tbuckley/cabot-search huggingface dataset:
From clinical trials to clinical practice: how should we design and evaluate prediction models in the care of IBD?
Authors: Ryan William Stidham, Andrew Vickers, Karandeep Singh, Akbar K Waljee
Journal: Gut (2021)

As medical treatment options for Crohn’s disease (CD) expand, clinicians need better tools to gauge a patient’s degree of disease burden and ultimately determine whether the therapeutic plan will provide sufficient benefit. Endoscopic scores such as the Simple Endoscopic Score for Crohn Disease (SES-CD) measure the degree of mucosal injury to assess therapeutic change. Though shown in uncontrolled studies to predict some CD clinical outcomes, the SES-CD was not expressly designed to predict the durability of sufficient therapeutic response.1 In Gut , Narula et al present their work optimising the weighting of individual endoscopic features on baseline colonoscopy to predict CD endoscopic remission at 1 year.2 This group demonstrated that the proposed modified multiplier SES-CD (MM-SES-CD) score better predicted endoscopic remission at 1 year compared with using the original SES-CD (area under the curve (AUC) 0.82 vs 0.60, respectively).

Beyond the improvement in model performance, MM-SES-CD feature weighting highlights and quantifies the differential importance of endoscopic feature distribution across anatomic segments. The MM-SES-CD model heavily weights findings in the ileum relative to other sections of the colon, indicating baseline severity at the ileum has a particular influence on outcomes and treatment response. This could be supported by emerging genomic and transcriptional data that suggest ileal or ileocolonic disease behave differently compared with purely colonic disease.3

As the field of gastroenterology prepares to move forward with prediction …
Association of accelerometer-derived sleep measures with lifetime psychiatric diagnoses: A cross-sectional study of 89,205 participants from the UK Biobank
Authors: Michael Wainberg, Samuel E. Jones, Lindsay Melhuish Beaupre, Sean L. Hill, Daniel Felsky, Manuel A. Rivas, Andrew S. P. Lim, Hanna M. Ollila, Shreejoy J. Tripathy
Journal: PLoS Medicine (2021)

Sleep problems are both symptoms of and modifiable risk factors for many psychiatric disorders. Wrist-worn accelerometers enable objective measurement of sleep at scale. Here, we aimed to examine the association of accelerometer-derived sleep measures with psychiatric diagnoses and polygenic risk scores in a large community-based cohort.In this post hoc cross-sectional analysis of the UK Biobank cohort, 10 interpretable sleep measures-bedtime, wake-up time, sleep duration, wake after sleep onset, sleep efficiency, number of awakenings, duration of longest sleep bout, number of naps, and variability in bedtime and sleep duration-were derived from 7-day accelerometry recordings across 89,205 participants (aged 43 to 79, 56% female, 97% self-reported white) taken between 2013 and 2015. These measures were examined for association with lifetime inpatient diagnoses of major depressive disorder, anxiety disorders, bipolar disorder/mania, and schizophrenia spectrum disorders from any time before the date of accelerometry, as well as polygenic risk scores for major depression, bipolar disorder, and schizophrenia. Covariates consisted of age and season at the time of the accelerometry recording, sex, Townsend deprivation index (an indicator of socioeconomic status), and the top 10 genotype principal components. We found that sleep pattern differences were ubiquitous across diagnoses: each diagnosis was associated with a median of 8.5 of the 10 accelerometer-derived sleep measures, with measures of sleep quality (for instance, sleep efficiency) generally more affected than mere sleep duration. Effect sizes were generally small: for instance, the largest magnitude effect size across the 4 diagnoses was β = -0.11 (95% confidence interval -0.13 to -0.10, p = 3 × 10-56, FDR = 6 × 10-55) for the association between lifetime inpatient major depressive disorder diagnosis and sleep efficiency. Associations largely replicated across ancestries and sexes, and accelerometry-derived measures were concordant with self-reported sleep properties. Limitations include the use of accelerometer-based sleep measurement and the time lag between psychiatric diagnoses and accelerometry.In this study, we observed that sleep pattern differences are a transdiagnostic feature of individuals with lifetime mental illness, suggesting that they should be considered regardless of diagnosis. Accelerometry provides a scalable way to objectively measure sleep properties in psychiatric clinical research and practice, even across tens of thousands of individuals.
Discovery of an Immune-Driven Gene Expression Signature That Predicts for Clinical Benefit to CC-122 in Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL)
Authors: Alberto Risueño, Patrick R. Hagner, Celia Fontanillo, Amira Djebbari, Joel S. Parker, Clifton P. Drew, Fadi Towfic, Michael Pourdehnad, Anita K. Gandhi, Matthew Trotter
Journal: Blood (2017)
Chimeric antigen receptor T‐cells, bispecific antibodies, and antibody‐drug conjugates for multiple myeloma: An update
Authors: Arjun Lakshman, Shaji K. Kumar
Journal: American Journal of Hematology (2021)

