tbuckley/cabot-search huggingface dataset:
Determinants of self-reported unacceptable outcome of intensive care treatment 1 year after discharge
Authors: Monika C. Kerckhoffs, Felicia F. L. Kosasi, Ivo W. Soliman, Johannes J. M. van Delden, Olaf L. Cremer, Dylan W. de Lange, Arjen J. C. Slooter, Jozef Kesecioglu, Diederik van Dijk
Journal: Intensive Care Medicine (2019)

Survivors of critical illness often suffer from reduced health-related quality of life (HRQoL) due to long-term physical, cognitive, and mental health problems, also known as post-intensive care syndrome (PICS). Some intensive care unit (ICU) survivors even consider their state of health unacceptable. The aim of this study was to investigate the determinants of self-reported unacceptable outcome of ICU treatment.Patients who were admitted to the ICU for at least 48 h and survived the first year after discharge completed validated questionnaires on overall HRQoL and the components of PICS and stated whether they considered their current state of health an acceptable outcome of ICU treatment. The effects of overall HRQoL and components of PICS on unacceptable outcome were studied using multiple logistic regression analysis.Of 1453 patients, 67 (5%) reported their health state an unacceptable outcome of ICU treatment. These patients had a lower score on overall HRQoL (EQ-5D-index value of 0.57 vs. 0.81; p < 0.001), but we could not determine a cutoff value of the EQ-5D-index value that reliably identified unacceptable outcome. In the multivariate analysis, only the hospital anxiety and depression scale was significantly associated with an unacceptable outcome (OR 2.06, 99% CI 1.18-3.61).Although there is a strong association between low overall HRQoL and self-reported unacceptable outcome of ICU treatment, patients with low overall HRQoL may still consider their outcome acceptable. The mental component of PICS, but not the physical and cognitive component, is strongly associated with self-reported unacceptable outcome.
Evolution of endoscopic resection for early esophageal squamous cell carcinoma in Western countries
Authors: Hajime Isomoto
Journal: Endoscopy (2019)

Few data exist in the Western literature about long-term outcomes following endoscopic resection for esophageal squamous cell carcinoma (SCC). Endoscopic mucosal resection (EMR) has been a well-established method for early esophageal SCCs confined to the mucosa; however, its major limitation lies in the difficulty of achieving en bloc resection for larger lesions [1] [2] [3]. EMR has been performed in a piecemeal manner, leading to increased risks of post-procedural local recurrence [1] [2]. Endoscopic submucosal dissection (ESD) allows en bloc resection regardless of tumor size and permits accurate pathological assessment of the risk of lymph node metastasis (LNM) risk [1] [2]. Hence it has been widely used for esophageal SCC in Eastern countries. In recent meta-analyses of Eastern comparative studies of esophageal ESD and EMR, ESD showed considerably higher rates of en bloc and curative resection [1] [2]. However, Western experience of ESD remains scarce owing to the lower incidence of esophageal SCC and the lesser capability of using ESD to treat early disease and dysplastic lesions than in Eastern countries. Santos-Antunes et al. reported adequate curative resection rates in the biggest Western ESD series; nevertheless this still included only a small number of patients with esophageal tumors [4]. Thus, in Western countries accumulation of data with larger cohorts is needed regarding the feasibility of ESD for esophageal SCC.
Association between Oncologist Ownership of Imaging Facilities and Utilization: An Analysis of Positron-Emission Tomography (PET) Use in Lymphoma Settings with Variable PET Utility
Authors: Scott F Huntington, Weiwei Zhu, Jessica Hoag, Rong Wang, Amer M. Zeidan, Smith Giri, Nikolai A. Podoltsev, Steven D. Gore, Xiaomei Ma, Cary P Gross, Amy J. Davidoff
Journal: Blood (2018)
Relationship of omission of adjuvant radiotherapy to outcomes of locoregional control and disease-free survival in patients with or without pCR after neoadjuvant chemotherapy for breast cancer: A meta-analysis on 3481 patients from the Gepar-trials.
Authors: David Krug, Bianca Lederer, Juergen Debus, Jens Uwe Blohmer, Serban Dan Costa, Holger Eidtmann, Claus Hanusch, Joern Hilfrich, Jens Bodo Huober, Christian Jackisch, Sherko Kümmel, Stefan Paepke, Andreas Schneeweiss, Michael Untch, Gunter Von Minckwitz, Sibylle Loibl
Journal: Journal of Clinical Oncology (2015)

