tbuckley/cabot-search huggingface dataset:
Microsatellite instability in resectable colorectal liver metastasis: An international multi-institutional analysis.
Authors: Georgios Antonios Margonis, Stefan Buettner, Doris Wagner, John McVey, Nikolaos Andreatos, Andrea Beer, Kazunari Sasaki, Jin He, Klaus Kaczirek, George A. Poultsides, John L. Cameron, Hans Jörg Mischinger, Federico Aucejo, Christopher Lee Wolfgang, Matthew J. Weiss
Journal: Journal of Clinical Oncology (2018)

220 Background: Microsatellite instability (MSI) is associated with favorable prognosis and distinct response to chemotherapy and immunotherapy for non-metastatic colorectal cancer (CRC). However, studies suggest that MSI may have minimal prognostic impact for widely metastatic CRC. Whether MSI is prognostic for the subset of patients with resectable colorectal liver metastases (CRLM) remains unknown. In this study, we analyze the impact of MSI status on patients with CRLM in the largest cohort reported to date. Methods: Patients who underwent curative-intent resection for CRLM between 2003 and 2017 in five participating tertiary centers and had available data on MSI status were included. Standard clinicopathologic and outcome data were collected. Survival was calculated using Kaplan-Meier analysis. Results: A total of 332 patients who met inclusion criteria were identified, of which 198 (59.6%) were male and 133 (40.7%) had rectal primary tumors. Sixteen patients (4.8%) were MSI positive. The majority of patients had T3 tumors (n = 193; 61.3%) and lymph node metastasis were present in 202 patients (64.5%). The median number of hepatic lesions was 1 [inter-quartile range (IQR):1-3] and median tumor diameter was 2.0 cm (1.2-3.5). Extrahepatic disease was present in 51 (15.7%) patients. Preoperative chemotherapy was administered to 220 (68.8%) patients. Of note, data on KRAS mutation status were available for the majority of the patients (95.5%). Baseline characteristics were similar between MSI positive and negative patients. At a median follow-up of 22.1 months, 154 (47.5%) patients experienced disease recurrence and 70 (21.1%) died. Importantly, neither disease-free survival (DFS, p = 0.168) nor overall survival (OS) were associated with MSI status (p = 0.759). Conclusions: MSI status did not appear to impact survival for patients with resectable CRLM. Additional research in larger cohorts from additional participating institutions is currently underway to assess these preliminary findings.
Diagnostic radiation and testicular germ cell tumor risk.
Authors: Kevin Thomas Nead, Nandita Mitra, Benita Weathers, Louisa T Pyle, Katherine L. Nathanson, Peter A Kanetsky
Journal: Journal of Clinical Oncology (2018)

556 Background: Both incidence of testicular germ cell tumor (TGCT) and use of diagnostic radiation have increased in recent decades. In a quarter of diagnostic scans in children, direct and indirect radiation dose to the testes exceeds 20 mSv, which surpasses thresholds associated with malignancy risk (~5 mSv). Here, we examine the association between exposure to diagnostic radiation and TGCT risk in a case-control study. Methods: Cases were enrolled in a hybrid hospital- and population-based setting and controls were recruited from the community. Participants reported on exposures to x-ray/CT below the waist and lower GI series, and we derived a combined variable for any exposure. After imputation to infer missing data, we compared baseline characteristics and used multivariable logistic regression adjusting for age and race to determine the risk of developing TGCT according to number of exposures and age at first exposure. Results: As expected, cases (n = 1088) were more likely than controls (n = 1458) to be white, have a family history of TGCT, and have a history of cryptorchidism (p &lt; 0.05). There was an increased risk of TGCT with a greater number of exposures for both x-ray/CT (p trend = 0.002) and the combined diagnostic radiation variable (p trend &lt; 0.001). Compared to those without any exposure, risk was greatest among those reporting ≥6 exposures for x-ray or CT (OR, 9.6; 95% CI, 4.6-19.9; p &lt; 0.001) and the combined variable (OR, 5.8; 95% CI, 3.2-10.4; p &lt; 0.001), after adjusting for age at first exposure. Early first exposure before eleven years of age increased risk of TGCT for x-ray/CT (OR, 2.36; 95% CI, 1.17-4.77) and combined radiation exposure (OR, 1.96; 95% CI, 1.05-3.67) compared to later first exposure after seventeen years of age, adjusting for total exposures. Analyses limited to observed data only yielded similar results. Conclusions: Exposure to diagnostic radiation below the waist, particularly among younger individuals, may increase TGCT risk. These results should be validated. As the testes are present outside the body and rarely examined using diagnostic radiation, a unique opportunity for shielding exists. Efforts to reduce testicular dose and optimize shielding practices should be prioritized.
Prognostic factors in men receiving androgen deprivation therapy (ADT) for recurrent prostate cancer: Using absolute PSA and PSA doubling time (DT) to guide timing of ADT initiation.
Authors: Praful Kumar Ravi, Jeffrey Karnes, Laureano J Rangel, Lance C. Pagliaro
Journal: Journal of Clinical Oncology (2018)

