tbuckley/cabot-search huggingface dataset:
Implementing clinical decision support for oncology advanced care planning: A systems engineering framework to optimize the usability and utility of a machine learning predictive model in clinical practice.
Authors: Teja Ganta, Stephanie Lehrman, Rachel Pappalardo, Madalene Crow, Meagan Will, Mark Liu, Robbie Freeman, Arash Kia, Prathamesh Parchure, Alla Keyzner, Madhu Mazumdar, Aarti Sonia Bhardwaj, Cardinale B. Smith
Journal: Journal of Clinical Oncology (2021)

330 Background: Machine learning models are well-positioned to transform cancer care delivery by providing oncologists with more accurate or accessible information to augment clinical decisions. Many machine learning projects, however, focus on model accuracy without considering the impact of using the model in real-world settings and rarely carry forward to clinical implementation. We present a human-centered systems engineering approach to address clinical problems with workflow interventions utilizing machine learning algorithms. Methods: We aimed to develop a mortality predictive tool, using a Random Forest algorithm, to identify oncology patients at high risk of death within 30 days to move advance care planning (ACP) discussions earlier in the illness trajectory. First, a project sponsor defined the clinical need and requirements of an intervention. The data scientists developed the predictive algorithm using data available in the electronic health record (EHR). A multidisciplinary workgroup was assembled including oncology physicians, advanced practice providers, nurses, social workers, chaplain, clinical informaticists, and data scientists. Meeting bi-monthly, the group utilized human-centered design (HCD) methods to understand clinical workflows and identify points of intervention. The workgroup completed a workflow redesign workshop, a 90-minute facilitated group discussion, to integrate the model in a future state workflow. An EHR (Epic) analyst built the user interface to support the intervention per the group’s requirements. The workflow was piloted in thoracic oncology and bone marrow transplant with plans to scale to other cancer clinics. Results: Our predictive model performance on test data was acceptable (sensitivity 75%, specificity 75%, F-1 score 0.71, AUC 0.82). The workgroup identified a “quality of life coordinator” who: reviews an EHR report of patients scheduled in the upcoming 7 days who have a high risk of 30-day mortality; works with the oncology team to determine ACP clinical appropriateness; documents the need for ACP; identifies potential referrals to supportive oncology, social work, or chaplain; and coordinates the oncology appointment. The oncologist receives a reminder on the day of the patient’s scheduled visit. Conclusions: This workgroup is a viable approach that can be replicated at institutions to address clinical needs and realize the full potential of machine learning models in healthcare. The next steps for this project are to address end-user feedback from the pilot, expand the intervention to other cancer disease groups, and track clinical metrics.
Recovery of cardiac function following <scp>COVID</scp>‐19 – <scp>ECHOVID</scp>‐19: a prospective longitudinal cohort study
Authors: Mats C.H. Lassen, Kristoffer Grundtvig Skaarup, Jannie N. Lind, Alia S. Alhakak, Morten Sengeløv, Anne B. Nielsen, Jakob Ø. Simonsen, Niklas D. Johansen, Filip S. Davidovski, Jacob Christensen, Henning Bundgaard, Christian Hassager, Reza Jabbari, Jørn Carlsen, Ole Kirk, Matias G. Lindholm, Ole P. Kristiansen, Olav W. Nielsen, Charlotte S. Ulrik, Pradeesh Sivapalan, Gunnar Gislason, Rasmus Møgelvang, Gorm B. Jensen, Peter Schnohr, Peter Søgaard, Scott D. Solomon, Kasper Iversen, Jens U.S. Jensen, Morten Schou, Tor Biering‐Sørensen
Journal: European Journal of Heart Failure (2021)
Racial disparities in mortality among patients with prurigo nodularis: A multi-center cohort study
Authors: Nishadh Sutaria, Waleed Adawi, Isabelle Brown, Varsha Parthasarathy, Youkyung S. Roh, Justin Choi, Zachary A. Bordeaux, Pavin Trinh, Thomas K. Le, Junwen Deng, Yevgeniy R. Semenov, Shawn G. Kwatra
Journal: Journal of the American Academy of Dermatology (2021)
P-82 Impact of type 2 diabetes mellitus in overall survival and clinical features of Latin patients with colorectal cancer: A 15-year follow-up
Authors: G. Calderillo-Ruiz, C. Diaz, H. Lopez Basave, E. Ruiz-Garcia, A. Apodaca, E. Trejo, A. Takahashi, B. Carbajal-López, A. Albarran
Journal: Annals of Oncology (2021)
Risk factors for ED visits and admissions during outpatient chemotherapy in head and neck cancer.
Authors: Navika Shukla, Anirudh Saraswathula, Saad A. Khan, Vasu Divi
Journal: Journal of Clinical Oncology (2021)

