tbuckley/cabot-search huggingface dataset:
The SEMITEP trial: De-escalating chemotherapy in low-volume metastatic seminoma based on early FDG-PET.
Authors: Yohann Loriot, Matthieu Texier, Stephane Culine, Aude Flechon, Thierry Nguyen, Gwenaelle Gravis, Lionnel Geoffrois, Christine Chevreau, Marine Gross-Goupil, Philippe Barthelemy, Emmanuelle Bompas, Hakim Mahammedi, Brigitte Laguerre, Sophie Abadie Lacourtoisie, Carole Helissey, Sylvain Ladoire, Christophe Massard, Serena Grimaldi, Karim Fizazi
Journal: Journal of Clinical Oncology (2020)

387 Background: A negative FDG-positron emission tomography/computerized tomography (PET) predicts the absence of viable seminoma cells after chemotherapy in men with metastatic seminoma. In this study, we assessed whether patients (pts) with low-volume metastatic seminoma can be treated with 2 cycles of etoposide-cisplatin (EP) followed by only one cycle of carboplatin (CARBO) on the basis of a negative interim PET, thereby limiting the burden of toxicity. Methods: In this non-randomised, multiple-center, phase 2 trial (NCT01887340), we enrolled pts with low-volume metastatic seminoma (with good prognosis according to IGCCCG and the Medical Research Council classifications). All pts with baseline PET-positive received EP for two cycles. After completion of first two cycles, pts underwent a second PET to assess response. Patients with a persistent positive PET (based on local review) proceeded directly to two additional EP cycles (for a total of 4); those who achieved a PET-negative received only one cycle of CARBO (AUC=7). The primary outcome was the proportion of pts who were PET-negative on interim PET and received de-escalating chemotherapy. Secondary endpoints include progression-free survival (PFS) and overall survival (OS). Results: Between June 2013 and July 2017, 102 pts were enrolled in the study. Three pts were deemed ineligible or not evaluable and thus 99 patients received treatment. After 2 first EP cycles, PET was available in 94 pts. Interim PET was negative in 68 pts (72%) and positive in 26 pts (28%). Overall, 63 pts (67.0%; 95% CI 57.5-76.5) were PET-negative and proceeded to one single cycle of CARBO. Overall, 24 (25.5%, 95% CI 17.1-34.9) patients had a PET positive after 2 EP and received 2 additional cycles of EP. After a median follow-up of 34.4 months, only 8 patients relapsed (2 in EP group and 6 in CARBO group). 2-year PFS rates were respectively 93.7% (95% CI 84.9-97.5) in the CARBO group and 92.9% (95% CI 77.4-98.0) in the EP group. Only one patient died during the 2 first cycles. Conclusions: De-escalating treatment based on a negative PET after 2 cycles of chemotherapy appears to be safe and feasible in the majority of patients with low-volume metastatic seminoma. Clinical trial information: NCT01887340.
A novel closure technique using the EndoTrac for mucosal incision closure in peroral endoscopic myotomy
Authors: Tomoya Sako, Shinwa Tanaka, Takashi Toyonaga, Hirofumi Abe, Hiroya Sakaguchi, Nobuaki Ikezawa, Yuzo Kodama
Journal: Endoscopy (2020)

Recently, peroral endoscopic myotomy (POEM) has been reported to be highly effective for treating patients with achalasia [1] [2]. In achalasia, patients may have severe esophageal dilatation and thickening of the mucosal layer due to their long history of the disease. Endoclips are usually used for closure of the mucosal incision, but this can be difficult due to the thickness of the mucosal layer. Alternative methods using an Endoloop or Over-The-Scope Clip (OTSC) have been described to manage difficult mucosal incision closure [3], but these methods are complex and require sufficient skill. We present a novel technique using EndoTrac (Top Corporation, Tokyo, Japan) for mucosal incision closure in POEM.
Breaking the Itch–Scratch Cycle in Prurigo Nodularis
Authors: Shawn G. Kwatra
Journal: New England Journal of Medicine (2020)

