Citations

ABSTRACT In this study, we demonstrate that manipulations of temperature and free calcium alter the morphology of the centrin-containing pericentriolar lattice of PtK2 cells. Immunofluorescence microscopy reveals that low-temperature incubation (4°C) causes anti-centrin-labeled pericentrosomal spots to coalesce in the peripheral cytoplasm, and fuses small spots into larger spots near the cell center. At electron microscopic resolution, well-formed pericentriolar satellites appear around the centrioles in response to incubation at 4°C. Elevated free calcium enhances these low-temperature-dependent effects. The data suggest that peri-centrosomal spots correspond to one or more pericentriolar satellites, and that pericentriolar satellites and centrosomal matrix are interconvertable forms of the same material. Transient elevation of intracellular free calcium at 37°C from a basal level of 3.7×10−8 M to a peak level of 2.0×10−7 M within 30 seconds with ionomycin results in a 35% increase in pericentrosomal spot number throughout the cytoplasm. The number of pericentrosomal spots is 50% larger 2 minutes after ionomycin addition; these spots are also nearer to the cell center as compared to 30 seconds after ionomycin addition. As intracellular free calcium returns to a basal level over 5 minutes, the number of spots and their cellular distribution resume a pretreatment value and pattern. We interpret these observations to indicate movement of pericentrosomal spots toward the cell center in response to the flux in intracellular free calcium. Alternatively, it is possible that no movement has occurred, but that the rise in free calcium has unmasked an epitope responsive to our anti-centrin antiserum. Regardless of the interpretation, we conclude that the pericentriolar lattice exhibits calcium-modulated behavior.

Objective Shared decision making (SDM) tools can help implement guideline recommendations for patients with atrial fibrillation (AF) considering stroke prevention strategies. We sought to characterize all available SDM tools for this purpose and examine their quality and clinical impact. Methods We searched through multiple bibliographic databases, social media, and an SDM tool repository from inception to May 2020 and contacted authors of identified SDM tools. Eligible tools had to offer information about warfarin and ≥1 direct oral anticoagulant. We extracted tool characteristics, assessed their adherence to the International Patient Decision Aids Standards, and obtained information about their efficacy in promoting SDM. Results We found 14 SDM tools. Most tools provided up-to-date information about the options, but very few included practical considerations (e.g., out-of-pocket cost). Five of these SDM tools, all used by patients prior to the encounter, were tested in trials at high risk of bias and were found to produce small improvements in patient knowledge and reductions in decisional conflict. Conclusion Several SDM tools for stroke prevention in AF are available, but whether they promote high-quality SDM is yet to be known. The implementation of guidelines for SDM in this context requires user-centered development and evaluation of SDM tools that can effectively promote high-quality SDM and improve stroke prevention in patients with AF.

Background: Artificial intelligence (AI) in healthcare delivery has become an important area of research due to the rapid progression of technology, which has allowed the growth of many processes historically reliant upon human input. AI has become particularly important in plastic surgery in a variety of settings. This article highlights current applications of AI in plastic surgery and discusses future implications. We further detail ethical issues that may arise in the implementation of AI in plastic surgery. Methods: We conducted a systematic literature review of all electronically available publications in the PubMed, Scopus, and Web of Science databases as of February 5, 2020. All returned publications regarding the application of AI in plastic surgery were considered for inclusion. Results: Of the 89 novel articles returned, 14 satisfied inclusion and exclusion criteria. Articles procured from the references of those of the database search and those pertaining to historical and ethical implications were summarized when relevant. Conclusions: Numerous applications of AI exist in plastic surgery. Big data, machine learning, deep learning, natural language processing, and facial recognition are examples of AI-based technology that plastic surgeons may utilize to advance their surgical practice. Like any evolving technology, however, the use of AI in healthcare raises important ethical issues, including patient autonomy and informed consent, confidentiality, and appropriate data use. Such considerations are significant, as high ethical standards are key to appropriate and longstanding implementation of AI.

AbstractBackgroundVascularized omental lymphatic transplant (VOLT) is an increasingly popular treatment of extremity lymphedema given its promising donor site. While the success of VOLT in the treatment of lymphedema has been reported previously, several questions remain.AimTo further elucidate appropriate use of VOLT in the treatment of lymphedema, specifically addressing patient selection, harvest technique, and operative methods.Methods and ResultsA systematic review of VOLT for upper extremity lymphedema was performed. Of 115 yield studies, seven were included for analysis based on inclusion and exclusion criteria. Included studies demonstrated significant reductions in extremity circumference/volume (average volume reduction, 22.7%‐39.5%) as well as subjective improvements using patient‐reported outcomes. Though studies are heterogenous and limited, when analyzed in aggregate, suggest the efficacy of VOLT in lymphedema treatment.ConclusionThis is the largest systematic review of VOLT to date. VOLT continues to show promise as a safe and efficacious surgical intervention for lymphedema in the upper extremity. Further studies are warranted to more definitively identify patients for whom this technique is appropriate as well as ideal harvest and inset technique.

PURPOSETumor tissue from metastatic castration-resistant prostate cancer (mCRPC) harbors frequent copy number variations (CNVs) in the PTEN-PI3K-AKT pathway. However, identifying CNVs in plasma cell–free DNA (cfDNA) has proven to be challenging. With emerging data supporting Akt inhibition in PTEN-deficient mCRPC, we profiled PTEN-PI3K-AKT pathway aberrations in patients with mCRPC using a novel cfDNA assay optimized for CNV detection.METHODSA next-generation sequencing–based cfDNA assay was used to profile 231 patients with mCRPC from two independent cohorts (Australian, n = 78; United States, n = 153). PTEN-PI3K-AKT pathway genomic aberrations were correlated with clinical outcomes, including progression-free survival and overall survival (OS).RESULTSPTEN loss and PIK3CA gain were detected in 37% (85 of 231) and 17% (39 of 231) of patients, respectively. Poorer outcomes were observed in patients with PTEN-PI3K-AKT pathway aberrations, including those with dual PTEN loss and PIK3CA gain (hazard ratio 2.3, 95% CI 1.2 to 4.4). Cumulative CNV burden in the PTEN-PI3K-AKT and androgen receptor (AR) pathways was associated with significantly worse clinical outcomes (0 v 1 v ≥ 2 CNVs in Australian cohort: median OS 33.5 v 17.2 v 9.7 months, P < .001; 0 v 1 v ≥ 2 CNVs in US cohort: median OS 35.5 v 14.3 v 9.2 months, P < .001). Notably, 21% (31 of 146) of PTEN-neutral patients harbored alternative PTEN-PI3K-AKT pathway aberrations.CONCLUSIONPTEN-PI3K-AKT pathway CNVs were readily detected using our cfDNA assay, with the prevalence of PTEN loss comparable with tissue-based studies. Additional PTEN-PI3K-AKT pathway aberrations were found in one fifth of PTEN-neutral cases. Concurrent CNVs in the PTEN-PI3K-AKT and AR pathways portended poor survival, and identifying this high-risk patient subset for dual AR/Akt inhibition may optimize precision treatment with Akt inhibitors in mCRPC.