tbuckley/cabot-search huggingface dataset:
Evaluation of the oncologic benefit of adjunctive surgery at time of postchemotherapy retroperitoneal lymph node dissection (PC-RPLND).
Authors: Tim Nestler, Pia Paffenholz, David Pfister, Andreas Hiester, Alessandro Nini, Peter Albers, Axel Heidenreich
Journal: Journal of Clinical Oncology (2020)

388 Background: PC-RPLND for advanced nonseminomatous germ cell tumors aims to resect all remaining metastatic tissue. The resection of adjacent visceral or vascular organs is commonly performed to achieving complete resection of the residual masses. However, the frequency of metastatic involvement of those organs with teratoma or vital cancer is currently unknown. Methods: We reviewed a cohort of 1181 patients who underwent PC-RPLND between 2008 and 2018 as a 2-center study and identified 235 (20%) cases of adjunctive surgery during PC-RPLND. We analysed the pathohistological presence of germ cell tumor elements in the resected organs: viable tumor (V), teratoma (T) or necrosis / fibrosis (N). Surgery associated complications were reported according to the Clavien-Dindo classification. Outcomes of subgroups were compared by using log-rank test. Results: V, T, N was present in 51 (21%), 91 (39%) and 93 (40%) of all patients with adjunct resected organs. In 235 patients, 316 adjunct organs were resected with 64 (27%) of these patients receiving a resection of multiple organs. The kidney was the most often resected organ (n = 74; V: 27% T: 39% N: 34%), followed by V. Cava (n = 66; V: 24% T: 36%, N: 40%) and partial liver resections (n = 48; V: 15%, T: 31%, N: 54%). Intraoperative complications occurred in 21% of patients (VT 32% vs N 17%, p = 0.021). Postoperative complications occurred in 35% of which 22% were Clavien Grad III-V showing no significant differences between VTN p = 0.093. 27% of all patients suffered from a relapse during a median follow-up of 22 months [0-180]. Patients with T or V in the resected specimens had a significantly reduced 5-year RFS compared to patients with only N (39%, 81%, p &lt; 0.001). Conclusions: This study shows for the first time that 40% of all resections of adjunct organs are oncologically unnecessary due to the presence of N only in the pathological specimens. In case of doubt we propose an organ safe procedure with multiple intraoperative frozen section to avoiding oncologically unnecessary adjunctive surgeries especially nephrectomies and vascular resections. Additionally, a more accurate presurgical workup is required to spare patients with N from PC-RPLND.
18F-FDG PET/CT in Tuberculosis
Authors: Apurva Sood, Bhagwant Rai Mittal, Manish Modi, Rajesh Chhabra, Roshan Verma, Nivedita Rana, Ashwin Singh Parihar, Swayamjeet Satapathy, Rajender Kumar
Journal: Clinical Nuclear Medicine (2020)

Purpose of the Report Tuberculosis (TB) is a major health problem. Activated macrophages in TB lesions show high metabolic activity and can be assessed using 18 F-FDG PET/CT. This retroprospective study was done to evaluate the utility of 18 F-FDG PET/CT in initial assessment and therapeutic response in patients with TB. Materials and Methods Eighty-seven patients (male-to-female ratio, 46:41) diagnosed with pulmonary TB and extrapulmonary TB underwent whole-body 18 F-FDG PET/CT for initial assessment and a follow-up scan 3 to 4 months after initiation of antitubercular therapy (ATT). Visual and semiquantitative (SUV max ) analyses were used for scan assessment. Treatment responses on interim scans were categorized as complete metabolic response (CMR), favorable response to therapy (FRT), stable disease (SD), and disease progression (DP). CMR, FRT, and SD cases were considered as responders and DP cases as nonresponders. Treatment response was correlated with clinical outcome (mortality) and ATT duration. Results Baseline 18 F-FDG PET/CT scans were positive in all the patients and detected additional disease sites than suspected clinically in 72% patients. On interim PET/CT, 13 patients showed CMR, 43 showed FRT, 8 showed SD, and 23 showed DP. A longer duration of ATT was seen in nonresponders ( P ≤ 0.001) than responders. During follow-up, 9/87 patients died, out of which 8 patients were of DP group and 1 patient belonged to SD. Nonresponders showed 35% mortality compared with 1.6% in the responder group ( P ≤ 0.001). Conclusions 18 F-FDG PET/CT is a valuable imaging modality for disease mapping and assessing therapeutic response. Treatment response in the interim PET/CT done at 3 to 4 months predicted the duration of ATT and clinical outcome of the patients.
Genomic characteristics associated with clinical activity of rucaparib in patients (pts) with <i>BRCA1</i> or <i>BRCA2</i> (<i>BRCA</i>)<i>-</i>mutated metastatic castration-resistant prostate cancer (mCRPC).
Authors: Wassim Abida, David Campbell, Akash Patnaik, Brieuc Sautois, Jeremy David Shapiro, Nicholas J. Vogelzang, Alan Haruo Bryce, Raymond S. McDermott, Francesco Ricci, Julie Haewon Rowe, Jingsong Zhang, Andrea Loehr, Darrin Despain, Melanie Dowson, Tony Golsorkhi, Simon Chowdhury
Journal: Journal of Clinical Oncology (2020)