Prurigo nodularis is a chronic dermatologic condition that features intensely itchy, excoriated nodules on the extensor surfaces of the arms and legs and on the trunk. The disorder is most common in middle age or later, and it can be associated with multiple systemic conditions, including chronic kidney disease, type 2 diabetes, and human immunodeficiency virus infection.1 The hallmark of prurigo nodularis is unrelenting itch, which is greater in intensity, frequency, and effect on quality of life than itch associated with other chronic, pruritic skin diseases such as atopic dermatitis and psoriasis.2 At the Johns Hopkins Itch Clinic, my colleagues . . .
Association of Ascending Aortic Dilatation and Long-term Endurance Exercise Among Older Masters-Level Athletes
Authors: Timothy W. Churchill, Erich Groezinger, Jonathan H. Kim, Garrett Loomer, J. Sawalla Guseh, Meagan M. Wasfy, Eric M. Isselbacher, Gregory D. Lewis, Rory B. Weiner, Christian Schmied, Aaron L. Baggish
Journal: JAMA Cardiology (2020)

<h3>Importance</h3> Aortic dilatation is frequently encountered in clinical practice among aging endurance athletes, but the distribution of aortic sizes in this population is unknown. It is additionally uncertain whether this may represent aortic adaptation to long-term exercise, similar to the well-established process of ventricular remodeling. <h3>Objective</h3> To assess the prevalence of aortic dilatation among long-term masters-level male and female athletes with about 2 decades of exercise exposure. <h3>Design, Setting, and Participants</h3> This cross-sectional study evaluated aortic size in veteran endurance athletes. Masters-level rowers and runners aged 50 to 75 years were enrolled from competitive athletic events across the United States from February to October 2018. Analysis began January 2019. <h3>Exposures</h3> Long-term endurance exercise. <h3>Main Outcomes and Measures</h3> The primary outcome was aortic size at the sinuses of Valsalva and the ascending aorta, measured using transthoracic echocardiography in accordance with contemporary guidelines. Aortic dimensions were compared with age, sex, and body size–adjusted predictions from published nomograms, and<i>z</i>scores were calculated where applicable. <h3>Results</h3> Among 442 athletes (mean [SD] age, 61 [6] years; 267 men [60%]; 228 rowers [52%]; 214 runners [48%]), clinically relevant aortic dilatation, defined by a diameter at sinuses of Valsalva or ascending aorta of 40 mm or larger, was found in 21% (n = 94) of all participants (83 men [31%] and 11 women [6%]). When compared with published nomograms, the distribution of measured aortic size displayed a rightward shift with a rightward tail (all<i>P</i> &lt; .001). Overall, 105 individuals (24%) had at least 1<i>z</i>score of 2 or more, indicating an aortic measurement greater than 2 SDs above the population mean. In multivariate models adjusting for age, sex, body size, hypertension, and statin use, both elite competitor status (rowing participation in world championships or Olympics or marathon time under 2 hours and 45 minutes) and sport type (rowing) were independently associated with aortic size. <h3>Conclusions and Relevance</h3> Clinically relevant aortic dilatation is common among aging endurance athletes, raising the possibility of vascular remodeling in response to long-term exercise. Longitudinal follow-up is warranted to establish corollary clinical outcomes in this population.
Phase I/II study of the oral HIF-2 α inhibitor MK-6482 in patients with advanced clear cell renal cell carcinoma (RCC).
Authors: Toni K. Choueiri, Elizabeth R. Plimack, Todd Michael Bauer, Jaime R. Merchan, Kyriakos P. Papadopoulos, David F. McDermott, M Dror Michaelson, Leonard Joseph Appleman, Sanjay Thamake, Naseem J. Zojwalla, Eric Jonasch
Journal: Journal of Clinical Oncology (2020)

