tbuckley/cabot-search huggingface dataset:
P12.01 The effectiveness of antiepileptic drug treatment in glioma patients: lamotrigine versus lacosamide
Authors: M P van Opijnen, P B van der Meer, L Dirven, M Fiocco, M C M Kouwenhoven, M J van den Bent, M J B Taphoorn, J A F Koekkoek
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Optimal treatment with antiepileptic drugs (AEDs) is an important part of care for brain tumor patients with epileptic seizures. Lamotrigine and lacosamide are both examples of frequently used non-enzyme inducing AEDs with limited to no drug-drug interactions, reducing the risk of unfavorable side effects. This study aimed to compare the effectiveness of lamotrigine versus lacosamide. MATERIAL AND METHODS In this multicenter study we retrospectively analyzed data of patients with diffuse grade 2–4 glioma with epileptic seizures. All patients received either lamotrigine or lacosamide during the course of their disease after treatment failure of first-line monotherapy with levetiracetam or valproic acid. Primary outcome was the cumulative incidence of treatment failure, from initiation of lamotrigine or lacosamide, with death as competing event, for which a competing risk model was used. Secondary outcomes were uncontrolled seizures after AED initiation and level of toxicity. RESULTS We included a total of 139 patients of whom 61 (44%) used lamotrigine and 78 (56%) used lacosamide. At 12 months, there was no statistically significant difference in the cumulative incidence of treatment failure for any reason between lamotrigine and lacosamide: 38% (95%CI: 26–51%) versus 30% (95%CI: 20–41%), respectively. The adjusted hazard ratio for treatment failure of lacosamide compared to lamotrigine was 0.84 (95%CI: 0.46–1.56). The cumulative incidences of treatment failure due to uncontrolled seizures (18% versus 11%) and due to adverse events (17% versus 19%) did not differ significantly between lamotrigine and lacosamide. CONCLUSION Lamotrigine and lacosamide show similar effectiveness in diffuse glioma patients with epilepsy.
Insulin resistance and insulin sensitizing agents
Authors: Lucia Mastrototaro, Michael Roden
Journal: Metabolism (2021)

Insulin resistance is a common feature of obesity and type 2 diabetes, but novel approaches of diabetes subtyping (clustering) revealed variable degrees of insulin resistance in people with diabetes. Specifically, the severe insulin resistant diabetes (SIRD) subtype not only exhibits metabolic abnormalities, but also bears a higher risk for cardiovascular, renal and hepatic comorbidities. In humans, insulin resistance comprises dysfunctional adipose tissue, lipotoxic insulin signaling followed by glucotoxicity, oxidative stress and low-grade inflammation. Recent studies show that aside from metabolites (free fatty acids, amino acids) and signaling proteins (myokines, adipokines, hepatokines) also exosomes with their cargo (proteins, mRNA and microRNA) contribute to altered crosstalk between skeletal muscle, liver and adipose tissue during the development of insulin resistance. Reduction of fat mass mainly, but not exclusively, explains the success of lifestyle modification and bariatric surgery to improve insulin sensitivity. Moreover, some older antihyperglycemic drugs (metformin, thiazolidinediones), but also novel therapeutic concepts (new peroxisome proliferator-activated receptor agonists, incretin mimetics, sodium glucose cotransporter inhibitors, modulators of energy metabolism) can directly or indirectly reduce insulin resistance. This review summarizes molecular mechanisms underlying insulin resistance including the roles of exosomes and microRNAs, as well as strategies for the management of insulin resistance in humans.
Heterozygous Mutation of Vegfr3 Reduces Renal Lymphatics without Renal Dysfunction
Authors: Hao Liu, Chitkale Hiremath, Quinten Patterson, Saumya Vora, Zhiguo Shang, Andrew R. Jamieson, Reto Fiolka, Kevin M. Dean, Michael T. Dellinger, Denise K. Marciano
Journal: Journal of the American Society of Nephrology (2021)

