tbuckley/cabot-search huggingface dataset:
Multi-institutional european single-arm phase II trial of pazopanib in advanced typical solitary fibrous tumors (SFT): A collaborative Spanish (GEIS), Italian (ISG), and French (FSG) sarcoma groups study.
Authors: Josefina Cruz Jurado, Sarah Naomie Dumont, Nicolas Penel, Pablo Luna Fra, Enrique Alava, Nadia Hindi, Jean-Yves Blay, Silvia Stacchiotti, Paola Collini, Andres Redondo, Daniel Bernabeu, Antonio Lopez-Pousa, Giovanni Grignani, David Silva Moura, Javier Martinez-Trufero, Philippe Terrier, Marie Karanian, Axel Le Cesne, Paolo Giovanni Casali, Javier Martin Broto
Journal: Journal of Clinical Oncology (2019)

11038 Background: SFT is a ubiquitous uncommon soft tissue sarcoma with a pronounced hemangiopericytoma-like vascular pattern, exhibiting rich VEGF (tumor and endothelial cells) and VEGFR1/2 (endothelial cells) expression. Pathologists distinguish typical SFT (T-SFT) and malignant SFT (M-SFT) based on mitosis (≤4 vs &gt; 4), pleomorphism or necrosis. Yet, not clear boundaries are always seen between both subtypes. We have recently published a phase II trial exploring the activity of pazopanib (P) in M-SFT (Lancet Oncol Dec 2018). Here, we present the outcome of the T-SFT cohort of the same trial. Methods: Most relevant inclusion criteria were: unresectable or metastatic, T-SFT (tumor tissue from diagnostic time) confirmed by central pathology review before accrual, with evidence of STAT6 overexpression (IHC and FISH and/or NGS), ≥18 years, ECOG 0-2, progressive, measurable disease and no previous antiangiogenic agents. Main endpoint was response rate according to Choi criteria. Central radiological assessment was mandatory. P was administered at 800 mg/d continuously till progression or toxicity. Results: From June 2014 to December 2018, 34 patients were enrolled in this cohort. The median age was 64 y (31-81). At baseline, ECOG 0/1/2 was distributed as 16/15/3; whereas, locally advanced/metastatic distribution was 11 (32%) and 23 (68%) respectively. At the time of the present analysis, 24 patients were deemed eligible and evaluable for response. Response rates according to local and central assessment were PR 6 (25%), SD 15 (62%), PD 3 (12%) and PR 12 (50%), SD 11 (46%), PD 1 (4%). With a median follow-up of 21 months, the median PFS following local and central assessment were 18.4 (6.6-30.1) and 9.8 (7.5-12.2) months respectively, both were clearly superior to that previously published in M-SFT cohort (5.57 m). The median of OS was 49.8 months. High tumor burden at baseline &gt; 116 mm, ECOG 1-2 vs 0, and PD by local or central response assessment showed significantly worse OS. Metastatic vs locally advanced patients had a similar outcome regarding OS. Conclusions: T-SFT cohort exhibited clearly longer PFS than previous reported M-SFT cohort to pazopanib treatment, and pazopanib showed to improve the historical outcome obtained with chemotherapy in advanced SFT. Clinical trial information: NCT02066285.
Comparison of HER2 expression in paired biopsies and surgical specimen of gastric and esophageal adenocarcinoma: Impact of neoadjuvant chemotherapy.
Authors: Sarah Watson, Pierre Validire, Pascale Cervera, Nabila Zorkani, Frederic Lemay, Thierry Perniceni, Francois Paye, Christophe Tournigand, Christophe Louvet
Journal: Journal of Clinical Oncology (2013)