223 Background: Despite the recent introduction of the CMS metric, OP-35, which tracks 30-day inpatient admissions and ED visits after outpatient chemotherapy administration, the risk factors driving acute care utilization (ACU) in the head and neck cancer treatment setting are not yet well understood. Further characterization of these risk factors could allow for improved care quality and reduce preventable inpatient and ED admissions. Methods: This was a retrospective cohort study utilizing the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked cancer registry-claims database. The study cohort consisted of patients aged 66 years or older diagnosed with head and neck cancer between 2004-2015 who received outpatient chemotherapy within the first two years after diagnosis. Multivariable logistic regression modeling was utilized to characterize the risk factors associated with an inpatient or ED admission within 30 days after receiving chemotherapy. Results: Of the 2,236 eligible patients, 735 (32.9%) had at least one inpatient or ED admission within 30 days of receiving outpatient chemotherapy. On multivariable analysis, cancer of the oral cavity [odds ratio (OR) 1.43; 95% confidence interval (CI) 1.04-1.96] and oropharynx/hypopharynx [OR 1.34; 95% CI 1.06-1.70] were associated with an increased odds of ACU. Other factors associated with ACU included NCI comorbidity index [OR 1.10; 95% CI 1.03-1.18], prior ACU [OR 1.06; 95% CI 1.02-1.09], second cycle of chemotherapy relative to the first cycle [OR 0.38, 95% CI 0.29-0.50], and third or greater cycle of chemotherapy [OR 0.17; 95% CI 0.13-0.21]. Certain chemotherapeutic agents also modified risk: use of an angiogenesis inhibitor [OR 0.18; 95% CI 0.06-0.45], alkylating agent [OR 1.24; 95% 1.01-1.53], plant alkaloid [OR 1.63; 95% CI 1.25-2.10], or antimetabolite [OR 2.69; 95% CI 1.78-4.09]. The most common admission diagnosis was pain (n = 243; 33.1%) followed by dehydration (n = 167; 22.7%). Conclusions: Multiple clinical variables modify risk of acute care utilization after outpatient chemotherapy in the head and neck cancer setting, providing several potential avenues of intervention for providers.
Peter Murray Richard Hemphill
Authors: Richard Hemphill
Journal: BMJ (2021)

Peter Murray Richard Hemphill was born in Bareilly, north India, the first son of Kathleen and Major Robert Hemphill (DSO), a doctor in the Royal Army Medical Corps (RAMC). Peter’s sister, Sheila, was born in 1921, and his younger brother, David, arrived in 1924. By this time the family was back in England, although his parents had further postings to Cyprus and Egypt during their children’s early years. 

Peter attended prep school at West Hill Park, Titchfield, until 1933. He then attended Wellington College, Crowthorne, until 1939. At Easter 1935, on a family holiday in north Cornwall, the children witnessed the death of their parents in an accidental fall from sea cliffs. It was Peter’s 15th birthday, and he showed amazing courage, skill, and presence of mind by climbing down to the sea unharmed in an attempt to rescue them. Unable to achieve this, he then climbed all the way back up unaided, again without slipping and falling himself, to run a significant distance to an unmanned coastguard hut, where he smashed a window, reached a phone and raised the alarm. Thus, the three children became orphans, and these terrible events irrevocably scarred the rest of their lives.

