tbuckley/cabot-search huggingface dataset:
Occupational dermatoses during the COVID‐19 pandemic: a multicentre audit in the UK and Ireland
Authors: H. O’Neill, I. Narang, D.A. Buckley, T.A. Phillips, C.G. Bertram, T.O. Bleiker, M.M.U. Chowdhury, S.M. Cooper, S. Abdul Ghaffar, G.A. Johnston, L.F. Kiely, J.E. Sansom, N. Stone, D.A. Thompson, P. Banerjee
Journal: British Journal of Dermatology (2020)

n = 12), the slope of QoL indices vs. PDAI became flatter at PDAI = 7 and the P-value decreased dramatically beginning at PDAI ≥ 7 to P < 0Á1 for the ABQOL and Skindex-E.These findings suggest that at PDAI ≥ 7, every incremental increase in PDAI had a smaller detrimental impact on QoL.For the ABSIS, there was no significant difference in slopes before and after a given score, along with a higher P-value overall.Our results support previous findings 6 that the PDAI is superior to the ABSIS at capturing disease severity, especially at the lower end of disease activity (Figure 1c,d).To significantly improve QoL for patients with mucosal and nonmucosal PV, complete disease clearance may be necessary.Small amounts of worsening activity have an increasingly significant impact on QoL at the lower end of the spectrum.Above mild levels of activity, increasing activity has linear but detrimental smaller effects on QoL.The findings for patients with mucosal PV further support this, likely because oral erosions are painful and impact eating.Consistent with prior findings, 2 the Skindex-S best correlates with PDAI score in all patients.A notable limitation of this study is that our population had milder disease, with a median PDAI of 6Á75 and ABSIS of 11Á75.However, we are still able to show a change in QoL as the PDAI decreases, even at lower PDAI levels.Our findings have important clinical implications in determining appropriate outcomes for therapies. 7Unlike dermatomyositis and systemic lupus erythematosus, 4 in patients with PV, complete clearance should be the goal.
Clinical Evaluation of 18F-PI-2620 as a Potent PET Radiotracer Imaging Tau Protein in Alzheimer Disease and Other Neurodegenerative Diseases Compared With 18F-THK-5351
Authors: Minyoung Oh, Seung Jun Oh, Sang Ju Lee, Jungsu S. Oh, Jee Hoon Roh, Sun Ju Chung, Jae-Hong Lee, Chong Sik Lee, Jae Seung Kim
Journal: Clinical Nuclear Medicine (2020)

Purpose PET is a useful tool for detecting the presence and extent of brain tau accumulation. However, most first-generation tau PET tracers are limited for high off-target binding and detection of tau in non-Alzheimer disease (AD). This study evaluated potential clinical applications of 18 F-PI-2620 as a novel PET tracer with a high binding affinity for tau deposition in AD and non-AD tauopathies. Methods Twenty-six participants diagnosed with either mild cognitive impairment, probable AD, frontotemporal dementia, or parkinsonism, as well as healthy controls underwent a 60- to 90-minute brain PET scan after 7 mci (259 MBq) injection of 18 F-PI-2620. Some participants had previous PET scans using 18 F-THK-5351 or 18 F-FP-CIT for dopamine transporter imaging. Results All participants showed no increase in off-target binding in basal ganglia on 18 F-PI-2620 PET images, as noted for first-generation tau tracers. Aβ+ mild cognitive impairment or AD patients showed diverse cortical 18 F-PI-2620 uptake in frontotemporoparietal cortex that correlated with Mini-Mental Status Examination (ρ = −0.692, P = 0.013). Aβ+ Parkinson disease with dementia and (Aβ unknown) primary progressive aphasia patients also showed increased 18 F-PI-2620 uptakes in the frontotemporoparietal cortex. Patients with parkinsonism showed increased uptakes in the pallidum compared with Aβ− healthy controls (left: 1.41 ± 0.14 vs 1.04 ± 0.13, P = 0.014; right: 1.18 ± 0.16 vs 0.95 ± 0.07, P = 0.014). Conclusions 18 F-PI-2620 PET might be a sensitive tool to detect cortical tau deposits in patients with Aβ+ AD and Aβ+ non-AD tauopathies. Furthermore, this study showed that “off-target” binding in the basal ganglia does not affect 18 F-PI-2620.
FDG PET/CT of Hepatoid Adenocarcinoma of the Gallbladder
Authors: Xia Ji, Hui Dong, Aisheng Dong
Journal: Clinical Nuclear Medicine (2020)