4069 Background: HER2 is overexpressed in 10 to 20% of gastro-esophageal adenocarcinoma (GE-ADK), and is a target for trastuzumab in metastatic patients. We conducted a study to compare HER2 expression between diagnostic biopsies (DB) and surgical specimens (SS) of GE-ADK, and to determine the influence of non-trastuzumab containing neoadjuvant chemotherapy (NAC) on this expression. Methods: Pathological specimens from biopsies of 228 patients operated on with a curative aim in two French hospitals between 2004 and 2011 were collected. Two cohorts treated (n=141) or not (n=87) with a NAC were constituted. Two blind independent pathological HER2 analyses on DB and on SS were performed using IHC and CISH. HER-2 overexpression (HER2 +) was defined by a score 3+ in IHC, or 2+ with a positive CISH test, and according to the specific HER2 scoring guidelines for GE-ADK. Results: Paired HER2 status could be determined for 218 out of the 228 patients (95.6%). HER2 + rates were 13.3% on DB (29/218) and 14.7% on SS (32/218). HER2 + tumors were mainly cardial or esophageal adenocarcinomas, with a well-differentiated, intestinal histological type. HER2 status differed between DB and SS in 13 patients (6%). When DB analyses were added to SS analyses, 5 additional patients were HER2 +, the relative increase in HER2 + cases being 13.5% (17.1% for patients with NAC versus 7.1% for patients without NAC, p=0.4, NS). Differences between DB and SS HER2 expression could be explained by the intratumoral heterogeneity and also by a possible HER2 expression decrease in SS after NAC. Conclusions: The determination of HER2 status on DB provides results that complete those obtained with SS. Combining the analysis of DB and of SS enables to optimize the selection of trastuzumab-eligible patients in case of metastatic relapse, especially in patients previously treated with NAC. [Table: see text]
Association of Sex With Perceived Career Barriers Among Surgeons
Authors: Nicole K. Zern, Sherene Shalhub, Douglas E. Wood, Kristine E. Calhoun
Journal: JAMA Surgery (2019)

no discharge prescription and 4 consumed their discharge prescription.There were 3 ED visits for pain (0.7%): 2 from constipation after appendectomy (no opioid prescription), and 1 from urinary retention after circumcision.Lack of a discharge opioid prescription was not associated with poor pain control (opioid: 3 of 88 respondents [3.4%]; no opioid: 15 of 315 respondents [4.8%]; P = .77),postdischarge opioid prescription (opioid: 4 of 88 respondents [4.6%]; no opioid: 4 of 316 respondents [1.3%]; P = .07),or pain-related ED visit (opioid: 1 of 88 respondents [1.1%]; no opioid: 2 of 316 respondents [0.6%]; P = .52).Discussion | Postoperative opioid prescribing for children is unnecessary following umbilical/epigastric herniorrhaphy, appendectomy, inguinal herniorrhaphy/hydrocelectomy, and adenoidectomy with adequate analgesia on nonopioid analgesics.Circumcision, elbow fracture, and orchiopexy had the highest opioid use; yet only 1 in 3 patients used an opioid, typically for 3 days or less.Excess opioid medication was often kept unlocked and undisposed.Although more than half of patients were prescribed an opioid in prior studies, postdischarge analgesia and analgesic use were not captured. [3]][5] This study is limited by the single-center, nonrandomized design; however, the low rates of prescribing and consequent adverse outcomes may supersede the clinical equipoise needed for future randomization.Given the iatrogenic risks of excess opioid, these findings suggest that safe opioid stewardship necessitates elimination of opioid exposure after many common children's operations. 2,
Two-photon AIE luminogen labeled multifunctional polymeric micelles for theranostics
Authors: Weihua Zhuang, Boxuan Ma, Jun Hu, Jizhou Jiang, Gaocan Li, Li Yang, Yunbing Wang
Journal: Theranostics (2019)

