tbuckley/cabot-search huggingface dataset:
Neoadjuvant Three-Dimensional Conformal Radiotherapy for Resectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Randomized, Open-Label, Multicenter Controlled Study
Authors: Xubiao Wei, Yabo Jiang, Xiuping Zhang, Shuang Feng, Bin Zhou, Xiaofei Ye, Hui Xing, Ying Xu, Jie Shi, Weixing Guo, Dong Zhou, Hui Zhang, Huichuan Sun, Cheng Huang, Congde Lu, Yaxin Zheng, Yan Meng, Bin Huang, Wenming Cong, Wan Yee Lau, Shuqun Cheng
Journal: Journal of Clinical Oncology (2019)

To compare the survival outcomes of neoadjuvant three-dimensional conformal radiotherapy (RT) followed by hepatectomy with hepatectomy alone in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT).A randomized, multicenter controlled study was conducted from January 2016 to December 2017 in patients with resectable HCC and PVTT. Patients were randomly assigned to receive neoadjuvant RT followed by hepatectomy (n = 82) or hepatectomy alone (n = 82). The modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines were used to evaluate the therapeutic effects of RT. The primary end point was overall survival. The expression of interleukin-6 (IL-6) in patients' serum before RT and in surgical specimens was correlated with response to RT.In the neoadjuvant RT group, 17 patients (20.7%) had partial remission. The overall survival rates for the neoadjuvant RT group at 6, 12, 18, and 24 months were 89.0%, 75.2%, 43.9%, and 27.4%, respectively, compared with 81.7%, 43.1%, 16.7%, and 9.4% in the surgery-alone group (P < .001). The corresponding disease-free survival rates were 56.9%, 33.0%, 20.3%, and 13.3% versus 42.1%, 14.9%, 5.0%, and 3.3% (P < .001). On multivariable Cox regression analyses, neoadjuvant RT significantly reduced HCC-related mortality and HCC recurrence rates compared with surgery alone (hazard ratios, 0.35 [95% CI, 0.23 to 0.54; P < .001] and 0.45 [95% CI, 0.31 to 0.64; P < .001]). Increased expressions of IL-6 in pre-RT serum and tumor tissues were significantly associated with resistance to RT.For patients with resectable HCC and PVTT, neoadjuvant RT provided significantly better postoperative survival outcomes than surgery alone. IL-6 may predict response to RT in these patients.
Abstract 12429: Reductions in Mean 24-Hour Ambulatory Blood Pressure After 6-Week Treatment of Canagliflozin in Patients With Type 2 Diabetes Mellitus and Hypertension
Authors: Raymond Townsend, Israel Machin, Jimmy Ren, Angelina Trujillo, Masato Kawaguchi, Ujjwala Vijapurkar, Michael Pfeifer
Journal: Circulation (2015)

Background: Canagliflozin (CANA), a sodium glucose co-transporter 2 inhibitor, decreases renal glucose reabsorption and increases urinary glucose excretion. In 26-wk clinical studies consistent and sustained reductions in BP have been observed. This study used ABPM to assess reduction of BP after the initiation of CANA. Methods: In this 6-wk, placebo (PBO)-controlled study, 169 pts (mean [SD] age 58.6 [8.4] y, A1C 8.1% [0.9], seated SBP 138.5 mmHg [9.6], seated DBP 82.7 mmHg [8.1]), on 1-3 antihyperglycemic agents (required metformin; excluded insulin) and 1-3 antihypertensive agents (required ACEi or ARB; excluded loop diuretics) received ≥1 dose of the study medication (CANA 100 mg [n = 57], CANA 300 mg [n = 56], or PBO [n = 56]). Primary endpoint was change from baseline to Wk 6 (LOCF) in mean 24-hr SBP between CANA 300 mg and PBO. Primary efficacy analysis was based on an ANCOVA model which included terms for treatment and beta-blocker use and baseline mean 24-hr SBP as a covariate. Key secondary endpoints included change from baseline in mean 24-hr DBP, and mean day- and nighttime SBP and DBP for CANA 100 and 300 mg. Results: At Wk 6, CANA 300 mg provided greater reductions in mean 24-hr SBP vs PBO (-4.9 mmHg, p = 0.006, Fig.). Reductions in mean 24-hr SBP were also observed with CANA 100 mg (-3.3 mmHg) vs PBO. Reductions in mean 24-hr DBP were observed for both CANA 100 mg (-1.94 mmHg) and CANA 300 mg (-2.92 mmHg*) vs PBO. CANA 100 and 300 mg resulted in greater reductions in mean daytime SBP (PBO-adjusted changes -4.0 mmHg* and -5.4 mmHg*) and DBP (PBO-adjusted changes -2.2 mmHg* and -3.0 mmHg*). Higher incidences of orthostasis, volume depletion and osmotic diuresis adverse events were observed with CANA 300 mg vs CANA 100 mg and PBO. Conclusion: At Wk 6, CANA 300 mg provided a rapid and significant reduction in mean 24-hr SBP. Both CANA doses reduced daytime SBP and DBP, and demonstrated an overall safety profile consistent with clinical studies. *nominal p value (p &lt; 0.05)
Ultrasonographic salivary gland evaluation in systemic sclerosis: is sicca syndrome secondary to an authentic overlap syndrome or another specific fibrotic manifestation of the disease?
Authors: Guillaume Coiffier, Sandrine Jousse-Joulin, Divi Cornec, Ronan Garlantézec, Aurore Bleuzen, Elisabeth Diot, Patrick Jego, Alice Ballerie, Alain Lescoat
Journal: Annals of the Rheumatic Diseases (2019)