Abstract Primary hepatoid adenocarcinoma of the gallbladder is rare. A 67-year-old woman presented with right upper quadrant abdominal pain with elevated α-fetoprotein level. Abdominal ultrasound and MRI showed a tumor in the gallbladder with normal liver. FDG PET/CT showed increased FDG uptake of the gallbladder tumor with retroperitoneal lymph node metastasis. Cholecystectomy was performed. Primary hepatoid adenocarcinoma of the gallbladder was confirmed by histopathology.
Overcoming immunotherapy resistance in non-small cell lung cancer (NSCLC) - novel approaches and future outlook
Authors: Lena Horvath, Bernard Thienpont, Liyun Zhao, Dominik Wolf, Andreas Pircher
Journal: Molecular Cancer (2020)

Abstract Immunotherapy (IO) has revolutionized the therapy landscape of non-small cell lung cancer (NSCLC), significantly prolonging the overall survival (OS) of advanced stage patients. Over the recent years IO therapy has been broadly integrated into the first-line setting of non-oncogene driven NSCLC, either in combination with chemotherapy, or in selected patients with PD-L1 high expression as monotherapy. Still, a significant proportion of patients suffer from disease progression. A better understanding of resistance mechanisms depicts a central goal to avoid or overcome IO resistance and to improve patient outcome. We here review major cellular and molecular pathways within the tumor microenvironment (TME) that may impact the evolution of IO resistance. We summarize upcoming treatment options after IO resistance including novel IO targets (e.g. RIG-I, STING) as well as interesting combinational approaches such as IO combined with anti-angiogenic agents or metabolic targets (e.g. IDO-1, adenosine signaling, arginase). By discussing the fundamental mode of action of IO within the TME, we aim to understand and manage IO resistance and to seed new ideas for effective therapeutic IO concepts.
Діагностичні можливості 13С-змішаного тригліцеридного дихального тесту у хворих після холецистектомії
Authors: V.I. Rusyn, Ye.S Sirchak, N.Yu. Kurchak
Journal: GASTROENTEROLOGY (2014)

Наведено результати комплексного обстеження 136 хворих після холецистектомії. Встановлена висока ефективність та інформативність 13С-змішаного тригліцеридного дихального тесту у хворих після холецистектомії для визначення зовнішньосекреторної недостатності підшлункової залози вже на ранніх стадіях її формування.
Clinical outcomes of COVID-19 in patients taking tumor necrosis factor inhibitors or methotrexate: A multicenter research network study
Authors: Ahmed Yousaf, Swapna Gayam, Steve Feldman, Zachary Zinn, Michael Kolodney
Journal: Journal of the American Academy of Dermatology (2020)