611 Background: Hypoxia-inducible factor (HIF)-2α is a transcription factor that is a key oncogenic driver in RCC. MK-6482 is a first-in-class small molecule HIF-2α inhibitor that blocks the heterodimerization of HIF-2α with HIF-1β and induces regression in mouse xenograft RCC models. Methods: Pts with advanced ccRCC who had received at least 1 prior therapy were enrolled in an expansion cohort from the first-in-human phase 1/2 study of MK-6482 in advanced solid tumors (NCT02974738). Pts were administered 120 mg of MK-6482 orally once daily. Primary end point: safety. Key secondary end points: ORR, duration of response (DOR), and PFS. Results: Fifty-five pts were enrolled in the dose expansion cohort. Median (range) number of prior therapies was 3 (1-9); 67% received anti–PD-1 and anti-VEGF agents. Five pts (9%) were favorable risk, 40 (73%) were intermediate risk, and 10 (18%) were poor risk by IMDC criteria. With a median follow-up of 13 mo the most common all-grade, all-cause AEs &gt; 30% were anemia (75%), fatigue (67%), dyspnea (47%), nausea (33%), and cough (31%). Anemia (26%) and hypoxia (15%) were the most common grade 3 AEs. No grade 4/5 drug-related AEs were observed. ORR was 24% with 13 confirmed PRs. Thirty-one pts (56%) had SD, with a disease control rate (CR+PR+SD) of 80%. Thirty-five of 52 (67%) pts with baseline and postbaseline assessments had tumor shrinkage. Median DOR was not reached; 81% of pts had response ≥6 mo per Kaplan-Meier estimate. Sixteen pts (29%) continued treatment beyond 12 mo. By IMDC risk, 2/5 pts with favorable risk had PR (ORR = 40%), 10/40 with intermediate risk had PR (ORR = 25%), and 1/10 with poor risk had PR (ORR = 10%); disease control rate was 100%, 80%, and 70%, respectively. Median PFS for the total population was 11.0 mo; the 12 mo PFS rate was 49%. Median PFS for favorable, intermediate, and poor IMDC risk was 16.5, 11.0, and 6.9 mo, respectively. As of May 15, 2019, 30 pts (55%) discontinued due to PD, 2 (4%) due to AEs. Sixteen pts (29%) had treatment ongoing. Conclusions: MK-6482 is well tolerated with a favorable safety profile and demonstrated promising single-agent activity in heavily pretreated pts with ccRCC across IMDC risk groups. A phase 3 trial in a similar population is planned. Clinical trial information: NCT02974738.
Defining the emergence of myeloid-derived suppressor cells in breast cancer using single-cell transcriptomics
Authors: Hamad Alshetaiwi, Nicholas Pervolarakis, Laura Lynn McIntyre, Dennis Ma, Quy Nguyen, Jan Akara Rath, Kevin Nee, Grace Hernandez, Katrina Evans, Leona Torosian, Anushka Silva, Craig Walsh, Kai Kessenbrock
Journal: Science Immunology (2020)

Myeloid-derived suppressor cells (MDSCs) are innate immune cells that acquire the capacity to suppress adaptive immune responses during cancer. It remains elusive how MDSCs differ from their normal myeloid counterparts, which limits our ability to specifically detect and therapeutically target MDSCs during cancer. Here, we sought to determine the molecular features of breast cancer-associated MDSCs using the widely studied mouse model based on the mouse mammary tumor virus (MMTV) promoter-driven expression of the polyomavirus middle T oncoprotein (MMTV-PyMT). To identify MDSCs in an unbiased manner, we used single-cell RNA sequencing to compare MDSC-containing splenic myeloid cells from breast tumor-bearing mice with wild-type controls. Our computational analysis of 14,646 single-cell transcriptomes revealed that MDSCs emerge through an aberrant neutrophil maturation trajectory in the spleen that confers them an immunosuppressive cell state. We establish the MDSC-specific gene signature and identify CD84 as a surface marker for improved detection and enrichment of MDSCs in breast cancers.
The economic and societal burden of excessive daytime sleepiness in patients with obstructive sleep apnea
Authors: Damien Léger, Carl Stepnowsky
Journal: Sleep Medicine Reviews (2020)

