tbuckley/cabot-search huggingface dataset:
Severe Tuberculosis Surged After Shelter-in-Place Lifted
Authors: Bridget M. Kuehn
Journal: JAMA (2021)

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Obituary Professor Michael N Marsh BTh, DPhil, DM, DSc, FRCP
Authors: Kamran Rostami, Chris JJ Mulder, David S Sanders
Journal: Gut (2021)

It is with deep respect that we announce the passing of Professor Michael Newton Marsh. He spent much of the last 50 years working on small intestine immunopathology, including electron microscopy and tissue structure. It was his determination, hard work and his ability to apply science to clinical practice that resulted in milestones not only in coeliac disease histology but also in his pioneering work on the recirculating of thoracic duct lymphocytes and tracking of labelled thoracic duct blasts to the intestinal lamina propria and differentiation in IgA-secreting plasma cells (Gut 1975).

He travelled and lectured as distinguished visiting Professor/International Medical Scholar on intestinal immunopathology and the mucosal responses to environmental antigenic challenges—food; parasitic; tropical diarrhoea-malabsorption syndrome; host–host immune histoincompatibilities. Marsh inspired the intestinal immunopathology scientists East-West, from San Francisco to Delhi (India): North-South, from Tampere (Finland) to Christchurch and Dunedin, New Zealand, Australia, Ankara, Tehran and so much more.

Dr Marsh elucidated …
Perception and barriers to virtual medicine in Hispanics and underrepresented populations.
Authors: Alvaro G. Menendez, Katarina Bade, Emily Hsu, Jyoti Chhabra
Journal: Journal of Clinical Oncology (2021)

169 Background: Perceptions and barriers to virtual medicine (VM) in Hispanics and underrepresented population (H/UP) are unknown. We investigated these parameters in a multicenter oncology trial in hopes of improving quality of care and minimizing potentially negative healthcare outcomes related to this increasingly popular healthcare delivery (HD) technique. Methods: An IRB-approved, 14-item questionnaire was offered in English and Spanish to all pts. receiving care at participating cancer centers over a 6-month period. Examined variables included demographic information, preferences and perceived barriers regarding VM. Multivariable analysis was performed using Chi Square test to determine association between demographic variables and participants preferences and perceived barriers. Results: A total of 180 pts were enrolled. H/UP rely more on social media to receive health information (32.6% vs 23.9%) as opposed to face-to-face. Fewer H/UP have received oncological care through VM (27.9% vs 32.9%) despite comparable preferences regarding incorporation or exclusive use of VM in HD (23.2 % vs 24.6%). Similar levels of satisfaction with current HD methods were reported (83.7% vs 86%). No significant difference by age, level of education, marital status or Hispanic ethnicity was noted although Spanish as primary language was statistically significant (p = 0.001) in patient satisfaction and preferences regarding use of VM. H/UP involve family members more frequently through VM (48.8% vs 29.1). H/UP have more technical barriers to VM as they were up to 2.6 times more likely to not have a phone/ipad/similar or have access to broadband connectivity (23.3% vs 9%; and 16.3% vs 8.2% respectively). Conclusions: H/UP are equally interested and satisfied in receiving oncological care through VM. Given the shift towards outpatient and home-based care, an aging population, and cultural appropriations, VM excitedly allows re-incorporation of family/caregiver in medical engagement. However, fewer H/UP are currently utilizing VM which could be secondary to H/UP’s specific barriers or healthcare bias. Although behavioral interventions may be explored, H/UP barriers are predominantly technical and targetable with appropriate policies that take into consideration institutional and reimbursement programs.
Wolframin-1–expressing neurons in the entorhinal cortex propagate tau to CA1 neurons and impair hippocampal memory in mice
Authors: Jean-Christophe Delpech, Dhruba Pathak, Merina Varghese, Srinidhi Venkatesan Kalavai, Emma C. Hays, Patrick R. Hof, W. Evan Johnson, Seiko Ikezu, Maria Medalla, Jennifer I. Luebke, Tsuneya Ikezu
Journal: Science Translational Medicine (2021)