Patients with multiple myeloma who are refractory to currently available effective therapies have short expected survival. Modalities harvesting the knowledge of the immune characteristics and microenvironment of myeloma such as chimeric antigen receptor (CAR) T-lymphocytes, bispecific antibodies (bsAbs), and antibody-drug conjugates (ADCs) have shown potential in early phase trials. Based on data from phase 2 studies, idecabtagene vicleucel (ide cel), an anti-B-cell maturation antigen CAR T-product and belantamab mafodotin (belamaf), an ADC are currently approved in the relapsed/refractory setting. bsAbs have shown promise with quick and deep responses. In this review, we summarize the available evidence on these treatments from clinical trials.
P56.02 Novel Low Malignant Potential/Vascular Invasive (LMPVI) Grade is Superior to WHO 2015 and IASLC 2020 Adenocarcinoma Grade
Authors: I. Yambayev, T. Sullivan, K. Suzuki, V. Litle, E. Servais, C. Stock, S. Quadri, K. Rieger-Christ, E. Burks
Journal: Journal of Thoracic Oncology (2021)
All eyes on a phosphatase in glioma stem cells
Authors: Robert A. Lindquist, William A. Weiss
Journal: The Journal of Experimental Medicine (2021)

In this issue of JEM, Zhang et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20202669) identify a dependency of glioma stem cells on tyrosine phosphatase activity of EYA2 and a new role for this phosphatase at the centrosome, offering a new therapeutic approach to target mitotic activity.
Fertility preservation in boys facing gonadotoxic cancer therapy
Authors: Christian F. S. Jensen, Lihua Dong, Murat Gul, Mikkel Fode, Simone Hildorf, Jorgen Thorup, Eva Hoffmann, Dina Cortes, Jens Fedder, Claus Y. Andersen, Jens Sønksen
Journal: Nature Reviews Urology (2021)
Immune checkpoint inhibitors in patients with pre-existing psoriasis: safety and efficacy
Authors: Briana Rose Halle, Allison Betof Warner, Farzana Y Zaman, Andrew Haydon, Prachi Bhave, Anna K Dewan, Fei Ye, Rebecca Irlmeier, Paras Mehta, Nicholas R Kurtansky, Mario E Lacouture, Jessica C Hassel, Jacob S Choi, Jeffrey A Sosman, Sunandana Chandra, Tracey S Otto, Ryan Sullivan, Meghan J Mooradian, Steven T Chen, Florentia Dimitriou, Georgina Long, Matteo Carlino, Alexander Menzies, Douglas B Johnson, Veronica M Rotemberg
Journal: Journal for ImmunoTherapy of Cancer (2021)

