Citations

Patient education has been transformed using digital media and online repositories which disseminate information with greater efficiency. In dermatology, this transformation has allowed for patients to gain education on common cutaneous conditions and improve health literacy. Xanthelasma palpebrarum is one of the most common cutaneous conditions, yet there is a poor understanding of how digital materials affect health literacy on this condition. Our study aimed to address this paucity of literature utilizing Brief DISCERN, Rothwell’s Classification of Questions, and six readability calculations. The findings of this study indicate a poor-quality profile (Brief DISCERN < 16) regarding digital materials and readability scores which do not meet grade-level recommendations in the United States. This indicates a need to improve the current body of educational materials used by clinicians for diagnosing and managing xanthelasma palpebrarum.

TPS4204 Background: The role of neoadjuvant chemotherapy in resectable pancreatic cancer has yet to be defined. Recent phase II trial results demonstrate a median overall survival time (mOS) of only 22.4 months after treatment with perioperative modified FOLFIRINOX (mFOLFIRINOX) with 36% not reaching surgery due to disease progression during neoadjuvant therapy. While potential benefits and shortcomings of neoadjuvant chemotherapy have been well documented, to date, no phase III trial has directly compared a perioperative versus an adjuvant chemotherapy strategy in resectable pancreatic cancer. Alliance for Clinical Trials in Oncology A021806 is an actively accruing randomized controlled phase III trial evaluating the efficacy of perioperative chemotherapy with mFOLFIRINOX in patients with resectable pancreatic cancer. Methods: To qualify for enrollment, patients must have biopsy-proven localized resectable pancreatic adenocarcinoma as defined by the National Comprehensive Cancer Network. Patients must have good performance status (ECOG 0 or 1) and be candidates to receive mFOLFIRINOX treatment. All patients enrolled undergo central radiologic eligibility review for quality control and are then randomized to either Arm 1 which consists of 8 cycles of neoadjuvant mFOLFIRINOX followed by 4 cycles of adjuvant mFOLFIRINOX or Arm 2 which includes upfront surgery followed by 12 cycles of adjuvant mFOLFIRINOX. The primary endpoint of the trial is overall survival with secondary endpoints evaluating disease-free survival, margin-negative resection rate, surgical complications, and chemotherapeutic adverse events. Additional correlative endpoints include quality of life and radiomic imaging assessments. A total enrollment of 352 patients is planned from the US and Canada; current enrollment for this trial is at 145 patients. An OS interim analysis will be performed when 50% of the events (124) are observed combining the two arms. If the trial continues after interim analysis, the final OS analysis will be performed with a total of 248 events (combined arms). If the Cox model (stratified by tumor location and ECOG PS) comparing OS between arms produces a one-sided p-value < 0.05, then we will conclude that the OS of the perioperative therapy arm is superior to adjuvant therapy. The Alliance A021806 phase III trial aims to define a new standard of care for patients with resectable pancreatic cancer. Clinical trial information: NCT04340141 .

Abstract Background/Objective A subset of patients with idiopathic inflammatory myopathy (IIM) develops highly fatal, rapidly progressive interstitial lung disease (RP-ILD). Treatment strategies consist of glucocorticoid and adjunctive immunosuppressive therapies. Plasma exchange (PE) is an alternative therapy, but its benefit is unclear. In this study, we aimed to determine whether PE benefited outcomes for patients with RP-ILD. Methods In this medical records review study, we compared baseline characteristics and clinical outcomes for 2 groups of patients with IIM-related RP-ILD: those who received and did not receive PE. Results Our cohort consisted of 15 patients, 9 of whom received PE. Baseline demographic characteristics and severity of lung, skin, and musculoskeletal disease between the 2 groups of patients were not significantly different. Five patients required mechanical ventilation (2, PE; 3, no PE). Plasma exchange was generally a third-line adjunctive treatment option. The PE group had a longer median (interquartile range) hospitalization (27.0 [23.0–36.0] days) than the non-PE group (12.0 [8.0–14.0] days) (p = 0.02). There was a potential benefit in 30-day mortality improvement in those receiving PE (0% vs 33%, p = 0.14), with a statistically significant improvement in 2 important composite end points including 30-day mortality or need for lung transplant (0% vs 50%, p = 0.04) and 1-year mortality or need for lung transplant or hospital readmission for RP-ILD in those receiving PE (22% vs 83%, p = 0.04). Conclusions Plasma exchange may be an underutilized, safe salvage therapy for patients with IIM-related RP-ILD when other immunosuppressive therapies fail.

