tbuckley/cabot-search huggingface dataset:
Emergence of new genetic lineage, ST-9316, of Neisseria meningitidis group W in Hauts-de-France region, France 2013–2018
Authors: Ala-Eddine Deghmane, Sylvie Haeghebaert, Eva Hong, Améliane Jousset, Anne-Sophie Barret, Muhamed-Kheir Taha
Journal: Journal of Infection (2020)

The epidemiology of invasive meningococcal disease (IMD) is continuously changing in incidence, age distribution and/or the expansion of new strains of Neisseria meningitidis. The epidemiology of IMD due to group W (IMDW) has changed recently at a global level with the emergence of isolates belonging to the clonal complex ST-11 (CC11) derived from the South America-UK strain. A more recent change has been detected in France with the emergence of a new genotype distinct from CC11 that we aimed to analyse.Epidemiological and microbiological surveillance data in France were used in combination with whole genome sequencing (WGS) to detect emerging phenotypes and genotypes of IMD causing strains, and their susceptibility to immunity induced by the 4CMenB vaccine. Transgenic mice expressing the human transferrin were used to analyse the virulence of emerging strain isolates by direct comparison with CC11 isolates.Our data showed a local increase of IMDW isolates in north France since 2013. The isolates belonged to ST-9316 and few were ST-11 isolates. WGS clustered ST-9316 isolates together and were distantly separated from the isolates of the clonal complex ST-11 (CC11). Unlike cases due to W/CC11 isolates, cases due to W/ST-9316 isolates were mostly observed amongst infants under the age of 1 year but with lower mortality compared to W/CC11 cases. Genomic comparison showed that the W/ST-9316, unlike W/CC11 isolates, lacked the hmbR gene encoding the haemoglobin receptor that is a virulence factor involved in the acquisition of iron from haemoglobin. W/ST-9316 further showed lower virulence in mice compared to W/CC11 isolates.We report the emergence of a novel sequence type (ST-9316) mostly associated with serogroup W, and exhibiting a lower virulence and a distinct age specific incidence profile than W/CC11 isolates. Surveillance requires powerful approaches combining WGS and pathophysiological analysis to adapt control measures.
Effective Care Practices in Patients Receiving Prolonged Mechanical Ventilation. An Ethnographic Study
Authors: Kimberly J. Rak, Laura Ellen Ashcraft, Courtney C. Kuza, Jessica C. Fleck, Lisa C. DePaoli, Derek C. Angus, Amber E. Barnato, Nicholas G. Castle, Tina B. Hershey, Jeremy M. Kahn
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Patients receiving prolonged mechanical ventilation experience low survival rates and incur high healthcare costs. However, little is known about how to optimally organize and manage their care.Objectives: To identify a set of effective care practices for patients receiving prolonged mechanical ventilation.Methods: We performed a focused ethnographic evaluation at eight long-term acute care hospitals in the United States ranking in either the lowest or highest quartile of risk-adjusted mortality in at least four of the five years between 2007 and 2011.Measurements and Main Results: We conducted 329 hours of direct observation, 196 interviews, and 39 episodes of job shadowing. Data were analyzed using thematic content analysis and a positive-negative deviance approach. We found that high- and low-performing hospitals differed substantially in their approach to care. High-performing hospitals actively promoted interdisciplinary communication and coordination using a range of organizational practices, including factors related to leadership (e.g., leaders who communicate a culture of quality improvement), staffing (e.g., lower nurse-to-patient ratios and ready availability of psychologists and spiritual care providers), care protocols (e.g., specific yet flexible respiratory therapy-driven weaning protocols), team meetings (e.g., interdisciplinary meetings that include direct care providers), and the physical plant (e.g., large workstations that allow groups to interact). These practices were believed to facilitate care that is simultaneously goal directed and responsive to individual patient needs, leading to more successful liberation from mechanical ventilation and improved survival.Conclusions: High-performing long-term acute care hospitals employ several organizational practices that may be helpful in improving care for patients receiving prolonged mechanical ventilation.