Immune checkpoint inhibitors (ICIs) are approved to treat multiple cancers. Retrospective analyses demonstrate acceptable safety of ICIs in most patients with autoimmune disease, although disease exacerbation may occur. Psoriasis vulgaris is a common, immune-mediated disease, and outcomes of ICI treatment in patients with psoriasis are not well described. Thus we sought to define the safety profile and effectiveness of ICIs in patients with pre-existing psoriasis.In this retrospective cohort study, patients from eight academic centers with pre-existing psoriasis who received ICI treatment for cancer were evaluated. Main safety outcomes were psoriasis exacerbation and immune-related adverse events (irAEs). We also assessed progression-free survival (PFS) and overall survival.Of 76 patients studied (50 (66%) male; median age 67 years; 62 (82%) with melanoma, 5 (7%) with lung cancer, 2 (3%) with head and neck cancer, and 7 (9%) with other cancers; median follow-up 25.1 months (range=0.2-99 months)), 51 (67%) received anti-PD-1 antibodies, 8 (11%) anti-CTLA-4, and 17 (22%) combination of anti-PD-1/CTLA-4. All patients had pre-existing psoriasis, most frequently plaque psoriasis (46 patients (61%)) and 15 (20%) with psoriatic arthritis. Forty-one patients (54%) had received any prior therapy for psoriasis although only two (3%) were on systemic immunosuppression at ICI initiation. With ICI treatment, 43 patients (57%) experienced a psoriasis flare of cutaneous and/or extracutaneous disease after a median of 44 days of receiving ICI. Of those who experienced a flare, 23 patients (53%) were managed with topical therapy only; 16 (21%) needed systemic therapy. Only five patients (7%) required immunotherapy discontinuation for psoriasis flare. Forty-five patients (59%) experienced other irAEs, 17 (22%) of which were grade 3/4. PFS with landmark analysis was significantly longer in patients with a psoriasis flare versus those without (39 vs 8.7 months, p=0.049).In this multicenter study, ICI therapy was associated with frequent psoriasis exacerbation, although flares were manageable with standard psoriasis treatments and few required ICI discontinuation. Patients who experienced disease exacerbation performed at least as well as those who did not. Thus, pre-existing psoriasis should not prevent patients from receiving ICIs for treatment of malignancy.
Intermediate Renal Outcomes, Kidney Failure, and Mortality in Obese Kidney Donors
Authors: Hassan N. Ibrahim, Dina N. Murad, Sean A. Hebert, Horacio E. Adrogue, Hana Nguyen, Duc T. Nguyen, Arthur J. Matas, Edward A. Graviss
Journal: Journal of the American Society of Nephrology (2021)

Obesity is associated with the two archetypal kidney disease risk factors: hypertension and diabetes. Concerns that the effects of diabetes and hypertension in obese kidney donors might be magnified in their remaining kidney have led to the exclusion of many obese candidates from kidney donation.
A common strategy to improve transmembrane transport in polarized epithelial cells based on sorting signals: Guiding nanocarriers to TGN rather than to the basolateral plasma membrane directly
Authors: Runyu Zhang, Hailiang Deng, Yuxing Lin, Xing Wang, Bing He, Wenbing Dai, Hua Zhang, Ying Zheng, Qiang Zhang, Xueqing Wang
Journal: Journal of Controlled Release (2021)
Readmission and reoperation rates after resection of malignant primary brain tumours in England 2013-2017
Authors: Adam Wahba, Nick Phillips, Peter Hutchinson, David Cromwell, Ryan Mathew
Journal: Neuro-Oncology (2021)

Abstract Aims Morbidity and mortality following resection of malignant primary brain tumours is high. The benefits of reoperation for recurrent tumours are uncertain and it is not known how frequently patients in England undergo further tumour resections. The aim of this study was to describe 30-day and one-year readmission rates, the clinical reasons for readmission and the rate of resections for recurrent tumours. Method Patient data was extracted from Hospital Episode Statistics (the hospital administrative data for NHS hospitals in England) for all supratentorial, malignant, primary brain tumour resections performed from April 2013 to March 2017. All subsequent non-elective readmissions to any NHS hospital and all readmissions for further tumour resection within 30 days and one year were analysed for the primary clinical diagnosis and primary procedure performed. Results A total of 6,982 patients were identified and the 30-day and one-year readmission rates were 18.6% (n=1,298) and 57.4% (n=4,007), respectively. The rates of reoperation for tumour resection were 0.5% (n=33) and 6.2% (n=432), respectively. The commonest reasons for 30-day readmission were post-operative complications (17.9% of admissions), general medical complications (17.3%) and surgical site infection (9.6%). The most frequently performed neurosurgical procedures were for treatment of surgical site infection (37.6% of procedures). The commonest reasons for readmission within one year were general medical complications (17.4%), seizures (14%), systemic infections (11.4%) and post-operative complications (11%). Almost half of all neurosurgical procedures performed within one year were reoperation for tumour resection (45.6%), while treatment of surgical site infection (17.9%) and CSF shunt insertions and revisions (9.1%) were also common. Conclusion This study provides a descriptive analysis of the rates of readmission, diagnosis on readmission, and the need for further neurosurgical procedures. The rate of non-elective readmissions within one year is high and these data may be useful for service planning and for counselling patients about their treatment. Additionally, these data contribute to the development of quality indicators, for benchmarking and comparing quality of care provision between neurosurgical units. Further research, with linkage to histology data and performance status, would support an analysis of the role of resection of recurrent, malignant, primary brain tumours.
PL02.01 Durvalumab ± Tremelimumab + Chemotherapy as First-line Treatment for mNSCLC: Results from the Phase 3 POSEIDON Study
Authors: M. Johnson, B.C. Cho, A. Luft, J. Alatorre-Alexander, S.L. Geater, K. Laktionov, A. Vasiliev, D. Trukhin, S. Kim, G. Ursol, M. Hussein, F. Lim, C. Yang, L. Araujo, H. Saito, N. Reinmuth, X. Shi, L. Poole, S. Peters, E. Garon, T. Mok
Journal: Journal of Thoracic Oncology (2021)
England’s stalled cancer progress: the enduring effect of the covid-19 pandemic
Authors: S Michael Crawford, Heather Edwards, Anna Zoltowski
Journal: BMJ (2021)

