tbuckley/cabot-search huggingface dataset:
Longitudinal NK cell kinetics and cytotoxicity in children with neuroblastoma enrolled in a clinical phase II trial
Authors: Rosa Nguyen, Natasha Sahr, April Sykes, Mary Beth McCarville, Sara M Federico, Amanda Sooter, David Cullins, Barbara Rooney, William E Janssen, Aimee C Talleur, Brandon M Triplett, Gwendolyn Anthony, Michael A Dyer, Alberto S Pappo, Wing H Leung, Wayne L Furman
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Natural killer (NK) cells are one of the main effector populations of immunotherapy with monoclonal antibody and cytokines, used in combination with chemotherapy to treat children with high-risk neuroblastoma on this phase II trial. However, the impact of chemoimmunotherapy on NK cell kinetics, phenotype, and function is understudied. Methods We prospectively examined NK cell properties from 63 children with newly diagnosed neuroblastoma enrolled in a phase II trial ( NCT01857934 ) and correlated our findings with tumor volume reduction after 2 courses of chemoimmunotherapy. NK cell studies were conducted longitudinally during chemoimmunotherapy and autologous hematopoietic cell transplantation (autoHCT) with optional haploidentical NK cell infusion and additional immunotherapy. Results Chemoimmunotherapy led to significant NK cytopenia, but complete NK cell recovery reliably occurred by day 21 of each therapy course as well as after autoHCT. Haploidentical NK cell infusion elevated the NK cell count transiently during autoHCT. NK cell cytotoxicity increased significantly during treatment compared with diagnosis. In addition, NK cells maintained their ability to respond to cytokine stimulation in culture longitudinally. Unsupervised cluster analysis of CD56 bright NK cell count and tumor volume at diagnosis and after two courses of chemoimmunotherapy identified two patient groups with distinct primary tumor sizes and therapy responses. Conclusion After profound NK cytopenia due to chemoimmunotherapy, endogenously reconstituted NK cells exhibit enhanced NK cytotoxicity compared with pretherapy measurements. Our data suggest a relationship between CD56 bright expression and tumor size before and after two courses of chemoimmunotherapy; however, future studies are necessary to confirm this relationship and its predictive significance. Trial registration number NCT01857934 .
Manual acupuncture versus sham acupuncture and usual care for prophylaxis of episodic migraine without aura: multicentre, randomised clinical trial
Authors: Shabei Xu, Lingling Yu, Xiang Luo, Minghuan Wang, Guohua Chen, Qing Zhang, Wenhua Liu, Zhongyu Zhou, Jinhui Song, Huitao Jing, Guangying Huang, Fengxia Liang, Hua Wang, Wei Wang
Journal: BMJ (2020)

Abstract Objective To assess the efficacy of manual acupuncture as prophylactic treatment for acupuncture naive patients with episodic migraine without aura. Design Multicentre, randomised, controlled clinical trial with blinded participants, outcome assessment, and statistician. Setting Seven hospitals in China, 5 June 2016 to 15 November 2018. Participants 150 acupuncture naive patients with episodic migraine without aura. Interventions 20 sessions of manual acupuncture at true acupuncture points plus usual care, 20 sessions of non-penetrating sham acupuncture at heterosegmental non-acupuncture points plus usual care, or usual care alone over 8 weeks. Main outcome measures Change in migraine days and migraine attacks per four weeks during weeks 1-20 after randomisation compared with baseline (four weeks before randomisation). Results Among 150 randomised patients (mean age 36.5 (SD 11.4) years; 123 (82%) women), 147 were included in the full analysis set. Compared with sham acupuncture, manual acupuncture resulted in a significantly greater reduction in migraine days at weeks 13 to 20 and a significantly greater reduction in migraine attacks at weeks 17 to 20. The reduction in mean number of migraine days was 3.5 (SD 2.5) for manual versus 2.4 (3.4) for sham (adjusted difference −1.4, 95% confidence interval −2.4 to −0.3; P=0.005) at weeks 13 to 16 and 3.9 (3.0) for manual versus 2.2 (3.2) for sham (adjusted difference −2.1, −2.9 to −1.2; P&lt;0.001) at weeks 17 to 20. At weeks 17 to 20, the reduction in mean number of attacks was 2.3 (1.7) for manual versus 1.6 (2.5) for sham (adjusted difference −1.0, −1.5 to −0.5; P&lt;0.001). No severe adverse events were reported. No significant difference was seen in the proportion of patients perceiving needle penetration between manual acupuncture and sham acupuncture (79% v 75%; P=0.891). Conclusions Twenty sessions of manual acupuncture was superior to sham acupuncture and usual care for the prophylaxis of episodic migraine without aura. These results support the use of manual acupuncture in patients who are reluctant to use prophylactic drugs or when prophylactic drugs are ineffective, and it should be considered in future guidelines. Trial registration Clinicaltrials.gov NCT02765581 .
Association of Magnetoencephalographically Measured High-Frequency Oscillations in Visual Cortex With Circuit Dysfunctions in Local and Large-scale Networks During Emerging Psychosis
Authors: Tineke Grent-‘t-Jong, Ruchika Gajwani, Joachim Gross, Andrew I. Gumley, Rajeev Krishnadas, Stephen M. Lawrie, Matthias Schwannauer, Frauke Schultze-Lutter, Peter J. Uhlhaas
Journal: JAMA Psychiatry (2020)