Data on the impact of biologics and immunomodulators on coronavirus disease 2019 (COVID-19)-related outcomes remain scarce.We sought to determine whether patients taking tumor necrosis factor inhibitors (TNFis) or methotrexate are at increased risk of COVID-19-related outcomes.In this large comparative cohort study, real-time searches and analyses were performed on adult patients who were diagnosed with COVID-19 and were treated with TNFis or methotrexate compared with those who were not treated. The likelihood of hospitalization and mortality were compared between groups with and without propensity score matching for confounding factors.More than 53 million (53,511,836) unique patient records were analyzed, of which 32,076 (0.06%) had a COVID-19-related diagnosis documented starting after January 20, 2020. Two hundred fourteen patients with COVID-19 were identified with recent TNFi or methotrexate exposure compared with 31,862 patients with COVID-19 without TNFi or methotrexate exposure. After propensity matching, the likelihood of hospitalization and mortality were not significantly different between the treatment and nontreatment groups (risk ratio = 0.91 [95% confidence interval, 0.68-1.22], P = .5260 and risk ratio = 0.87 [95% confidence interval, 0.42-1.78], P = .6958, respectively).All TNFis may not behave similarly.Our study suggests that patients with recent TNFi or methotrexate exposure do not have increased hospitalization or mortality compared with patients with COVID-19 without recent TNFi or methotrexate exposure.
The Induction of Mild Hypothermia Improves Myocardial beta-Adrenergic Responsiveness During Endotoxemia in Pigs
Authors: M. Wallner, M. Schwarzl, S. Seiler, S. Huber, P. Steendijk, H. Machler, M. Truschnig-Wilders, B. Pieske, D. von Lewinski, H. Post
Journal: Circulation (2011)
Impact of Transcatheter Aortic Valve Replacement on Severity of Chronic Kidney Disease
Authors: Robert J. Cubeddu, Craig R. Asher, Ashley M. Lowry, Eugene H. Blackstone, Samir R. Kapadia, Maria C. Alu, Vinod H. Thourani, Michael J. Mack, Susheel K. Kodali, Howard C. Herrmann, Jessica Forcillo, Vasilis C. Babaliaros, Chandan M. Devireddy, S. Chris Malaisrie, Charles J. Davidson, Wael A. Jaber, Martin B. Leon, Lars G. Svensson
Journal: Journal of the American College of Cardiology (2020)
Nurse-Administered Propofol Continuous Infusion Sedation for Gastrointestinal Endoscopy in Patients Who Are Difficult to Sedate
Authors: Hyun Seok Lee, Navroop Nagra, Danielle La Selva, Richard A. Kozarek, Andrew Ross, Wade Weigel, Ryan Beecher, Michael Chiorean, Michael Gluck, Elisa Boden, Nanda Venu, Rajesh Krishnamoorthi, Michael Larsen, Otto S. Lin
Journal: Clinical Gastroenterology and Hepatology (2020)
Leukemia escape in immune desert: intraocular relapse of pediatric pro-B-ALL during systemic control by CD19-CAR T cells
Authors: Semjon Willier, Johannes Raedler, Franziska Blaeschke, Dana Stenger, Montserrat Pazos Escudero, Florian Jurgeleit, Thomas G P Grünewald, Vera Binder, Irene Schmid, Michael H Albert, Armin Wolf, Tobias Feuchtinger
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Relapsed/refractory B-precursor acute lymphoblastic leukemia (BCP-ALL) remains a major therapeutic challenge in pediatric hematology. Chimeric antigen receptor (CAR) T cells targeting CD19 have shown remarkable initial response rates in BCP-ALL patients, while long-term leukemia control rate is only about 50%. So far, main mechanisms of BCP-ALL relapse after CD19-CAR T-cell therapy have been either insufficient CAR T-cell persistence in vivo or loss of surface CD19. Case Report Here, we report an exceptional presentation of BCP-ALL relapse in the eye during the systemic control through CAR T-cell therapy. We report a case of fatal intraocular relapse in a pediatric patient with pro-B-ALL after initial response to CD19-CAR T-cell therapy. One month after CD19-CAR T-cell therapy, remission was documented by bone marrow aspirate analysis with absence of CD19 + cells and CD19-CAR T cells could be detected in both peripheral blood and bone marrow. At the same time, however, the patient presented with progressive visual disturbance and CD19 + cells were found within the anterior chamber of the eye. Despite local and systemic therapy, ocular relapse led to BCP-ALL dissemination and systemic relapse within weeks. The eye represents a rare site for local manifestation of BCP-ALL, but isolated intraocular relapse is a clinically unreckoned presentation of BCP-ALL in the era of CD19-CAR T cells. Conclusion During systemic control of BCP-ALL through CD19-CAR T cells, relapse can emerge in the eye as an immune-privileged organ. Ocular symptoms after CD19-CAR T-cell therapy should guide the clinician to elucidate the etiology in a timely fashion in order to adjust leukemia treatment strategy. Both, local immune escape as well as insufficient CAR T-cell persistence may have contributed to relapse in the reported patient. Mechanisms of relapse in an immune desert under CAR T-cell therapy require future clinical and experimental attention. In particular, ocular symptoms after CAR T-cell therapy should be considered a potentially early sign of leukemia relapse.
HepatoScore‐14: Measures of Biological Heterogeneity Significantly Improve Prediction of Hepatocellular Carcinoma Risk
Authors: Jeffrey S. Morris, Manal M. Hassan, Ye Emma Zohner, Zeya Wang, Lianchun Xiao, Asif Rashid, Abedul Haque, Reham Abdel‐Wahab, Yehia I. Mohamed, Karri L. Ballard, Robert A. Wolff, Bhawana George, Liang Li, Genevera Allen, Michael Weylandt, Donghui Li, Wenyi Wang, Kanwal Raghav, James Yao, Hesham M. Amin, Ahmed Omar Kaseb
Journal: Hepatology (2020)