The questions being asked by the House of Commons Health and Social Care Select committee in its inquiry into cancer services are timely. 1 Much of the evidence that has been presented so far covers the entry of patients into the diagnostic process and the ways in which this must be enhanced.The effects of the covid-19 pandemic and the policies established to mitigate the disruption of NHS function on these pathways have been well documented.We described the change in demand for cancer antigen 125 (CA125) blood tests and the more profound and sustained effect on the number of requests for chest radiography from primary care in the first months of the initial lockdown. 2 The nadir in radiography requests was in April 2020, with a reduction of more than 90% compared with 2019.There was some recovery by June of that year.The evidence presented to the committee included a submission from the UK Lung Cancer and Mesothelioma Clinical Expert Group, which showed how referrals to diagnostic services for this disease have shown a prolonged reduction. 3Data from our hospital show that this is associated with a continuing reduction in the number of requests for chest radiography compared with 2019.The number of requests partially recovered in 2020 but never to the number of requests seen in 2019, and there was a further dip in the second lockdown period in winter 2020-21.Even in the summer of 2021 the number of requests for chest radiography from general practitioners was around 20-30% fewer than in 2019.Given that chest radiography is a basic investigation for patients consulting GPs for respiratory symptoms, this is an important reduction in activity.It may be caused by fewer patients consulting about such symptoms or by GPs being reluctant to request investigations.Whatever its precise mechanism, a reduction in referrals raises concerns of barriers to lung cancer presentation in addition to those that led to the select committee inquiry.
Abstract 14185: Effects of Protease Activated Receptor-1 Signaling Inhibition on Cardiac Hypertrophy and Fibrosis in Renin Overexpressing Hypertensive Mice
Authors: Yoshikazu Yokono, Masato Narita, Yousuke Kawamura, Tomo Kato, Natsumi Kudo, Michiko Tsushima, Yuichi Toyama, Kenji Hanada, Michiko Shimada, Tomohiro Osanai, Hirofumi Tomita
Journal: Circulation (2019)

Introduction: Protease activated receptor-1 (PAR-1) is widely expressed in the vasculature and the heart, and plays important roles in the progression of cardiovascular disease. Recent studies show...
There is still time to save the NHS, but time is running out
Authors: Chris Ham
Journal: BMJ (2021)

The NHS is falling over. Not everywhere, but in some places and in some services the signs of extreme stress are manifest. These signs are the result of the irresistible force of rising demand for care meeting the immovable object of constrained capacity.

Something has to give. For an increasing number of patients, timely access to acceptable standards of care is no longer possible. For staff the challenge is to deal with unprecedented workloads when vacancy and sickness levels among their colleagues remain high. The psychological safety of staff is at risk with consequences for themselves and the patients they treat.

Evidence of stress can be found in many places. University Hospitals Birmingham NHS Foundation Trust was recently downgraded by the Care Quality Commission with standards of care in emergency departments a particular concern. At Brighton and Sussex University Hospitals NHS Trust surgeons and anaesthetists have expressed concerns about delays in the treatment of time-critical emergency and trauma cases. Nottingham University Hospitals NHS Trust has restricted the provision of chemotherapy services because of staff shortages and has been downgraded by the Care Quality Commission, with emergency services and maternity services both being a concern.

