Citations

ABSTRACTDespite advancements in the neurophysiology of language and presurgical evaluation for epilepsy surgery, there is a paucity of information in the literature regarding presurgical evaluation of multilingual patients. We present a case of a 52‐year‐old right‐handed woman with refractory epilepsy who was fluent in six languages and underwent subsequent trilingual presurgical evaluation which included neuropsychological testing, Wada testing, functional magnetic resonance imaging (fMRI), and electrocortical stimulation. These studies suggested a seizure focus in the left temporal lobe and language localization that was predominantly right‐hemispheric; she subsequently underwent left temporal laser interstitial thermal therapy without clinical disturbance in language function while remaining seizure‐free. A multidisciplinary effort was integral in providing an optimal outcome for this patient.

Background: Isolation measures used to contain epidemics generate social interaction restrictions and impose changes in routines of the public that increase negative psychological outcomes. Anxiety and depression are the most common symptoms. Objective: To evaluate the mental health of the Brazilian population during the SARs-CoV-2 pandemic and its relationship with demographic and health characteristics. Methods: Adults from all Brazilian States participated (n = 12,196; women: 69.8%, mean age = 35.2 years). The Depression, Anxiety and Stress Scale, and the Impact of Event Scale–revised were used (online survey). Data validity and reliability were verified by confirmatory factor analysis and ordinal alpha coefficient. The probability of presenting psychological symptoms was calculated by multiple logistic regression and odds ratio (OR) (0 = without symptoms, 1 = with mild, moderate, and severe levels of symptoms). Results: High prevalence of depression (61.3%), anxiety (44.2%), stress (50.8%), and psychological impact (54.9%) due to the isolation experienced from the pandemic was found. Younger individuals (OR = 1.58–3.58), those that felt unsafe (OR = 1.75–2.92), with a previous diagnosis of mental health (OR = 1.72–2.64) and/or had general health problems before the pandemic (OR = 1.17–1.51), who noticed changes in their mental state due to the pandemic context (OR = 2.53–9.07), and excessively exposed to the news (OR = 1.19–2.18) were at increased risk of developing symptoms. Women (OR = 1.35–1.65) and those with lower economic status (OR = 1.38–2.69) were more likely to develop psychological symptoms. Lower educational levels increased the likelihood of depressive (OR = 1.03–1.34) and intrusive symptoms (OR = 1.09–1.51). Conclusions: The pandemic and related factors can have a high impact on the mental health of the population. Demographic characteristics can influence the occurrence of psychological symptoms.

Abstract Our objective was to validate the NSABP 8-gene trastuzumab-benefit signature, developed and initially validated in NRG Oncology/NSABP B-31 in Alliance/NCCTG N9831. The B-31 and N9831 trials demonstrated the benefit of adding trastuzumab to chemotherapy in the adjuvant setting for HER2+ breast cancer patients. NSABP investigators utilized gene expression profiles of N9831 patients (N = 892) to blindly assign patients to large-, moderate-, or no-trastuzumab benefit groups and then NCCTG investigators assessed the degree of trastuzumab benefit using Cox models adjusted for age, nodes, estrogen receptor/progesterone receptor status, tumor size, and grade. Hazard ratios and 2-sided P values for recurrence-free survival of the predicted large- (n = 387), moderate- (n = 401), and no-benefit (n = 104) groups, based on the 8-gene signature were 0.47 (95% CI = 0.31 to 0.73, P < .001), 0.60 (95% CI = 0.39 to 0.92, P = .02), and 1.54 (95% CI = 0.59 to 4.02, P = .38), respectively (Pinteraction = .02), providing validation of the 8-gene signature in an independent study.