Excessive daytime sleepiness (EDS) is common in patients with obstructive sleep apnea (OSA) and continues to persist in many patients despite adequate OSA treatment. EDS in OSA is associated with decreased quality of life (QOL) as well as increased societal burden, which may impact health care utilization and costs. However, economic burden is often not the primary focus in the treatment of EDS in OSA. This targeted literature review aimed to examine the published literature on the economic burden of EDS in OSA. This review identified available literature using a targeted PubMed search strategy using search terms related to EDS in OSA in adults. Results demonstrate that there are few studies that detailed the direct costs associated with EDS in OSA, though several studies indicated an association between EDS in OSA and indirect economic burdens, including motor vehicle accidents (MVAs), near misses, work productivity, mood, and QOL. Data from the literature confirmed that persistent EDS in OSA following continuous positive airway pressure persists in 12%–65% of patients. Future studies should further describe the direct costs of EDS in OSA, quantify the cost associated with MVAs and lost work productivity, and detail QOL and social impacts of the condition.
Predictors of Persistent and Recurrent Wheeze in Children in The Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (M-PAACH) Cohort
Authors: Rosario Alarcon, John Kroner, Asel Baatyrbek Kyzy, Amen An, Gurjit Khurana Hershey, Jocelyn Biagini Myers
Journal: Journal of Allergy and Clinical Immunology (2020)
95P Comparison of Expression Levels of Twist, Snail and Slug in Primary Tumors and Lymph Node Metastases in Breast Cancer Patients
Authors: T. Ahrends, A. Markiewicz, P. Nowialis, B. Seroczynska, J. Skokowski, J. Szade, M. Welnicka-Jaskiewicz, A.J. Zaczek
Journal: Annals of Oncology (2012)
Covid-19: school closures and bans on mass gatherings will need to be considered, says England’s CMO
Authors: Tom Moberly
Journal: BMJ (2020)

School closures and bans on mass gatherings will need to be considered if there is evidence of onward transmission of covid-19 in the UK, England’s chief medical officer has said.

Speaking at the Nuffield Trust annual summit in Windsor on 27 February, Chris Whitty said that it was “only a matter of time” before there is onward transmission of coronavirus in the UK. Measures to reduce transmission, such as school closures and banning mass gatherings for at least two months, would then need to be considered, he said.

“I expect there will be some onward transmission in the UK,” he said. “We haven’t had it to date, as far as I can …
Fecal MicroRNA-Based Algorithm Increases Effectiveness of Fecal Immunochemical Test–Based Screening for Colorectal Cancer
Authors: Saray Duran-Sanchon, Lorena Moreno, Javier Gómez-Matas, Josep M. Augé, Miquel Serra-Burriel, Míriam Cuatrecasas, Leticia Moreira, Anna Serradesanferm, Àngels Pozo, Jaume Grau, Maria Pellisé, Meritxell Gironella, Antoni Castells
Journal: Clinical Gastroenterology and Hepatology (2020)

<h3>Background & Aims</h3> An algorithm based on fecal levels of 2 microRNAs (miR-421 and miR-27a-3p), fecal hemoglobin concentration, and patient age and sex can identify patients with advanced colorectal neoplasia. We investigated whether this algorithm, called miRFec, could increase effectiveness and efficiency of fecal immunochemical test (FIT)-based colorectal cancer (CRC) screening programs. <h3>Methods</h3> We obtained data and fecal samples from 767 persons with a positive result from the FIT who then underwent colonoscopy examination while participating a population-based CRC screening program, from March 2011 through May 2017 in Barcelona, Spain. Fecal miRNAs were isolated from the buffer contained in the original FIT collection device and analyzed by quantitative reverse transcription PCR. Aims were to evaluate the usefulness of the miRFec algorithm in identifying persons at greatest risk for CRC who should be prioritized for colonoscopy examination and individuals at low risk for whom colonoscopy could be avoided. <h3>Results</h3> Of the 767 study subjects, 414 (54.0%) were found by colonoscopy to have advanced colorectal neoplasia (67 with CRC and 347 with advanced adenomas) and 353 (46.0%) were found to have either non-advanced adenomas (n = 136) or a normal examination (n = 217). MiRFec algorithm scores (1–4) were independently associated with the presence of advanced colorectal neoplasia (P < .001). The miRFec algorithm differentiated patients with CRC from those with non-advanced adenomas or normal colonoscopy with an area under the receiver operating characteristic curve of 90% (95% CI, 86–94). Subjects with miRFec scores in the 4th quartile (above 3.09, high-risk group) were 8-fold more likely to have advanced colorectal neoplasia than subjects with miRFec scores in the 1st quartile (below 2.14, low-risk group). Subjects in the low-risk group had a positive predictive value below 30% for detection of advanced colorectal neoplasia. When we used a 50% specificity cut-off value, the miRFec algorithm identified 97% of patients with CRC and would allow 264 subjects (34.4%) to avoid colonoscopy examination. <h3>Conclusions</h3> An algorithm based on fecal levels of 2 miRNAs and hemoglobin, patient age and sex (miRFec) differentiated patients with CRC from those with non-advanced adenomas or normal colonoscopy with an area under the receiver operating characteristic curve value of 90% and avoided 34% of colonoscopies. Inclusion of this algorithm in FIT-based CRC screening programs could increase their effectiveness and efficiency.
Prognostic impact of LDH and HCG levels in marker-positive seminomas.
Authors: Christoph Alexander Seidel, Gedske Daugaard, Tim Nestler, Alexey Tryakin, Christian Daniel Fankhauser, Thomas Hermanns, Jorge Aparicio, Julia Heinzelbecker, Pia Paffenholz, Axel Heidenreich, Ugo De Giorgi, Richard Cathomas, Anja Lorch, Felix Bremmer, Patrizia Giannatempo, Andrea Necchi, Gaetano Aurilio, Chiara Casadei, Christoph Oing, Carsten Bokemeyer
Journal: Journal of Clinical Oncology (2020)