Figure 1 US axial view of a normal (A) and pathologic (B-C) parotid gland.(B) shows pathological glandular parenchyma with multiple pseudo-cystichypoechoic areas and some fibrotic hyperechoic bands.This gland would be classified as grade 3 of Cornec's score and grade 2 according to OMERACT classification.(C)shows a pathological glandular parenchyma with hyperechoic bands that develop into fibrotic tissue indistinguishable from the adjacent soft tissues and with only few pseudo-cystic hypoechoic areas.This gland would be difficult to classify according to Cornec's score (considered as grade 1 or 2) and would on the contrary easily reach grade 3 according to the recent OMERACT score.on August 31,
Final treatment outcomes of delamanid-containing regimens in patients with MDR-/XDR-TB in South Korea
Authors: Jeongha Mok, Hyungseok Kang, Won-Jung Koh, Byung Woo Jhun, Jae-Joon Yim, Nakwon Kwak, Taehoon Lee, Bohyoung Kang, Doosoo Jeon
Journal: European Respiratory Journal (2019)

<b>The optimised use of delamanid combined with effective repurposed drugs could achieve a high treatment success rate, even in pre-extensively drug-resistant (XDR)-TB and XDR-TB patients</b>http://bit.ly/2plvEOT
Author Correction: High-dimensional detection of imaging response to treatment in multiple sclerosis
Authors: Baris Kanber, Parashkev Nachev, Frederik Barkhof, Alberto Calvi, Jorge Cardoso, Rosa Cortese, Ferran Prados, Carole H. Sudre, Carmen Tur, Sebastien Ourselin, Olga Ciccarelli
Journal: npj Digital Medicine (2019)

[This corrects the article DOI: 10.1038/s41746-019-0127-8.].
Responses to immune checkpoint therapy in pulmonary sarcomatoid carcinoma: A retrospective review.
Authors: Vineeth Sukrithan, Jason Sandler, Rasim A. Gucalp, Richard J. Gralla, Balazs Halmos
Journal: Journal of Clinical Oncology (2019)

115 Background: Advanced Pulmonary Sarcomatoid Carcinoma (PSC) is associated with poor response to chemotherapy and a median survival of 4-6 months. PSC have a high frequency of PD-L1 positivity and high tumor mutational burden, which are markers of benefit with immune checkpoint inhibitors (ICPI). The parameters of response and survival for PSC treated in the era of immune checkpoint inhibition are unknown. Methods: A review of all cases of advanced PSC diagnosed at two institutions in Bronx, NY between 6/2015-6/2018 was performed. Responses were assessed by serial imaging obtained during routine care and graded by RECIST criteria v 1.1. Results: Five cases of advanced Stage IV PSC are reported. The median age was 57 years and all had received ICPI. All cases were smokers with a median of 30 pack-years and TPS &gt; 75%. Three patients received Pembrolizumab as front-line therapy. Responses were seen in four out of five patients, including one complete response. The fifth patient had prolonged disease stability. After a median follow-up of 13 months, none of the patients had progressed. One patient died of infectious complications after 23 months with no evidence of progression. Four patients continue to be alive with ongoing OS ranging between 14-33 months. Conclusions: ICPI therapy has robust activity in advanced PSC and offers an effective line of therapy in this treatment-refractory aggressive malignancy. [Table: see text]
18F-FDG uptake on positron emission tomography in gefitinib-treated non-small cell lung cancer patients
Authors: I. Na, B. Byun, H. Kang, G. Cheon, C. Kim, J. Koh, D. Choe, B. Ryoo, S. Lim, J. Lee, S. Yang
Journal: Journal of Clinical Oncology (2007)