129 Background: ADT is the first-line treatment for men experiencing recurrence after undergoing radical therapy for prostate cancer. However, timing of ADT initiation is controversial and there are limited data on prognostic factors in patients starting ADT. Methods: We identified consecutive men who underwent radical prostatectomy (RP) for localized prostate cancer at our institution between 1987 and 2007 and who subsequently received salvage ADT. Early progression on ADT was defined as development of metastatic disease within 2yrs of initiation. The primary outcomes of interest were cancer-specific (CSS) and overall survival (OS). Results: A total of 2418 men were included. Median age at RP was 64yrs and median follow-up was 13.9yrs. 48% and 20% of men had pathologic Gleason scores of 7 and 8-10 respectively. The median PSA was 2.6ng/ml, while 385 men (16%) had metastatic disease at receipt of ADT. Overall, 1060 men (44%) developed clinical metastases, with 625 (59%) of these doing so within 2yrs of starting ADT. On multivariable analysis, longer PSA DT before ADT was associated with lower odds of early progression on ADT (DT 3-9mths, OR = 0.19; DT ≥9mths, OR = 0.10, both p &lt; 0.001). 10- and 20-year CSS were 89% and 70%, and 10- and 20-year OS were 82% and 40% respectively. Independent predictors of lower CSS included metastatic disease at time of ADT (HR = 2.60), PSA at ADT of 5-50ng/ml (HR = 2.68) and &gt; 50ng/ml (HR = 4.33, all p &lt; 0.001), while longer PSA DT was associated with higher CSS (DT 3-9mths, HR = 0.54; DT ≥9mths, HR = 0.45, both p &lt; 0.001). PSA at ADT of 5-50ng/ml (HR = 3.10) and &gt; 50ng/ml (HR = 5.20, both p &lt; 0.001) were independent predictors of OS. Conclusions: PSA DT &lt; 3mths and absolute PSA at ADT initiation of ≥ 5ng/ml are adverse prognostic indicators in men receiving salvage ADT for relapse after RP. For patients with these features, their risk of early progression and death should be part of a discussion about the timing of ADT and consideration given to more aggressive treatment strategies. Conversely, men with biochemical relapse who have longer DT and PSA &lt; 5ng/ml are at lower risk and could make an informed decision to defer ADT initiation.
Erratum: The microenvironment of classical Hodgkin lymphoma: heterogeneity by Epstein-Barr virus presence and location within the tumor
Authors: R Wu, A Sattarzadeh, B Rutgers, A Diepstra, A van den Berg, L Visser
Journal: Blood Cancer Journal (2018)

Correction to: Blood Cancer Journal (2016) 6, e417; doi:10.1038/bcj.2016.26 Since the publication of the paper the authors have noticed that R Wu was listed as the sole first author. This is incorrect; R Wu and A Sattarzadeh contributed equally to this paper and are co-first authors. The authors wish to apologize for any inconvenience caused.
Impact of immunosuppression on incidence, aetiology and outcome of ventilator-associated lower respiratory tract infections
Authors: Anne-Sophie Moreau, Ignacio Martin-Loeches, Pedro Povoa, Jorge Salluh, Alejandro Rodriguez, Arnaud W. Thille, Emilio Diaz Santos, Elisa Vedes, Suzana Margareth Lobo, Bruno Mégarbane, Esperanza Molero Silvero, Luis Coelho, Laurent Argaud, Rafael Sanchez Iniesta, Julien Labreuche, Anahita Rouzé, Saad Nseir
Journal: European Respiratory Journal (2018)