Sociodemographic disparities in young adults with colorectal cancer (CRC): Analysis of 26,768 patients in the National Cancer Database (NCDB).
Authors: Ashley Matusz-Fisher, Sally Jeanne Trufan, Kunal C. Kadakia, Reza Nazemzadeh, Seungjean Chai, Stuart Salmon, William Mills Worrilow, Laura W. Musselwhite, Joshua Hill, Jonathan C. Salo, Edward S. Kim, Jimmy J. Hwang, Mohamed E. Salem
Journal: Journal of Clinical Oncology (2020)

13 Background: The incidence of colorectal cancer (CRC) in young adults (YA) is rising. Impact of sociodemographic status on YA with CRC is not well described. Methods: Data obtained from the NCDB were used to examine the impact of sociodemographic status on clinicopathological features and outcomes of YA with CRC. Patients (pts) were categorized based on whether they lived in areas of low or high income and education. Logistic regression and chi-square were used to examine the differences between the groups. Results: In total, 26,768 YA (≤40 yrs) pts diagnosed with CRC between 2004 and 2016 were retrospectively studied. The majority of pts were male (51.6%), and 78.7% were white, 14.6% black, and 6.6% of other races. Of the entire cohort, 32.3% pts resided in the highest income areas (median ≥$68,000), whereas 18.4% were in the lowest ( &lt; $38,000); 23% lived in areas that had the highest high school graduation rate ( &gt; 93%), while 20% lived in areas of the lowest graduation rate ( &lt; 79%); and 32.3% came from metropolitan areas, while 18.4% came from urban areas. Pts in the lowest compared to highest income and education areas were more likely to be black (OR: 6.4, 5.6-7.4), not have private insurance (OR: 6.3, 5.6-7.0), have T3/T4 stage (OR: 1.4, 1.3-1.6), have positive nodes (OR: 1.2, 1.1-1.3), be rehospitalized within 30 days (OR: 1.3, 1.1-1.6), or have a Charlson-Deyo score ≥ 1 (OR: 1.6, 1.4-1.9), and were less likely to have surgery (OR: 0.63, 0.6-0.7). After adjusting for race, insurance status, T/N stage, and Charlson-Deyo comorbidity scores, pts from lowest vs. highest income and education areas had a 24% increased risk of death (HR adj : 1.24, CI 1.1-1.44, p = 0.004), and pts from urban vs. metropolitan areas had a 10% increased risk of death (HR adj = 1.10 (1.01-1.20), P = 0.02). Pts with stage IV disease in the lowest vs. highest income populations had worse mOS (1.72 vs. 2.17 years, p &lt; 0.001). Conclusions: YA with CRC in the lowest income and education population were more likely to have worse OS. Furthermore, regardless of income, pts in metropolitan areas seemed to have a lower risk of death likely due to greater access to care. More efforts are needed to eliminate disparities and achieve health equity.
A randomized phase III trial comparing primary tumor resection plus chemotherapy with chemotherapy alone in incurable stage IV colorectal cancer: JCOG1007 study (iPACS).