Objectives: There remains a paucity of data describing the efficacy of non-operative treatment following an index anterior instability event. The purpose of this study was to describe the long-term outcomes of non-operative treatment following index anterior instability event, define the success rate of initial non-operative treatment for anterior shoulder instability, and describe factors that predict conversion to surgery after initial non-operative management to help guide surgical decision making in these patients. Methods: An established geographic database was utilized to identify patients under the age of 40 treated for anterior shoulder instability between 1994 and 2016. Patient demographics, comorbidities, injury characteristics, instability history, activity level, x-rays, advanced imaging, treatment course, and outcomes were evaluated. Patients treated non-operatively for the first 6 months following index instability event were analyzed to determine long-term outcomes, success rate of continued non-operative treatment, and factors associated with conversion to surgery. Results: 739 patients met criteria with an average follow-up of 190 months (range 0.13 to 490 months). Average age was 23.8, mean BMI was 25.6, 9.1% had a history of hyperlaxity, and 83.9% of instability events were due to trauma. 29.7% of patients had a Hill-Sachs lesion on index x-ray, and 6.3% had a bony Bankart. 198 shoulders went on to operative treatment (26.8%) with a mean time to surgery of 62.7 months following initial instability event. At final follow-up, 24.0% reported mild pain, 6.2% as moderate, 0.2% as severe. 13.8% of patients had evidence of glenohumeral arthritis on final follow-up x-rays compared to 1.6% on initial radiographs. Factors associated with conversion to surgery included 2 or more dislocations prior to first clinical evaluation (OR=1.75, p<0.001), labor intense occupation (OR=1.49, p=0.031), Hill Sachs lesion on index x-ray (OR=1.31, p=0.034), and MRI findings including: anteroinferior labral tear (OR=2.15, p<0.001), posteroinferior labral tear (OR=1.38, p=0.049), SLAP tear (OR=1.29, p=0.054), Hill-Sachs lesion (OR=1.85, p<0.001), and glenohumeral cartilage injury (OR=1.26, p=0.041). Conclusion: The majority of patients less than 40 can be definitively treated non-operatively after an initial 6 month episode of non-operative treatment. A small proportion will report pain over the long-term and/or develop glenohumeral arthritis. Multiple factors upon initial evaluation were associated with future conversion to surgery including: increasing number of prior instability events, occupation, and degree of soft tissue injury on MRI.

Objectives: The rate of osteoarthritis (OA) in patients with anterior shoulder instability (ASI) varies within the literature, with the majority of studies investigating rates after surgical stabilization. ASI appears to lead to increased rates of OA, although risk factors for developing OA in non-operative and operative cohorts are not well defined. The purpose of this study was to determine the incidence of clinically symptomatic OA and identify potential risk factors for the development of OA following ASI in a U.S. geographic population of patients under the age of 40. Methods: An established geographic database was used to identify patients less than 40 years old diagnosed with anterior should instability between 1994 and 2016. Patient information, including demographics, imaging and surgical details, was collected and comparative analysis was performed between groups with and without OA at final follow-up, as well as patients who underwent surgical and non-surgical management. Results: The study population consisted of 154 patients with a mean follow-up of 15.2 years (range 5.1-29.8). Overall, 22.7% of patients developed clinically symptomatic glenohumeral OA. Twenty-eight percent of patients who underwent at least 1 surgical intervention and 17% of patients who underwent non-operative management of anterior shoulder instability developed glenohumeral OA (p=0.176). Patients who developed arthritis were older at initial instability event (p=0.002) and had higher BMI (p=0.007). Additionally, patients with OA were more likely to be current or former smokers (p=0.004), have a seizure disorder (p=0.033), and be manual laborers (p=0.044). Risk factors for developing OA included seizure disorders (RR 2.61, 95 % CI 1.34-5.07), cartilage injury on initial MRI (RR 2.48, (1.00-6.13), current or former smoker (RR 2.46, 95% CI 1.37-4.42), laborer occupation (RR 2.14, 95% CI 1.14-4.01), and age at initial instability event (OR 1.09 per year, 95% 1.03-1.17). Athletes (RR 0.51, 95% CI 1.08-3.54), specifically contact athletes at the time of initial instability (RR 0.45, 95% CI 0.21-0.97), were less likely to develop OA. There was no difference in the number of dislocations or number of instability events in patients with and without symptomatic osteoarthritis. Conclusions: In a U.S. geographic population of patients less than 40 years old with ASI, approximately one-fourth of patients developed symptomatic OA at a mean follow-up of 15 years from their first instability event. When accounting for differences in patient demographics, there was no significant difference in the rates of OA in patients who underwent surgical and non-surgical management. Overall, there was an increased risk for the development of OA in patients with seizure disorders, cartilage injury on initial MRI, current or former smokers, laborer occupation and increased age at the initial instability event.

