Search

Within the clinical and research spheres, there is increasing recognition of the importance of understanding the lived experience of ongoing illness and incorporating this voice into research and clinical practice. The current paper provides insights into the lived experience of undergoing epilepsy surgery, explored through the lens of art therapy. Six pieces of self-portraiture are presented that highlight key features of the burden of normality as experienced by joint first author Sarah Brown (SB) after her epilepsy surgery. Self-reflections from SB about her artwork are integrated with findings from the empirical literature that detail experiences of post-operative adjustment, providing novel insights into the post-operative adjustment process from the lived experience perspective. This approach highlights ways in which key findings from the research literature, which summates experiences at the group level, can be applied to the individual situation. The study also underscores the potential value of art therapy as a complementary therapy for holistic post-operative rehabilitation practices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: There is emerging evidence for poor health outcomes among Black people with MS, and Black people with MS may have worse walking performance than White counterparts., Purpose: The current study examined if Black participants with MS had slower walking speed (timed 25-foot walk, T25FW) and shorter walking distance (six-minute walk, 6MW) than White participants, and if these differences were accounted for by demographic variables, physical activity, disease/clinical characteristics, and Social Determinants of Health (SDOH)., Method: The analysis included samples of Black (N = 105) and White (N = 246) participants with MS who completed the T25FW and 6MW, underwent a neurological exam for generating an Expanded Disability Status Scale (EDSS) score, and provided data on demographic variables (i.e., age and gender), physical activity, disease/clinical characteristics (i.e., EDSS and MS type), and SDOH (i.e., insurance and employment status) as part of screening and baseline data collection for a clinical trial of exercise training in MS., Results: The Black participants (1.75±3.82 f/s) had a slower T25FW speed (-1.16 f/s, 95 % CI = -2.23, -0.82) than the White participants (2.91±4.97 f/s). The Black participants (842.3 ± 375.7 f) further had a shorter 6MW distance (-119.2 f, 95 % CI = -213.6, -24.7) than the White participants (961.5 ± 339.9 f). The differences in T25FW speed (-0.22 f/s; 95 % CI = -0.40, -0.04) and 6MW distance (-82.2 f; 95 % CI = -158.4, -6.0) were attenuated, but still different when controlling for other variables in multivariable analyses., Conclusion: Black participants with MS had worse walking performance than the White participants. Our results support future research on examining mobility-focused rehabilitation modalities for improving walking performance in Black people with MS., Registration: The study was registered on ClinicalTrials.gov on March 19, 2018 (NCT03468868)., Competing Interests: Declaration of competing interest The authors report no conflicts of interest in the publication of this paper., (Copyright © 2025. Published by Elsevier B.V.)

Persons with germline variants in the tumor suppressor gene phosphatase and tensin homolog, PTEN, are molecularly diagnosed with PTEN hamartoma tumor syndrome (PHTS). PHTS confers high risks of specific malignancies, and up to 23% of the patients are diagnosed with autism spectrum disorder (ASD) and/or developmental delay (DD). The accurate prediction of these two seemingly disparate phenotypes (cancer vs. ASD/DD) for PHTS at the individual level remains elusive despite the available statistical prevalence of specific phenotypes of the syndrome at the population level. The pleiotropy of the syndrome may, in part, be due to the alterations of the key multi-functions of PTEN. Maintenance of genome integrity is one of the key biological functions of PTEN, but no integrative studies have been conducted to quantify the DNA damage response (DDR) in individuals with PHTS and to relate to phenotypes and genotypes. In this study, we used 43 PHTS patient-derived lymphoblastoid cell lines (LCLs) to investigate the associations between DDR and PTEN genotypes and/or clinical phenotypes ASD/DD vs. cancer. The dynamics of DDR of γ-irradiated LCLs were analyzed using the exponential decay mathematical model to fit temporal changes in γH2AX levels which report the degree of DNA damage. We found that PTEN nonsense variants are associated with less efficient DNA damage repair ability resulting in higher DNA damage levels at 24 hours after irradiation compared to PTEN missense variants. Regarding PHTS phenotypes, LCLs from PHTS individuals with ASD/DD showed faster DNA damage repairing rate than those from patients without ASD/DD or cancer. We also applied the reaction-diffusion partial differential equation (PDE) mathematical model, a cell growth model with a DNA damage term, to accurately describe the DDR process in the LCLs. For each LCL, we can derive parameters of the PDE. Then we averaged the numerical results by PHTS phenotypes. By performing simple subtraction of two subgroup average results, we found that PHTS-ASD/DD is associated with higher live cell density at lower DNA damage level but lower cell density level at higher DNA damage level compared to LCLs from individuals with PHTS-cancer and PHTS-neither., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Rationale: The proportion of patients who develop progressive pulmonary fibrosis (PPF), along with risk factors for progression remain poorly understood., Objectives: To examine factors associated with an increased risk of developing PPF among patients at a referral center., Methods: We identified patients with a diagnosis of interstitial lung disease (ILD) seen within the Cleveland Clinic Health System. Utilizing a retrospective observational approach we estimated the risk of developing progression by diagnosis group and identified key clinical predictors using the FVC component of both the original progressive fibrotic interstitial lung disease (PFILD) and the proposed PPF (ATS) criteria., Results: We identified 5934 patients with a diagnosis of ILD. The cumulative incidence of progression over the 24 months was similar when assessed with the PFILD and PPF criteria (33.1 % and 37.9 % respectively). Of those who met the ATS criteria, 9.5 % did not meet the PFILD criteria. Conversely, 4.3 % of patients who met PFILD thresholds did not achieve the 5 % absolute FVC decline criteria. Significant differences in the rate of progression were seen based on underlying diagnosis. Steroid therapy (HR 1.46, CI 1.31-1.62) was associated with an increased risk of progressive fibrosis by both PFILD and PPF criteria., Conclusion: Regardless of the definition used, the cumulative incidence of progressive disease is high in patients with ILD in the 24 months following diagnosis. Some differences are seen in the risk of progression when assessed by PFILD and PPF criteria. Further work is needed to identify modifiable