18136 Background: This study evaluated the clinical significance of 18 F-fluoro-2-deoxy-glucose (FDG) uptake on positron emission tomography (PET) in gefitinib-treated non-small-cell lung cancer (NSCLC) patients. Method: We retrospectively analyzed PET scans of 66 NSCLC patients with stage IIIB-IV and its association with gefitinib responsiveness. Response rate and time-to- progression (TTP) were analyzed according to the maximum standardized uptake value (SUV) at presentation. Cut-off vale of SUV was obtained from receiver operating characteristic analysis. Univariate and multivariate analyses were performed. Results: According to smoking history and pathology, different response rates were observed (P = 0.012 and 0.048, respectively). Thirteen patients were categorized into low SUV group. Patients with low SUV showed higher RR compared with those with high SUV (46% vs 13%, P = 0.007). In univariate analysis, prolonged TTP was observed in never-smoker (P = 0.007). Low SUV was associated with prolonged TTP (P = 0.010). Multivariate analysis confirmed that low SUV and never-smoker remained favorable prognostic factors (P = 0.046 and 0.043, respectively). Conclusion: These results suggest that FDG uptake may be predictive of outcome in gefitinib-treated non-small-cell lung cancer patients. No significant financial relationships to disclose.
Treating HER2-mutant advanced biliary tract cancer with neratinib: benefits of HER2-directed targeted therapy in the phase 2 SUMMIT ‘basket’ trial
Authors: J. Harding, J. Cleary, G. Shapiro, I. Braña, V. Moreno, D. Quinn, M. Borad, S. Loi, I. Spanggaard, S. Stemmer, M. Dujka, R. Cutler, F. Xu, L. Eli, S. Macia, A. Lalani, R. Bryce, F. Meric Bernstam, D. Solit, D. Hyman, S. Piha-Paul
Journal: Annals of Oncology (2019)
The anti-tumor effect of oral cancer vaccine using <i>Bifidobacterium</i> as a platform for displaying Wilms’ tumor 1 protein.
Authors: Hikaru Minagawa, Yoshiko Hashii, Natsuki Nakagawa, Hiroko Nakajima, Yoshihiro Oka, Takane Katayama, Toshiro Shirakawa, Keiichi Ozono
Journal: Journal of Clinical Oncology (2019)

72 Background: The gut microbiota plays an important role in shaping systemic immune responses. We have developed a WT1 oral cancer vaccine using a recombinant Bifidobacterium Longum ( B. Longum) as a platform for displaying murine WT1 protein ( B. Longum-mWT1). The Wilms’ tumor 1 (WT1) gene, which encodes a zinc finger transcription factor, is reportedly overexpressing in various tumors and one of the most promising tumor-associated antigens for cancer immunotherapy. In order to examine anti-tumor effects of this oral vaccine, we administered it orally into mice inoculated with WT1 + -expressing brain tumor which doesn’t respond to existing treatment. Methods: The synthesized murine-WT1 gene (117-439 amino acid residues) was fused to galacto-N-biose/lacto-N-biose I binding protein (GLBP) coding gene. GLBP is a membrane protein on the wild-type B. Longum cell wall, which is used as an anchor to display antigen. The resulting plasmid carrying GLBP-WT1 was introduced into B. Longum by electroporation. We inoculated mouse glioma cell lines (Gl261) subcutaneously into the C57BL/6J. C57BL/6J mice received oral administration of B. Longum-mWT1 every day or subcutaneous administration of WT1 126 peptide with montanide adjuvant on days 1, 8, 15, 22, 29, and 36. Results: The tumor volume of the mice treated with B. Longum-mWT1 (n = 5) was significantly smaller than that of the mice given WT1 peptide vaccine (n = 5) ( P &lt; 0.05). The frequency of CD8 + /WT1-tetramer + CTLs was higher in B. Longum-mWT1 and WT1 peptide vaccine groups than in PBS group, and the high frequency was maintained in B. Longum-mWT1 group. In the mouse with B. Longum-mWT1, the frequency CD8 + /WT1-tetramer + CTLs in mesenteric lymph node and spleen was higher than that in Peyer’s patch. The number of invasive CD8 + T cells in brain tumor was higher in the B. Longum-mWT1 group than in the PBS group. B. Longum-mWT1 induced significantly higher in vitro cytotoxicity against Gl261 cells than WT1 peptide. Conclusions: We confirmed that B. Longum-mWT1 can induce strong cellular immunity and the maintenance of this effect. These results suggest that it is a novel oral anti-cancer agent for treating glioblastoma, for which no effective treatment has been developed.
Management of acute lower GI bleeding: evidence-based medicine?
Authors: John S Leeds, Anthoor Jayaprakash, David S Sanders
Journal: Gut (2019)