Authors: Yukihide Kanemitsu, Kohei Shitara, Junki Mizusawa, Tetsuya Hamaguchi, Dai Shida, Koji Komori, Satoshi Ikeda, Hitoshi Ojima, Seiji Hasegawa, Akio Shiomi, Jun Watanabe, Yasumasa Takii, Takashi Yamaguchi, Kenji Katsumata, Masaaki Ito, Jyunji Okuda, Ryoji Hyakudomi, Yasuhiro Shimada, Hiroshi Katayama, Haruhiko Fukuda
Journal: Journal of Clinical Oncology (2020)

7 Background: It is still controversial whether primary tumor resection (PTR) before chemotherapy (CTX) improves overall survival (OS) of colorectal cancer (CRC) patients (pts) with synchronous unresectable metastases. There are several retrospective analyses suggesting better outcomes in pts who underwent PTR compared to pts without it, but no prospective studies confirming these results. We conducted a randomized controlled trial to confirm the superiority of PTR plus CTX to CTX alone in asymptomatic unresectable stage IV CRC patients. Methods: Eligibility criteria included histologically proven colon and upper rectal adenocarcinoma, cT1-4 without involvement of other organs, presence of three or less unresectable factors confined to either liver, lungs, distant lymph nodes, or peritoneum, aged 20-74, no symptoms due to primary tumor and PS 0-1. Eligible patients were randomized to either PTR followed by CTX or CTX alone. CTX regimens were declared before study entry; options included mFOLFOX6 plus bevacizumab or CapeOX plus bevacizumab. The primary endpoint was the OS. The planned sample size was 140 pts per arm, with one-sided alpha of 5%, and 70% power detecting a median OS difference of 8 months (24 months vs. 32 months). Results: Between Jun 2012 and Apr 2019, 160 patients were randomized. 78 pts were allocated to PTR plus CTX, and 82 pts to CTX alone. When the first interim analysis was performed in Sep 2019, with 50% (114/227) of the expected events observed, the DSMC recommended the early termination of the trial based on its futility. With a median follow-up period of 22.0 months for 160 patients, median OS was25.9 months (95% CI 19.9 – 31.5) with PTR plus CTX and 26.7(21.9 – 32.5) with CTX alone (hazard ratio 1.10 [0.76 – 1.59], one-sided p = 0.69). Median PFS was 10.4 (8.6-13.4) with PTR plus CTX and 12.1 (9.4 – 13.2) with CTX alone (hazard ratio 1.08 [0.77 – 1.50]). There were three treatment related deaths following PTR due to postoperative complications. Conclusions: PTR followed by CTX has no survival benefit over CTX alone. PTR is not recommended for CRC patients with asymptomatic primary tumor and synchronous unresectable metastases. Clinical trial information: UMIN000008147.
Circulating free DNA (cfDNA) and tissue next-generation sequencing analysis in a phase II study of infigratinib (BGJ398) for cholangiocarcinoma with <i>FGFR2</i> fusions.
Authors: Shalini Makawita, Robin Kate Kelley, Sameek Roychowdhury, Karl Heinz Weiss, Ghassan K. Abou-Alfa, Teresa Macarulla, Saeed Sadeghi, Dirk Waldschmidt, Andrew X. Zhu, Lipika Goyal, Wei-Peng Yong, Ivan Borbath, Anthony B. El-Khoueiry, Philip Agop Philip, Susan Moran, Yining Ye, Harris S. Soifer, Gary Li, Craig Berman, Milind M. Javle
Journal: Journal of Clinical Oncology (2020)

579 Background: Fibroblast growth factor receptor 2 (FGFR2) alterations occur in 11% of cholangiocarcinomas, 85% of which are fusions. A multicenter, open-label, phase II study is currently evaluating the efficacy of infigratinib, a selective FGFR1–3 tyrosine kinase inhibitor, in patients with previously treated advanced cholangiocarcinoma containing FGFR2 fusions. We report detailed biomarker analyses from this study. Methods: Patients with advanced or metastatic cholangiocarcinoma containing FGFR2 fusions whose disease had progressed following cisplatin- or gemcitabine-based therapy were eligible. Patients received oral infigratinib 125 mg once daily on days 1–21 every 28 days. Comprehensive genomic profiling (CGP) was performed on tumor tissue and cfDNA collected prior to the start of therapy. The primary endpoint was investigator-assessed overall response rate (ORR) [RECIST version 1.1]. Data cut-off (prespecified): August 8, 2018. Trial registration: NCT02150967. Results: At data cut-off, 71 patients with FGFR2 fusions were included (62% women; median age 53 years; 55% received ≥2 prior lines of therapy). Median duration of treatment was 5.5 months. ORR (confirmed and unconfirmed) was 31.0% (95% CI 20.5–43.1%) and confirmed ORR was 26.9% (95% CI 16.8–39.1%). 33 unique FGFR2 fusion genes were identified in 71 enrolled patients. The most common fusion gene partner was BICC1 (32%; 23/71). Pathogenic variants in 9 other druggable genes were identified in 32% of patients (13/37) who underwent CGP. FGFR2 fusions were concordant in 67% (8/12) of patients with tumor tissue and cfDNA at screening. Conclusions: The large assortment of FGFR2 fusion genes identified in this study underscores the diversity of FGFR2 rearrangements that may drive cholangiocarcinoma. Although cfDNA analysis was performed in a minority, these preliminary data suggest that cfDNA analysis may be valuable for the identification of FGFR2 fusions and to study intratumoral heterogeneity. Clinical trial information: NCT02150967.