Psychotic disorders are characterized by impairments in neural oscillations, but the nature of the deficit, the trajectory across illness stages, and functional relevance remain unclear.To examine whether changes in spectral power, phase locking, and functional connectivity in visual cortex are present during emerging psychosis and whether these abnormalities are associated with clinical outcomes.In this cross-sectional study, participants meeting clinical high-risk criteria for psychosis, participants with first-episode psychosis, participants with affective disorders and substance abuse, and a group of control participants were recruited. Participants underwent measurements with magnetoencephalography and magnetic resonance imaging. Data analysis was carried out between 2018 and 2019.Magnetoencephalographical activity was examined in the 1- to 90-Hz frequency range in combination with source reconstruction during a visual grating task. Event-related fields, power modulation, intertrial phase consistency, and connectivity measures in visual and frontal cortices were associated with neuropsychological scores, psychosocial functioning, and clinical symptoms as well as persistence of subthreshold psychotic symptoms at 12 months.The study participants included those meeting clinical high-risk criteria for psychosis (n = 119; mean [SD] age, 22 [4.4] years; 32 men), 26 patients with first-episode psychosis (mean [SD] age, 24 [4.2] years; 16 men), 38 participants with affective disorders and substance abuse (mean [SD] age, 23 [4.7] years; 11 men), and 49 control participants (mean age [SD], 23 [3.6] years; 16 men). Clinical high-risk participants and patients with first-episode psychosis were characterized by reduced phase consistency of β/γ-band oscillations in visual cortex (d = 0.63/d = 0.93). Moreover, the first-episode psychosis group was also characterized by reduced occipital γ-band power (d = 1.14) and altered visual cortex connectivity (d = 0.74-0.84). Impaired fronto-occipital connectivity was present in both clinical high-risk participants (d = 0.54) and patients with first-episode psychosis (d = 0.84). Importantly, reductions in intertrial phase coherence predicted persistence of subthreshold psychosis in clinical high-risk participants (receiver operating characteristic area under curve = 0.728; 95% CI, 0.612-0.841; P = .001).High-frequency oscillations are impaired in the visual cortex during emerging psychosis and may be linked to behavioral and clinical impairments. Impaired phase consistency of γ-band oscillations was also associated with the persistence of subthreshold psychosis, suggesting that magnetoencephalographical measured neural oscillations could constitute a biomarker for clinical staging of emerging psychosis.
Transmucosal diverticular myotomy for the treatment of oesophageal diverticula associated with spastic motility disorders
Authors: Mayenaaz Sidhu, David J Tate, Michael J Bourke
Journal: Gut (2020)

Thoracic oesophageal diverticula are often associated with spastic motility disorders. Despite correction of the underlying motility disorder, in a subgroup of patients, symptoms persist, primarily regurgitation. Surgical diverticulectomy is then proposed; however, as the approach is thoracoscopic or via thoracotomy, it is associated with significant morbidity and cost. Descriptions of endoscopic techniques for the treatment of symptomatic midoesophageal diverticula are few. We propose the novel technique of diverticular myotomy (DM) to treat this disorder. In this case series, we describe two patients who successfully underwent DM with no adverse outcomes and excellent clinical results at 24-month follow-up.
Abstract P1-19-36: Exploratory analysis of TreatER+ight; a Canadian prospective real-world observational study in HR+ advanced breast cancer
Authors: Catherine Doyle, Nadia Califaretti, Cristiano Ferrario, Nayyer Iqbal, John Hilton, Theodore Vandenberg, Mihaela Mates, Vivian Glenns, Swati Kulkarni, Puneet Bains, Sina Haftchenary, Sabrina Perri, Stephen Chia
Journal: Cancer Research (2020)