Lymphatic abnormalities are observed in several types of kidney disease, but the relationship between the renal lymphatic system and renal function is unclear. The discovery of lymphatic-specific proteins, advances in microscopy, and available genetic mouse models provide the tools to help elucidate the role of renal lymphatics in physiology and disease.We utilized a mouse model containing a missense mutation in Vegfr3 (dubbed Chy ) that abrogates its kinase ability. Vegfr3 Chy/+ mice were examined for developmental abnormalities and kidney-specific outcomes. Control and Vegfr3 Chy/+ mice were subjected to cisplatin-mediated injury. We characterized renal lymphatics using tissue-clearing, light-sheet microscopy, and computational analyses.In the kidney, VEGFR3 is expressed not only in lymphatic vessels but also, in various blood capillaries. Vegfr3 Chy/+ mice had severely reduced renal lymphatics with 100% penetrance, but we found no abnormalities in BP, serum creatinine, BUN, albuminuria, and histology. There was no difference in the degree of renal injury after low-dose cisplatin (5 mg/kg), although Vegfr3 Chy/+ mice developed perivascular inflammation. Cisplatin-treated controls had no difference in total cortical lymphatic volume and length but showed increased lymphatic density due to decreased cortical volume.We demonstrate that VEGFR3 is required for development of renal lymphatics. Our studies reveal that reduced lymphatic density does not impair renal function at baseline and induces only modest histologic changes after mild injury. We introduce a novel quantification method to evaluate renal lymphatics in 3D and demonstrate that accurate measurement of lymphatic density in CKD requires assessment of changes to cortical volume.
Are Platinum Drugs Ineffective for Triple-Negative Breast Cancer With Residual Invasive Disease After Neoadjuvant Chemotherapy?
Authors: Yumiko Shimanuki, Akihiko Shimomura, Kenichi Yoshimura, Hiroyuki Terakado, Chikako Shimizu
Journal: Journal of Clinical Oncology (2021)

Mayer et al 1 reported that the use of platinum in adjuvant chemotherapy was not noninferior to capecitabine in terms of invasive disease-free survival and increased toxicity in patients with triple-negative breast cancer (TNBC) who had residual invasive disease (RD) after completion of neoadjuvant chemotherapy (NAC).This study was designed to investigate the important clinical question of the effect of platinum as adjuvant therapy for patients with TNBC with RD after NAC.However, several concerns should be addressed.
Metabolomic identification of α-ketoglutaric acid elevation in pediatric chronic graft-versus-host disease
Authors: Divya Subburaj, Bernard Ng, Amina Kariminia, Sayeh Abdossamadi, Madeline Lauener, Eneida R. Nemecek, Jacob Rozmus, Sandhya Kharbanda, Carrie L. Kitko, Victor A. Lewis, Tal Schechter-Finklestein, David A. Jacobsohn, Andrew C. Harris, Michael A. Pulsipher, Henrique Bittencourt, Sung Won Choi, Emi H. Caywood, Kimberly A. Kasow, Monica Bhatia, Benjamin R. Oshrine, Donald Coulter, Joseph H. Chewning, Michael Joyce, Anna B. Pawlowska, Gail C. Megason, Anita Lawitschka, Elena Ostroumov, Ramon Klein Geltink, Geoffrey D. E. Cuvelier, Kirk R. Schultz
Journal: Blood (2021)
Influence of social determinants of health on oncology care quality rankings.
Authors: Benjamin Urick, Sabree Burbage, Christopher Baggett, Jennifer Elston Lafata, Hanna Kelly Sanoff, Justin G. Trogdon
Journal: Journal of Clinical Oncology (2021)