392 Background: The prognostic impact of LDH and HCG serum levels in marker positive metastatic seminoma patients is uncertain. This analysis evaluated the association between LDH and HCG levels with oncological outcomes in this patient population. Methods: Seminoma patients with elevated HCG levels were retrospectively analyzed. After stratification according to tumor marker levels pre- and post-orchiectomy, outcomes of subgroups were compared using log-rank test and cox-regression analysis. Study endpoints were cancer specific- (CSS) and recurrence-free survival (RFS). Results: In total, 429 HCG-positive metastatic seminoma patients (stage II n=291; stage III n=138) diagnosed between 1981 and 2018 were included. LDH + HCG levels ranged from 124 U/l to 8833 U/l (median: 619; IQR: 955) + 2 IU/l to 283,782 IU/l (median: 20; IQR: 63) pre- and from 107 U/l to 8650 U/l (median: 324; IQR: 481) + 0 IU/l to 36700 IU/l post-orchiectomy (median: 30; IQR: 121), respectively. Five-year CSS and RFS rates were 90% and 79%, respectively. Patients with LDH levels pre-orchiectomy &lt;1.5 UNL (n=142) had a 5-year CSS (RFS) rate of 97% (88%), compared to 86% (81%) for ≥1.5 to 3 UNL (n=40), 83% (77%) for &gt;3 to 5 UNL (n=44) and 83% (72%) for &gt;5 UNL (n=44) (CSS p &lt;0.001; RFS p=0.142). Concerning LDH levels post-orchiectomy this stratification was not significant but patients with LDH levels ≥3 UNL (n=77) displayed an impaired prognosis associated with a 5-year CSS (RFS) rate of 85% (79%) compared to 94% (82%) for levels &lt;3 UNL (n=186) (CSS p=0.025; RFS p=0.447). Patients with HCG levels ≥2000 IU/l (n=17) pre- but not post-orchiectomy had a 5-year CSS (RFS) rate of 73% (60%) compared to 94% (79%) for patients with HCG levels &lt;2000 IU/l (n=855) (CSS p=0.09; RFS p=0.04). In cox-regression analysis LDH ≥1.5 UNL (p=0.037; HR 3.32, CI95%1.08-10.26) and HCG levels ≥2000 IU/l (p=0.044; HR 3.69, 95%CI1.04-13.13) pre-orchiectomy were confirmed as prognostic factors for CSS. Conclusions: LDH levels inversely correlate with survival outcomes, suggesting ≥1.5 UNL pre- and ≥3 UNL post-orchiectomy as potential cut-off values for further risk assessment. Patients with extensive HCG elevations may represent an unfavorable subgroup concerning RFS and CSS, but only few patients were affected.
Clinicopathologic predictors of outcomes in children with stage I germ cell tumors: A pooled <i>post hoc</i> analysis of trials from the Children’s Oncology Group.
Authors: Shyamli Singla, Justin Wong, Nirmish Singla, Mark D. Krailo, Li Huang, Furqan Shaikh, Deborah F. Billmire, Frederick J. Rescorla, Jonathan H. Ross, Bryan J. Dicken, James F. Amatruda, A. Lindsay Frazier, Aditya Bagrodia
Journal: Journal of Clinical Oncology (2020)