risk factors for the development of progressive fibrosis., Competing Interests: Declaration of competing interest The study is funded by Boehringer Ingelheim Pharmaceuticals, Inc (BIPI). The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). Maeve Macmurdo, Xinge Ji, Alex Milinovich, Blaine Martyn-Dow, Aman Pande, Alex Zajichek, Janine Bauman, David Sugano, Michael W. Kattan and Daniel A. Culver are employed by the Cleveland Clinic which received research support from BIPI to collaborate on this project. Pratik Pimple, Amy L. Olson, Shaun Bender, and Craig Conoscenti are employees of BIPI. Daniel Culver received honoraria from BIPI for his participation in a Steering Committee, from Pliant for his participation in an Adjudication Committee and coverage for travel costs from Roche. All other members of the Cleveland Clinic study team cited no other disclosures., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: We sought to create a laparoscopic-based model to predict the ability to perform a minimally invasive (MIS) cytoreductive surgery in advanced epithelial ovarian cancer patients who have received neoadjuvant chemotherapy (NACT)., Methods: Fifty women were enrolled in a multi-institutional prospective pilot study (NCT03378128). Each patient underwent laparoscopic evaluation of 43 abdominopelvic sites followed by surgeon dictated surgical approach, either continue MIS or laparotomically. However, if the procedure continued MIS, the placement of a hand-assist port for manual palpation was mandated to emulate a laparotomic approach and all 43 sites were re-evaluated. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were calculated for each site to predict MIS resectability. Each parameter was assigned a numeric value based on the strength of statistical association and a total predictive index score (PIV) was assigned for each patient. Receiver operating characteristic curve analysis was used to assess the ability of the model to predict the MIS approach., Results: Twenty-seven patients (61%) underwent MIS surgery. The following abdominopelvic sites were selected for inclusion in the model: gastrosplenic ligament, rectum, left mesocolon, transverse colon, right colon, cecum, appendix, liver capsule, intrahepatic fossa/gallbladder, ileum/jejunum. Using the PIV, a ROC was generated with an AUC = 0.695. In the final model, a PIV <2 identified patients able to undergo an optimal MIS cytoreductive surgery with an accuracy of 68.2%. The specificity, or the ability to identify patients who would not be able to undergo an optimal MIS interval cytoreductive surgery, was 66.7%., Conclusion: This predictive index model may help to guide future inclusion criteria in randomized studies evaluating the MIS approach in advanced epithelial ovarian cancer., Competing Interests: Declaration of competing interest The authors have no relevant conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The current standard of stethoscope hygiene doesn't eliminate the transmission of harmful pathogens, including multi-drug resistant organisms (MDROs). In the era of the increasing prevalence of MDRO infections, the use of new systems providing touch free barriers may improve patient safety versus traditional stethoscope cleaning practices with chemical agents. Our purpose was to provide a narrative literature review regarding barriers as an improvement over the current standard of care for stethoscope hygiene. Searching PubMed, articles were identified if they were in English and published after 1990, using the search term "stethoscope barrier", or if they were from a previously published stethoscope hygiene article using "author's name + stethoscope". Included articles evaluated or discussed stethoscope barriers. Of 28 manuscripts identified, 15 met the inclusion criteria. Barriers were considered superior to alternatives if they were single use, disposable, applied in a touch free fashion, were impervious to pathogens, provided an aseptic patient contact, and were acoustically invisible. Use of a practitioner's personal stethoscope with a disposable diaphragm barrier should be recommended as a new standard of care as this represents an improvement in patient safety and patient experience when compared to the disposable stethoscope or isopropyl alcohol stethoscope diaphragm cleaning., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: W. Frank Peacock, MD, FACEP, FACC, FESC, has served as the chief medical officer, and the other authors have served as intermittent consultants for Aseptiscope., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction and Background: Recent medical advances, including closure of myelomeningocele defects, shunting of hydrocephalus, and focusing on renal preservation have led to many individuals with spina bifida (SB) living into adulthood. This has led to more individuals with SB transitioning their care from pediatric-based to adult-based care models., Objective: We seek to explore the process of transition, with a focus on difficulties in transitioning individuals with SB. Additionally, we explore new problems that arise during the period of transition related to sexual function and dysfunction. We also discuss some of the difficulties managing neurogenic bladder and the sequalae of their prior urologic surgeries., Study Design: Each of the authors was asked to provide a summary, based on current literature, to highlight the challenges faced in their area of expertise., Conclusions: Transitioning care for individuals with SB is especially challenging due to associated neurocognitive deficits and neuropsychological functioning issues. Sexual function is an important component of transition that must be addressed in young adults with SB. Management of neurogenic bladder in adults with SB can be challenging due to the heterogeneity of the population and the sequelae of their prior urologic surgeries. The aim is to ensure that all individuals with SB receive appropriate, evidence-based care throughout their lifetime., (Copyright © 2023 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Facial nerve function is essential for a multitude of processes in the face, including facial movement; expression; and functions, such as eating, smiling, and blinking. When facial nerve function is disrupted, facial paralysis may occur and various complications for the patient may result. Much research has been conducted on the physical diagnosis, management, and treatment of facial paralysis. However, there is a lack of knowledge of the psychological and social effects of the condition. Patients may be at an increased risk for anxiety and depression, as well as negative self and social perceptions. This review analyzes the current literature on the various adverse psychological and psychosocial effects of facial paralysis, factors that may play a role, and treatment options that may help improve patients' quality of life., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Introduction: Auditory Neuropathy Spectrum Disorder (ANSD) accounts for 10 % to 15 % of pediatric hearing loss. In most cases, otoacoustic emissions (OAE) are present as the