Chronic nausea and vomiting syndromes (NVSs) are prevalent and debilitating disorders. Putative mechanisms include gastric neuromuscular disease and dysregulation of brain-gut interaction, but clinical tests for objectively defining gastric motor function are lacking. A medical device enabling noninvasive body surface gastric mapping (BSGM) was developed and applied to evaluate NVS pathophysiology. BSGM was performed in 43 patients with NVS and 43 matched controls using Gastric Alimetry (Alimetry), a conformable high-resolution array (8 × 8 electrodes; 20-mm interelectrode spacing), wearable reader, and validated symptom-logging app. Continuous measurement encompassed a fasting baseline (30 minutes), 482-kilocalorie meal, and 4-hour postprandial recording, followed by spectral and spatial biomarker analyses. Meal responses were impaired in NVS, with reduced amplitudes compared to controls (median, 23.3 microvolts versus 38.0 microvolts, P < 0.001), impaired fed-fasting power ratios (1.1 versus 1.6, P = 0.02), and disorganized slow waves (spatial frequency stability, 13.6 versus 49.5; P < 0.001). Two distinct NVS subgroups were evident with indistinguishable symptoms (all P > 0.05). Most patients (62%) had normal BSGM studies with increased psychological comorbidities (43.5% versus 7.7%; P = 0.03) and anxiety scores (median, 16.5 versus 13.0; P = 0.035). A smaller subgroup (31%) had markedly abnormal BSGM, with biomarkers correlating with symptoms (nausea, pain, excessive fullness, early satiety, and bloating; all r > 0.35, P < 0.05). Patients with NVS share overlapping symptoms but comprise distinct underlying phenotypes as revealed by a BSGM device. These phenotypes correlate with symptoms, which should inform clinical management and therapeutic trial design.

Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P &amp;lt; .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P &amp;lt; .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P &amp;lt; .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

Background Current mortality data for pulmonary arterial hypertension (PAH) in the United States are based on registries that enrolled patients prior to 2010. We sought to determine mortality in PAH in the modern era using the PHAR (Pulmonary Hypertension Association Registry). Methods and Results We identified all adult patients with PAH enrolled in the PHAR between September 2015 and September 2020 (N=935). We used Kaplan‐Meier survival analysis and Cox proportional hazards models to assess mortality at 1, 2, and 3 years. Patients were stratified based on disease severity by 3 validated risk scores. In treatment‐naïve patients, we compared survival based on initial treatment strategy. The median age was 56 years (44–68 years), and 76% were women. Of the 935 patients, 483 (52%) were ≤6 months from PAH diagnosis. There were 121 deaths (12.9%) during a median follow‐up time of 489 days (281–812 days). The 1‐, 2‐, and 3‐year mortality was 8% (95% CI, 6%–10%), 16% (95% CI, 13%–19%), and 21% (95% CI, 17%–25%), respectively. When stratified into low‐, intermediate‐, and high‐risk PAH, the mortality at 1, 2, and 3 years was 1%, 4% to 6%, and 7% to 11% for low risk; 7% to 8%, 11% to 16%, and 18% to 20% for intermediate risk; and 12% to 19%, 22% to 38%, and 28% to 55% for high risk, respectively. In treatment‐naïve patients, initial combination therapy was associated with better 1‐year survival (adjusted hazard ratio, 0.43 [95% CI, 0.19–0.95]; P =0.037). Conclusions Mortality in the intermediate‐ and high‐risk patients with PAH remains unacceptably high in the PHAR, suggesting the importance for early diagnosis, aggressive use of available therapies, and the need for better therapeutics.

BACKGROUND Malnutrition is common among patients with cancer and is a known risk factor for poor postoperative outcomes; however, preoperative nutritional optimization guidelines are lacking in this high-risk population. The objective of this study was to review the evidence regarding preoperative nutritional optimization of patients undergoing general surgical operations for the treatment of cancer. METHODS A literature search was performed across the Ovid (MEDLINE), Cochrane Library (Wiley), Embase (Elsevier), CINAHL (EBSCOhost), and Web of Science (Clarivate) databases. Eligible studies included randomized clinical trials, observational studies, reviews, and meta-analyses published between 2010 and 2020. Included studies evaluated clinical outcomes after preoperative nutritional interventions among adult patients undergoing surgery for gastrointestinal cancer. Data extraction was performed using a template developed and tested by the study team. RESULTS A total of 5,505 publications were identified, of which 69 studies were included for data synthesis after screening and full text review. These studies evaluated preoperative nutritional counseling, protein-calorie supplementation, immunonutrition supplementation, and probiotic or symbiotic supplementation. CONCLUSIONS Preoperative nutritional counseling and immunonutrition supplementation should be considered for patients undergoing surgical treatment of gastrointestinal malignancy. For malnourished patients, protein-calorie supplementation should be considered, and for patients undergoing colorectal cancer surgery, probiotics or symbiotic supplementation should be considered.