Abnormally phosphorylated tau, an early neuropathologic marker of Alzheimer’s disease (AD), first occurs in the brain’s entorhinal cortex layer II (ECII) and then spreads to the CA1 field of the hippocampus. Animal models of tau propagation aiming to recapitulate this phenomenon mostly show tau transfer from ECII stellate neurons to the dentate gyrus, but tau pathology in the dentate gyrus does not appear until advanced stages of AD. Wolframin-1–expressing (Wfs1+) pyramidal neurons have been shown functionally to modulate hippocampal CA1 neurons in mice. Here, we report that Wfs1+ pyramidal neurons are conserved in the ECII of postmortem human brain tissue and that Wfs1 colocalized with abnormally phosphorylated tau in brains from individuals with early AD. Wfs1+ neuron–specific expression of human P301L mutant tau in mouse ECII resulted in transfer of tau to hippocampal CA1 pyramidal neurons, suggesting spread of tau pathology as observed in the early Braak stages of AD. In mice expressing human mutant tau specifically in the ECII brain region, electrophysiological recordings of CA1 pyramidal neurons showed reduced excitability. Multielectrode array recordings of optogenetically stimulated Wfs1+ ECII axons resulted in reduced CA1 neuronal firing. Chemogenetic activation of CA1 pyramidal neurons showed a reduction in c-fos+ cells in the CA1. Last, a fear conditioning task revealed deficits in trace and contextual memory in mice overexpressing human mutant tau in the ECII. This work demonstrates tau transfer from the ECII to CA1 in mouse brain and provides an early Braak stage preclinical model of AD.
Development of PRO-PMs assessing symptoms following completion of curative-intent chemotherapy.
Authors: Katherine Eresian Chenok, Feifei Ye, Kristen K. McNiff Landrum, Emma Hoo, Valerie Kong, Jennifer J. Griggs, Rachel Brodie
Journal: Journal of Clinical Oncology (2021)

171 Background: Few patient-reported outcome performance measures (PRO-PMs) have been validated for the cancer population. The testing that has occurred mostly focuses on advanced cancers despite the fact that the majority of people with cancer are diagnosed with earlier stage disease. We developed and tested PRO-PMs to assess quality of life, pain and fatigue in adult patients completing curative-intent chemotherapy for breast, colon and non-small cell lung cancers. Our goal is to develop measures that target symptoms that impact entry into the survivorship phase. Methods: We recruited 20 diverse test sites from the Michigan Oncology Quality Collaborative (MOQC) and the Alliance of Dedicated Cancer Centers (ADCC). Test sites enrolled patients, administered surveys, and collected clinical and demographic data. A Technical Expert Panel and the Patient and Caregiver Council selected PROMs and provided testing guidance. We assessed data collection feasibility and clinician/staff/patient burden throughout the testing process. Results: PROMIS instruments were selected due to psychometric testing in the target population, public availability and acceptability to patients and test sites. 1,753 patients were enrolled between 10/1/19 – 3/31/21. The COVID public health emergency disrupted testing and resulted in lower than expected enrolled patients/completed surveys; however, adaptations led to expansions in survey administration methods. Preliminary practice-level performance results from 10 sites show variation across sites for pain interference (mean = 50.5, SD = 2.8, with a range of 44.6—54.6) and fatigue (mean 49.2, SD = 2.8, with a range of 44.6--54.3). Some test sites reported PRO implementation to be burdensome; however, most patients evaluated did not find survey completion to be burdensome. Conclusions: Next steps include testing risk adjustment variables/model, creating adjusted performance scores, reliability and validity testing. Despite the consensus goal of PRO-PMs in oncology, barriers to implementation persist and important methodologic barriers exist (e.g., ability to achieve sufficient sample size in an oncology practice; defining the most appropriate numerator calculation that reports the desired quality concept and is appropriate for the PROM being used; analytic best practices for PRO-PM adjustment/testing). This project is contributing to the knowledge base as we seek to ensure that PRO-PMs provide meaningful, actionable, patient-centered quality data with benefits that outweigh the burden of implementation.
The Gut Microbiome and Inflammatory Bowel Diseases
Authors: Yue Shan, Mirae Lee, Eugene B. Chang
Journal: Annual Review of Medicine (2021)

Inflammatory bowel diseases (IBD) arise from a convergence of genetic risk, environmental factors, and gut microbiota, where each is necessary but not sufficient to cause disease. Emerging evidence supports a bidirectional relationship between disease progression and changes in microbiota membership and function. Thus, the study of the gut microbiome and host-microbe interactions should provide critical insights into disease pathogenesis as well as leads for developing microbiome-based diagnostics and interventions for IBD. In this article, we review the most recent advances in understanding the relationship between the gut microbiota and IBD and highlight the importance of going beyond establishing description and association to gain mechanistic insights into causes and consequences of IBD. The review aims to contextualize recent findings to form conceptional frameworks for understanding the etiopathogenesis of IBD and for the future development of microbiome-based diagnostics and interventions.
Implementation of an EHR-embedded decision support tool in community oncology practices.
Authors: Rebecca Maniago, Sylvia S. Richey, Sarah DeVincenzo, Stephanie Jou, Robin Linzmayer, Janet Donegan, Gregory Sampang Calip, Ivy Altomare
Journal: Journal of Clinical Oncology (2021)