Intelligent polymeric micelles with fluorescence imaging feature have been emerged as promising tools for theranostics.However, conventional fluorescent dyes are limited by short wavelength excitation, interference of tissue autofluorescence, limited imaging depth and quenched emission in aggregation state.Methods: We synthesized a novel mPEG-SS-Poly (AEMA-co-TBIS) (mPEATss) copolymer to develop multifunctional polymeric micelles with great AIE feature for cancer therapy and AIE active two-photon bioimaging.The stimuli-responsive behavior and AIE active two-photon cell and tissue imaging as well as in vitro and in vivo antitumor ability of DOX-loaded mPEATss were studied.Results: mPEATss micelles showed excellent AIE active two-photon cell imaging ability and deep tissue imaging ability.Antitumor drug DOX could be encapsulated to form a drug-loaded micellar system with a small diameter of 65 nm.The disassembly and charge-conversion of mPEATss micelles could be triggered by acidic environment, resulting in accelerated drug release and great antitumor efficacy.In vivo, ex vivo imaging and in vivo pharmacokinetic study demonstrated that mPEATss micelles could efficiently accumulate in tumor sites, which ensured ideal anticancer effect.Conclusions: This pH and redox dual responsive and AIE active two-photon imaging polymeric micelles would be a promising candidate for theranostics.
Brain somatic mutations in MTOR reveal translational dysregulations underlying intractable focal epilepsy
Authors: Jang Keun Kim, Jun Cho, Se Hoon Kim, Hoon-Chul Kang, Dong-Seok Kim, V. Narry Kim, Jeong Ho Lee
Journal: Journal of Clinical Investigation (2019)