178 Background: The phase 2 TRITON2 study (NCT02952534) is evaluating the PARP inhibitor rucaparib in pts with mCRPC and a deleterious germline or somatic alteration in BRCA ( BRCA pts) or 1 of 13 other DNA damage repair (DDR) genes. Methods: Eligible pts had progressed on 1–2 lines of androgen receptor-directed therapy and 1 taxane-based chemotherapy. Deleterious DDR gene alterations were identified from central testing of plasma and/or tissue samples by Foundation Medicine or from local testing. Results: As of Jul 2, 2019 (visit cutoff), 98 BRCA pts had received rucaparib; median (range) duration of follow-up was 13.0 (4.1–25.8) mo. Confirmed objective response rate (ORR) in BRCA pts (with investigator-assessed measurable disease) and PSA response rates (in pts with and without measurable disease) are shown in the Table. A biallelic alteration was observed in 81.4% (35/43) of BRCA pts for whom zygosity could be determined, and pts with homozygous BRCA loss (20.4%; 20/98) demonstrated high ORR (66.7% [95% CI, 38.4-88.2]; 10/15) and PSA response rates (75.0% [95% CI, 50.9-91.3]; 15/20). The safety profile in BRCA pts was consistent with the overall TRITON2 pt population. Conclusions: Results from TRITON2 showed antitumor activity with rucaparib in pts with mCRPC and a deleterious BRCA alteration. Responses were observed in patients with germline or somatic alterations in BRCA1 or BRCA2. The activity of rucaparib in these and additional genomic subgroups (e.g., based on zygosity, plasma genomic testing, or co-occurring alterations) will be reported. Clinical trial information: NCT02952534. [Table: see text]
NRF2 activates growth factor genes and downstream AKT signaling to induce mouse and human hepatomegaly
Authors: Feng He, Laura Antonucci, Shinichiro Yamachika, Zechuan Zhang, Koji Taniguchi, Atsushi Umemura, Georgia Hatzivassiliou, Merone Roose-Girma, Miguel Reina-Campos, Angeles Duran, Maria T. Diaz-Meco, Jorge Moscat, Beicheng Sun, Michael Karin
Journal: Journal of Hepatology (2020)
Post-discharge prognosis of patients admitted to hospital for heart failure by world region, and national level of income and income disparity (REPORT-HF): a cohort study
Authors: Jasper Tromp, Sahiddah Bamadhaj, John G F Cleland, Christiane E Angermann, Ulf Dahlstrom, Wouter Ouwerkerk, Wan Ting Tay, Kenneth Dickstein, Georg Ertl, Mahmoud Hassanein, Sergio V Perrone, Mathieu Ghadanfar, Anja Schweizer, Achim Obergfell, Carolyn S P Lam, Gerasimos Filippatos, Sean P Collins
Journal: The Lancet Global Health (2020)

