphylaxis. Moreover, we aimed to validate previous observations about the histopathology of calciphylaxis compared with skin biopsies from patients with end-stage renal disease but without calciphylaxis. After a meticulous clinical chart review, we assessed the corresponding skin biopsies for the presence of vessel calcification, thromboses, and dermal angioplasia in skin biopsies from patients with calciphylaxis (n = 57) and compared with those from patients with end-stage renal disease but without calciphylaxis (n = 26). Histopathologic findings were correlated with clinical features such as chronic kidney disease, diabetes, or associated malignancy. Our results validated a prior observation that calciphylaxis was significantly more likely to show calcification of dermal vessels and diffuse dermal thrombi. This study reports the frequent finding of dermal angioplasia, a potential marker of chronic low-grade ischemia, as another frequent microscopic finding in calciphylaxis. Among cases of calciphylaxis, histopathologic changes in patients with chronic kidney disease were indistinguishable from those in patients without chronic kidney disease, thereby implying a final common pathogenic pathway in both uremic and nonuremic calciphylaxis. In future, larger, prospective studies may be useful in validating these findings.