outer hair cell function is normal, and the auditory brainstem response (ABR) is abnormal. Newborn hearing screen (NBHS) is completed using OAE or ABR depending on the institution. Because OAEs are often present in ANSD, NBHS done solely with OAE can miss and delay diagnosis of patients with ANSD., Objectives: To assess whether NBHS methodology impacts the age of diagnosis of ANSD., Methods: This is a retrospective study of patients, 0-18 years of age, diagnosed with ANSD at two tertiary pediatric hospitals from 1/01/2010 to 12/31/2018 after referral from NBHS performed in the community. Data recorded included patient demographics, method of NBHS, NICU stay, and age at ANSD diagnosis., Results: 264 patients were diagnosed with ANSD. Of those, 123 (46.6 %) were female, and 141 (53.4 %) were male. Ninety-seven (36.8 %) were admitted to NICU and the mean stay was 6.98 weeks (STD = 10.7; CI = 4.8-9.1). The majority (244, 92.4 %) of patients had NBHS with ABR, and 20 (7.5 %) had NBHS with OAE. Patients screened with ABR were diagnosed with ANSD earlier than those who screened with OAE, with a mean age of 14.1 versus 27.3 weeks (p = 0.0397, CI = 15.2-39.3). Among those screened with ABR, median age at diagnosis was 4 months for NICU infants and 2.5 months for infants with no history of NICU stay over 5 days. In comparison, median diagnosis age was 8 months for non-NICU infants screened with OAEs., Conclusion: Patients with ANSD who had NBHS with ABR were diagnosed earlier than those with OAE. Our data suggest that universal screening with ABR may facilitate earlier diagnosis of ANSD and earlier evaluation for aural rehabilitation, especially in high-risk cohorts such as NICU patients. Further research is needed into factors that contribute to earlier diagnosis among patients screened with ABR., Competing Interests: Declaration of competing interest Dr. Daniela Carvalho has a research agreement with Cochlear Corporation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Higher rate of substance use, including cannabis, has been reported in individuals with a history of childhood trauma, but less is known about the association between cannabis use with lifetime history of trauma and chronic stress, and potential gender differences in this association. This study systematically examined this association in a cross-sectional study of 841 individuals recruited between 2007 and 2012 from the community in New Haven, Connecticut. The Cumulative Adversity Index (CAI) was used to measure cumulative lifetime major life events, life trauma, and recent life events and chronic stress. Childhood Trauma Questionnaire (CTQ) was used to measure childhood trauma. Current and regular use of drugs were assessed using self-report questionnaires and objectively verified with urine drug testing. Higher rates of childhood trauma as well as lifetime trauma, and major life events were found in cannabis users, compared to non-users. The association between cannabis use with childhood trauma (total CTQ scores) was significant after controlling for age, gender, ethnicity and regular use of alcohol or cocaine. In logistic regression analysis, cannabis use had a significant positive association with major life events and lifetime trauma, but not with chronic stress, controlling for confounding factors including age, gender, ethnicity, and regular use of alcohol and cocaine. When analyzed separately, only in women the association between cannabis use and childhood trauma was significant. These associations point to further assessment of the impact of these gender differences on neurobiology of stress and cannabis misuse risk., Competing Interests: Declaration of competing interest Anahita Bassir Nia is a member of the Scientific Advisory Committee of Synendos Therapeutics AG, Switzerland. Rajita Sinha is on the Scientific Advisory Board of Embera Neurotherapeutics; she has also received research support from CT Pharma and AELIS Farma. The remaining authors report no disclosures or potential conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: At-home Ketamine-assisted therapy (KAT) with psychosocial support and remote monitoring through telehealth platforms addresses access barriers, including the COVID-19 pandemic. Large-scale evaluation of this approach is needed for questions regarding safety and effectiveness for depression and anxiety., Methods: In this prospective study, a large outpatient sample received KAT over four weeks through a telehealth provider. Symptoms were assessed using the Patient Health Questionnaire (PHQ-9) for depression, and the Generalized Anxiety Disorder scale (GAD-7) for anxiety. Demographics, adverse events, and patient-reported dissociation were also analyzed. Symptom trajectories were identified using Growth Mixture Modeling, along with outcome predictors., Results: A sample of 1247 completed treatment with sufficient data, 62.8 % reported a 50 % or greater improvement on the PHQ-9, d = 1.61, and 62.9 % on the GAD-7, d = 1.56. Remission rates were 32.6 % for PHQ-9 and 31.3 % for GAD-7, with 0.9 % deteriorating on the PHQ-9, and 0.6 % on the GAD-7. Four patients left treatment early due to side effects or clinician disqualification, and two more due to adverse events. Three patient subpopulations emerged, characterized by Improvement (79.3 %), Chronic (11.4 %), and Delayed Improvement (9.3 %) for PHQ-9 and GAD-7. Endorsing side effects at Session 2 was associated with delayed symptom improvement, and Chronic patients were more likely than the other two groups to report dissociation at Session 4., Conclusion: At-home KAT response and remission rates indicated rapid and significant antidepressant and anxiolytic effects. Rates were consistent with laboratory- and clinic-administered ketamine treatment. Patient screening and remote monitoring maintained low levels of adverse events. Future research should assess durability of effects., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Compare transversus abdominis plane (TAP) blocks with liposomal bupivacaine were to epidural analgesia for pain at rest and opioid consumption in patients recovering from abdominal surgery., Background: ERAS pathways suggest TAP blocks in preference to epidural analgesia for abdominal surgery. However, the relative efficacies of TAP blocks and epidural analgesia remains unknown., Methods: Patients having major abdominal surgery were enrolled at six sites and randomly assigned 1:1 to thoracic epidural analgesia or bilateral/4-quadrant TAP blocks with liposomal bupivacaine. Intravenous opioids were used as needed. Non-inferiority margins were a priori set at 1 point on an 11-point pain numeric rating scale for pain at rest and at a 25% increase in postoperative opioid consumption., Results: Enrollment was stopped per protocol at 3rd interim analysis after crossing an a priori futility boundary. 