We read with interest the guidelines concerning the management of acute lower GI bleeding (LGIB) by Oakland et al including the assessment algorithm and congratulate the authors for their work in what is an evidence light area.1 LGIB is a common presenting condition; however, previous data show that in the majority of cases, bleeding stops without the need for any intervention.2 In the national audit, only 3.1% of 2528 cases received any direct intervention to help control LGIB of which 2.1% was endoscopic, 0.8% embolisation and 0.2% surgery and overall mortality was low (3.4%).3 It is well recognised in upper GI bleeding that the role of endoscopy is for delivering a therapeutic intervention to reduce the risk of rebleeding and need for surgery. There is …
Universal Testing, Expanded Treatment, and Incidence of HIV Infection in Botswana
Authors: Joseph Makhema, Kathleen E. Wirth, Molly Pretorius Holme, Tendani Gaolathe, Mompati Mmalane, Etienne Kadima, Unoda Chakalisa, Kara Bennett, Jean Leidner, Kutlo Manyake, Atang M. Mbikiwa, Selebaleng V. Simon, Rona Letlhogile, Kutlwano Mukokomani, Erik van Widenfelt, Sikhulile Moyo, Refeletswe Lebelonyane, Mary G. Alwano, Kathleen M. Powis, Scott L. Dryden-Peterson, Coulson Kgathi, Vlad Novitsky, Janet Moore, Pamela Bachanas, William Abrams, Lisa Block, Shenaaz El-Halabi, Tafireyi Marukutira, Lisa A. Mills, Connie Sexton, Elliot Raizes, Simani Gaseitsiwe, Hermann Bussmann, Lillian Okui, Oaitse John, Roger L. Shapiro, Sherri Pals, Haben Michael, Michelle Roland, Victor DeGruttola, Quanhong Lei, Rui Wang, Eric Tchetgen Tchetgen, M. Essex, Shahin Lockman
Journal: New England Journal of Medicine (2019)