Brain somatic mutations confer genomic diversity in the human brain and cause neurodevelopmental disorders. Recently, brain somatic activating mutations in MTOR have been identified as a major etiology of intractable epilepsy in patients with cortical malformations. However, the molecular genetic mechanism of how brain somatic mutations in MTOR cause intractable epilepsy has remained elusive. In this study, translational profiling of intractable epilepsy mouse models with brain somatic mutations and genome-edited cells revealed a novel translational dysregulation mechanism and mTOR activation–sensitive targets mediated by human MTOR mutations that lead to intractable epilepsy with cortical malformation. These mTOR targets were found to be regulated by novel mTOR-responsive 5′-UTR motifs, distinct from known mTOR inhibition–sensitive targets regulated by 5′ terminal oligopyrimidine motifs. Novel mTOR target genes were validated in patient brain tissues, and the mTOR downstream effector eIF4E was identified as a new therapeutic target in intractable epilepsy via pharmacological or genetic inhibition. We show that metformin, an FDA-approved eIF4E inhibitor, suppresses intractable epilepsy. Altogether, the present study describes translational dysregulation resulting from brain somatic mutations in MTOR, as well as the pathogenesis and potential therapeutic targets of intractable epilepsy.
Recovery from secondary adrenal insufficiency in a patient with immune checkpoint inhibitor therapy induced hypophysitis
Authors: Sahityasri Thapi, Amanda Leiter, Matthew Galsky, Emily J. Gallagher
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Hypophysitis is a well-recognized immune-related adverse event in patients treated with immune checkpoint inhibitors for cancer. Some anterior pituitary hormones may recover; however, secondary adrenal insufficiency is usually permanent. <h3>Case presentation</h3> A 26-year old male with metastatic clear cell renal cell carcinoma was started on treatment with the anti-programmed cell death-1 monoclonal antibody (anti-PD-1 mAb) nivolumab, followed by combined nivolumab and the anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) mAb, ipilimumab. After starting nivolumab monotherapy the patient developed thyroiditis, which resolved without treatment. Prior to commencing combined ICI therapy, a random serum cortisol drawn at 1:30 pm and was 15.0 μg/dL (414 nmol/L). Three weeks after starting combined ICI therapy he developed sudden onset of severe fatigue and 1 pm serum cortisol was 2.0 μg/dL (55.2 nmol/L), adrenocorticotropic hormone (ACTH) was 16 pg/mL (3.52 pmol/L). A diagnosis of hypophysitis was made, and he was immediately started on prednisone 1 mg/kg. His symptoms resolved rapidly, and he continued immune checkpoint inhibitor therapy. He was noted to also have low gonadotropic hormones and testosterone (nadir testosterone 81.19 ng/dL). The prednisone was tapered slowly over the next six weeks to a maintenance dose of 5 mg daily. Four months after the initial presentation his cortisol remained low, but his testosterone level had increased to 973.43 ng/dL. After five months his random serum cortisol (1 pm) increased to 11.0 μg/dL (303.6 nmol/L). The prednisone was cautiously discontinued with close monitoring. Two months off glucocorticoid replacement he remained asymptomatic with an ACTH of 24.1 pg/mL (5.3 pmol/L), and cortisol of 13.0 μg/dL (358.8 nmol/L). <h3>Conclusions</h3> This case documents the unusual recovery from secondary adrenal insufficiency in a patient who developed hypophysitis from immune checkpoint inhibitor therapy. Repeated pituitary hormone testing every three months for the first year after the development of hypophysitis may identify more patients with hypothalamic-pituitary-adrenal axis recovery.
Effect of a Standard vs Enhanced Implementation Strategy to Improve Antibiotic Prescribing in Nursing Homes
Authors: James H. Ford, Lillian Vranas, DaRae Coughlin, Kathi M. Selle, Susan Nordman-Oliveira, Brenda Ryther, Tola Ewers, Victoria L. Griffin, Anna Eslinger, Joe Boero, Paula Hardgrove, Christopher J. Crnich
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Suspicion of urinary tract infection (UTI) is the major driver of overuse and misuse of antibiotics in nursing homes (NHs). Effects of interventions to improve the recognition and management of UTI in NHs have been mixed, potentially owing to differences in how interventions were implemented in different studies. An improved understanding of how implementation approach influences intervention adoption is needed to achieve wider dissemination of antibiotic stewardship interventions in NHs. <h3>Objective</h3> To compare the effects of 2 implementation strategies on the adoption and effects of a quality improvement toolkit to enhance recognition and management of UTIs in NHs. <h3>Design, Setting, and Participants</h3> This cluster-randomized hybrid type 2 effectiveness-implementation clinical trial will be performed over a 6-month baseline (January to June 2019) and 12-month postimplementation period (July 2019 to June 2020). A minimum of 20 Wisconsin NHs with 50 or more beds will be recruited and randomized in block sizes of 2 stratified by rurality (rural vs urban). All residents who are tested and/or treated for UTI in study NHs will be included in the analysis. All study NHs will implement a quality improvement toolkit focused on enhancing the recognition and management of UTIs. Facilities will be randomized to either a usual or enhanced implementation approach based on external facilitation (coaching), collaborative peer learning, and peer comparison feedback. Enhanced implementation is hypothesized to be associated with improvements in adoption of the quality improvement toolkit and clinical outcomes. Primary outcomes of the study will include number of (1) urine cultures per 1000 resident days and (2) antibiotic prescriptions for treatment of suspected UTI per 1000 resident-days. Secondary outcomes of the study will include appropriateness of UTI treatments, treatment length, use of fluoroquinolones, and resident transfers and mortality. A mixed-methods evaluation approach will be used to assess extent and determinants of adoption of the UTI quality improvement toolkit in study NHs. <h3>Discussion</h3> Knowledge gained during this study could help inform future efforts to implement antibiotic stewardship and quality improvement interventions in NHs. <h3>Trial Registration</h3> ClinicalTrials.gov identifier:NCT03520010
Results from Ongoing Phase 2 Trial of SL-401 in Patients with Advanced, High-Risk Myeloproliferative Neoplasms Including Chronic Myelomonocytic Leukemia
Authors: Mrinal M Patnaik, Vikas Gupta, Jason R. Gotlib, Hetty E. Carraway, Martha Wadleigh, Gary J. Schiller, Moshe Talpaz, Cecilia Arana-Yi, James K. McCloskey, Sangmin Lee, Abdulraheem Yacoub, Haris Ali, Minakshi S. Taparia, Janice Chen, Shay Shemesh, Christopher L. Brooks, Animesh Pardanani, Ayalew Tefferi, Srdan Verstovsek, Naveen Pemmaraju
Journal: Blood (2016)
Noninvasive application of mesenchymal stem cell spheres derived from hESC accelerates wound healing in a CXCL12-CXCR4 axis-dependent manner
Authors: Xiaoyan Wang, Bin Jiang, Huiyan Sun, Dejin Zheng, Zhenwu Zhang, Li Yan, Enqin Li, Yaojiong Wu, Ren-He Xu
Journal: Theranostics (2019)