498 patients were analyzed (255 had TAP blocks and 243 had epidurals). Pain scores at rest in patients assigned to TAP blocks were significantly non-inferior to those given epidurals, with an estimated difference of 0.09 points (CI: -0.12, 0.30; noninferiority P < 0.001). Opioid consumption during the initial 3 postoperative days in TAP patients was not non-inferior to epidurals, with an estimated ratio of geometric means of 1.37 (CI: 1.05, 1.79; non-inferiority P = 0.754). However, the absolute difference was only 21 mg morphine equivalents over the 3 days. Patients with epidurals were more likely to experience mean arterial pressures <65 mmHg than those given TAP blocks: 48% versus 31%, P = 0.006., Conclusion: Pain scores at rest during the initial three days after major abdominal surgery were similar. Patients assigned to TAP blocks required more opioid then epidural patients but had less hypotension. Clinicians should reconsider epidural analgesia in patients at risk from hypotension., Trial Registration: ClinicalTrials.gov Identifier: NCT02996227., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Stimulator of interferon genes (STING) plays an important role in infection, autoimmune disease and cancer. STING-mediated type I interferon (IFN) signaling is well recognized and extensively studied. Several IFN-independent activities of STING were also discovered in recent years and their physiological importance has begun to be appreciated. Here, we review recent advance in the evolutionary origin and molecular mechanisms of STING-mediated IFN-independent activities. New insights from these studies suggest that STING is not just a simple IFN-producing machine, rather, it functions as a hub that converts multiple environmental cues into diverse cellular responses . This expanded view of STING biology should guide future clinical testing of STING agonists in cancer and treatment of STING-associated human diseases., Competing Interests: Declaration of Competing Interests The authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Major Depressive Disorder (MDD) is frequently associated with risk factors for the development of Bipolar Disorder (BD). Using graph theory, we investigated brain network properties associated with BD risk factors in young MDD subjects., Methods: Resting-state fMRI was acquired from a large cohort (N= 104) of medication-free currently depressed participants (25 BD depression (BDD), 79 MDD). Lifetime mania symptom count (LMSC), current Young Mania Rating Scale (YMRS) score, and family history of mood disorders (FHMD) were examined as BD risk factors. Functional connectivity matrices from 280 regions of interests (ROIs) were first entered into the Network Based Statistic (NBS) toolbox to identify connections that varied with each risk factor. Next, within the correlated network for each risk factor, global and nodal graph properties for the top five linked nodes were calculated. Last, using identified graph properties, machine learning classification (MLC) between BDD, MDD with BD risk factors (MDD+), and without BD risk factors (MDD-) was conducted., Results: LMSC positively correlated with left lateral orbitofrontal cortex (LOFC) Communication Efficiency and with left middle temporal Eigenvector Centrality. Current YMRS score positively correlated with right amygdala Communication Efficiency and Closeness Centrality. FHMD positively correlated with right insula Eigenvector Centrality. Acceptable MLC accuracy was seen between BDD and MDD- using middle temporal Eigenvector Centrality, whereas moderate accuracy was seen between MDD+ and MDD- using OFC Communication Efficiency., Limitation: Although participants were medication-free, they were not medication-naïve., Conclusion: Functional connectome graph properties may serve as BD vulnerability biomarkers in young individuals with MDD., (Copyright © 2022. Published by Elsevier B.V.)

Objectives: This study aimed to explore the association of socioeconomic status and discharge destination with 30-day readmission after ischemic stroke., Materials and Methods: We examined 30-day all-cause readmission among patients hospitalized for ischemic stroke in states of Arkansas, Iowa, and Wisconsin in 2016 and 2017 and New York in 2016 using Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases., Results: Among the 52301 patients included, 51.1% were female. The 30-day readmission rates were 10.2%, 8.2%, 9.3%, 10.4%, 11.6%, and 11.2% for age group 18-34, 35-44, 45-54, 55-64, 65-74, and ≥75 years, respectively (p<0.001). In Generalized Estimating Equation analysis, patients with Medicare and Medicaid insurance were more likely to be readmitted, compared with private insurance, (adjusted Odds Ratio [aOR] 1.37, 95% CI 1.23-1.53; and aOR 1.26, 95% CI 1.09-1.45, respectively). Patients in the bottom quartile of zip code level median household income had higher 30-day readmission rate (12.4%) than those in the 2nd, 3rd and 4th quartile (10.3%, 10.1%, and 10.7%, respectively, p<0.001). Compared with those discharged home with self-care which had the lowest readmission rate (8.4%), patients who left against medical advice had the highest readmission rate (18.6%; aOR 2.23, 95% CI 1.75-2.83), followed by rehabilitation and skilled nursing facilities (13.2%; aOR 1.33, 95% CI 1.22-1.46), and home with home health care (11.3%, aOR 1.18, 95% CI 1.08-1.28)., Conclusions: Socioeconomic status and discharged destination affect readmission after stroke. These results provide evidence to inform vulnerable patient population as targets for readmission prevention., Competing Interests: Declaration of Competing Interest Dr. Shumei Man reports no disclosures. Statistician David Bruckman reports no disclosures. Statistician Anne S. Tang reports no disclosures. Dr. Ken Uchino reports no disclosures. Dr. Jesse D. Schold reports no disclosures., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Establishing anatomical coordinate systems (CS) from anatomical landmarks is sensitive to landmark selection. Vastly different results can be obtained amongst observers which can greatly affect the resulting joint kinematics. The aim of this study is to introduce an objective method for calculating functional CS definitions for bones in joints that observe three-cylindrical-joint kinematic chain decomposition methods and to apply the method on tibiofemoral joint specimens. This method is driven by low resistance joint motion during loading profiles and not from anatomical landmark selection. Two anatomical CS definitions were established from points collected by five observers, for twelve knees. The knees underwent passive flexion and internal/external rotation using the anatomical CSs. The kinematics from these profiles were used in linear least squares minimization of off-axis motions to redefine the tibia and femur origins, the femur flexion axis and the tibia internal rotation axis. Significant improvements in reproducibility of 7.4 mm (tibia origin, p < 0.001), 3.4 mm (femur origin, p < 0.001), and 2.9° (femur FE-axis, p < 0.001) between the two functional CSs compared to the two anatomical CSs were observed. Functional CSs led to significant decreases in off-axis motion during discrete passive flexion profiles. This new strategy for establishing functional CSs provides an objective approach that will reduce the effects of observer error in establishing CSs. Additionally, functional CSs allow for better