274 Background: Clinical decision support (CDS) tools facilitate value based cancer care delivery and can enable measurement of guideline concordance, but can be challenging to implement. Flatiron Assist is an EHR-embedded and customizable CDS tool which facilitates selection and documentation of NCCN Guideline concordant and NCCN Preferred treatment regimens. We assessed performance metrics after the first year of use of this tool at eleven sites of care. Methods: We reviewed all non-small cell lung cancer (NSCLC) treatment orders as entered at 11 community practice sites of care in the northeast and southeast US from launch May 15, 2020, through May 23, 2021. Use of the CDS tool is not mandatory at these practices, and is deployed via prescriber choice. The tool documents and reports various quality metrics. We describe monthly prevalence of the CDS tool use, proportion of orders documented as guideline concordant, and prescriber-reported reasons for non-concordance. Results: All 954 NSCLC treatment regimen orders by the 89 prescribers who had the option to use the CDS tool were analyzed during the 1 year observation period. 658 regimens (69%) were ordered via the tool. Table describes prescriber users and non-users over time. The tool was deployed for 60% of NSCLC orders at 2 months, 69% at 6 months and 78% at 1 year post launch. Over the observed time period, 92% of treatment regimens ordered via the tool were documented as guideline concordant (94% at 2 months, 96% at 6 months and 85% at 1 year post-launch). Prescriber-reported reasons for ordering non-concordant regimens were “physician choice” (59%), “patient status” (12%), “newly published evidence” (10%), “second opinion from outside institution” (9%), “financial burden on patient/insurance doesn’t cover” (5%), “patient choice” (2%) and “other (allergy, disease progression, atypical disease)” (3%). Conclusions: At the study sites, this EHR-embedded CDS tool was rapidly adopted by most prescribers (approximately two thirds within 6 months of launch), and used for the majority of NSCLC candidate order sets during the 1 year observation period. NCCN concordance among users was empirically high overall and declined slightly over time, perhaps due to increased usage and/or greater comfort with the optional tool with ongoing use. Prescribers most commonly self-attributed the selection of non-concordant therapy to “physician choice” as opposed to factors such as financial hardship or patient choice. Further research will characterize workflow time, predictors of non-use and non-concordant orders, and evaluate whether Flatiron Assist improves clinical outcomes.[Table: see text]
SPI2 T3SS effectors facilitate enterocyte apical to basolateral transmigration of <i>Salmonella</i>-containing vacuoles <i>in vivo</i>
Authors: Marcus Fulde, Kira van Vorst, Kaiyi Zhang, Alexander J. Westermann, Tobias Busche, Yong Chiun Huei, Katharina Welitschanski, Isabell Froh, Dennis Pägelow, Johanna Plendl, Christiane Pfarrer, Jörn Kalinowski, Jörg Vogel, Peter Valentin-Weigand, Michael Hensel, Karsten Tedin, Urska Repnik, Mathias W. Hornef
Journal: Gut Microbes (2021)

Salmonella pathogenicity island (SPI) 2 type three secretion system (T3SS)-mediated effector molecules facilitate bacterial survival in phagocytes but their role in the intestinal epithelium in vivo remains ill-defined. Using our neonatal murine infection model in combination with SPI2 reporter technology and RNA-Seq of sorted primary enterocytes, we demonstrate expression of SPI2 effector molecules by intraepithelial Salmonella Typhimurium (S. Typhimurium). Contrary to expectation, immunostaining revealed that infection with SPI2 T3SS-mutants resulted in significantly enlarged intraepithelial Salmonella-containing vacuoles (SCV) with altered cellular positioning, suggesting impaired apical to basolateral transmigration. Also, infection with isogenic tagged S. Typhimurium strains revealed a reduced spread of intraepithelial SPI2 T3SS mutant S. Typhimurium to systemic body sites. These results suggest that SPI2 T3SS effector molecules contribute to enterocyte apical to basolateral transmigration of the SCV during the early stage of the infection.
EVALUATION OF CIRCULATING TUMOUR CELLS (CTCS) IN SMALL CELL LUNG CANCER (SCLC) PATIENTS UNDERGOING CHEMOTHERAPY
Authors: J. Hou, A. Greystoke, A. Williamson, L. Lancashire, L. F. Ashcroft, P. Lorigan, S. Hughes, C. Dive, F. H. Blackhall
Journal: Annals of Oncology (2008)
Efficacy of a password-protected pill-dispensing device to enhance disposal of unused opioids after cancer surgery.
Authors: Jacob Cogan, Melissa Kate Accordino, Melissa Parsons Beauchemin, Sophie Ulene, Elena B. Elkin, Bret Taback, Jason Dennis Wright, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2021)