Heart failure is a global public health problem, affecting a large number of individuals from low-income and middle-income countries. REPORT-HF is, to our knowledge, the first prospective global registry collecting information on patient characteristics, management, and prognosis of acute heart failure using a single protocol. The aim of this study was to investigate differences in 1-year post-discharge mortality according to region, country income, and income inequality.Patients were enrolled during hospitalisation for acute heart failure from 358 centres in 44 countries on six continents. We stratified countries according to a modified WHO regional classification (Latin America, North America, western Europe, eastern Europe, eastern Mediterranean and Africa, southeast Asia, and western Pacific), country income (low, middle, high) and income inequality (according to tertiles of Gini index). Risk factors were identified on the basis of expert opinion and knowledge of the literature.Of 18 102 patients discharged, 3461 (20%) died within 1 year. Important predictors of 1-year mortality were old age, anaemia, chronic kidney disease, presence of valvular heart disease, left ventricular ejection fraction phenotype (heart failure with reduced ejection fraction [HFrEF] vs preserved ejection fraction [HFpEF]), and being on guideline-directed medical treatment (GDMT) at discharge (p<0·0001 for all). Patients from eastern Europe had the lowest 1-year mortality (16%) and patients from eastern Mediterranean and Africa (22%) and Latin America (22%) the highest. Patients from lower-income countries (ie, ≤US$3955 per capita; hazard ratio 1·58, 95% CI 1·41-1·78), or with greater income inequality (ie, from the highest Gini tertile; 1·25, 1·13-1·38) had a higher 1-year mortality compared with patients from regions with higher income (ie, >$12 235 per capita) or lower income inequality (ie, from the lowest Gini tertile). Compared with patients with HFrEF, patients with HFpEF had a lower 1-year mortality with little variation by income level (pinteraction for HFrEF vs HFpEF <0·0001).Acute heart failure is associated with a high post-discharge mortality, particularly in patients with HFrEF from low-income regions with high income inequality. Regional differences exist in the proportion of eligible patients discharged on GDMT, which was strongly associated with mortality and might reflect lack of access to post-discharge care and prescribing of GDMT.Novartis Pharma.
Junior doctor convicted of dangerous driving in “acutely anxious state” escapes sanction
Authors: Clare Dyer
Journal: BMJ (2020)

A junior doctor who was convicted of dangerous driving after he panicked about getting to work on time has escaped a sanction at a medical practitioners’ tribunal hearing.

Andrew Sadler, 24, had been expected to arrive for a hospital shift in his first job, just weeks after qualifying at Edinburgh University. The night before, he kept waking and tossing and turning in bed, fearing that he might be late for his shift at the University Hospital of North Tees.

In an acutely anxious state, he got up at 1am on 4 October 2018 and drove the wrong way …
Does Pancreaticogastrostomy Reduce the Risk of Postoperative Pancreatic Fistula After Pancreatoduodenectomy?
Authors: O. Joe Hines, John A. Windsor
Journal: JAMA Surgery (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
N95 Respirators vs Medical Masks in Outpatient Settings—Reply
Authors: Lewis J. Radonovich, Michael S. Simberkoff, Trish M. Perl
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
制定有关 EB 患者足部症状最佳治疗方法的新指南
Authors: M.T. Khan, M. O'Sullivan, B. Faitli, J.E. Mellerio, R. Fawkes, M. Wood, L.D. Hubbard, A.G. Harris, L. Iacobaccio, T. Vlahovic, L. James, L. Brains, M. Fitzpatrick, K. Mayre‐Chilton
Journal: British Journal of Dermatology (2020)

大疱性表皮松解症 (EB) 是一种复杂的罕见疾病,累及皮肤和身体的许多部位。先天 EB 患者皮肤非常脆弱,被称为“蝴蝶宝贝”,他们的皮肤与蝴蝶的蝶翼一样脆弱。 据估计,英国有超过 5,000 例 EB 患者,全球超过 500,000 例。在国际 DEBRA 开始制定临床实践指南 (CPG) 计划之前,很少有临床护理指导。目前没有关于 EB 患者足部护理的指南,且只有少数已发表的研究,因此治疗决策主要基于个人观点和经验。 该小组由代表澳大利亚、英国和美国的临床专家和 EB 患者组成,旨在描述各个年龄段 EB 患者的足部问题,并总结当前的证据和治疗。作者进行了关注 EB 患者足科(足部)护理的逻辑文献综述。 作者发现,该领域的证据有限,但足科医生目前正在实施的几种干预(治疗)均显示出积极的结果。该研究使该小组就如何治疗 EB 患者的足和趾甲疾病提出了建议。此外,作者得出结论,需要进一步研究。 本摘要涉及研究: 大疱性表皮松解症的足部护理: 循证指南
Systematic review of the efficacies and adverse effects of treatments for pityriasis lichenoides
Authors: F. Jung, C. Sibbald, M. Bohdanowicz, J.R. Ingram, V. Piguet
Journal: British Journal of Dermatology (2020)