Abstract Background: TreatER+ight is the 1st prospective observational study in Canadian HR+ HER2- advanced breast cancer patients currently receiving endocrine therapy (ET) alone or in combination with targeted therapy (TT) (NCT02753686). Methods: This exploratory analysis displays real-world evidence on baseline demographics, treatment patterns, sequencing, and method of access to therapy. More specifically this abstract focuses on treatment decisions around CDK4/6-based therapy at various lines of treatment. At data cut-off of April 1st 2019, 305 patients were enrolled from 24 sites since Mar'16 with 113 patients receiving CDK4/6is at baseline. 300 patients were evaluable for treatment analysis. Results: Baseline CharacteristicsOverall (n=305)CDK4/6 + ET (n=113)Median age, years (range)67 (23 - 92)67 (23-87)ECOG 0,1,2*95, 104, 1941,32, 4Post-menopausal*21468Pre/peri-menopausal*6530Therapy by disease severity at baselineVisceral (n = 196)Bone only (n = 101)CDK4/6 + ET7338ET5941mTOR + ET6421PI3K + ET01Current therapy on the study Overall (N = 300)CDK4/6 + ET113ET100mTOR + ET86 PI3K + ET1Current CDK therapy by line of treatmentAll CDK4/6 (N = 113)First line60Second line38Third line13 Fourth line2Overall treatment patterns by lineFirst-Line (n = 154)Second-Line (n = 111)Third-Line (n = 64)CDK 4/6i + ET855317ET582711mTOR + Exemestane82114Chemo31022Median duration on therapy in months1L2LCDK4/6 + ET8.87 (median follow-up of 9.6 mos)8.77 (median follow-up of 11.6 mos)*Data missing for some patients at the time of this analysis Conclusions: The majority of patients enrolled (66.6%) are receiving combination therapy with the most common treatment being a CDK4/6-based therapy (56.5%). Of the patients receiving CDK4/6 at baseline a majority are receiving this therapy in the 1L (53.1%) and 2L (33.6%), with the median duration on therapy of respectively 8.87 and 8.77 months. For patients receiving CDK4/6 therapy in 1L, the most common 2L treatment is either endocrine therapy single agent and in certain parts of the country everolimus + exemestane. Further sequencing information will be analyzed and shared for this abstract. Citation Format: Catherine Doyle, Nadia Califaretti, Cristiano Ferrario, Nayyer Iqbal, John Hilton, Theodore Vandenberg, Mihaela Mates, Vivian Glenns, Swati Kulkarni, Puneet Bains, Sina Haftchenary, Sabrina Perri, Stephen Chia. Exploratory analysis of TreatER+ight; a Canadian prospective real-world observational study in HR+ advanced breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-36.
Doctors as leaders: I expect more of leaders than empty platitudes
Authors: George R Huntington
Journal: BMJ (2020)

I’m aware that Carrie MacEwen’s recent interview in The BMJ has been taken out of context in the tabloids, but as one of her young doctors three years out of medical school, I think her comments are likely to fall on weary ears.1 I don’t feel hopeful that we’re onto a “new phase”; …
Abstract P4-10-11: PIK3CA status as a predictor of benefit from drugs targeting the PI3K/AKT/mTOR pathway: A meta-analysis of randomized trials
Authors: Fahad A Almugbel, Ramy Saleh, Alberto Ocana, Atanasio Pandiella, Eitan Amir
Journal: Cancer Research (2020)