264 Background: Opioid misuse is a public health crisis. Initial opioid exposures often occur post-operatively, and 10% of opioid-naïve patients who undergo cancer surgery subsequently become long-term opioid users. It has been shown that 70% of opioids prescribed post-operatively go unused, but only 9% of unused pills are disposed appropriately, which increases the risk of unintended use. We evaluated the impact of an inexpensive, password-protected dispensing device with mail return capacity on retrieval of unused pills after cancer surgery. Methods: Adult patients scheduled for major cancer-related surgery were eligible. Enrolled patients received opioid prescriptions in a password-protected, pill-dispensing device (Addinex) from a specialty pharmacy. The mechanical device links to a smartphone app, which provides passwords on a prescriber-defined schedule. Patients request a password when they are in pain, enter the password into the device and receive a pill if the prescribed time has elapsed. The smartphone app provides clinical guidance based on patient-reported pain levels, and suggests tapering strategies. Patients are instructed to return the device in a DEA-approved mailer when opioid use is no longer required for pain control. Unused pills are destroyed upon receipt. The primary objective was to determine the feasibility of device return, defined as &gt; 50% of patients with device return. We also explored patterns of device use, patient reported outcomes, and device satisfaction via surveys and semi-structured interviews. Results: Between October, 2020 and April, 2021, 13 patients completed the study; 4 patients are currently enrolled. Among the initial 13 patients, 7 underwent abdominal hysterectomy, 4 underwent mastectomy and 2 underwent cutaneous tumor resections. The majority of these patients (n = 10, 77%) returned the device, and more than half (n = 7, 54%) returned the device within 6 weeks of surgery. Only a minority of patients (n = 5, 38%) used the device to obtain opioids; most (n = 8, 62%) used no opioids at home, and all of these patients returned the device and the unused pills. Of 11 patients who participated in semi-structured interviews, most (n = 7, 64%) said they felt safer having opioids in the device instead of a regular pill bottle. Among device users, the majority (n = 4, 80%) reported an overall positive experience. All non-users reported having no opioid requirement for pain control. Conclusions: Our early findings suggest that use of an inexpensive, password-protected, pill-dispensing device to assist with opioid dispensing and return is feasible, with a high rate of device and unused opioid return to the pharmacy. This strategy may be effective for reducing opioid diversion. Analyses and recruitment are ongoing to evaluate the benefits of reducing post-operative opioid consumption.
Resident memory CD8+ T cells in regional lymph nodes mediate immunity to metastatic melanoma
Authors: Aleksey K. Molodtsov, Nikhil Khatwani, Jennifer L. Vella, Kathryn A. Lewis, Yanding Zhao, Jichang Han, Delaney E. Sullivan, Tyler G. Searles, Nicholas K. Preiss, Tamer B. Shabaneh, Peisheng Zhang, Aaron R. Hawkes, Brian T. Malik, Fred W. Kolling, Edward J. Usherwood, Sandra L. Wong, Joseph D. Phillips, Keisuke Shirai, Christina V. Angeles, Shaofeng Yan, Tyler J. Curiel, Yina H. Huang, Chao Cheng, Mary Jo Turk
Journal: Immunity (2021)
Influence of treatment with neutralizing monoclonal antibodies on the SARS-CoV-2 nasopharyngeal load and quasispecies
Authors: Camille Vellas, Arnaud Del Bello, Alexa Debard, Zara Steinmeyer, Laure Tribaudeau, Noémie Ranger, Nicolas Jeanne, Guillaume Martin-Blondel, Pierre Delobel, Nassim Kamar, Jacques Izopet
Journal: Clinical Microbiology and Infection (2021)
The impact of the COVID-19 pandemic on people with psoriasis: findings from a global patient-reported registry
Authors: S. Mahil, M. Yates, Z. Yiu, S. Langan, T. Tsakok, N. Dand, K. Mason, H. McAteer, F. Meynell, B. Coker, A. Vincent, D. Urmston, A. Vesty, J. Kelly, C. Lancelot, L. Moorhead, H. Bachelez, F. Capon, C. R. Contreras, C. De La Cruz, P. Di Meglio, P. Gisondi, D. Jullien, J. Lambert, L. Naldi, S. Norton, L. Puig, P. Spuls, T. Torres, R. Warren, H. Waweru, J. Weinman, C. Griffiths, J. Barker, M. Brown, J. Galloway, C. Smith
Journal: British Journal of Dermatology (2021)
Individual and differential treatment responses to once-daily long acting bronchodilators, glycopirronium and indacaterol, and combination of both drugs in the patients with moderate or severe COPD
Authors: Yoshiki Ishii, Akihiro Takemasa, Kazuyuki Chibana, Ryo Arai, Taichi Shiobara, Taiji Watanabe
Journal: European Respiratory Journal (2014)