However, Peter buckled down and prospered at school and secured a place to read medicine at Clare College, Cambridge, fulfilling his ambition …
Plasmonic Oxygen Defects in MO<sub>3−</sub><i><sub>x</sub></i> (M = W or Mo) Nanomaterials: Synthesis, Modifications, and Biomedical Applications
Authors: Mingzhu Zhou, Yachong Liu, Yan Su, Qianqian Su
Journal: Advanced Healthcare Materials (2021)

Abstract Nanomedicine is a promising technology with many advantages and provides exciting opportunities for cancer diagnosis and therapy. During recent years, the newly developed oxygen‐deficiency transition metal oxides MO 3− x (M = W or Mo) have received significant attention due to the unique optical properties, such as strong localized surface plasmon resonance (LSPR) , tunable and broad near‐IR absorption, high photothermal conversion efficiency, and large X‐ray attenuation coefficient. This review presents an overview of recent advances in the development of MO 3− x nanomaterials for biomedical applications. First, the fundamentals of the LSPR effect are introduced. Then, the preparation and modification methods of MO 3− x nanomaterials are summarized. In addition, the biological effects of MO 3− x nanomaterials are highlighted and their applications in the biomedical field are outlined. This includes imaging modalities, cancer treatment, and antibacterial capability. Finally, the prospects and challenges of MO 3− x and MO 3− x ‐based nanomaterial for fundamental studies and clinical applications are also discussed.
Abstract 14371: Unplanned 30-Day Readmission Risk Among Patients with Acute Myocardial Infarction: A Report from TRANSLATE-ACS
Authors: Connie N Hess, Tracy Y Wang, Lisa Kaltenbach, Emily Honeycutt, John C Messenger, William T Smith, Marjorie E Zettler, Mark B Effron, Timothy D Henry, Eric D Peterson, Gregg C Fonarow
Journal: Circulation (2012)

Background: Hospital readmissions after acute MI are a CMS hospital performance measure. Current readmission models have relied on administrative data, included planned readmissions, and/or examine...
Intracranial Hemorrhage During Dual Antiplatelet Therapy
Authors: Andrew C.T. Ha, Deepak L. Bhatt, James T. Rutka, S. Claiborne Johnston, C. David Mazer, Subodh Verma
Journal: Journal of the American College of Cardiology (2021)

Dual antiplatelet therapy (DAPT) with acetylsalicylic acid and a P2Y12 inhibitor is an established therapy for a broad spectrum of patients with cardiovascular disease. The ischemic benefit of DAPT is partially offset by its increased bleeding risk, with intracranial hemorrhage (ICH) being the most serious complication. Although uncommon (0.2%-0.3% annually), its cumulative burden can be substantial given the number of patients afflicted by cardiovascular disease worldwide. Patients with a history of stroke or transient ischemic attack harbor a particularly high risk for ICH when treated with DAPT. Prediction rules may assist clinicians when weighing the risk/benefit ratio of prescribing DAPT for patients with stroke/transient ischemic attack in the nonacute, ambulatory setting. Currently, there are no reversal agents that can rapidly and effectively reverse the effect of P2Y12 inhibitors in routine practice, although a reversal agent for ticagrelor is under clinical investigation.
Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma
Authors: Paul Nathan, Jessica C. Hassel, Piotr Rutkowski, Jean-Francois Baurain, Marcus O. Butler, Max Schlaak, Ryan J. Sullivan, Sebastian Ochsenreither, Reinhard Dummer, John M. Kirkwood, Anthony M. Joshua, Joseph J. Sacco, Alexander N. Shoushtari, Marlana Orloff, Josep M. Piulats, Mohammed Milhem, April K.S. Salama, Brendan Curti, Lev Demidov, Lauris Gastaud, Cornelia Mauch, Melinda Yushak, Richard D. Carvajal, Omid Hamid, Shaad E. Abdullah, Chris Holland, Howard Goodall, Sophie Piperno-Neumann
Journal: New England Journal of Medicine (2021)