Background and Aims Therapeutic, clinical trial entry and stratification decisions for hepatocellular carcinoma (HCC) are made based on prognostic assessments, using clinical staging systems based on small numbers of empirically selected variables that insufficiently account for differences in biological characteristics of individual patients’ disease. Approach and Results We propose an approach for constructing risk scores from circulating biomarkers that produce a global biological characterization of individual patient’s disease. Plasma samples were collected prospectively from 767 patients with HCC and 200 controls, and 317 proteins were quantified in a Clinical Laboratory Improvement Amendments–certified biomarker testing laboratory. We constructed a circulating biomarker aberration score for each patient, a score between 0 and 1 that measures the degree of aberration of his or her biomarker panel relative to normal, which we call HepatoScore . We used log‐rank tests to assess its ability to substratify patients within existing staging systems/prognostic factors. To enhance clinical application, we constructed a single‐sample score, HepatoScore‐14 , which requires only a subset of 14 representative proteins encompassing the global biological effects. Patients with HCC were split into three distinct groups (low, medium, and high HepatoScore) with vastly different prognoses (medial overall survival 38.2/18.3/7.1 months; P &lt; 0.0001). Furthermore, HepatoScore accurately substratified patients within levels of existing prognostic factors and staging systems ( P &lt; 0.0001 for nearly all), providing substantial and sometimes dramatic refinement of expected patient outcomes with strong therapeutic implications. These results were recapitulated by HepatoScore‐14, rigorously validated in repeated training/test splits, concordant across Myriad RBM (Austin, TX) and enzyme‐linked immunosorbent assay kits, and established as an independent prognostic factor. Conclusions HepatoScore‐14 augments existing HCC staging systems, dramatically refining patient prognostic assessments and therapeutic decision making and enrollment in clinical trials. The underlying strategy provides a global biological characterization of disease, and can be applied broadly to other disease settings and biological media.
RUNX1 and CBFβ-SMMHC transactivate target genes together in abnormal myeloid progenitors for leukemia development
Authors: Tao Zhen, Yaqiang Cao, Gang Ren, Ling Zhao, R. Katherine Hyde, Guadalupe Lopez, Dechun Feng, Lemlem Alemu, Keji Zhao, P. Paul Liu
Journal: Blood (2020)
Correspondence on ‘Effectiveness of secukinumab versus an alternative TNF inhibitor in patients with axial spondyloarthritis previously exposed to TNF inhibitors in the Swiss Clinical Quality Management cohort’ by Micheroli<i>et al</i>
Authors: Jin-Xian Huang, Pui-Ying Leong, James Cheng-Chung Wei
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the article by Micheroli et al 1 for comparison of effectiveness between secukinumab (SEC) and tumour necrosis factor inhibitor (TNFi) in axial spondylitis (axSpA), with evidence conform to the current recommendation in a Swiss real-world setting.

According to current guidelines,2 ,3 ,4interleukin-17 inhibitor (IL-17i) or alternative TNFi are both recommended as the switch option of biological disease-modifying antirheumatic drug in patients with previous TNFi failure. Although head-to-head comparison clinical trials between IL-17 inhibition and TNF blockade have been conducted in psoriatic arthritis recently5 6 and is ongoing in axSpA, we appreciated Micheroli et al 1 for their new information in this real-world indirect comparison study. However, some issues can be further discussed.

First, regarding the study design, it was not mentioned whether treatment adjustment was due to drug inefficacy or intolerability and the types of TNFi, receptor fusion protein or monoclonal antibody …
Precision medicine in Parkinson’s disease patients with LRRK2 and GBA risk variants – Let’s get even more personal
Authors: Christian U. von Linstow, Ziv Gan-Or, Patrik Brundin
Journal: Translational Neurodegeneration (2020)

Abstract Parkinson’s disease (PD) is characterized by motor deficits and a wide variety of non-motor symptoms. The age of onset, rate of disease progression and the precise profile of motor and non-motor symptoms display considerable individual variation. Neuropathologically, the loss of substantia nigra dopaminergic neurons is a key feature of PD. The vast majority of PD patients exhibit alpha-synuclein aggregates in several brain regions, but there is also great variability in the neuropathology between individuals. While the dopamine replacement therapies can reduce motor symptoms, current therapies do not modify the disease progression. Numerous clinical trials using a wide variety of approaches have failed to achieve disease modification. It has been suggested that the heterogeneity of PD is a major contributing factor to the failure of disease modification trials, and that it is unlikely that a single treatment will be effective in all patients. Precision medicine, using drugs designed to target the pathophysiology in a manner that is specific to each individual with PD, has been suggested as a way forward. PD patients can be stratified according to whether they carry one of the risk variants associated with elevated PD risk. In this review we assess current clinical trials targeting two enzymes, leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA), which are encoded by two most common PD risk genes. Because the details of the pathogenic processes coupled to the different LRRK2 and GBA risk variants are not fully understood, we ask if these precision medicine-based intervention strategies will prove “precise” or “personalized” enough to modify the disease process in PD patients. We also consider at what phases of the disease that such strategies might be effective, in light of the genes being primarily associated with the risk of developing disease in the first place, and less clearly linked to the rate of disease progression. Finally, we critically evaluate the notion that therapies targeting LRRK2 and GBA might be relevant to a wider segment of PD patients, beyond those that actually carry risk variants of these genes.
Breast cancer radiosensitization by Lapatinib
Authors: Randall Kimple, Terese Camp, Yeon-Sil Kim, Mara Mashek, Laura Esler, Xihui Yang, Chad Livasey, Charles Perou, Elizabeth Dees, Carolyn Sartor
Journal: Cancer Research (2008)