Background: Individual and differential treatment responses to LAMA or LABA in patients with COPD are not fully elucidated.  Objective: We investigated the differences in response to new once-daily LAMA or LABA monotherapy, or combination therapy of both drugs in the same individuals.  Methods: In this open label, three-period, crossover study, 30 patients aged 56-75 years with moderate or severe COPD were randomized to glycopirronium (GLY) or indacaterol (IND) monotherapy for 4W, followed by another drug for 4W and combination therapy of both drugs for 4W. Each treatment period was separated by a minimum 14-day washout. Spirometry, airway resistance (IOS), and shuttle walking test (SWT) were performed before and after each treatment period.  Results: 22 cases (stage II:19 and stage III:3) completed the study. GLY significantly increased FEV1 by 110±120 ml (p  Conclusions: Both GLY and IND significantly increased lung function accompanied by improvement of symptom score and QOL score. Effects of both treatments were almost similar. Maximal bronchodilation by combination of GLY and IND provided maximal clinical benefit.
Institutional chart review on same-day pegfilgrastim administration in small cell lung cancer (SCLC) patients receiving myelotoxic chemotherapy.
Authors: Briana Choi, Neda Alrawashdh, Jamie Vraney, Ali McBride, Ivo Abraham
Journal: Journal of Clinical Oncology (2021)

71 Background: Pegfilgrastim administration is recommended at least 24 hours after the end of chemotherapy (CTX) treatment for prevention of chemotherapy-induced (febrile) neutropenia (CIN/FN). Published studies have found no differences in the risk of FN between same-day and next-day pegfilgrastim administrations in certain cancers. To evaluate the efficacy and safety of same-day compared to next-day pegfilgrastim administration in SCLC patients, we evaluated our own institutional data. Methods: Using ICD-9 and ICD-10 codes for SCLC, electronic health records were reviewed retrospectivey for the period 11/1/2013-8/31/2018 at the University of Arizona Cancer Center (UACC). Inclusion criteria were age 18 or older, biopsy confirmed SCLC diagnosis, treated at UACC, and pegfilgrastim administration on the same day as CTX. Outcomes collected in the first cycle and all cycles of CTX were: FN incidence, CIN grade 3/4, and treatment delay or hospitalizations due to CIN/FN. Results: Out of 1,181 patient records, 34 patients met inclusion criteria. The median age was 67.5 years, 23.5% of patients had stage 3 or 4 SCLC while 50% had 0-1 ECOG status. 44.1% of patients had a risk based on the type of CTX. Average baseline absolute neutrophil count was 5.55x10 9 cells/L (SD=1.27x10 9 cells/L). A total of 104 CTX cycles were given. Outcomes are summarized in the Table below. After the first cycle, the incidence rate of CIN grade 3/4 was 5.88%, but 0% for all other outcomes. Conclusions: After the first cycle, there were s of FN and no patients experienced treatment delays or hospitalizations related to CIN/FN; only two cases for CIN grade 3/4 were observed. Across all cycles, CIN grade 3/4 was observed in 17 cycles. In only two cycles, treatment was delayed or patient was hospitalized due to CIN/FN, not involving same patients. FN was observed in only 3/104 cycles. All observed rate were comparable or lower than known rates for next-day pegfilgrastim administration. Future studies including randomized trials should be further evaluated.[Table: see text]