interpretations of kinematic responses due to loading because effects of kinematic cross-talk is minimized., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Outcomes for patients with systemic light-chain (AL) amyloidosis have improved over the last two decades with timely diagnosis, use of novel chemotherapeutic agents, risk stratification and better patient selection criteria before hematopoietic autologous stem cell transplant (ASCT). However, majority of patients have advanced stage disease at initial presentation and at relapse rendering them ineligible for intensive cytotoxic chemotherapy or ASCT. Daratumumab (Dara) with or without standard chemotherapy appears to be an excellent treatment option for newly diagnosed and relapsed refractory AL amyloidosis. This is largely due to its tolerable safety and remarkable efficacy as seen in multiple retrospective, small phase II studies as well as a phase III randomized controlled trial. Here we review published clinical trials and retrospective data of Dara in AL amyloidosis that explore its role as a valuable addition to the treatment armamentarium for this challenging disease., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: Mobile stroke unit (MSU) has been shown to rapidly provide pre-hospital thrombolysis in acute ischemic stroke (AIS). MSU encounters neurological disorders other than AIS that require emergent treatment., Methods/materials: We obtained pre-hospital diagnosis and treatment data from the prospectively collected dataset on 221 consecutive MSU encounters. Based on initial clinical evaluation and neuroimaging obtained on MSU, the diagnosis of AIS (definite, probable, and possible AIS, transient ischemic attack), intracranial hemorrhage, and likely stroke mimics was made., Results: From July 2014 to April 2015, 221 patients were treated on MSU. 78 (35%) patients had initial clinical diagnosis of definite/probable AIS or TIA, 69 (31%) were diagnosed as possible AIS or TIA, 15 (7%) had intracranial hemorrhage while 59 patients (27%) were diagnosed as likely stroke mimics. Stroke mimics encountered included 13 (6%) metabolic encephalopathy, 11 (5%) seizures, 9 (4%) migraines, 3 (1%) substance abuse, 2 (1%) CNS tumor, 3 (1%) infectious etiology and 3 (1%) hypoglycemia. Fifty-four (24%) patients received non-thrombolytic treatments on MSU CONCLUSION: About one third of MSU encounters were not AIS initially, including intracranial hemorrhage and stroke mimics. MSU can be utilized to provide pre-hospital treatments in emergent neurological conditions other than AIS., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Hyperthermic intraperitoneal chemotherapy following cytoreductive surgery (CRS) is a treatment strategy that has been evaluated in recurrent ovarian cancer. The aim of this study was to examine if survival was similar regardless of platinum sensitivity., Methods: A retrospective study of women with recurrent platinum sensitive or resisteant epithelial ovarian cancer who were treated with cytoreductive surgery (CRS) and HIPEC between the years 2010-2018 was performed. Recurrence free (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method., Results: Thirty-five (72.9 %) were platinum sensitive (PS) and 13 (27.1 %) were platinum resistant (PR). The complete cytoreduction (R0) rate was higher in the PS patients as compared to PR (85.7 % vs 53.8 %; p = 0.017). Median follow-up was 16.9 (range, 11.7-34.5) months. The median recurrence free survival in the patients who had a R0 resection was 22.3 months in PS and 11.1 months in PR patients (p = 0.017), respectively. Median overall survival was 26.9 months in the PR patients, while it had not been reached in the PS patients. In the patients with PS recurrence, the mean treatment free interval (TFI) prior to HIPEC was 1.6 years and following HIPEC, 40 % of those patients were recurrence free at 2 years. In the patients with PR recurrence, the mean TFI prior to HIPEC was 4.6 months and following HIPEC, 61.5 % of those patients had a longer TFI, with a mean increase of 10.1 months., Conclusion: Although surgery is not considered standard treatment in PR ovarian cancer, in carefully selected patients, surgery with HIPEC could extend the treatment-free interval., Competing Interests: Declaration of Competing Interest The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

A considerable amount of continuous proliferation and differentiation is required to produce daily a billion new neutrophils in an adult human. Of the few cytokines and factors known to control neutrophil production, G-CSF is the guardian of granulopoiesis. G-CSF/CSF3R signaling involves the recruitment of non-receptor protein tyrosine kinases and their dependent signaling pathways of serine/threonine kinases, tyrosine phosphatases, and lipid second messengers. These pathways converge to activate the families of STAT and C/EBP transcription factors. CSF3R mutations are associated with human disorders of neutrophil production, including severe congenital neutropenia, neutrophilia, and myeloid malignancies. More than three decades after their identification, cloning, and characterization of G-CSF and G-CSF receptor, fundamental questions remain about their physiology., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: While neoadjuvant chemoradiation therapy (nCRT) is accepted as standard of care for locally advanced rectal cancer, the approach to treatment of patients with clinically staged T3N0 disease has been increasingly debated. This study examines the accuracy of clinical staging for cT3N0 rectal cancer as recorded in the National Cancer Data Base and evaluates the role of nCRT in treating these patients., Methods: Total of 15,843 patients with clinically staged T3N0M0 rectal cancer who either received nCRT or proceeded to surgery-first met inclusion criteria. Propensity score matching was employed to balance the groups., Results: 23% of cT3N0 patients undergoing surgery-first were found to have pathologically positive nodes. Another 16% turned out to have < stage II disease on surgical pathology. Survival curves for matched nCRT and surgery-first groups demonstrated a survival advantage for cT3N0 patients treated with nCRT., Conclusions: Poor clinical staging accuracy can result in both undertreatment and overtreatment of cT3N0 rectal cancer., Competing Interests: Declaration of competing interest This work received no outside funding. The authors have no conflicts of interest and no disclosures relevant to the research presented herein., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Purpose: Inter-hospital transfer for ischemic stroke is an essential part of stroke system of care. This study aimed to understand the national patterns and outcomes of ischemic stroke transfer., Methods and Results: This retrospective study examined Medicare beneficiaries aged ≥65 years undergoing inter-hospital transfer for ischemic stroke in 2012. Cox proportional hazards model was used to compare 30-day and one-year mortality between transferred patients and direct admissions from the emergency department (ED admissions). Among 312,367 ischemic stroke admissions, 