Hyperthermic intraperitoneal chemotherapy post cytoreductive surgery in management of peritoneal carcinomatosis of colorectal primaries: Tertiary center experience.
Authors: Ahmed Badran Sobh, Ahmed Al-Wusaibie, Mahmoud Abdelsatar Elshenawy, Marwa Ismail Abdelgawad, Hakeam Hakeam, Ayman Azzam, Rania Naguib AbdelRehem, Zyad Al-Yahya, Tarek Amin
Journal: Journal of Clinical Oncology (2020)

28 Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) in addition to Cytoreductive surgery (CRS) has survival benefit observed in management of Peritoneal Carcinomatosis (PC) from Colo-rectal cancer (CRC)origin. We report the outcomes and prognostic factors of patients with CRC, who presented with PC and underwent CRS and HIPEC at King Faisal Specialist Hospital &amp; Research Center, Riyadh, Saudi Arabia. Methods: Patients presented with PC from CRC origin and underwent CRS and HIPEC; from February 2009 to September 2015 were recruited. Results: 52 patients identified. A total of 55 CRS procedures were performed, where 3 patients underwent repeated CRS and HIPEC for tumor recurrence. All except 3 used mitomycin-C for HIPEC, the remaining received either melphalan (2 patients) or cisplatin plus mitomycin-C regimen (1 patient). Melphalan used for patients who underwent repeated HIPEC as 2nd line chemotherapeutic agent. Intraoperative Radiation therapy performed in 5 patients with tumor invading the surrounding structures, where performing a safe or complete resection was either technically difficult or carried high risk. Complication assessment by Clavien-Dindo score, 62 % grade (I-II), while 31% had grade (3–4). Two patients (3.6%) died postoperatively; both from sepsis. Respiratory complications were the most commonly encountered morbidities. The 5-year overall survival(OS) was 50% with disease free survival (DFS) 29.5%. Univariate analysis showed poor OS and DFS encountered in; Signet-ring tumors (p &lt; 0.0001) for both, peritoneal cancer index (PCI) ≥ 6 (p &lt; 0.0009) for both, completeness of cytoreduction(CC) score &gt;1 (p &lt; 0.0001) for both, and high 3-month postoperative carcinoembryonic antigen value (p &lt;0.0001) for both. In multivariate analysis; DFS was significant for (PCI) ≥ 6 (p &lt; 0.0131) and (CC) score &gt;1 (p &lt; 0.0031) while PCI &gt; 6 was the only significant factor (p &lt; 0.0030) for OS. Conclusions: Addition of HIPEC to CRS was safe, and improved survival in patient with peritoneal Carcinomatosis of colo-rectal origin. PCI and CC score are prognostic factors of survival, signet-ring subtype may not benefit of this procedure.
Home Noninvasive Ventilation for Patients With Chronic Obstructive Pulmonary Disease and Chronic Respiratory Failure
Authors: John M. Coleman, Khalilah L. Gates, Ravi Kalhan
Journal: JAMA (2020)

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Prognostic factors in patients with nonmetastatic gastric cancer treated with contemporary multimodality strategies.