1008 Background: There is controversy whether the response to neoadjuvant chemotherapy should be incorporated into the decision-making process for adjuvant radiotherapy in breast cancer. Methods: We presenta pooled analysis of the randomized neoadjuvant trials GeparTrio, GeparQuattro and GeparQuinto including 3,481 patients with operable and non-operable breast cancer for which information on the use of radiotherapy (RT) was available. 94% received any RT. Locoregional recurrence was defined as a recurrence in the breast, at the chest wall or in the regional lymph nodes. Results: Patients in the RT-group were older and received more mastectomies. Their tumors were more likely to be HER2-positive and there was a higher rate of pathologic complete response (pCR, ypT0 ypN0). The overall risk of locoregional recurrence (LR) was 8.3% after a median follow-up of 55.9 months. RT conferred a significant benefit in terms of 5-year LR-free survival (LRFS, 90% vs. 81.5% without RT, logrank p < 0.001) and 5-year disease-free survival (DFS, 75.4% vs. 67.4%, logrank p < 0.001). The absolute advantage of RT regarding both LRFS and DFS was highest among patients with clinically positive lymph nodes at first diagnosis (HR 2.32, 95% CI 1.54-3.50; p < 0.001; HR 1.97, 95% CI 1.48-2.62; p < 0.001 respectively). In patients with pCR, the 5-yr LRFS was 95.7%% with RT vs 86.6% without RT (HR 3.32, 95% CI 1.00-11.08; p = 0.051) and 5-yr DFS was 86.9% and 56.1% (HR 3.52, 95% CI 1.82-6.83; p < 0.001). In patients without pCR, the LRFS was 88.6% with RT vs 80.7% without RT (HR 1.86, 95% CI 1.29-2.67; p < 0.001) and 5-yr DFS was 72.6% vs 65.7%; HR 1.39, 95% CI 1.07-1.81; p = 0.014). Multivariate analyses with adjustment for baseline parameters as well as for pathologic tumor stage and pCR confirmed RT as an independent prognostic factor for LRFS (HR 0.54, 95% CI 0.35-0.82; p = 0.004) and DFS (HR 0.69, 95% CI 0.51-0.93; p = 0.016). Conclusions: This retrospective analysis suggests thatpatients managed withoutRT after neoadjuvant chemotherapy for breast cancer have a significantly worse outcome even if they achieved a pCR.
A maresin 1/RORα/12-lipoxygenase autoregulatory circuit prevents inflammation and progression of nonalcoholic steatohepatitis
Authors: Yong-Hyun Han, Kyong-Oh Shin, Ju-Yeon Kim, Daulat B. Khadka, Hyeon-Ji Kim, Yong-Moon Lee, Won-Jea Cho, Ji-Young Cha, Bong-Jin Lee, Mi-Ock Lee
Journal: Journal of Clinical Investigation (2019)

Retinoic acid-related orphan receptor α (RORα) is considered a key regulator of polarization in liver macrophages that is closely related to nonalcoholic steatohepatitis (NASH) pathogenesis. However, hepatic microenvironments that support the function of RORα as a polarity regulator were largely unknown. Here, we identified maresin 1 (MaR1), a docosahexaenoic acid (DHA) metabolite with a function of specialized proresolving mediator, as an endogenous ligand of RORα. MaR1 enhanced the expression and transcriptional activity of RORα and thereby increased the M2 polarity of liver macrophages. Administration of MaR1 protected mice from high-fat diet-induced NASH in a RORα-dependent manner. Surprisingly, RORα increased the level of MaR1 through transcriptional induction of 12-lipoxygenase (12-LOX), a key enzyme in MaR1 biosynthesis. Furthermore, we demonstrated that modulation of 12-LOX activity enhanced the protective function of DHA against NASH. Together, these results suggest that the MaR1/RORα/12-LOX autoregulatory circuit could offer potential therapeutic strategies for curing NASH.
Prospective study of concomitant stereotaxic reirradiation and mitomycin with cetuximab for recurrent head and neck cancer.
Authors: Lemoine Nathalie, Gautier Lefebvre, Emmanuelle Tresch, Marian Degardin, Sophie Maillard, Bernard Coche-DequÃÂ©ant, Stephane Singier, Audrey Mailliez, Guillaume Marliot, Ilyes Sakji, Eric Amela, Nuria Kotecki, Nicolas Penel, Sophie El Bedoui, Morbize Julieron, Eric Lartigau
Journal: Journal of Clinical Oncology (2015)