Abstract Introduction: A number of different drugs have been developed to target the PI3 kinase/AKT/mTOR pathway. Most randomized trials in breast cancer have been performed in patients unselected for pathway activation although aberrations of components of this pathway are common. Here we explore the predictive value of PIK3CA and AKT mutations in randomized trials of drugs targeting this signaling route. Methods: We searched PubMed for randomized trials of drugs targeting the PI3 kinase/AKT/mTOR pathway in metastatic breast cancer. The search was supplemented by a manual search of recent ASCO and ESMO meetings. Eligible studies needed to report efficacy data based on presence or absence of PIK3CA or AKT status measured either in tumor specimens or in circulating DNA. Hazard ratios (HR) for progression-free survival (PFS) in PIK3CA or AKT mutant and wild-type groups were extracted and pooled in a meta-analysis using generic inverse variance and random effects modeling. Sensitivity analyses were performed based on the mechanism of action of the experimental drug. Results: Of the 15 studies identified, 10 studies comprising of 3615 patients were eligible for analysis. Studies included pan-PI3kinase inhibitors (n=5), alpha-specific PI3kinase inhibitors (n=1), AKT inhibitors (n=2) and mTOR inhibitors (n=2). Approximately 38% of patients had either PIK3CA or AKT mutations. The addition of drugs targeting the PI3 kinase/AKT/mTOR pathway was associated with a significantly longer improvement in PFS in patients with PIK3CA or AKT mutations than in those with wild-type status (HR 0.61, 95% CI 0.50-0.75 versus HR 0.83, 95% CI 0.67-1.02, p for difference = 0.04). Similar results were observed in sensitivity analyses (see Table). Conclusion: Benefit from drugs targeting the PI3 kinase/AKT/mTOR pathway in breast cancer appears to occur exclusively in those with PIK3CA or AKT mutations. Future trials of these drugs should be designed only in biomarker selected patients. TableGroupPIK3CA or AKT mutationPIK3CA and AKT wildtypep for differenceHR95% CIHR95% CIExcluding AKT inhibitors0.640.52-0.790.810.63-1.030.16Excluding pan-PI3 kinase inhibitors0.580.47-0.710.710.51-1.150.24Excluding AKT and alpha-specific PI3 kinase inhibitors0.690.48-1.000.980.83-1.150.09Excluding mTOR inhibitors0.620.49-0.800.920.80-1.060.008 Citation Format: Fahad A Almugbel, Ramy Saleh, Alberto Ocana, Atanasio Pandiella, Eitan Amir. PIK3CA status as a predictor of benefit from drugs targeting the PI3K/AKT/mTOR pathway: A meta-analysis of randomized trials [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-11.
Abstract 16753: Adiponectin Regulates Microrna449b/nfe2l1 Endogenous Antioxidative Pathway, to Ameliorate Cardiac Ischemia Reperfusion Injury in Diabetic Mice
Authors: Yajing Wang, Rui Guo, Han Wang, Bin Liang, Yunhui Du, Wayne Bond Lau, Erhe Gao, Theodore Christopher, Bernard Lopez, Xinliang L Ma
Journal: Circulation (2017)

Myocardial ischemic/reperfusion (MI/R) injury is significantly enhanced in diabetic individuals. Hypoadiponectinemia during diabetes enhances oxidative stress and exaggerates MI/R injury. However, ...
Incidence of Type 2 Diabetes in Patients With Chronic Hepatitis C Receiving Interferon-Based Therapy
Authors: Ming-Chieh Tsai, Kai-Liang Kao, Hui-Chun Huang, Weishan Chen, Chun-Kai Fang, Fung-Chang Sung, Shu-I Wu, Robert Stewart
Journal: Diabetes Care (2020)

Type 2 diabetes (T2D) has been associated with hepatitis C virus (HCV) infection as an independent risk factor. The increased insulin resistance induced by the HCV core protein or the treatment with interferon-based therapy (IBT) may have a role (1). It is generally agreed that IBT for patients with chronic hepatitis C (CHC) may trigger short-term insulin resistance. However, the long-term risk of developing T2D for CHC patients with IBT remains unclear. Studies suggested that if viral clearance is achieved after IBT, the risk of T2D might be reduced by two-thirds in CHC patients (2,3). An Italian study argued that a lower insulin resistance at baseline may be the reason for reduced risk of T2D (4). We therefore conducted a retrospective cohort study, using insurance claims data of Taiwan, to examine 1 ) whether CHC patients are at an elevated risk of developing T2D and 2 ) whether CHC patients receiving IBT are at a reduced risk of T2D, not only through viral clearance but also through possible alterations of glucose metabolism.

The health insurance of Taiwan is a universal insurance system with 99% of all 23 million residents covered. We used a subset of claims data of 1 million beneficiaries randomly selected from all residents to …
Abstract P6-03-14: Conditional reprogrammed cells enable us to examine the drug resistance for recurrent metastatic hormone receptor-positive, human epidermal receptor 2-negative breast cancer
Authors: Rei Mimoto, Satomi Yogosawa, Atsushi Fushimi, Hiroko Nogi, Tadashi Asakura, Kiyotsugu Yoshida, Hiroshi Takeyama
Journal: Cancer Research (2020)