5.7% underwent inter-hospital transfer. Using this value as cut-off, the hospitals were classified into receiving (n = 411), sending (n = 559), and low-transfer (n = 1863) hospitals. Receiving hospitals were larger than low-transfer and sending hospitals as demonstrated by the median bed number (371, 189, and 88, respectively, p < 0.001); more frequently to be certified stroke centers (75%, 47%, and 16%, respectively, p < 0.001); and less commonly located in the rural area (2%, 7%, and 24%, respectively, p < 0.001). For receiving hospitals, transfer-in patients and ED admissions had comparable mortality at 30 days (10% vs 10%; adjusted HR [aHR]=1.07; 95% CI, 0.99-1.14) and 1 year (23% vs 24%; aHR=1.03; 95% CI, 0.99-1.08). For sending hospitals, transfer-out patients, compared to ED admissions, had higher mortality at 30 days (14% vs 11%; aHR=1.63; 95% CI, 1.39-1.91) and 1 year (30% vs 27%; aHR=1.33; 95% CI, 1.20-1.48). For low-transfer hospitals, overall transfer-in and transfer-out patients, compared to ED admissions, had higher mortality at 30 days (13% vs 10%; aHR=1.46; 95% CI, 1.33-1.60) and 1 year (28% vs 25%; aHR=1.27; 95% CI, 1.19-1.36)., Conclusions: Hospitals in the US, based on their transfer patterns, could be classified into 3 groups that shared distinct characteristics including hospital size, rural vs urban location, and stroke certification. Transferred patients at sending and low-transfer hospitals had worse outcomes than their ED admission counterpart., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: We did a comparative analysis of matched and mismatched defects in pre- and post-operative V/Q scans in CTEPH patients. We correlated the number of these defects with pre-operative clinical and hemodynamic parameters., Methods: This was a retrospective study on 27 patients with CTEPH who underwent surgery. Pre- and post-operative V/Q scans were graded for each lung segment as normal, matched or mismatched defect. Additional pre- and post-operative clinical and hemodynamic parameters that were collected include New York Heart Association functional class, six-minute walk distance in feet, N-terminal pro b-type natriuretic peptide, forced expiratory volume in one second/forced vital capacity, diffusing capacity of the lung for carbon monoxide, pulmonary arterial pressure (systolic, diastolic and mean), right atrial pressure, cardiac output and cardiac index. Pulmonary vascular resistance was then calculated., Results: On a segmental basis, 176 mismatched defects were noted in 27 patients, of which 111 improved post-surgery (63%). 22 of the 34 matched defects improved following surgery (64%). 31 new mismatched defects were observed. The number of pre-operative matched defects per patient ranged from 0 to 6. No statistically significant associations were observed between the number of pre-operative matched defects and pre-operative clinical parameters. No statistically significant associations were observed between the number of improved matched defects and the change in clinical parameters (pre- to post-surgery)., Conclusion: Both matched and mismatched defects on preoperative V/Q scans can show normalization post-surgery. The extent of matched defects on a preoperative V/Q scan does not correlate significantly with other clinical and hemodynamic parameters., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To determine if the Argus II retinal prosthesis can operate during functional MRI (fMRI) and diffusion tensor imaging (DTI) acquisitions and if currents induced in the prosthesis by imaging are at safe levels., Materials and Methods: One Argus II retinal prosthesis was modified to enable current measurements during imaging. Active electronics were modified to enable operation during scans. Induced current was measured during diagnostic scans, which were previously shown to be safe for implanted patients, and during fMRI and DTI scans. All measurements were performed using an ASTM phantom to ensure reproducible placement., Results: The prosthesis was able to maintain communication with the external RF coil during the fMRI and DTI scans except briefly during pre-scans. Current levels induced during fMRI and DTI scans were consistently below those measured during diagnostic scans., Conclusions: fMRI and DTI may be safely performed while the Argus II retinal prosthesis is operating., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Psychological symptoms are frequently reported in patients with Postural Orthostatic Tachycardia Syndrome (POTS); however, the nature of these symptoms is not well understood. The current study described baseline psychological symptoms in patients with POTS, and examined associations between psychological and self-report autonomic symptoms. Participants reported mild anxiety symptoms, moderate depressive symptoms, severe somatization, and elevated anxiety sensitivity. Depressive symptoms and pain catastrophizing were significantly associated with autonomic symptoms. The current study adds to the literature by documenting elevated levels of anxiety sensitivity, and relationships between psychological and autonomic symptoms., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: POTS patients undergo labial salivary gland biopsies (LSGB) for histologic confirmation of Sjogren's syndrome (SS). Predictive features of positive results are unknown., Methods: 161 POTS patients underwent LSGB. Their charts were reviewed for antibody and diagnostic testing results., Results: Only 11% (17/161) of POTS patients were SS positive. There were more positive ANA antibodies in those with positive LSGB (65% v 28%, p = .0026). Positive skin nerve biopsy for small fiber neuropathy (SFN) was associated with positive LSGB (p = .046)., Conclusion: A positive ANA and skin biopsy for SFN are two helpful features in selecting POTS patients for LSGB., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Artificial intelligence, and more narrowly machine-learning, is beginning to expand humanity's capacity to analyze increasingly large and complex datasets. Advances in computer hardware and software have led to breakthroughs in multiple sectors of our society, including a burgeoning role in medical research and clinical practice. As the volume of medical data grows at an apparently exponential rate, particularly since the human genome project laid the foundation for modern genetic inquiry, informatics tools like machine learning are becoming crucial in analyzing these data to provide meaningful tools for diagnostic, prognostic, and therapeutic purposes. Within medicine, hematologic diseases can be particularly challenging to understand and treat given the increasingly complex and intercalated genetic, epigenetic, immunologic, and regulatory pathways that must be understood to optimize patient outcomes. In acute myeloid leukemia (AML), new developments in machine learning algorithms have enabled a deeper understanding of disease biology and the development of better prognostic and predictive tools. Ongoing work in the field brings these developments incrementally closer to clinical implementation., (Copyright © 2020. Published by Elsevier Ltd.)