Uveal melanoma is a disease that is distinct from cutaneous melanoma, with a low tumor mutational burden and a 1-year overall survival of approximately 50% in patients with metastatic uveal melanoma. Data showing a proven overall survival benefit with a systemic treatment are lacking. Tebentafusp is a bispecific protein consisting of an affinity-enhanced T-cell receptor fused to an anti-CD3 effector that can redirect T cells to target glycoprotein 100-positive cells.In this open-label, phase 3 trial, we randomly assigned previously untreated HLA-A*02:01-positive patients with metastatic uveal melanoma in a 2:1 ratio to receive tebentafusp (tebentafusp group) or the investigator's choice of therapy with single-agent pembrolizumab, ipilimumab, or dacarbazine (control group), stratified according to the lactate dehydrogenase level. The primary end point was overall survival.A total of 378 patients were randomly assigned to either the tebentafusp group (252 patients) or the control group (126 patients). Overall survival at 1 year was 73% in the tebentafusp group and 59% in the control group (hazard ratio for death, 0.51; 95% confidence interval [CI], 0.37 to 0.71; P<0.001) in the intention-to-treat population. Progression-free survival was also significantly higher in the tebentafusp group than in the control group (31% vs. 19% at 6 months; hazard ratio for disease progression or death, 0.73; 95% CI, 0.58 to 0.94; P = 0.01). The most common treatment-related adverse events in the tebentafusp group were cytokine-mediated events (due to T-cell activation) and skin-related events (due to glycoprotein 100-positive melanocytes), including rash (83%), pyrexia (76%), and pruritus (69%). These adverse events decreased in incidence and severity after the first three or four doses and infrequently led to discontinuation of the trial treatment (2%). No treatment-related deaths were reported.Treatment with tebentafusp resulted in longer overall survival than the control therapy among previously untreated patients with metastatic uveal melanoma. (Funded by Immunocore; ClinicalTrials.gov number, NCT03070392; EudraCT number, 2015-003153-18.).
CD47 blockade enhances the efficacy of intratumoral STING-targeting therapy by activating phagocytes
Authors: Akemi Kosaka, Kei Ishibashi, Toshihiro Nagato, Hidemitsu Kitamura, Yukio Fujiwara, Syunsuke Yasuda, Marino Nagata, Shohei Harabuchi, Ryusuke Hayashi, Yuki Yajima, Kenzo Ohara, Takumi Kumai, Naoko Aoki, Yoshihiro Komohara, Kensuke Oikawa, Yasuaki Harabuchi, Masahiro Kitada, Hiroya Kobayashi, Takayuki Ohkuri
Journal: The Journal of Experimental Medicine (2021)