139 Background: Adjustment for social determinants of health (SDOH) when assessing provider care quality remains limited. The Oncology Care Model (OCM), for example, includes low-income status/dual eligibility (LIS/DE) as a part of the risk adjustment model for some quality measures, but does not account for any social risk variables in the hospice measure. No measures within the OCM account for additional social risk factors beyond LIS/DE such as patients’ race, rurality, and social deprivation. Additional SDOH adjustment could increase the accuracy of provider quality rankings and better align performance-based payments with true provider quality. Methods: North Carolina Medicare claims from 2015-2017 comprised the data for this study. The year 2015 was used to establish baseline covariates. Episodes were attributed to physician practices’ Tax Identification Number (TIN), lasted 6 months, and were divided into performance years beginning 1/1/2016 and 7/1/2016. Three measures were used: 1) all-cause hospital admissions; 2) all-cause emergency department visits or observation stays; and 3) admission to hospice for 3 days or more among patients who died. SDOH included patient-level race as well as county-level rurality and social deprivation, measured using the social deprivation index (SDI). TIN-level scores with and without expanded SDOH variables were divided into quintiles and compared descriptively as well as using weighted kappa statistics. Results: No SDOH were significantly associated with the hospitalization outcome (P = 0.118-0.944). For the ED measure, Black patients and rural patients were significantly more likely to have an ED visit or observation stay during an episode than white patients and urban patients (P &lt; 0.0001). For the hospice measure, greater SDI values were associated with less hospice use (P &lt; 0.05). Accordingly, including SDOH variables for ED visit/observation stay and hospice measures had a greater impact on TIN rankings than for the hospitalization measure (Table). Conclusions: Because quintile rankings in determine potential shared savings under models like the OCM, differences in rankings due to additional SDOH variables could have a meaningful impact on TIN-level revenue. Additional work is needed to expand the scope of patient-level SDOH variables used for risk adjustment and to explore differences across TINs which contribute to SDOH-sensitive changes in rankings.[Table: see text]
Molecular Design of Ultrabright Semiconducting Polymer Dots with High NIR‐II Fluorescence for 3D Tumor Mapping
Authors: Yi‐Xuan Li, Shih‐Po Su, Chou‐Hsun Yang, Ming‐Ho Liu, Pin‐Ho Lo, Yi‐Chen Chen, Chao‐Ping Hsu, Yi‐Jang Lee, Huihua Kenny Chiang, Yang‐Hsiang Chan
Journal: Advanced Healthcare Materials (2021)

Abstract Fluorescence probes emitting in the second near‐infrared (NIR‐II, 1000–1700 nm) window with the ability for deep‐tissue imaging in mammals herald a new era in surgical methodology. However, the brightness of these NIR‐II probes is still far from satisfactory due to their low fluorescence quantum yields (QYs), preventing the observation of high‐resolution images such as whole‐organ vascular networks in real time. Described here is the molecular engineering of a series of semiconducting polymer dots (Pdots) incorporated with aggregation‐induced emission moieties to exhibit the QYs as high as 14% in the NIR‐II window. Benefiting from the ultrahigh brightness, a 1400 nm long‐pass filter is utilized to realize in vivo 3D tumor mapping in mice. To further understand how the geometrical and electron structures of the semiconducting polymers affect their optical properties, the in‐depth and thorough density‐functional theory calculations are performed to interpret the experimental results. This study lays the groundwork for further molecular design of highly bright NIR‐II Pdots.
ApoA-I mimetics favorably impact cyclooxygenase 2 and bioactive lipids that may contribute to cardiometabolic syndrome in chronic treated HIV
Authors: M. Daskou, M. Sharma, W. Mu, R. Heymans, E. Ritou, V. Rezek, P. Hamid, A. Kossyvakis, S. Sen Roy, V. Grijalva, A. Chattopadhyay, J. Papesh, D. Meriwether, S.G. Kitchen, A.M. Fogelman, S.T. Reddy, T. Kelesidis
Journal: Metabolism (2021)

We investigated whether apolipoprotein A-I (apoA-I) mimetic peptides 4F and 6F can be a novel therapeutic strategy to reduce blood and gut bioactive lipids, proinflammatory effects of endotoxin (LPS) and aberrant activation of cyclooxygenase 2 (COX-2) as instigators of increased risk for cardiometabolic disease in chronic treated HIV.We used two humanized murine models of chronic treated HIV infection (n = 109 mice) and gut explants from HIV infected (n = 10) persons to determine whether Tg6F and 4F attenuate in vivo and ex vivo increased blood and gut bioactive lipids (measured by mass spectrometry) and intestinal protein levels of COX-2 (measured by immunoassays) in chronic treated HIV.In these models of HIV, when compared to HIV-1 infected mice on antiretroviral therapy (ART) alone, oral Tg6F in combination with ART attenuated increases in plasma and gut bioactive lipids (and particularly COX lipids) and intestinal COX-2. 4F and Tg6F also reduced ex vivo production of COX-2 protein and associated secretion of bioactive lipids in gut explants from HIV-1 infected persons treated with LPS.ApoA-I mimetics favorably impact the proinflammatory effects of LPS, COX-2 and production of bioactive lipids that collectively drive gut and systemic inflammation in chronic treated HIV. Given prior experimental evidence that the proinflammatory effects of LPS, COX-2 and gut dysfunction contribute to cardiometabolic syndrome in chronic HIV, apoA-I mimetic peptides may be a novel therapy to treat cardiometabolic syndrome in chronic HIV.
Timing of endoscopy for acute upper gastrointestinal bleeding: a territory-wide cohort study
Authors: Cosmos L T Guo, Sunny H Wong, Louis H S Lau, Rashid N S Lui, Joyce W Y Mak, Raymond S Y Tang, Terry C F Yip, William K K Wu, Grace L H Wong, Francis K L Chan, James Y W Lau, Joseph J Y Sung
Journal: Gut (2021)