e17024 Background: Despite the improvement in the initial management of the head and neck cancer (HNC) recurrences are common. The development of targeted radiation techniques and the use of new medical treatments may offer the possibility of re-treated these patients with a curative intent. A multi-institutional phase II study suggested that short stereotactic body radiotherapy (SBRT) with cetuximab may be the reference treatment of these patients. The aim of our study is to evaluate the efficacy and toxicity of SBRT with cetuximab and mitomycin. Mitomycin C is a radiosensitizer and hypoxia-directed drug. Methods: Between 06/2011 and 06/2014, 12 patients with inoperable recurrent HNC were received SBRT with concomitant chemotherapy (30-36 Gy in 6 fractions of 5-6 Gy plus initial dose of mitomycin 10 mg/m² and 4 weekly injections of cetuximab). Results: All tumors were squamous carcinoma. The recurrent tumors were localized in oropharynx in 33%, lymph node in 25%, rhinopharynx in 17% and hypopharynx in 17%. The median size of tumors was 20 mm. Eight patients (67%) had a performance status ≤ 1. The median age was 60 years. Mean time between previous radiotherapy and the SBRT was 61 months. Cutaneous toxicity was observed for 10 patients, with grade 3 in one. Three patients presented hematotoxicity, all grade 1. Mucositis grade ≤ 2 occurred in 5 patients (42%). Median follow-up was 5 months. At 3 months, response rate was 75% (IC95%: 42.8-94.5%) and disease control rate was 83.3% (IC95%: 51.6-97.9%). Progression free survival at three and six months were 90.9% (IC95%: 50.8-98.7%) and 81.8% (IC95%: 44.7-95.1%) respectively. The six-months overall survival rate was 80.8% (IC95%: 42.4-94.9%). Conclusions: These results suggested that combined SBRT and cetuximab with mitomycin is an effective salvage treatment with acceptable toxicity. Accordingly we advise to continue the inclusion of patients in this study to evaluate the long-term efficacy of this treatment in a larger number of patients.
Abstract P286: Short-Term Repeatability of Electrocardiographic Criteria of Left Ventricular Hypertrophy
Authors: Michelle L Meyer, Elsayed Z Soliman, Dominique Drager, Gerardo Heiss
Journal: Circulation (2019)

Background: Left ventricular hypertrophy (LVH) is a marker of cardiac end-organ damage and a risk factor for cardiovascular morbidity and mortality. Although electrocardiogram (ECG) is the most common tool for LVH assessment in contemporary clinical trials and cohort studies, the repeatability of ECG-LVH criteria has not been sufficiently examined. Objectives: Characterize the repeatability and minimal detectable change of ECG-LVH criteria. Methods: A total of 63 participants (mean age 50 years; 31 females) underwent two visits one week apart. At each visit, two digital ECGs were obtained following a standardized protocol. The ECG data were processed centrally to automatically obtain waveform measurements needed to calculate Cornell voltage (CV) LVH (SV3 + RaVL &gt;2800 μV for men and &gt;2000 μV for women), Cornell voltage product (CVP) LVH ((RaVL + SV3) X QRS duration ≥244 mV sec; for both Cornell criteria, 0.8 mV was added to the voltage sum for women), and Sokolow-Lyon (SL) LVH (SV1 +RV5/V6 ≥3500 μV). In addition to using these criteria as dichotomous LVH variables, we also used the waveforms measurements composing them as continuous variables, referred to here as CV-index, CVP-index, and SL-index. We used random-effects, mixed models to parse the variance of the variables into their between-participant, between-visit, and within-visit components, and calculated the intra-class correlation coefficient (ICC), minimal detectable change (95% confidence), and Kappas. Results: Between-participant variation accounted for 93% to 97% of the total variation in CV-index, CVP-index, and log of SL-index. The ICCs (95% confidence intervals) were 0.97 (0.96, 0.98) for CV-index, 0.97 (0.95, 0.98) for CVP-index, and 0.93 (0.90, 0.96) for log of SL-index. Minimal detectable change between repeat measures of CV-index, CVP-index, and log of SL-index were ≥236.7 μV, ≥26.7 mV, and ≥0.09 μV, respectively. The within-visit Kappa (95% confidence limits) was 0.73 (0.38, 1.00) for SL LVH and 1 for the other two LVH criteria. The between-visit Kappa was 1 for CV LVH, 0.66 (0.04, 1.00) for CVP LVH, and 0.40 (-0.03, 0.83) and 0.64 (0.26, 1.00) for the SL LVH first and second measurements of each visit, respectively. When defining ECG-LVH as presence of ≥1 ECG-LVH criteria, the within visit Kappa became 0.78 (0.49, 1.00) for the first visit and 1 for the second visit; the between visit Kappa values became 0.50 (0.12, 0.88) and 0.70 (0.38, 1.00) for the first and second measurements of each visit. Conclusion: CV, CVP, SL indices as continuous variables have excellent repeatability. The dichotomous ECG-LVH criteria have excellent within visit agreement, but between visit agreement ranges from fair to poor, which improved by combining multiple criteria. These results alleviate concerns about the repeatability the ECG LVH use in clinical trials and epidemiologic studies.
Does increasing time to surgery affect survival in stage I renal cell carcinoma? Analysis of the national cancer database.
Authors: Brittney Cotta, Stephen Ryan, Ahmed Eldefrawy, Reith Sarkar, Aaron Bradshaw, Margaret Frances Meagher, Zachary Hamilton, James Don Murphy, Ithaar Derweesh
Journal: Journal of Clinical Oncology (2019)