Activation of STING signaling plays an important role in anti-tumor immunity, and we previously reported the anti-tumor effects of STING through accumulation of M1-like macrophages in tumor tissue treated with a STING agonist. However, myeloid cells express SIRPα, an inhibitory receptor for phagocytosis, and its receptor, CD47, is overexpressed in various cancer types. Based on our findings that breast cancer patients with highly expressed CD47 have poor survival, we evaluated the therapeutic efficacy and underlying mechanisms of combination therapy with the STING ligand cGAMP and an antagonistic anti-CD47 mAb using E0771 mouse breast cancer cells. Anti-CD47 mAb monotherapy did not suppress tumor growth in our setting, whereas cGAMP and anti-CD47 mAb combination therapy inhibited tumor growth. The combination therapy enhanced phagocytosis of tumor cells and induced systemic anti-tumor immune responses, which rely on STING and type I IFN signaling. Taken together, our findings indicate that coadministration of cGAMP and an antagonistic anti-CD47 mAb may be promising for effective cancer immunotherapy.
P04.11 10-Year Institutional Retrospective Case Series of WHO Grade II Gliomas and Correlation of Seizures, Lobar Location, Histopathological Subtype and IDH-1 Mutation (2010–2020)
Authors: S Lammy, E Bridgman, H Johnson, A Taylor, A Grivas
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND A 10-year retrospective case series was undertaken of all patients who had a tissue diagnosis of a World Health Organisation (WHO) Grade II glioma, i.e. low grade glioma (LGGM), at the Institute of Neurological Sciences (INS) between January 2010 and January 2020 (NB: pre-2016 World Health Organisation classification). The objective was to assess the correlation of World Health Organisation (WHO) Grade II gliomas to seizure symptomology, intracerebral tumour location, histopathological glioma sub-type and molecular markers including isocitrate dehydrogenase-1 (IDH-1) mutation. MATERIAL AND METHODS We extracted data regarding clinical, radiological, histological, molecular discriminators and functional outcomes in patients. The pre-operative symptomology was restricted to seizures, headache and focal neurological deficits. RESULTS 84 patients underwent resection and had a mean age of 42rs (range: 21-77yrs]). Seizures (NB: pre-2017 International League against Epilepsy classification [ILAE]) occurred in 71% and of these 52% were generalised, 37% partial and 11% mixed. 31% had ongoing seizures postoperatively. Headache occurred in 38% (of these 50% had headache and seizures). Focal neurological deficits (FNDs) occurred in 21% (of these 61% had FNDs and seizures). Seizure, as an isolated pre-operative symptom occurred in 48% patients compared to isolated headache in 10% and isolated FNDs in 4%. Anatomically, 58% of lesions were frontal. The seizure spatial frequency was 60% frontal. Histologically, 60% were diffuse astrocytomas and 40% oligodendrogliomas. Furthermore, 71% of oligodendrogliomas and 49% of diffuse astrocytomas had a frontal location. IDH-1 mutation occurred in 80% patients (75% of these had seizures) and of these 66% were frontal. CONCLUSIONS Our analysis confirms a correlation between incidence of seizures, frontal lobar location, histopathological subtype and IDH-1 mutations (p = &amp;lt;0.05
Clinical Characteristics of Multisystem Inflammatory Syndrome in Adults
Authors: Pragna Patel, Jennifer DeCuir, Joseph Abrams, Angela P. Campbell, Shana Godfred-Cato, Ermias D. Belay
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Multisystem inflammatory syndrome in adults (MIS-A) has not been well described. Improved diagnosis and treatment of MIS-A might mitigate COVID-19 morbidity and mortality. <h3>Objective</h3> To summarize the descriptive epidemiology and clinical characteristics of MIS-A. <h3>Evidence Review</h3> This systematic review identified patients with MIS-A using 3 strategies: (1) literature review from May 1, 2020, to May 25, 2021, by searching MEDLINE, Embase, Global Health, CAB Abstracts, PsycINFO, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Academic Search Complete, Scopus, World Health Organization Global COVID-19 Literature Database, and Google Scholar; (2) voluntary reports of MIS-A to the Centers for Disease Control and Prevention (CDC); and (3) reports among persons aged 18 to 20 years in the CDC surveillance system for MIS in children. <h3>Findings</h3> Of 221 patients with MIS-A, the median age was 21 (interquartile range [IQR], 19-34) years, and 154 of 219 (70%) with data available were men. Sixty of 169 patients (36%) were non-Hispanic Black individuals, and 122 of 209 (58%) had no underlying comorbidity. One hundred two of 149 patients (68%) noted a previous symptomatic COVID-19–like illness (median, 28 [IQR, 20-36] days previously). Most patients with MIS-A presented with fever (197 of 205 [96%]), hypotension (133 of 220 [60%]), cardiac dysfunction (114 of 210 [54%]), shortness of breath (102 of 198 [52%]), and/or diarrhea (102 of 197 [52%]). The median number of organ systems involved was 5 (IQR, 4-6). Median hospital stay was 8 (IQR, 5-12) days; 115 of 201 patients (57%) were admitted to the intensive care unit; 101 of 213 (47%) required respiratory support, and 15 of 220 (7%) died. Most patients (176 of 195 [90%]) had elevated markers of coagulopathy and/or inflammation and a positive SARS-CoV-2 serologic finding (139 of 194 [72%]). Ten patients with MIS-A presented with Kawasaki disease. <h3>Conclusions and Relevance</h3> These findings suggest that MIS-A is a serious hyperinflammatory condition that presents approximately 4 weeks after onset of acute COVID-19 with extrapulmonary multiorgan dysfunction.
BAY 2253651 for the treatment of obstructive sleep apnoea: a multicentre, double-blind, randomised controlled trial (SANDMAN)
Authors: Thomas Gaisl, Chris D. Turnbull, Gerrit Weimann, Sigrun Unger, Rudolf Finger, Charles Xing, Peter A. Cistulli, Sophie West, Alan K.I. Chiang, Danny J. Eckert, John R. Stradling, Malcolm Kohler
Journal: European Respiratory Journal (2021)