Mesenchymal stem cells (MSC) derived from adult tissues effectively promote wound healing. However, MSC quality varies, and the quantity of MSC is limited, as MSC are acquired through donations. Moreover, the survival and functioning of dissociated MSC delivered to an inflammatory lesion are subject to challenges. Methods: Here, spheres (EMSCSp) generated from human embryonic stem cell-derived MSC (EMSC) were directly dropped onto excised wounds in mice; the effects of EMSCSp were compared to those of dissociated EMSC (EMSCDiss). Following transplantation, we measured the extent of wound closure, dissected the histological features of the wounds, determined transcriptomic changes in cells isolated from the treated and control wounds, and evaluated the molecular mechanism of the effects of EMSC. Results: The application of EMSCSp onto murine dermal wounds substantially increased survival and efficacy of EMSC compared to the topical application of EMSCDiss. RNA sequencing (RNA-Seq) of cells isolated from the wounds highlighted the involvement of CXCL12-CXCR4 signaling in the effects of EMSCSp, which was verified in EMSC via CXCL12 knockdown and in target cells (vascular endothelial cells, epithelial keratinocytes, and macrophages) via CXCR4 inhibition. Finally, we enhanced the biosafety of EMSCSp by engineering cells with an inducible suicide gene. Conclusions: Together, these data suggest the topical application of EMSCSp as an unlimited, quality-assured, safe, and noninvasive therapy for wound healing and the CXCL12-CXCR4 axis as a key player in this treatment.
Media: Science, sense, and substance
Authors: G. Watts
Journal: BMJ (1998)

Body Story , Channel 4, Thursdays 900 pm

It's a pity that Channel 4's medical series Body Story has appeared so soon after The Human Body , the BBC's venture into similar territory. The irresistible temptation to make comparisons leaves Channel 4's offering outgunned—visually, technologically, and financially. While Auntie could afford to hire Ennobled of Hammersmith and cart him to all sorts of exotic locations—from the top of an Egyptian pyramid to the bottom of a swimming pool—the producers of Body Story had to make do with actors playing such parts as football-loving construction workers and motorcycle couriers who are would-be pop singers.

It might have been better if Wall to Wall Television, the production company which made Body Story , had chosen a different title. Using the word “body” again invites those unfair comparisons and casts a shadow over what might otherwise have been seen as a modest but rather good series. Each of the six programmes sets the biology that it is describing in the context of a simple dramatised story: …
Diagnosis of asthma in children: the contribution of a detailed history and test results
Authors: Carmen C.M. de Jong, Eva S.L. Pedersen, Rebeca Mozun, Myrofora Goutaki, Daniel Trachsel, Juerg Barben, Claudia E. Kuehni
Journal: European Respiratory Journal (2019)