Introduction Delirium is commonly missed in older adults presenting to the emergency department (ED). Although current recommendations for active screening of delirium in the ED, this might not be feasible or practical. Identifying patients at high risk for prevalent and incident delirium in the ED will help to improve the screening process and to build interventions. There is currently scattered synthesis of evidence on risk factors associated with delirium in the ED. To address this gap, we are conducting a systematic review to describe the risk factors (patient vulnerability factors and precipitating factors) for delirium in the ED. Methods and analysis A literature search was performed from inception to March 2020 in Ovid EBM Reviews, Ovid EMBASE, Ovid MEDLINE, Scopus and Web of Science. We will include original research studies that report a quantitative relationship between at least one risk factor and delirium in the ED setting. Two investigators will use eligibility criteria from this protocol to independently screen titles and abstracts, and select studies based on full-text review of potentially eligible studies. After arriving at a final set of included studies, two investigators will extract data using a standardised data collection form. If appropriate, data regarding each risk factor will be pooled through a random-effect meta-analysis. The Grading of Recommendations Assessment, Development and Evaluation approach will be used to evaluate the overall quality of evidence. Ethics and dissemination To our knowledge, this will be the first systematic review evaluating risk factors for prevalent and incident delirium specifically related to the ED setting. Results of this study will aid in the identification of older adults at risk for delirium in the ED. We aim to publish the results of this systematic review in a peer-reviewed journal with good visibility for the fields of emergency medicine and geriatrics. PROSPERO registration number CDR42020175261

AbstractPancreatic ductal adenocarcinoma (PDAC) is resistant to virtually all chemo‐ and targeted therapeutic approaches. Epigenetic regulators represent a novel class of drug targets. Among them, BET and HDAC proteins are central regulators of chromatin structure and transcription, and preclinical evidence suggests effectiveness of combined BET and HDAC inhibition in PDAC. Here, we describe that TW9, a newly generated adduct of the BET inhibitor (+)‐JQ1 and class I HDAC inhibitor CI994, is a potent dual inhibitor simultaneously targeting BET and HDAC proteins. TW9 has a similar affinity to BRD4 bromodomains as (+)‐JQ1 and shares a conserved binding mode, but is significantly more active in inhibiting HDAC1 compared to the parental HDAC inhibitor CI994. TW9 was more potent in inhibiting tumor cell proliferation compared to (+)‐JQ1, CI994 alone or combined treatment of both inhibitors. Sequential administration of gemcitabine and TW9 showed additional synergistic antitumor effects. Microarray analysis revealed that dysregulation of a FOSL1‐directed transcriptional program contributed to the antitumor effects of TW9. Our results demonstrate the potential of a dual chromatin‐targeting strategy in the treatment of PDAC and provide a rationale for further development of multitarget inhibitors.

Background: Donor site morbidity after anterior cruciate ligament (ACL) reconstruction with a bone–patellar tendon–bone (BTB) autograft is clinically significant, but evidence with contemporary techniques is lacking. Purpose: To (1) evaluate donor site morbidity at a single institution using modern techniques of BTB autograft harvest at 2-year follow-up, (2) develop a 10-question donor site morbidity instrument, and (3) compare this instrument against traditional outcome tools. Study Design: Case series; Level of evidence, 4. Methods: We analyzed the 2-year follow-up outcomes of 200 consecutive patients who underwent ACL reconstruction with a BTB autograft performed by 2 surgeons at a single institution. The surgical technique utilized modern and consistent BTB autograft harvest, including graft sizing, patellar tendon and peritenon closure, and patellar and tibial donor site bone grafting. There were 187 patients included, with 13 patients undergoing revision ACL reconstruction excluded. An original 10-question scoring instrument evaluating donor site morbidity was administered to each patient (score, 0-100) and compared against each patient’s International Knee Documentation Committee (IKDC) and Lysholm scores. Results: Overall, 13.9% of patients were noted to have anterior knee pain with activity at 2-year follow-up. Moreover, 3.7% of patients reported an inability to kneel on hard surfaces but had no problems on soft surfaces; 5.9% of patients reported mild discomfort but were able to kneel on all surfaces. Additionally, 75.4% of patients had a perfect (100/100) donor site morbidity score. The mean donor site morbidity score at 2-year follow-up was 98.3 ± 3.4. There was a very strong correlation between the IKDC and Lysholm scores but only a strong and moderate correlation when the donor site morbidity score was compared with the IKDC and Lysholm scores, respectively. Conclusion: Donor site morbidity after ACL reconstruction with a BTB autograft was less frequent than reported in the existing literature. Some patients developed anterior knee pain; therefore, an informed discussion is advised. IKDC and Lysholm scores may not capture donor site symptoms after surgery. The 10-question donor site morbidity instrument may provide a more accurate assessment.