Abstract Objectives: Various new drugs have been developed for treating recurrent hormone receptor-positive/human epidermal receptor 2-negative breast cancer. However, directly identifying effective drugs remains difficult. In this study, we elucidated the clinical relevance of cultured cells derived from patients with recurrent hormone receptor-positive/human epidermal receptor 2-negative metastatic breast cancer. Methods: We generated conditional reprogrammed cells from primary and metastatic breast cancer. CR cells were co-cultured with irradiated mouse fibroblast feeder cells in the presence of the Rho kinase inhibitor Y-27632. We performed microarray analysis using a SurePrint G3 Human GE microarray kit Ver. 2.0, and DNA target sequence using QIAseq Targeted DNA Panels to analyze the genetic variants of the 93 most commonly mutated genes in human breast cancer samples. We examined the pathological features by xenograft model. For drug screening assay, we used Cambridge Cancer Compound Library. Results: The results of microarray analysis, DNA target sequencing and xenograft experiments indicated that the mutation status and pathological features were preserved in CR cells, whereas RNA expression was different from that in the primary tumor cells, especially with respect to cell adhesion-associated pathways. The results of drug sensitivity assays involving the use of primary breast cancer CR cells were consistent with the result of Oncotype Dx. We performed drug screening assays using liver metastases, which were sensitive to 66 drugs. The result reflected the actual clinical course of this patient, resistant to taxanes and sensitive to fulvestrant plus palbociclib. Conclusion: These results supported the use of CR cells obtained from the metastatic lesions of patients with HR+/HER2− breast cancer for predicting the clinical drug efficacy. Citation Format: Rei Mimoto, Satomi Yogosawa, Atsushi Fushimi, Hiroko Nogi, Tadashi Asakura, Kiyotsugu Yoshida, Hiroshi Takeyama. Conditional reprogrammed cells enable us to examine the drug resistance for recurrent metastatic hormone receptor-positive, human epidermal receptor 2-negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-03-14.
Correction: NK cell–derived GM-CSF potentiates inflammatory arthritis and is negatively regulated by CIS
Authors: Cynthia Louis, Fernando Souza-Fonseca-Guimaraes, Yuyan Yang, Damian D’Silva, Tobias Kratina, Laura Dagley, Soroor Hediyeh-Zadeh, Jai Rautela, Seth Lucian Masters, Melissa J. Davis, Jeffrey J. Babon, Bogoljub Ciric, Eric Vivier, Warren S. Alexander, Nicholas D. Huntington, Ian P. Wicks
Journal: The Journal of Experimental Medicine (2020)

JEM regrets that in the original version of this paper,  Souza-Fonseca-Guimaraes's name was mistakenly written as Fernando Guimaraes. The corrected author list appears above.
Reply to Rizzatti et al.
Authors: Ruben D. van der Bogt, Berend J. van der Wilk, Jan J. B. van Lanschot, Manon C. W. Spaander
Journal: Endoscopy (2020)

See also: Endoscopic ultrasound and fine-needle aspiration for the detection of residual nodal disease after neoadjuvant chemoradiotherapy for esophageal cancerEndoscopy 2020; 52(03): 186-192DOI: 10.1055/a-1065-1759 See also: Lymph node staging in esophageal/junctional tumors after chemoradiotherapy: should we change strategy?Endoscopy 2020; 52(04): 316-316DOI: 10.1055/a-1103-1977
Non-invasive diagnosis of patients with ‘at-risk’ NAFLD : only fibrosis counts?
Authors: Andreas Geier, Jerome Boursier
Journal: Gut (2020)

In Gut , Loomba and Adams refer to the recent advances in non-invasive assessment of hepatic fibrosis.1 Not surprisingly, many recent studies in the field were conducted in patients at risk or with clinically diagnosed non-alcoholic fatty liver disease (NAFLD). The implications of non-invasive testing are particularly far reaching in this group of patients since this disease affects 25% of Western populations. The principal need to identify the small subset of NAFLD patients at-risk of progressive disease and liver-related outcomes is obvious.

Recent retrospective longitudinal studies have shown that non-alcoholic steatohepatitis (NASH) is not an independent predictor of liver-related complication or mortality in NAFLD.2 3 NASH is a risk factor of fibrosis progression rather than an immediate risk of liver related complication and therefore positions at a lower prognostic significance in the hierarchical model of NAFLD.4 The diagnosis of NASH still requires a liver biopsy, a procedure not suitable for the very large NAFLD population because it is invasive and not widely accepted among non-specialised physicians and patients. No non-invasive test (NIT) has so far achieved enough accuracy and validation for the non-invasive diagnosis of NASH. One explanation is that most of the known candidate blood markers for NASH are not specific of the liver and could be produced by other organs, especially the expanded adipose tissue observed in NAFLD. Moreover, liver biopsy results are limited by a fairly high discordance …