Authors: Ariceli Alfaro, Tuyen Hoang, Jasmine Huynh, Jingran Ji, Andrew H. Ko, May Thet Cho, Darryl Hiyama, Farshid Dayyani
Journal: Journal of Clinical Oncology (2020)

451 Background: We conducted a retrospective study to evaluate clinical outcomes in patients with non-metastatic gastric adenocarcinoma (nmGA) treated at two high-volume academic institutions within the University of California (UC) system. Methods: Electronic Health Records and California Cancer Registry of demographic and clinical data were collected for pts with nmGA who underwent surgery with curative intent from 2010-2017. Medical chart reviews were conducted to validate outcomes. We used multivariate Cox regression to determine prognostic factors for cancer recurrence and overall survival. Results: Demographics of study cohort (n = 406): mean age 65 years; 71% male; 58% Caucasian, 26% Asian, 13% Latino. There was an even distribution between pts with locoregionally advanced (defined as pT4 or pN1+) vs. localized (pT1-3, pN0) disease. Tumor histology: 49% intestinal, 19% diffuse, 13% mixed, 19% unknown. Type of surgery: 27% open gastrectomy, 59% laparoscopic, 14% unknown. Multimodality therapy: 29% received perioperative systemic rx alone (48% adjuvant only, 52% neoadjuvant +/- adjuvant), 35% received perioperative systemic rx plus radiation (40% adjuvant only, 60% neoadjuvant +/- adjuvant), 36% underwent surgery only. With median f/u time after surgery of 5 years, 21% of pts developed cancer recurrence and 43% had died. Weight loss prior to diagnosis, locoregional stage, and positive resection margins were a/w recurrence (HR = 1.6-2.5, p &lt; .05). Only locoregional stage was prognostic for worse survival (HR = 2.7, p &lt; .0001). Positive resection margins were seen in 6% of pts and were a/w diffuse histology and tumor size &gt; 4cm (odds ratio = 2.9-8.8, p &lt; .02). Multimodality therapy was not a/w recurrence but was a/w longer survival after adjusting for stage (HR = 0.3, p &lt; .0001). Addition of radiation to systemic rx did not confer further improvements in either recurrence or survival. Conclusions: This study highlights contemporary practice patterns for pts with nmGA and demonstrates a survival benefit with multimodality rx. Additional data are being gathered from other UC medical centers to confirm these findings and explore differences across institutions and ethnicities.
Preliminary analysis of total neoadjuvant therapy for patients with locally advanced gastric (G) and gastroesophageal (GE) adenocarcinoma.
Authors: Eric Roeland, Katie Kanter, Jennifer Yon-Li Wo, Madeleine Fish, Ryan David Nipp, Emily E. Van Seventer, Aparna Raj Parikh, Jill N. Allen, Bruce J. Giantonio, Lawrence Scott Blaszkowsky, Florence Keane, Samuel J. Klempner, David P. Ryan, Hugh G. Auchincloss, Harald Ott, Michael Lanuti, Christopher Morse, John Thomas Mullen, Theodore S. Hong
Journal: Journal of Clinical Oncology (2020)

393 Background: Nearly half of patients with G/GE cancer do not receive or complete post-operative chemotherapy and/or chemoradiation (CRT). Total neoadjuvant therapy (TNT) is as an emerging alternate treatment strategy. We have previously reported a 28% pCR with FOLFIRINOX followed by CRT. However, TNT outcomes with FLOT or FOLFOX followed by CRT are lacking. Methods: We retrospectively analyzed patients after resection of locally advanced G/GE after receiving TNT. Patient received neoadjuvant FOLFOX or FLOT x 8 cycles, CRT (G 45 Gy, GE 50.4 Gy) with concurrent chemotherapy (5FU, carboplatin/paclitaxel). The primary aim was to explore TNT completion rates. Secondary aims included pCR and toxicity. We performed descriptive statistics, t-test, chi-squared, and Fisher’s exact tests as appropriate. Results: From 12/2015 to 8/2019, 57.1% (40/70) completed TNT and resection (15.7% active