While it is recommended that patients presenting with acute upper gastrointestinal bleeding (AUGIB) should receive endoscopic intervention within 24 hours, the optimal timing is still uncertain. We aimed to assess whether endoscopy timing postadmission would affect outcomes.We conducted a retrospective, territory-wide, cohort study with healthcare data from all public hospitals in Hong Kong. Adult patients (age ≥18) that presented with AUGIB between 2013 and 2019 and received therapeutic endoscopy within 48 hours (n=6474) were recruited. Patients were classified based on endoscopic timing postadmission: urgent (t≤6), early (6<t≤24) and late (24<t≤48). Baseline characteristics were balanced with inverse probability of treatment weighting. 30-day all-cause mortality, repeated therapeutic endoscopy rate, intensive care unit (ICU) admission rate and other endpoints were compared.Results showed that urgent timing (n=1008) had worse outcomes compared with early endoscopy (n=3865), with higher 30-day all-cause mortality (p<0.001), repeat endoscopy rates (p<0.001) and ICU admission rates (p<0.001). Late endoscopy (n=1601) was associated with worse outcomes, with higher 30-day mortality (p=0.003), in-hospital mortality (p=0.022) and 30-day transfusion rates (p=0.018).Compared with urgent and late endoscopy among patients who have received therapeutic endoscopies, early endoscopy was associated with superior outcomes especially among patients with non-variceal bleeding. This supports the notion that non-variceal AUGIB patients should receive endoscopy within 24 hours, but also emphasises the importance of prior resuscitation and pharmacotherapy.
Dissociation of Glycated Albumin and HbA1c Is Associated With a Decline of Glomerular Filtration Rate as Evaluated by Inulin Clearance
Authors: Akihiro Tsuda, Katsuhito Mori, Shinya Nakatani, Yuri Machiba, Hideki Uedono, Masafumi Kurajoh, Shinsuke Yamada, Tomoaki Morioka, Masaaki Inaba, Eiji Ishimura, Junji Uchida, Masanori Emoto
Journal: Diabetes Care (2021)

Hemoglobin A1c (HbA1c), microalbuminuria, and estimated glomerular filtration rate (eGFR) are widely used for assessment of diabetic kidney disease (DKD). However, we have shown that eGFR is inaccurate in DKD (1). Further, HbA1c has several limitations as a glycemic marker (2). Guidelines for hemodialysis patients in Japan recommend evaluation of glycemic control using glycated albumin (GA) rather than HbA1c, which is affected by conditions such as anemia and renal failure (3). Renal anemia is a common complication in chronic kidney disease (CKD), including in predialysis patients with CKD. Thus, we evaluated the correlations between GFR measured accurately by inulin clearance (Cin) and the dissociation of GA and HbA1c in nondialysis patients with CKD.

The study protocol was approved by the Ethics Committee of Osaka City University Graduate School of Medicine (#3506) as an opt-out study. The study was performed between January 2009 and March 2020 at Osaka City University Hospital.

The subjects were 133 patients (60.6 ± 12.5 years, 66 males) with glycemic disorder. Diagnosis of type 2 diabetes (87 subjects) was based on a history of diabetes or criteria in the “Report of the Expert Committee on the …
One Week Sustained In Vivo Therapeutic Release and Safety of Novel Extended‐Wear Silicone Hydrogel Contact Lenses
Authors: Stephen A. DiPasquale, Liana D. Wuchte, Robert J. Mosley, Renee M. Demarest, Meredith L. Voyles, Mark E. Byrne
Journal: Advanced Healthcare Materials (2021)