413  Aberrant expression or activation of epidermal growth factor receptor (EGFR) family members contributes to radioresistance. We have previously shown that lapatinib, a dual EGFR/HER2 kinase inhibitor, inhibits proliferation and radiosensitizes EGFR overexpressing breast cancer cell lines in vitro. We hypothesized that lapatinib would radiosensitize EGFR and HER2 overexpressing breast cancer cells to ionizing radiation in vivo.  Using an EGFR overexpressing breast cancer xenograft system, we show that lapatinib (100 mg twice daily) inhibits EGFR phosphorylation and decreases tumor volume by nearly 50% when combined with radiation, consistent with an enhancement ratio of 1.34 and a fractional tumor volume (FTV) ratio of 2.28. This data suggests a synergistic effect of radiation and lapatinib in this model and is consistent with results from in vitro systems previously reported. According to our predefined endpoint of tumor volume at 21 days, we saw no benefit from the addition of lapatinib to radiation in HER2 overexpressing xenografts (FTV ratio of 0.13). However, we did observe durable tumor control with the combination therapy (time to quadrupling of tumor volume: 102 days for radiation + lapatinib, 39 days for radiation, 31 days for lapatinib, and 12 days for control. In the HER2 overexpressing cell lines, inhibition of phospho-Akt was seen in all treatment groups, suggesting an important role for the PI3-K/Akt pathway in growth delay. Next, we developed several primary human tumor xenografts in which breast cancer patient biopsies were implanted into the gonadal fat pad of mice. Using gene expression analysis, we showed that the molecular subtype remained consistent following serial passage. Finally, we showed that, in our initial primary xenograft, there was no synergistic effect of radiation and lapatinib treatment on phospho-Akt, phospho-ERK, apoptosis, or proliferation. These results suggest that EGFR overexpressing breast cancers may be susceptible to radiosensitization by lapatinib and that primary tumor xenografts may aid in the testing of hypotheses from clinical/translational research.
A socially just recovery from the COVID-19 pandemic: a call for action on the social determinants of urban health inequalities
Authors: Katarina Hoernke
Journal: Journal of the Royal Society of Medicine (2020)

From bustling business districts to vibrant cultural life, many of the things that make life in cities advantageous can be attributed to their ability to bring people together. Diverse social networks, which promote productivity and innovation, can, however, act as a vector for disease transmission during a pandemic. The social distancing and lockdown measures implemented during the COVID-19 pandemic have brought fast-paced city life to a standstill, giving citizens pause to recognise the necessity of adequate living conditions, the value of access to healthcare and the privilege of digital technology. Many of these response efforts have left the most socioeconomically disadvantaged at greater risk of catching and dying from COVID-19. They have exacerbated existing health inequalities and given rise to new ones. Many are calling for a socially just recovery, including 5 million health professionals representing over 50 countries in their open letter to the United Nations calling for ethical global leadership.1 The need for action on health inequalities was evident before the pandemic but this crisis provides an unprecedented opportunity for change and cities can be a focal point for this. While each city will require a unique recovery strategy from the pandemic, this commentary calls for a health equity approach to be universally adopted. Grounded in the Social Determinants of Health framework, this commentary suggests three ways cities could change as a result of the COVID-19 pandemic in the housing, healthcare and technology sectors. Public and urban health professionals could engage multi-level stakeholders from civil society to governments at local and national levels to improve daily living conditions, promote access to healthcare and harness the power of digital technologies to address urban health inequalities.
GP is restored to medical register after second attempt
Authors: Clare Dyer
Journal: BMJ (2020)

A GP who was struck off in 2013 for dishonesty has won restoration to the medical register at her second attempt and is free to resume practice.

Kirsten Guest was a salaried partner at a Wolverhampton general practice and a member of the professional executive committee of the local primary care trust. Without the knowledge of her practice partners, she submitted 11 claims to the PCT for reimbursement of …