The aim of this planned analysis of the prospective multinational TAVeM database was to determine the incidence, aetiology and impact on outcome of ventilator-associated lower respiratory tract infections (VA-LRTI) in immunocompromised patients.All patients receiving mechanical ventilation for >48 h were included. Immunocompromised patients (n=663) were compared with non-immunocompromised patients (n=2297).The incidence of VA-LRTI was significantly lower among immunocompromised than among non-immunocompromised patients (16.6% versus 24.2%; sub-hazard ratio 0.65, 95% CI 0.53-0.80; p<0.0001). Similar results were found regarding ventilator-associated tracheobronchitis (7.3% versus 11.6%; sub-hazard ratio 0.61, 95% CI 0.45-0.84; p=0.002) and ventilator-associated pneumonia (9.3% versus 12.7%; sub-hazard ratio 0.72, 95% CI 0.54-0.95; p=0.019). Among patients with VA-LRTI, the rates of multidrug-resistant bacteria (72% versus 59%; p=0.011) and intensive care unit mortality were significantly higher among immunocompromised than among non-immunocompromised patients (54% versus 30%; OR 2.68, 95% CI 1.78-4.02; p<0.0001). In patients with ventilator-associated pneumonia, mortality rates were higher among immunocompromised than among non-immunocompromised patients (64% versus 34%; p<0.001).Incidence of VA-LRTI was significantly lower among immunocompromised patients, but it was associated with a significantly higher mortality rate. Multidrug-resistant pathogens were more frequently found in immunocompromised patients with VA-LRTI.
Cardiac Abnormalities in Patients With Hutchinson-Gilford Progeria Syndrome
Authors: Ashwin Prakash, Leslie B. Gordon, Monica E. Kleinman, Ellen B. Gurary, Joseph Massaro, Ralph D’Agostino, Mark W. Kieran, Marie Gerhard-Herman, Leslie Smoot
Journal: JAMA Cardiology (2018)

Hutchinson-Gilford progeria syndrome (HGPS) is an ultrarare disorder associated with premature death due to cardiovascular events during the second decade of life. However, because of its rarity (107 identified living patients), the natural history of cardiac disease remains uncharacterized. Therefore, meaningful cardiac end points for clinical trials have been difficult to establish.To examine the course of appearance of cardiac abnormalities in patients with HGPS to identify meaningful cardiac end points for use in future clinical trials.In this prospective, cross-sectional, observational study, 27 consecutive patients with clinically and genetically confirmed classic HGPS were evaluated at a single center for 1 visit from July 1, 2014, through February 29, 2016, before initiation of treatment.Classic HGPS.Echocardiography was used to assess ventricular and valve function using standard techniques. Diastolic left ventricular (LV) function was assessed using tissue Doppler imaging. Previously published normative data were used to adjust findings to age and body size.This study included 27 patients (median age, 5.6 years; age range, 2-17 years; 15 [56%] male). Among echocardiographic indicators, LV diastolic dysfunction, defined as a tissue Doppler septal or lateral early velocity z score less than -2, was the most prevalent abnormality, seen in 16 patients (59%). Diastolic dysfunction was seen in all age groups, and its prevalence increased with age, mirroring findings seen during normal aging. Indicators of LV diastolic function were more abnormal in older patients. The z scores for lateral and septal early velocities were lower (r = -0.77, P < .001; and r = -0.66, P < .001, respectively), whereas those for the ratio of early mitral inflow velocity to early diastolic tissue Doppler myocardial velocity were higher (r = 0.80, P < .001; and r = 0.72, P < .001, respectively) in older patients. Other echocardiographic findings, including LV hypertrophy, LV systolic dysfunction, and valve disease, were less prevalent in the first decade and were seen more frequently in the second decade.In this largest-to-date cohort of patients with HGPS, LV diastolic dysfunction was the most prevalent echocardiographic abnormality and its prevalence increased with aging. Echocardiographic indicators of LV diastolic function may be useful end points in future clinical trials in this patient population.
End-of-Life Care Options and Decision Making for Older Patients With Malignant Brain Tumors
Authors: Andrew K. Conner, Robert G. Briggs, Michael E. Sughrue
Journal: JAMA Oncology (2018)

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 Oncology 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 Oncology journal
Stable lines and clones of long-term proliferating normal, genetically unmodified murine common lymphoid progenitors
Authors: Yohei Kawano, Georg Petkau, Christina Stehle, Pawel Durek, Gitta Anne Heinz, Kousuke Tanimoto, Hajime Karasuyama, Mir-Farzin Mashreghi, Chiara Romagnani, Fritz Melchers
Journal: Blood (2018)
An International Interobserver Variability Reporting of the Nuclear Scoring Criteria to Diagnose Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: a Validation Study
Authors: Lester D. R. Thompson, David N. Poller, Kennichi Kakudo, Raoul Burchette, Yuri E. Nikiforov, Raja R. Seethala
Journal: Endocrine Pathology (2018)
Superior Pituitary Border Analysis in Immunotherapy-Induced Hypophysitis
Authors: Darko Pucar, Anne Marie Boustani, Richard A. Bronen, Lawrence Saperstein
Journal: Clinical Nuclear Medicine (2018)