Background Pityriasis lichenoides (PL) is a papulosquamous dermatosis affecting both children and adults, for which no standard treatment currently exists. Objectives To characterize different treatment options and develop an evidence-based treatment algorithm for PL. Methods A systematic search of published literature on PL treatments was performed on 23 December 2017 via the MEDLINE, Embase, CINAHL, CENTRAL, ClinicalTrials.gov and the EU Clinical Trials Register databases. Results Of 1090 abstracts retrieved, 27 full-text articles with 502 participants were included for analysis. Seventeen of the full-text articles were retrospective cohort studies and two were randomized controlled studies. Treatment modalities included in these articles were phototherapy, antibiotics, methotrexate, pyrimethamine and trisulfapyrimidine, corticosteroids and conservative treatment. Of these treatments, phototherapy led to complete remission in the highest proportion of patients, and topical corticosteroids were found to have been trialled in the highest number of patients. Conclusions The current literature consists almost entirely of uncontrolled studies, and none provides compelling data to support an evidence-based approach to PL treatment. Pityriasis lichenoides chronica and pityriasis lichenoides et varioliformis acuta should be distinguished in response to treatment, and definitions of response to treatment must be standardized. Additional randomized control studies with longer follow-up will help better differentiate between treatment efficacies and adverse effects.
Atezolizumab + intravesical BCG (Bacillus Calmette-Guerin) in high-risk non-muscle invasive bladder cancer (NMIBC) patients: Institutional clinical and translational study (BladderGATE).
Authors: Daniel Castellano, Guillermo de Velasco, Maria Cruz Martin Soberón, Alberto Carretero-González, Marta Dueñas, Jesus Paramio, Federico De La Rosa, Juan Luis Sanz, Félix Guerrero
Journal: Journal of Clinical Oncology (2020)

TPS598 Background: Intravesical Bacillus Calmette-Guerin (BCG) induction + BCG maintenance after transurethral resection (TURBT) is the current standard of care for patients (pt) with high-risk non-muscle invasive bladder cancer (NMIBC). Recurrence rate at 2 years is around 30%, which is clearly unsatisfactory. Programmed death ligand 1 (PD-L1) is a surface glycoprotein that functions as an inhibitor of T-cells and plays a crucial role in suppression of cellular immune response. Atezolizumab is a humanized IgG1 monoclonal antibody targeting PD-L1 and is associated with long-term durable remissions in pts with metastatic urothelial cancer (Powles T. Lancet. 2018). Atezolizumab in combination with standard BCG could be beneficial in pts with NMIBC. BladderGATE (NCT04134000) is a phase Ib-II study aims to evaluate the clinical impact and safety of the combination of Atezolizumab + intravesical BGC (medac strain), including a translational study (microbioma and urobioma) in pts with NMIBC. Methods: Eligible pt have confirmed histopathology of NMIBC, BCG naïve or stopped &gt;3 years ago, WHO PS 0-1, no prior radiation to bladder and adequate hematologic and end-organ function. We propose a de-escalation design to enroll patients to identify DLT and MTD proposed to safety and efficacy expansion cohort. Pt will receive induction BCG, 1 instillation every week (qw) (dose level 0) or BCG, 1/2 instillation qw (dose level -1) + intravenously atezolizumab 1200 mg every 3 w (q3w), during 6 w. After induction, BCG will be administered as maintenance treatment at weeks 12, 24 and 48 and atezolizumab 1200 mg q3w up to 1 year. Pt will be accrued to each dose level in cohorts of 10 pt until the MTD is achieved (the highest dose at which &lt;4 out of 10 pt experience DLT). DLT will be evaluated during induction treatment. Additional pt will be included in the expansion cohort up to 40 pt. DLT and safety profile will be evaluated according to NCI-CTCAE v 5.0 criteria. Recurrence-free survival will be assessed per RECIST 1.1. Tissue, plasma and urine sample will be collected for translational study. Clinical trial information: NCT04134000.
A post-transcriptional program of chemoresistance by AU-rich elements and TTP in quiescent leukemic cells
Authors: Sooncheol Lee, Douglas Micalizzi, Samuel S. Truesdell, Syed I. A. Bukhari, Myriam Boukhali, Jennifer Lombardi-Story, Yasutaka Kato, Min-Kyung Choo, Ipsita Dey-Guha, Fei Ji, Benjamin T. Nicholson, David T. Myers, Dongjun Lee, Maria A. Mazzola, Radhika Raheja, Adam Langenbucher, Nicholas J. Haradhvala, Michael S. Lawrence, Roopali Gandhi, Christopher Tiedje, Manuel D. Diaz-Muñoz, David A. Sweetser, Ruslan Sadreyev, David Sykes, Wilhelm Haas, Daniel A. Haber, Shyamala Maheswaran, Shobha Vasudevan
Journal: Genome biology (2020)