635 Background: Optimal timing for surgical treatment of localized renal cell carcinoma (RCC) remains undefined. We sought to determine the survival impact of time to definitive surgical treatment for Stage 1 RCC and elucidate factors associated with a delay in surgical care utilizing the National Cancer Database (NCDB). Methods: The NCDB was queried for Stage 1 RCC cases (cT1N0M0) from 2004-2013 treated with partial or radical nephrectomy. Quartiles were formed from the range of time to surgery of the entire cohort in days: early defined as the first two quartiles and delayed as the fourth. Descriptive analyses were conducted between early and delayed groups. Overall survival (OS) between early and delayed groups was calculated with Kaplan-Meier analysis. Multivariable analysis was performed to determine factors associated with delay in surgical care. Results: 38,859 patients were analyzed. Median time to treatment was 40 days (IQR 22-68). Early (≤40 days, n = 23,712) and delayed ( &gt; 68 days, n = 15,147) groups had a median follow-up of 44.8 and 41 months, respectively (p &lt; 0.001). Delayed surgery was more frequent with African-Americans (14.8% vs. 9.1%, p &lt; 0.001), patients with government or no insurance (53.7% vs. 45.1%, p &lt; 0.001), males (60.7% vs. 58.3%, p = 0.001), and Charlson Comorbidity Index (CCI) ≥2 (9.7% vs. 6.7%, p &lt; 0.001). Kaplan-Meier analysis demonstrated survival benefit to the earlier treatment group, with 5 year OS of 85.5% and 80.9% (p &lt; 0.001; Figure). On multivariable analysis, increasing age (OR = 1.001, p = 0.015), African-American race (OR = 1.5, p &lt; 0.001), increasing distance from treatment center (OR = 1.005, p = 0.001), residence in areas with low high school graduation rates (OR = 1.42, p &lt; 0.001), residence in an area of &gt; 1 million population (OR = 1.6, p &lt; 0.001), and CCI ≥2 (OR = 1.4, p &lt; 0.001) were independently associated with increasing time to surgery. Conclusions: Surgery of T1 RCC carried out beyond 9 weeks after diagnosis is associated with reduced overall survival compared to patients treated within 6 weeks. Time to definitive surgical treatment should be a quality of care metric, with special attention given to populations most at risk for delays in care.
Nationwide cloud-based integrated database of idiopathic interstitial pneumonias for multidisciplinary discussion
Authors: Tomoyuki Fujisawa, Kazutaka Mori, Masashi Mikamo, Takashi Ohno, Kensuke Kataoka, Chikatoshi Sugimoto, Hideya Kitamura, Noriyuki Enomoto, Ryoko Egashira, Hiromitsu Sumikawa, Tae Iwasawa, Shoichiro Matsushita, Hiroaki Sugiura, Mikiko Hashisako, Tomonori Tanaka, Yasuhiro Terasaki, Shinobu Kunugi, Masashi Kitani, Ryo Okuda, Yasuoki Horiike, Yasunori Enomoto, Hideki Yasui, Hironao Hozumi, Yuzo Suzuki, Yutaro Nakamura, Junya Fukuoka, Takeshi Johkoh, Yasuhiro Kondoh, Takashi Ogura, Yoshikazu Inoue, Yoshinori Hasegawa, Naohiko Inase, Sakae Homma, Takafumi Suda
Journal: European Respiratory Journal (2019)