treatment, 15.7% progressive disease, 11% treated elsewhere). Median age was 66.0 (range:27-79) and 73% male. Tumor locations included 57.5% G, 30.0% GE, and 12.5% overlapping. Neoadjuvant chemotherapy included FLOT 22.5% (n = 9) or FOLFOX 77.5% (n = 31). Overall we found a 25% pCR without significant differences between type of neoadjuvant chemotherapy. Conclusions: TNT followed by resection is feasible with acceptable rates of treatment completion and toxicity. Notable limitations include the retrospective analysis, small sample size, and heterogenous treatment. The pCR rate is promising and warrants further prospective study to optimize TNT approaches. [Table: see text]
The Role of Neoadjuvant Chemotherapy in Patients With Resectable Malignant Pleural Mesothelioma—An Institutional and National Analysis
Authors: Soraya L Voigt, Vignesh Raman, Oliver K Jawitz, Muath Bishawi, Chi-Fu Jeffrey Yang, Betty C Tong, Thomas A D’Amico, David H Harpole
Journal: JNCI Journal of the National Cancer Institute (2020)

Abstract Background There is no standard of care with respect to the use of neoadjuvant chemotherapy (NAC) in resectable malignant pleural mesothelioma (MPM). We performed an intention-to-treat analysis with data from a single institution and the National Cancer Database (NCDB) to identify whether the use of NAC impacts survival in resectable MPM. Methods Patients with MPM who had surgery with curative intent at Duke University from 1995 to 2017 were selected, and the 2004–2015 NCDB was used to identify MPM patients with clinical stage I–IIIB who underwent definitive surgery. For both cohorts, patients were stratified by receipt of NAC. Primary outcomes were overall survival and postresection survival (RS), which were estimated using Kaplan-Meier and multivariable Cox proportional hazards models. Results A total of 257 patients met inclusion criteria in the Duke cohort. Compared with immediate resection (IR), NAC was associated with similar overall survival but an increased risk for postresection mortality in both unmatched (adjusted hazard ratio [HR] = 1.85, 95% confidence interval [CI] = 1.21 to 2.83) and propensity-matched (HR = 1.62, 95% CI = 1.03 to 2.55) cohorts. A total of 1949 NCDB patients were included: 1597 (81.9%) IR and 352 (18.1%) NAC. RS was worse for patients undergoing NAC in both unmatched (HR = 1.85, 95% CI = 1.21 to 2.83) and propensity-matched (HR = 1.29, 95% CI = 1.06 to 1.57) analyses compared with patients receiving IR. Conclusions In this intention-to-treat study, NAC was associated with worse RS compared with IR in patients with MPM. The risks and benefits of induction therapy should be weighed before offering it to patients with resectable MPM.
Efficacy and safety of microneedling and oral tranexamic acid in the treatment of facial melasma in women: An open, evaluator-blinded, randomized clinical trial
Authors: Daniel Cassiano, Ana Cláudia Cavalcante Esposito, Karime Hassun, Ediléia Bagatin, Mariana Modesto D.A. Lima, Emerson V.A. Lima, Luciane Donida Bartoli Miot, Hélio Amante Miot
Journal: Journal of the American Academy of Dermatology (2020)
Distinct immune phenotypes in infants developing asthma during childhood
Authors: Anna Hammerich Thysen, Johannes Waage, Jeppe Madura Larsen, Morten Arendt Rasmussen, Jakob Stokholm, Bo Chawes, Nadia Rahman Fink, Tine Marie Pedersen, Helene Wolsk, Sunna Thorsteinsdottir, Thomas Litman, Harald Renz, Klaus Bønnelykke, Hans Bisgaard, Susanne Brix
Journal: Science Translational Medicine (2020)

Early immune responses are associated with different asthma trajectories in children.
標的化学療法の製剤障害の克服 細胞毒性薬物負荷イムノナノ粒子のin vitroおよびin vivoにおける評価 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Debotton Nir, Parnes Marcela, Kadouche Jean, Benita Simon
Journal: Journal of Controlled Release (2008)