Immunotherapy-induced hypophysitis presents with headache, fatigue, and visual disturbances. The diagnosis is supported by imaging findings of pituitary swelling, enhancement, and hypermetabolism and established by low levels of pituitary hormones. A 64-year-old man with metastatic melanoma on nivolumab presented with a severe headache, initially attributed to sinus disease. Contrast CT was interpreted as minor sinus disease and no pituitary abnormality. Hypophysitis was eventually diagnosed and successfully treated based on PET and laboratory findings. Our retrospective analysis demonstrated abnormal convex superior pituitary border visible on contrast and noncontrast CT and PET. This feature may aid diagnosis in the challenging cases.
P096 Synovial tissue remodelling as a means of tissue memory
Authors: I Olmos Calvo, RA Byrne, M Bonelli, B Niederreiter, F Alasti, T Karonitsch, J Holinka, G Steiner, JS Smolen, P Ertl, HP Kiener
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> The synovium demonstrates a distinct cellular structure with a densely packed synovial lining layer that sits on top of a loosely organised sublining layer. In rheumatoid arthritis (RA), this tissue hosts the inflammatory reaction and undergoes drastic structural changes. We hypothesise that this inflammatory remodelling results in tissue dysfunction, thereby perpetuating the inflammatory process. To explore the relationship between tissue structure and function, we use a 3D human synovial organoid culture system to model healthy and diseased synovium. <h3>Methods</h3> FLS from RA patients were resuspended in Matrigel and cultured as 3D organoids for an extended period of time. This allows FLS to re-establish a synovial tissue-like structure. To mimic inflammation, 3D synovial organoids were challenged with TNF. A re-stimulation experiment was designed in which synovial organoids were exposed to TNF for 10 days, followed by a 3 day wash out phase. Thereafter, the organoids were re-stimulated with TNF. To prevent TNF-driven remodelling, Marimastat, a broad MMP inhibitor, was added during the first TNF stimulation. For selected experiments, synovial tissue-like structure was assessed by HE staining in paraffin embedded sections of synovial organoids. qPCR and RNA Seq were used in gene expression profiling. IL-6, IL-8 and MMP3 protein production was determined by ELISA. <h3>Results</h3> TNF-stimulated synovial organoids demonstrated lining layer hyperplasia and cellular condensation in the sublining layer. After TNF-stimulation, gene expression of MMP1, MMP3 and IL-6 and protein production of IL-6, IL-8 and MMP3 was upregulated. Upon re-stimulation of synovial organoids with TNF, protein levels of IL-6, IL-8 and MMP3 were significantly increased when compared to previous stimulations. In order to explore whether this effect is due to TNF-induced structural changes, tissue remodelling was blocked using Marimastat. IL-6 protein level was reduced in 21%. To further explore the increased TNF response upon re-stimulation, epigenetic mechanisms are currently being tested. <h3>Conclusions</h3> TNF stimulation has a direct effetc in synovial organoids function and structure. TNF-driven tissue remodelling is associated with an increased in IL-6, IL-8 and MMP3 expression response upon re-stimulation. Inhibition of TNF-induced remodelling partially prevents this effect. Additional epigenetic mechanisms may account for tissue memory. <h3>Disclosure of interest</h3> None declared
Objective testing is cost effective
Authors: Andrew N Menzies-Gow, John Alexander
Journal: BMJ (2018)

As co-chairs of the National Institute for Health and Care Excellence’s guideline committee on asthma, we support the aim of a guideline with contributions from both NICE and the British Thoracic Society (with the Scottish Intercollegiate Guideline Network), covering all aspects of management and care.1 NICE …
Association of Rooming-in With Outcomes for Neonatal Abstinence Syndrome
Authors: Kathryn Dee L. MacMillan, Cassandra P. Rendon, Kanak Verma, Natalie Riblet, David B. Washer, Alison Volpe Holmes
Journal: JAMA Pediatrics (2018)