Multidisciplinary discussion (MDD) requiring close communication between specialists (clinicians, radiologists and pathologists) is the gold standard for the diagnosis of idiopathic interstitial pneumonias (IIPs). However, MDD by specialists is not always feasible because they are often separated by time and location. An online database would facilitate data sharing and MDD. Our aims were to develop a nationwide cloud-based integrated database containing clinical, radiological and pathological data of patients with IIPs along with a web-based MDD system, and to validate the diagnostic utility of web-based MDD in IIPs. Clinical data, high-resolution computed tomography images and lung biopsy slides from patients with IIPs were digitised and uploaded to separate servers to develop a cloud-based integrated database. Web-based MDD was performed using the database and video-conferencing to reach a diagnosis. Clinical, radiological and pathological data of 524 patients in 39 institutions were collected, uploaded and incorporated into the cloud-based integrated database. Subsequently, web-based MDDs with a pulmonologist, radiologist and pathologist using the database and video-conferencing were successfully performed for the 465 cases with adequate data. Overall, the web-based MDD changed the institutional diagnosis in 219 cases (47%). Notably, the MDD diagnosis yielded better prognostic separation among the IIPs than did the institutional diagnosis. This is the first study of developing a nationwide cloud-based integrated database containing clinical, radiological and pathological data for web-based MDD in patients with IIPs. The database and the web-based MDD system that we built made MDD more feasible in practice, potentially increasing accurate diagnosis of IIPs.
Crohn’s Disease Is Associated With an Increased Prevalence of Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study Using Magnetic Resonance Proton Density Fat Fraction Mapping
Authors: Scott McHenry, Yeshika Sharma, Ankita Tirath, Richard Tsai, Aaron Mintz, Tyler J. Fraum, Amber Salter, Jeffrey D. Browning, Avegail G. Flores, Nicholas O. Davidson, Kathryn J. Fowler, Matthew A. Ciorba, Parakkal Deepak
Journal: Clinical Gastroenterology and Hepatology (2019)
Programmed Cell Death Receptor (PD-1), PD-1 Ligand (PD-L1) Expression in Philadelphia Chromosome Negative Myeloid Neoplasms
Authors: Chi Chen, Anita Pandey, Ajay Kundra, Sreenath Kodali, Ching Wong, Tony W. Cheung, Vladimir K. Gotlieb, Gardith Joseph, Sophia Tribie, Jen-Chin Wang
Journal: Blood (2018)
Immune-related adverse events are associated with improved outcomes in ICI-treated renal cell carcinoma patients.
Authors: Roy Elias, Flora Yan, Nirmish Singla, Nicholas Levonyack, Joseph Formella, Alana Christie, Payal Kapur, Alex Isaac Bowman, Hans J. Hammers, Raquibul Hannan, James Brugarolas
Journal: Journal of Clinical Oncology (2019)

645 Background: With the approval of immune-checkpoint inhibitors (ICI) as first and second line agents for treating metastatic renal cell carcinoma (RCC), immune-related adverse events (irAE) are a growing concern. In this study, we present the safety profile and outcomes of 90 patients with RCC treated at two centers, including a university (UT Southwestern/Clements University Hospital) and a county hospital (UT Southwestern/Parkland). Methods: All patients with RCC treated with ICI were identified from 2013 to January 31, 2018. We examined the incidence of any treatment-related adverse events and “select” irAEs and evaluated their impact on patient outcomes and therapeutic decisions. Kaplan-Meier methods and Cox proportional hazards regression models were used to compare overall survival (OS) and time to next therapy (TTNT) by the presence of irAEs. Results: Of 90 patients treated with ICI, 65 (72.2%) patients experienced adverse events, most commonly fatigue (37.8%), nausea (14%), and decreased appetite (12.2%). Select irAEs were seen in 38 (42.2%) with the most common irAEs involving the skin (15.6%), gastrointestinal tract (14%), endocrine organs (11%), and lungs (7.8%). There were 15 (16.7%) grade III/IV irAEs resulting in cessation of therapy for 12 (13.3%) patients. The median OS was 35.9 (95% CI: 24.3-not reached) and 26.5 months (95% CI: 10.2-28.8; p = 0.002) for patients with and without irAEs, respectively. The median TTNT was 17.8 (95% CI: 11.3-29.3) and 6.6 months (95% CI: 4.5-9.6; p = 0.002) for patients with and without irAEs, respectively. In multivariate analysis of irAE status and Heng prognostic score, irAEs were associated with improved OS, HR 0.376 (95% CI 0.179–0.792; p = 0.010) and TTNT, HR 0.482 (95% CI 0.280–0.829; p = 0.008). Conclusions: ICI in RCC is well tolerated with only 16.7% of patients experiencing an adverse event resulting in cessation of therapy. The development of an irAE correlated with both an improved median OS as well as median TTNT, a benefit that persisted after multivariate analysis including Heng prognostic scoring. These findings suggest that the development of irAEs may be an independent positive prognostic factor in patients with RCC treated with ICI.