General practices are also in the …
Usefulness of CGM-Derived Metric, the Glucose Management Indicator, to Assess Glycemic Control in Non-White Individuals With Diabetes
Authors: Elena Toschi, Amy Michals, Atif Adam, Dai’Quann Davis, Astrid Atakov-Castillo, Christine Slyne, Medha Munshi
Journal: Diabetes Care (2021)

OBJECTIVE To assess the relationship between the glucose management indicator (GMI) and HbA1c in non-White individuals with diabetes. RESEARCH DESIGN AND METHODS We performed a retrospective analysis of continuous glucose monitoring metrics in individuals with diabetes divided by race into non-White and White cohorts. RESULTS We evaluated 316 individuals (non-White n = 68; White n = 248). Although GMI was not different (7.6 vs. 7.7; P = not significant) between the cohorts, HbA1c was higher in the non-White cohort (8.7% vs. 8.1%; P = 0.004). HbA1c higher than GMI by ≥0.5% was more frequently observed in the non-White cohort (90% vs. 75%; P = 0.02). In the non-White cohort only, duration of hypoglycemia was longer among those with HbA1c higher than GMI by ≥0.5% compared with those with HbA1c and GMI within 0.5%. CONCLUSIONS A differential relationship between HbA1c and GMI in non-White versus White individuals with diabetes was observed. In non-White individuals, a greater difference between HbA1c and GMI was associated with higher risk of hypoglycemia.
A two-step strategy for removing over-the-scope clip buried in contact with the heart
Authors: Hirohisa Sakurai, Takashi Kanesaka, Masaaki Yamamoto, Takeshi Omori, Yasuhiro Tani, Tomoki Michida, Ryu Ishihara
Journal: Endoscopy (2021)

An over-the-scope (OTS) clip allows tight endoscopic closure of gastrointestinal perforation [1] [2]. However, OTS clips remain in vivo for long periods. Several devices were reportedly useful for OTS clip removal [3] [4], but these were not commercially available in Japan. A method for removing OTS clips using an existing device was previously reported [5]. We encountered a case wherein the OTS clip was buried and in contact with the heart ([Video 1]).
MR-guided focused ultrasound enhances delivery of trastuzumab to Her2-positive brain metastases
Authors: Ying Meng, Raymond M. Reilly, Rossanna C. Pezo, Maureen Trudeau, Arjun Sahgal, Amit Singnurkar, James Perry, Sten Myrehaug, Christopher B. Pople, Benjamin Davidson, Maheleth Llinas, Chinthaka Hyen, Yuexi Huang, Clement Hamani, Suganth Suppiah, Kullervo Hynynen, Nir Lipsman
Journal: Science Translational Medicine (2021)

MRgFUS is a safe, noninvasive method to deliver spatially targeted monoclonal antibody across the BBB in patients with brain tumors.
Occurrence of Pancytopenia Among Patients With Cancer Treated With Poly(Adenosine Diphosphate–Ribose) Polymerase Inhibitors
Authors: Pierre-Marie Morice, Basile Chrétien, Angélique Da Silva, Charles Dolladille, Joachim Alexandre
Journal: JAMA Oncology (2021)

This cross-sectional study uses pharmacovigilance data to investigate the occurrence of pancytopenia among patients with cancer treated with poly(adenosine diphosphate–ribose) polymerase inhibitors and examines the clinical features of pancytopenia related to these drugs.
A Randomized, Controlled Trial of the Pan-PPAR Agonist Lanifibranor in NASH
Authors: Sven M. Francque, Pierre Bedossa, Vlad Ratziu, Quentin M. Anstee, Elisabetta Bugianesi, Arun J. Sanyal, Rohit Loomba, Stephen A. Harrison, Rozalina Balabanska, Lyudmila Mateva, Nicolas Lanthier, Naim Alkhouri, Christophe Moreno, Jörn M. Schattenberg, Diana Stefanova-Petrova, Luisa Vonghia, Régine Rouzier, Maeva Guillaume, Alexander Hodge, Manuel Romero-Gómez, Philippe Huot-Marchand, Martine Baudin, Marie-Paule Richard, Jean-Louis Abitbol, Pierre Broqua, Jean-Louis Junien, Manal F. Abdelmalek
Journal: New England Journal of Medicine (2021)

Management of nonalcoholic steatohepatitis (NASH) is an unmet clinical need. Lanifibranor is a pan-PPAR (peroxisome proliferator–activated receptor) agonist that modulates key metabolic, inflammatory, and fibrogenic pathways in the pathogenesis of NASH.