418 Background: Patients with clinical stage I (CS I: cN0M0) germ cell tumors (GCT) exhibit favorable oncologic outcomes. While prognostic features can help inform treatment in adults with CS I GCT, we lack reliable means to predict relapse among pediatric patients. We sought to identify predictors of relapse in children with CS I GCT. Methods: We performed a pooled post hoc analysis on pediatric CS I GCT patients enrolled in 3 prospective trials: INT-0097 (phase II), INT-0106 (phase III), and AGCT0132 (phase III). Pathology was centrally reviewed. Patient demographics, pT stage, serum tumor markers, margin status, histology, relapse, and survival were compiled. Cox regression analyses were used to identify predictors of outcomes. Results: 88 patients were identified with histologic data available. Most patients were pT1-2 stage. Yolk sac tumor was present in 75%, while 16% had embryonal carcinoma, and 9% had choriocarcinoma. When evaluable, lymphovascular invasion (LVI) was present in 36/66 (55%) of patients. Over a median follow-up of 5.0 years, no patients died and 24 patients (27%) relapsed (median relapse-free survival not reached). Predictors of relapse included presence of choriocarcinoma (HR 4.3, p=0.004), embryonal carcinoma (HR 3.8, p=0.002), pT3 stage (HR 6.9, p=0.027), and age &gt;12 years (HR 3.1, p=0.011). LVI (HR 2.4, p=0.072), serum tumor markers, and dominant tumor size did not reach significance. Pediatric CS I GCT patients exhibit remarkable 5-year survival. Conclusions: Using combined data from multiple prospective trials, our study identifies clinicopathologic features that predict relapse and potentially inform personalized treatment for these patients.
Cancer of unknown primary (CUP): A population-based analysis of temporal change and socioeconomic disparities.
Authors: Damien Urban, Aparna Rao, Mathias Bressel, Yaacov Richard Lawrence, Linda R. Mileshkin
Journal: Journal of Clinical Oncology (2013)

e17535 Background: CUP is the 4th most common cause of cancer death. With advanced diagnostic investigations and treatment of cancer, we hypothesized that the proportion of cancers diagnosed as CUP and survival outcomes of CUP have changed and examination of these changes may identify socioeconomic disparities in the US. Methods: We analysed trends in CUP diagnosis and outcome within the SEER registry between 1973-2008. The relationship between demographic and tumour characteristics with survival was investigated. Results: The incidence and percentage of all cancers diagnosed as CUP have decreased over time (incidence 8.9 vs 6.2 per 100,000 and percentage 3.9% vs 1.9% of all cancer diagnoses in 1973 vs 2008 respectively). Significantly more females were labelled as CUP without a pathological confirmation (25% vs 20% in males, p&lt;0.001). A higher proportion of CUP was diagnosed in females, blacks and residents of less affluent or less educated counties. The 5 year survival significantly improved in those with squamous histology (SqC) but only marginally in those with non-SqC CUP. The improvement in survival over time within SqCC was more pronounced among some socioeconomic groups (SEG; Table). For the entire cohort, factors associated with a longer survival on multivariate analysis included: white race; female; &lt;65 years old; most recent decade at diagnosis; grade 1; SqC; married; a histologic diagnosis and treatment with radiotherapy (all p&lt;0.001). Despite the improvement in survival with radiotherapy (RT), the use of RT was less frequent in females and blacks. Conclusions: The percentage of cancers diagnosed as CUP is decreasing but prognosis remains poor, particularly in non-SqCC CUP. However, significant disparities in the diagnosis and survival between SEG exist, suggesting inequalities in access to diagnostic investigations and treatment. [Table: see text]