Bizarre (atypical/symplastic) cells have been described in various gynecologic normal tissues and benign neoplasms. This type of bizarre cytologic change is usually an incidental finding and is regarded as a benign process. We describe 17 cases of bizarre chorionic-type trophoblast in second-trimester and third-trimester placentas that created concern for an underlying/undersampled or incipient intraplacental trophoblastic neoplasm, predominantly found in intervillous trophoblastic islands (11/17), placental septae (6/17), chorionic plate (1/17), and/or the chorion layer of fetal membranes (2/17). The bizarre trophoblastic cells exhibited sheet-like or nested architecture, had a multifocal/patchy distribution, and/or were present as individual cells within hyaline stroma; they were characterized by large nuclei with smudgy chromatin and occasional intranuclear pseudoinclusions. The degree of atypia was classified as mild (0/17), moderate (3/17), or severe (14/17). Mitotic figures and necrosis were not identified. A dual immunohistochemical stain for trophoblast (hydroxyl-delta-5-steroid dehydrogenase) and a proliferation marker (Ki-67), performed in 15 cases, demonstrated 0% to very low proliferative activity within the bizarre trophoblast (0% to 2% [10/15], 3% to 8% [5/15]). Immunohistochemical stains for fumarate hydratase showed intact/retained expression in the bizarre cells in 7 of 7 cases. Clinical follow-up ranged from 1 to 45 months, and all patients were alive and well without subsequent evidence of a gestational trophoblastic or other neoplasms. We conclude that bizarre chorionic-type trophoblast in second-trimester or third-trimester placentas have the potential to mimic an intraplacental trophoblastic neoplasm but are likely a benign degenerative change. This study expands the spectrum of bizarre cells that occur in the gynecologic tract.

Abstract Background Since its emergence in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose a risk to healthcare personnel (HCP) and patients in healthcare settings. Although all clinical interactions likely carry some risk of transmission, human actions, such as coughing, and care activities, such as aerosol-generating procedures, likely have a higher risk of transmission. The rapid emergence and global spread of SARS-CoV-2 continues to create significant challenges in healthcare facilities, particularly with shortages of the personal protective equipment (PPE) used by HCP. Evidence-based recommendations for what PPE to use in conventional, contingency, and crisis standards of care continue to be needed. Where evidence is lacking, the development of specific research questions can help direct funders and investigators. The purpose of the current study was to develop evidence-based rapid guidelines intended to support HCP in their decisions about infection prevention when caring for patients with suspected or known coronavirus disease 2019 (COVID-19). Methods The Infectious Diseases Society of America (IDSA) formed a multidisciplinary guideline panel including frontline clinicians, infectious disease specialists, experts in infection control, and guideline methodologists, with representation from the disciplines of public health, medical microbiology, pediatrics, critical care medicine and gastroenterology. The process followed a rapid recommendation checklist. The panel prioritized questions and outcomes. Then a systematic review of the peer-reviewed and gray literature was conducted. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations. Results The IDSA guideline panel agreed on 8 recommendations, including 2 updated recommendations and 1 new recommendation added since the first version of the guideline. Narrative summaries of other interventions undergoing evaluations are also included. Conclusions Using a combination of direct and indirect evidence, the panel was able to provide recommendations for 8 specific questions on the use of PPE by HCP providing care for patients with suspected or known COVID-19. Where evidence was lacking, attempts were made to provide potential avenues for investigation. There remain significant gaps in the understanding of the transmission dynamics of SARS-CoV-2, and PPE recommendations may need to be modified in response to new evidence. These recommendations should serve as a minimum for PPE use in healthcare facilities and do not preclude decisions based on local risk assessments or requirements of local health jurisdictions or other regulatory bodies.

Wolframin-1–positive neurons in the entorhinal cortex of mouse brain propagate tau to the hippocampal CA1 region resulting in memory impairment.