Rising incidence of neonatal abstinence syndrome (NAS) is straining perinatal care systems. Newborns with NAS traditionally receive care in neonatal intensive care units (NICUs), but rooming-in with mother and family has been proposed to reduce the use of pharmacotherapy, length of stay (LOS), and cost.To systematically review and meta-analyze if rooming-in is associated with improved outcomes for newborns with NAS.MEDLINE, CINAHL, The Cochrane Library, and clinicaltrials.gov were searched from inception through June 25, 2017.This investigation included randomized clinical trials, cohort studies, quasi-experimental studies, and before-and-after quality improvement investigations comparing rooming-in vs standard NICU care for newborns with NAS.Two independent investigators reviewed studies for inclusion. A random-effects model was used to pool dichotomous outcomes using risk ratio (RR) and 95% CI. The study evaluated continuous outcomes using weighted mean difference (WMD) and 95% CI.The primary outcome was newborn treatment with pharmacotherapy. Secondary outcomes included LOS, inpatient cost, and harms from treatment, including in-hospital adverse events and readmission rates.Of 413 publications, 6 studies (n = 549 [number of patients]) met inclusion criteria. In meta-analysis of 6 studies, there was consistent evidence that rooming-in is preferable to NICU care for reducing both the use of pharmacotherapy (RR, 0.37; 95% CI, 0.19-0.71; I2 = 85%) and LOS (WMD, -10.41 days; 95% CI, -16.84 to -3.98 days; I2 = 91%). Sensitivity analysis resolved the heterogeneity for the use of pharmacotherapy, significantly favoring rooming-in (RR, 0.32; 95% CI, 0.18-0.57; I2 = 13%). Three studies reported that inpatient costs were lower with rooming-in; however, significant heterogeneity precluded quantitative analysis. Qualitative analysis favored rooming-in over NICU care for increasing breastfeeding rates and discharge home in familial custody, but few studies reported on these outcomes. Rooming-in was not associated with higher rates of readmission or in-hospital adverse events.Opioid-exposed newborns rooming-in with mother or other family members appear to be significantly less likely to be treated with pharmacotherapy and have substantial reductions in LOS compared with those cared for in NICUs. Rooming-in should be recommended as a preferred inpatient care model for NAS.
Chagas disease knocks on our door: a cross-sectional study among Latin American immigrants in Milan, Italy
Authors: S. Antinori, L. Galimberti, R. Grande, R. Bianco, L. Oreni, L. Traversi, D. Ricaboni, G. Bestetti, A. Lai, D. Mileto, M.R. Gismondo, M. Petullà, S. Garelli, G. De Maio, C. Cogliati, D. Torzillo, A.M. Villa, A.M. Egidi, E.C. Repetto, A.L. Ridolfo, M. Corbellino, M. Galli
Journal: Clinical Microbiology and Infection (2018)
IPMNs with co-occurring invasive cancers: neighbours but not always relatives
Authors: Matthäus Felsenstein, Michaël Noë, David L Masica, Waki Hosoda, Peter Chianchiano, Catherine G Fischer, Gemma Lionheart, Lodewijk A A Brosens, Antonio Pea, Jun Yu, Georgios Gemenetzis, Vincent P Groot, Martin A Makary, Jin He, Matthew J Weiss, John L Cameron, Christopher L Wolfgang, Ralph H Hruban, Nicholas J Roberts, Rachel Karchin, Michael G Goggins, Laura D Wood
Journal: Gut (2018)

Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions that can give rise to invasive pancreatic carcinoma. Although approximately 8% of patients with resected pancreatic ductal adenocarcinoma have a co-occurring IPMN, the precise genetic relationship between these two lesions has not been systematically investigated.We analysed all available patients with co-occurring IPMN and invasive intrapancreatic carcinoma over a 10-year period at a single institution. For each patient, we separately isolated DNA from the carcinoma, adjacent IPMN and distant IPMN and performed targeted next generation sequencing of a panel of pancreatic cancer driver genes. We then used the identified mutations to infer the relatedness of the IPMN and co-occurring invasive carcinoma in each patient.We analysed co-occurring IPMN and invasive carcinoma from 61 patients with IPMN/ductal adenocarcinoma as well as 13 patients with IPMN/colloid carcinoma and 7 patients with IPMN/carcinoma of the ampullary region. Of the patients with co-occurring IPMN and ductal adenocarcinoma, 51% were likely related. Surprisingly, 18% of co-occurring IPMN and ductal adenocarcinomas were likely independent, suggesting that the carcinoma arose from an independent precursor. By contrast, all colloid carcinomas were likely related to their associated IPMNs. In addition, these analyses showed striking genetic heterogeneity in IPMNs, even with respect to well-characterised driver genes.This study demonstrates a higher prevalence of likely independent co-occurring IPMN and ductal adenocarcinoma than previously appreciated. These findings have important implications for molecular risk stratification of patients with IPMN.