Introduction There are few data on the usefulness of different tests to diagnose asthma in children. Aim We assessed the contribution of a detailed history and a variety of diagnostic tests for diagnosing asthma in children. Methods We studied children aged 6–16 years referred consecutively for evaluation of suspected asthma to two pulmonary outpatient clinics. Symptoms were assessed by parental questionnaire. The clinical evaluation included skin-prick tests, measurement of exhaled nitric oxide fraction ( F eNO ), spirometry, bronchodilator reversibility and bronchial provocation tests (BPT) by exercise, methacholine and mannitol. Asthma was diagnosed by the physicians at the end of the visit. We assessed diagnostic accuracy of symptoms and tests by calculating sensitivity, specificity, positive and negative predictive values and area under the curve (AUC). Results Of the 111 participants, 80 (72%) were diagnosed with asthma. The combined sensitivity and specificity was highest for reported frequent wheeze (more than three attacks per year) (sensitivity 0.44, specificity 0.90), awakening due to wheeze (0.41, 0.90) and wheeze triggered by pollen (0.46, 0.83) or by pets (0.29, 0.99). Of the diagnostic tests, the AUC was highest for F eNO measurement (0.80) and BPT by methacholine (0.81) or exercise (0.74), and lowest for forced expiratory volume in 1 s (FEV 1 ) (0.62) and FEV 1 /forced vital capacity ratio (0.66), assessed by spirometry. Conclusion This study suggests that specific questions about triggers and severity of wheeze, measurement of F eNO and BPT by methacholine or exercise contribute more to the diagnosis of asthma in school-aged children than spirometry, bronchodilator reversibility and skin-prick tests.
Water-Soluble Phthalocyanines Selectively Bind to Albumin Dimers: A Green Approach Toward Enhancing Tumor-Targeted Photodynamic Therapy
Authors: Xingshu Li, Keunsoo Jeong, Yoonji Lee, Tian Guo, Dayoung Lee, Jeongmin Park, Nahyun Kwon, Jung-Hyun Na, Seung Kon Hong, Sun-Shin Cha, Jian-Dong Huang, Sun Choi, Sehoon Kim, Juyoung Yoon
Journal: Theranostics (2019)

Targeted delivery of therapeutic agents is of particular interest in the field of cancer treatment.However, there is an urgent need for developing clinically promising targeting approaches that can be readily administered in a green manner.Methods: Five phthalocyanine derivatives bearing different anionic and cationic groups were designed and synthesized.Then, their binding affinity with albumin were studied using gel assays, optical spectra and computational simulation.Finally, in vitro and in vivo fluorescence imaging and photodynamic therapy (PDT) evaluations were carried out.Results: The two positively charged compounds could selectively bind to albumin dimer over albumin monomer, while the three negatively charged phthalocyanines could bind to both albumin monomer and dimer.Following systemic administration, the phthalocyanines show improved tumor accumulation via transport by natural albumin.PDT evaluations indicate that one of the positively charged compounds, ZnPcN 4 , shows outstanding phototherapeutic efficacy against tumors in preclinical models. Conclusion:Our findings demonstrate that the use of water-soluble phthalocyanines as photosensitizers and in vivo albumin as a natural carrier may provide a green and efficient approach for tumor-targeted imaging and therapy.
Underwater endoscopic papillectomy using double-balloon endoscopy
Authors: Tatsuhiro Yamazaki, Daisuke Uchida, Yasushi Yamasaki, Takeshi Tomoda, Kazuyuki Matsumoto, Hironari Kato, Hiroyuki Okada
Journal: Endoscopy (2019)

A 70-year-old woman with familial adenomatous polyposis (FAP), who had undergone proctocolectomy for FAP and laparoscopic total gastrectomy with Roux-en-Y reconstruction for multiple early gastric cancers, underwent double-balloon endoscopy (DBE) for duodenal adenoma screening. DBE revealed an ampullary tumor, diagnosed as a tubular adenoma by biopsy ([Fig. 1 a]). For resection of the ampullary tumor, we planned an underwater endoscopic papillectomy.
BMA calls for legislation to stop doctors being blamed when under “unmanageable pressure”
Authors: Elisabeth Mahase
Journal: BMJ (2019)

The BMA has written to the government to call for new legislation to ensure accountability for safe staffing levels and that “individual clinicians are not blamed when the system places them under unmanageable pressure.”1

The call came as the BMA published a year long study looking at the changes needed to improve care of patients and the working lives of doctors in the NHS, alongside a “manifesto for change” outlining all the recommendations.1

The …