Background: SARS-CoV-2 enters cells by binding of its spike protein to angiotensin-converting enzyme 2 (ACE2). Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) have been reported to increase ACE2 expression in animal models, and worse outcomes are reported in patients with co-morbidities commonly treated with these agents, leading to controversy during the COVID-19 pandemic over whether these drugs might be helpful or harmful., Methods: Animal, in vitro and clinical data relevant to the biology of the renin-angiotensin system (RAS), its interaction with the kallikrein-kinin system (KKS) and SARS-CoV-2, and clinical studies were reviewed., Findings and Interpretation: SARS-CoV-2 hijacks ACE2to invade and damage cells, downregulating ACE2, reducing its protective effects and exacerbating injurious Ang II effects. However, retrospective observational studies do not show higher risk of infection with ACEI or ARB use. Nevertheless, study of the RAS and KKS in the setting of coronaviral infection may yield therapeutic targets., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

The treatment of locally advanced oral cavity cancer is often multimodal, involving surgical resection, radiotherapy (RT), and chemotherapy. Systemic therapy is the mainstay of treatment for recurrent/metastatic disease. While the concurrent use of cisplatin with post-operative RT is well established in patients with high risk features of extranodal extension and/or positive surgical margins following resection, the role of chemotherapy in other curative settings is not clear. Studies reporting success of induction chemotherapy or definitive chemoradiotherapy in absence of primary resection include all anatomic sites of head and neck cancer, and oral cavity cancer subset is rarely reported as a separate analysis, thus limiting the interpretation of results. This article will focus on the use of systemic therapy for locoregionally advanced oral cavity cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background/aim: Episodes of non-severe hypoglycemia can be captured through diagnoses documented in the electronic medical record. We aimed to create a clinically useful prediction model for a severe hypoglycemia event, requiring an emergency department visit or hospitalization, in patients with Type 2 diabetes with a history of non-severe hypoglycemia., Methods: Using electronic medical record data from 50,439 patients with Type 2 diabetes in one health system, number of severe hypoglycemia events and associated patient characteristics from 2006 to 2015 were previously defined. Using the landmarking method, a dynamic prediction model was built using the subset of 1876 patients who had a documented non-severe hypoglycemia diagnosis code, using logistic regression to obtain landmark-specific odds of severe hypoglycemia in this group. For model performance, the bootstrap procedure was employed for internal validation and area under the curve (AUC) and index of prediction accuracy (IPA) were calculated., Results: Glycosylated hemoglobin (HbA1c) less than 7% (53 mmol/mol) was associated with increased odds ratio (OR) of severe hypoglycemia at 3 months (OR 1.92 95% Confidence Interval (CI) 1.19-3.10 at HbA1c 5% (31 mmol/mol) and OR 1.21, CI 1.03-1.41 at HbA1c 6%(42 mmol/mol).) History of non-severe hypoglycemia within the past 3 months increased odds for severe hypoglycemia (OR 2.58 95% CI 1.80-3.70) as did Black race, insulin use with the past 3 months, and comorbidities. Metformin and sulfonlylurea use in the past 3 months, increasing age and body mass index had lower odds of a future severe hypoglycemia event. For the prediction model for 3 month risk of severe hypoglycemia, the AUC was 0.890 (CI 0.843-0.907) and the IPA was 10.8% (CI 4.4% - 12.4%)., Conclusion: In patients with a documented diagnosis of non-severe hypoglycemia, a dynamic prediction model identifies patients with Type 2 diabetes with 3-month increased risk of severe hypoglycemia, allowing for preventive efforts, such as medication changes, at the point of care., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Multiple sclerosis is a central nervous system demyelinating disease that affects women of reproductive potential. It is important to identify the frequency and risk factors of unplanned or disease-modifying therapy-exposed pregnancies to create interventions to reduce these., Methods: This retrospective, single-center, observational chart review study aims to identify risk factors for unplanned pregnancy to identify a target population for family counseling., Results: In total, 63 live births in 45 patients (20 unplanned and 43 planned) were analyzed. The percentage of unplanned pregnancy was 32%. The proportion of those receiving family planning counseling was lower in the patients with unplanned pregnancies ( p  < 0.001). The main risk factors for unplanned pregnancy were younger age ( p  = 0.004), disease-modifying therapy exposure ( p  < 0.001), and being unmarried ( p  < 0.001). Overall, 16 pregnancies had disease-modifying therapy exposure and in a subsequent study the risk for disease-modifying therapy exposure was unplanned status ( p  < 0.001). Birth outcomes were not different between groups. There were more enhancing lesions in the post-partum magnetic resonance imaging of women with planned pregnancy ( p  < 0.04)., Conclusion: Prevention of unplanned pregnancy could lead to less disease-modifying therapy exposed pregnancies. This study suggests a targeted intervention of family planning counseling in younger, unmarried multiple sclerosis patients could potentially lead to less unintended in utero disease-modifying therapy exposure., (© The Author(s) 2019.)

Healthcare decisions depend on the characteristics of patients and providers. However, how these decisions are influenced by provider interpretations of biological processes and the sociopolitical context in which they work remains unclear. To answer these questions, we explore providers' prescribing of emergency contraception (EC), methods that can prevent pregnancy after sex has already occurred. Despite the consensus mainstream medical definition that pregnancy begins after a fertilized egg implants in the uterus, an alternative perspective holds that pregnancy instead begins when a sperm fertilizes an egg. How providers define pregnancy may affect their willingness to prescribe EC. However, the ability of providers to recommend treatments consistent with their understandings of medical processes may depend on the sociopolitical context in which the patient-provider interaction occurs. We test whether EC prescribing practices vary by providers' definition of pregnancy and the interaction of this definition with the sociopolitical context in which they practice. Data from U.S. medical providers were collected as part of a survey on EC knowledge and practices (N = 1308). We merged voting results from the county in which the provider practices to data on provider EC prescribing and pregnancy counseling practices. Because recent Republican party platforms have explicitly endorsed a definition of pregnancy that begins at fertilization and party advocacy frequently uses this definition, we use the county vote share for the Republican presidential candidate as a contextual measure of views that pregnancy begins at fertilization. We find a significant interaction such that providers who counsel that pregnancy begins at fertilization are significantly less likely to prescribe EC if they practice in counties with higher Republican vote shares. Our results highlight that patient access to EC may depend on both place of residence and provider views and that providers' EC prescribing may depend jointly on their understanding of pregnancy and sociopolitical context., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

•This case reports the treatment of neuroendocrine carcinoma of the cervix with a PARPi based on NGS.•NGS reports have demonstrated somatic mutations BRCA in neuroendocrine carcinoma of the cervix.•The use of a PARPi in neuroendocrine carcinoma of the cervix has not been previously reported., Competing Interests: None., (© 2019 Published by Elsevier Inc.)