Abstract Since the seminal work of Wichterle in 1965 describing the first soft contact lenses and their potential for ocular drug delivery, the field has yet to realize his vision. Maintaining all lens commercial properties combined with a mechanism for controlled drug release of therapeutically relevant concentrations for duration of wear is a major challenge. Here, successful in vivo week‐long sustained release of a small molecular weight therapeutic in rabbits from extended‐wear silicone hydrogel contact lenses meeting all commercial specifications by utilizing a novel macromolecular memory strategy is reported for the first time. Lens‐treated eyes show a continuous, therapeutically relevant bromfenac tear concentration of 256.4 ± 23.1 µg mL −1 for 8 days. Bromday (bromfenac ophthalmic solution, 0.09%, Bausch+Lomb) topical drops exhibit a quick peak concentration of 269.3 ± 85.7 µg mL −1 and 100 min duration. Bioavailability (AUC 0‐8days ) and mean residence time of lenses are 26 and 155 times higher than drops, respectively. Lenses are safe, well tolerated, and no corneal histological differences are observed. This work highlights the enormous potential of drug releasing lenses as a platform strategy, and offers a new dropless clinical strategy for post‐cataract, uveitis, post‐LASIK, and corneal abrasion treatment.
Associations of School Closures with and without Social Lockdown on Physical and Mental Health of Children and Young People during the First COVID-19 Wave: A Systematic Review
Authors: R. Viner, S. Russell, R. Saulle, H. Croker, C. Stansfield, J. Packer, D. Nicholls, A. L. Goddings, C. Bonell, L. Hudson, S. Hope, J. Ward, N. Schwalbe, A. Morgan, S. Minozzi
Journal: JAMA Pediatrics (2021)

Importance: School closures during COVID-19 are likely to be associated with significant health harms to children and young people. A systematic review of the evidence is needed to inform policy decisions around school closures and reopenings. Objective: To assess the associations of school closures on health and well-being outcomes in children and young people aged 0 to 19 years, excluding associations with transmission of infection. Evidence Review: Eleven databases were searched from inception to September 2020, and machine learning was applied for screening articles. A total of 16817 records were screened, 151 were reviewed in full text, and 43 studies were included. Quality assessment was tailored to study type. A narrative synthesis of results was undertaken because data did not allow meta-analysis. Findings: A total of 43 studies from 12 countries with 104630 study individuals were included in analysis. Of those, 9 (21%) were longitudinal pre-post studies, 5 (12%) were cohort, 28 (65%) were cross-sectional, and 1 (1%) was a modeling study;all assessed change by comparison with population reference data. Eighteen studies (42%) were high quality, 19 (45%) were medium quality, and 6 (14%) were low quality. Cause of closure in all studies was the first COVID-19 wave with the exception of 5 influenza studies (11.6%). Twenty-seven studies (62.8%) concerning mental health identified considerable associations across emotional, behavioral, and restlessness/inattention problems;18% to 60% of children and young people scored above risk thresholds for distress, particularly anxiety and depressive symptoms. Two studies reported nonsignificant rises in suicide. Child protection referrals fell 27% to 39% to half the expected number of referrals originating in schools. Data suggested marked rises in screen time and social media use and reductions in physical activity;however, data on sleep and diet were inconclusive. Available data suggested likely higher harms in children and young people from more low-resource populations. Conclusions and Relevance: School closures as part of social distancing measures are associated with considerable harms to children and young people's health and well-being. Associations of school closure were not able to be separated from broader lockdown. Available data are short term;longer-term harms are likely to be magnified. Data on longer-term associations using strong research designs are needed, particularly among vulnerable groups. These findings are important for policy makers seeking to balance the risks of transmission through school-aged children with the harms of closing schools..
Inappropriate Access to the Adolescent Patient Portal and Low Rates of Proxy Account Creation
Authors: Chase R. Parsons
Journal: JAMA Network Open (2021)

Wui Ip, MD; Samuel Yang, MD; Jacob Parker, BS; Austin Powell, MS; James Xie, MD; Keith Morse, MD, MBA; Rachael C. Aikens, MS; Jennifer Lee, MD; Manjot Gill, MD; Shravani Vundavalli, MD; Yungui Huang, PhD, MBA; Jeannie Huang, MD, MPH; Jonathan H. Chen, MD, PhD; Jeffrey Hoffman, MD; Cynthia Kuelbs, MD; Natalie Pageler, MD, MEd