Abstract Background Quiescence (G0) is a transient, cell cycle-arrested state. By entering G0, cancer cells survive unfavorable conditions such as chemotherapy and cause relapse. While G0 cells have been studied at the transcriptome level, how post-transcriptional regulation contributes to their chemoresistance remains unknown. Results We induce chemoresistant and G0 leukemic cells by serum starvation or chemotherapy treatment. To study post-transcriptional regulation in G0 leukemic cells, we systematically analyzed their transcriptome, translatome, and proteome. We find that our resistant G0 cells recapitulate gene expression profiles of in vivo chemoresistant leukemic and G0 models. In G0 cells, canonical translation initiation is inhibited; yet we find that inflammatory genes are highly translated, indicating alternative post-transcriptional regulation. Importantly, AU-rich elements (AREs) are significantly enriched in the upregulated G0 translatome and transcriptome. Mechanistically, we find the stress-responsive p38 MAPK-MK2 signaling pathway stabilizes ARE mRNAs by phosphorylation and inactivation of mRNA decay factor, Tristetraprolin (TTP) in G0. This permits expression of ARE mRNAs that promote chemoresistance. Conversely, inhibition of TTP phosphorylation by p38 MAPK inhibitors and non-phosphorylatable TTP mutant decreases ARE-bearing TNFα and DUSP1 mRNAs and sensitizes leukemic cells to chemotherapy. Furthermore, co-inhibiting p38 MAPK and TNFα prior to or along with chemotherapy substantially reduces chemoresistance in primary leukemic cells ex vivo and in vivo. Conclusions These studies uncover post-transcriptional regulation underlying chemoresistance in leukemia. Our data reveal the p38 MAPK-MK2-TTP axis as a key regulator of expression of ARE-bearing mRNAs that promote chemoresistance. By disrupting this pathway, we develop an effective combination therapy against chemosurvival.
Prognostic understanding in advanced genitourinary cancer and its association with clinical characteristics.
Authors: Cristiane Decat Bergerot, Errol James Philip, Paulo Gustavo Bergerot, Nicholas Salgia, Meghan Salgia, Joann Hsu, Nazli Dizman, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2020)

665 Background: Despite promotion of a shared decision-making model of care in oncology, studies suggest that many patients with advanced cancer still possess inaccurate perceptions of their prognosis. Such inaccuracies can influence treatment choices, patient satisfaction and care planning. Novel immunotherapies and targeted treatments, which can yield exceptional responses in a small proportion of patients, are making the difficult task of discussing prognosis with patients even more challenging. We sought to identify clinical factors associated with expectations of cure. Methods: A cross-sectional survey study was conducted among patients diagnosed with incurable genitourinary cancers. Patients’ expectations of cure were assessed based on 4 quartiles: (1) cure is very likely and is in the range of 76 to 100% certainty, (2) cure is likely and is in the range of 51 to 75% certainty, (3) cure is possible but not likely and is in the range of 26 to 50% certainty, and (4) cure is not at all likely and is in the range of 0 to 25% certainty. Linear regression was used to identify clinical factors associated with such expectations. Results: A total of 145 patients were enrolled in the study from July 2017 to September 2019. Most patients were male (76%), white (70%), married (81%) and well-educated (76%). Patients were diagnosed with advanced kidney (66%), bladder (20%) or prostate (14%) cancers. A high proportion of patients (73%) were receiving first or second line (1L/2L) therapy; predominantly immunotherapy (53%) and targeted therapy (24%). Overall, 47% had an inaccurate expectation of cure (in the range of 26 to 100%). Inaccurate expectations of cure were associated with older age (P=0.04) and were also more likely to be reported among patients receiving 1L/2L compared to those receiving later courses of therapy (P=0.009). Conclusions: Our findings highlight the high proportion of patients harboring inaccurate perceptions regarding prognosis, more pronounced with older age and within the first two lines of therapy for metastatic disease. These groups may be ideal target populations for more extensive counseling around prognosis.