<b>BAY 2253651 is a nasally applied genioglossus muscle activator <i>via</i> pharyngeal mucosal receptor stimulation (potassium channel blocker) aimed to treat obstructive sleep apnoea. Although well-tolerated and safe, there was no significant therapeutic effect.</b>https://bit.ly/3zDbyia
Histone H3K27 demethylase KDM6A is an epigenetic gatekeeper of mTORC1 signalling in cancer
Authors: Steffie Revia, Agnieszka Seretny, Lena Wendler, Ana Banito, Christoph Eckert, Kersten Breuer, Anand Mayakonda, Pavlo Lutsik, Matthias Evert, Silvia Ribback, Suchira Gallage, Ismaiel Chikh Bakri, Kai Breuhahn, Peter Schirmacher, Stefan Heinrich, Matthias M Gaida, Mathias Heikenwälder, Diego F Calvisi, Christoph Plass, Scott W Lowe, Darjus F Tschaharganeh
Journal: Gut (2021)

Large-scale genome sequencing efforts of human tumours identified epigenetic modifiers as one of the most frequently mutated gene class in human cancer. However, how these mutations drive tumour development and tumour progression are largely unknown. Here, we investigated the function of the histone demethylase KDM6A in gastrointestinal cancers, such as liver cancer and pancreatic cancer.Genetic alterations as well as expression analyses of KDM6A were performed in patients with liver cancer. Genetic mouse models of liver and pancreatic cancer coupled with Kdm6a-deficiency were investigated, transcriptomic and epigenetic profiling was performed, and in vivo and in vitro drug treatments were conducted.KDM6A expression was lost in 30% of patients with liver cancer. Kdm6a deletion significantly accelerated tumour development in murine liver and pancreatic cancer models. Kdm6a-deficient tumours showed hyperactivation of mTORC1 signalling, whereas endogenous Kdm6a re-expression by inducible RNA-interference in established Kdm6a-deficient tumours diminished mTORC1 activity resulting in attenuated tumour progression. Genome-wide transcriptional and epigenetic profiling revealed direct binding of Kdm6a to crucial negative regulators of mTORC1, such as Deptor, and subsequent transcriptional activation by epigenetic remodelling. Moreover, in vitro and in vivo genetic epistasis experiments illustrated a crucial function of Deptor and mTORC1 in Kdm6a-dependent tumour suppression. Importantly, KDM6A expression in human tumours correlates with mTORC1 activity and KDM6A-deficient tumours exhibit increased sensitivity to mTORC1 inhibition.KDM6A is an important tumour suppressor in gastrointestinal cancers and acts as an epigenetic toggle for mTORC1 signalling. Patients with KDM6A-deficient tumours could benefit of targeted therapy focusing on mTORC1 inhibition.