Fluorescence and autofluorescence have been shown by several recent studies to be valuable adjuncts in identifying parathyroid glands during thyroidectomy and parathyroidectomy. The aim of this chapter is to review the impact of this new technology on surgical strategy concerning identification and preservation of parathyroid glands during thyroidectomy, identification of parathyroid glands in hyperparathyroidism, and the potential role in thyroid cancer surgery., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: We propose a Phase III trial that compares the effectiveness of an exercise training program delivered in a facility-based setting with direct, in-person supervision or a home-based setting with remote supervision via telerehabilitation for improving walking performance in persons with multiple sclerosis(MS) who have walking dysfunction and mobility disability., Methods/design: The study was developed with stakeholder engagement and is a multi-site trial that follows a 2-stage, randomized choice design. The trial compares the effectiveness of a 16-week evidence-based, individualized exercise program delivered in a supervised, facility-based setting versus a remotely coached/guided, home-based setting using telerehabilitation in physically inactive and cognitively intact people with MS who have walking dysfunction and mobility disability(N = 500). The primary outcome is walking speed. The secondary outcomes are walking endurance, disability status, and patient-reported outcomes of physical activity, walking impairment, fatigue, and quality of life. The components of the exercise program itself are similar between the groups and follow the Guidelines for Exercise in MS protocol. This includes a program manual, exercise prescription, exercise equipment, social-cognitive theory materials including newsletters, logs, and calendars, and one-on-one behavioral coaching by exercise specialists with background in MS. The main difference between groups is the coaching approach and setting for delivering the exercise training program. The outcomes will be collected by treatment-blinded assessors at baseline(week 0), mid-intervention(week 8), post-intervention(week 16), and follow-up(week 52)., Discussion: The proposed study will provide evidence for the effectiveness of a novel, widely-scalable program for delivering exercise training in persons with MS who have walking dysfunction and mobility disability., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Pinterest is a visual search based, the fourth largest social networking site in the U.S. with 81% of its users being women. Because of Pinterest's popularity and the high incidence of psychogenic nonepileptic seizures (PNES) among women, the aim of our current study was to perform a thorough content analysis of information available about PNES on Pinterest. The systematic search of Pinterest using various PNES related keywords revealed 57 unique pins. This was followed by content analysis by two independent reviewers. Most (87.7%) pins included in the final analysis reported at least one factor indicative of PNES. Most common were the consistent association of PNES with emotional triggers (61.4%), history of current or remote abuse (57.9%), and seizure's unresponsiveness to antiepileptic drugs (38.6%). Semiology of PNES was reported in 77.2% pins and two-thirds (66.6%) mentioned diagnostic procedures. Psychogenic nonepileptic seizure treatment and prognosis were reported in 68.4% and 56.1% pins, respectively. Around one-third of pins were from academic resources. More than 80% of pins targeted lay people with the primary aim of education and awareness and used a neutral or positive tone. To our knowledge, even though most pins have scientifically sound information, this widely popular web-based resource seems to be underutilized by academia, healthcare workers, and stakeholders for the dissemination of awareness about PNES., (Published by Elsevier Inc.)

Major depressive disorder (MDD) is the most common mental illness and the leading cause of disability worldwide. Electroconvulsive therapy (ECT) is the most effective treatment for MDD and the gold-standard therapy for treatment-resistant depression (TRD), yet it remains underutilized due to factors such as limited availability, stigma, and concerns about cognitive side effects. Ketamine has emerged as the first rapid-acting antidepressant and shows robust short-term efficacy in clinical trials, but there are concerns about its long-term safety and efficacy. While response rates are similar between ECT and ketamine in clinical trials, these treatments have never been compared head-to-head in a sufficiently large, well-powered randomized study. Here we describe the study protocol for ELEctroconvulsive therapy (ECT) vs. Ketamine in patients with Treatment-resistant Depression (ELEKT-D), a non-inferiority, comparative effectiveness trial. Patients with TRD seeking clinical treatment are randomized (1:1) to receive ECT (thrice weekly) or intravenous ketamine (twice weekly) for 3-5 weeks. The primary outcome is the proportion of responders in each group at the end of study visit, as measured by a patient-reported outcome measure (Quick Inventory of Depressive Symptomatology-Self Report). The study is powered such that the non-inferiority margin allows for ketamine to retain 90% of the ECT treatment effect, with a projected sample size of 400 patients (200 per group). Secondary outcomes include remission rates, depression severity, cognitive functioning, quality of life, adverse events, and tolerability. The results of the ELEKT-D study will have important implications for patient choice, clinical practice, and health insurance policies., (Copyright © 2018. Published by Elsevier Inc.)

Frozen section intraoperative consultation is a well-established means of evaluating brain tumors at the time of surgery. Limitations to the procedure are also well recognized resulting in less than perfect specificity of diagnosis. This study retrospectively reviewed 424 consecutive meningioma cases (N = 310 females; mean age 57.3 years) to examine concordance between frozen section evaluation of meningioma subtype and grade as compared with the final diagnosis subtype and grade. A discrepancy between frozen section diagnosis and final diagnosis was observed in 114 (26.9%) of cases. Of the WHO grade I subtypes, the most common discrepancy involved transitional meningiomas (N = 31) which were most commonly diagnosed at frozen section as either fibrous (N = 18) or meningothelial (N = 13) meningiomas. None of the grade I tumors were diagnosed as higher grade lesions. Of the higher grade meningiomas (WHO grade II and III) (N = 145) reviewed, concordance between tumor type and grade was seen in only 26.2% of cases; most commonly, 73/98 atypical meningiomas were under-graded as some subtype of WHO grade I meningioma (71/73 cases). In conclusion, discrepancies at frozen section with respect to accurately identifying higher grade meningiomas and higher grade meningioma subtypes are common and are generally due to tumor sampling and heterogeneity., (Copyright © 2018 Elsevier Inc. All rights reserved.)