The feasibility of reducing the population-level incidence of human immunodeficiency virus (HIV) infection by increasing community coverage of antiretroviral therapy (ART) and male circumcision is unknown.
Sprouty1 Controls Genitourinary Development via its N-Terminal Tyrosine
Authors: Marta Vaquero, Sara Cuesta, Carlos Anerillas, Gisela Altés, Joan Ribera, M. Albert Basson, Jonathan D. Licht, Joaquim Egea, Mario Encinas
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement Sprouty1 is a critical regulator of genitourinary development that ensures only one kidney forms on each side of the embryo. The molecular mechanisms that Sprouty1 uses to do this are largely unknown. The authors show that removing a single tyrosine from Sprouty1 in mice is enough to inactivate its function during genitourinary development. Knockin mice lacking this tyrosine develop supernumerary kidneys, megaureter, and vesicoureteral reflux, the same defects seen in Sprouty1 knockout mice. These findings shed light on the elusive mechanisms of action of Sprouty proteins and provide a valuable tool to investigate the developmental origin of human congenital anomalies of kidney and lower urinary tract. Background Studies in mice suggest that perturbations of the GDNF-Ret signaling pathway are a major genetic cause of congenital anomalies of the kidney and urinary tract (CAKUT). Mutations in Sprouty1, an intracellular Ret inhibitor, results in supernumerary kidneys, megaureters, and hydronephrosis in mice. But the underlying molecular mechanisms involved and which structural domains are essential for Sprouty1 function are a matter of controversy, partly because studies have so far relied on ectopic overexpression of the gene in cell lines. A conserved N-terminal tyrosine has been frequently, but not always, identified as critical for the function of Sprouty1 in vitro . Methods We generated Sprouty1 knockin mice bearing a tyrosine-to-alanine substitution in position 53, corresponding to the conserved N-terminal tyrosine of Sprouty1. We characterized the development of the genitourinary systems in these mice via different methods, including the use of reporter mice expressing EGFP from the Ret locus, and whole-mount cytokeratin staining. Results Mice lacking this tyrosine grow ectopic ureteric buds that will ultimately form supernumerary kidneys, a phenotype indistinguishable to that of Sprouty1 knockout mice. Sprouty1 knockin mice also present megaureters and vesicoureteral reflux, caused by failure of ureters to separate from Wolffian ducts and migrate to their definitive position. Conclusions Tyrosine 53 is absolutely necessary for Sprouty1 function during genitourinary development in mice.
Liver organoids: from basic research to therapeutic applications
Authors: Nicole Prior, Patricia Inacio, Meritxell Huch
Journal: Gut (2019)

Organoid cultures have emerged as an alternative in vitro system to recapitulate tissues in a dish. While mouse models and cell lines have furthered our understanding of liver biology and associated diseases, they suffer in replicating key aspects of human liver tissue, in particular its complex architecture and metabolic functions. Liver organoids have now been established for multiple species from induced pluripotent stem cells, embryonic stem cells, hepatoblasts and adult tissue-derived cells. These represent a promising addition to our toolbox to gain a deeper understanding of this complex organ. In this perspective we will review the advances in the liver organoid field, its limitations and potential for biomedical applications.
IgE reactivity against herpes simplex virus 1 in patients with atopic dermatitis complicated by eczema herpeticum
Authors: Beatriz Cabanillas, Heike Weighardt, Elena Izquierdo, Irmgard Förster, Natalija Novak
Journal: Allergy (2019)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Clare Gerada: Doctors’ mental health and stigma—the tide is turning
Authors: Clare Gerada
Journal: BMJ (2019)

I’ve recently been unwell. Thankfully, nothing too serious—a broken bone in my foot and some dental surgery. Both resulted in visible manifestations of illness: an orthopaedic boot for my foot, and heavy swelling and bruising to my face. The overwhelming response from medical colleagues and friends was sympathetic, with a constant chatter of advice, suggestions for healing, and tales of their own injuries and operations.

It set me wondering what my experience would have been if, instead of obvious physical injuries, I’d admitted to hidden psychological ones. Would the sympathy have been as free flowing, …
Focal Immunotherapy-Induced Pancreatitis Mimicking Metastasis on FDG PET/CT
Authors: Jeeban Paul Das, Darragh Halpenny, Richard K. Do, Gary A. Ulaner
Journal: Clinical Nuclear Medicine (2019)

Abstract A 46-year-old man with metastatic lung adenocarcinoma was treated with pembrolizumab. FDG PET/CT was performed after 3 cycles of treatment and revealed a focal region of pancreatic tail enlargement with an SUVmax value of 7. Following treatment with corticosteroids and discontinuation of pembrolizumab, radiological resolution was observed, and a diagnosis of focal immunotherapy-induced pancreatitis was made. A unique spectrum of FDG-avid adverse events can develop in patients treated with immune-checkpoint inhibitors that may mimic metastatic disease. Knowledge of the radiologic features of these potential imaging pitfalls is crucial among those interpreting FDG PET/CT to allow prompt and decisive treatment.
A simple real-time model for predicting acute kidney injury in hospitalized patients in the US: A descriptive modeling study
Authors: Michael Simonov, Ugochukwu Ugwuowo, Erica Moreira, Yu Yamamoto, Aditya Biswas, Melissa Martin, Jeffrey Testani, F. Perry Wilson
Journal: PLoS Medicine (2019)

Background Acute kidney injury (AKI) is an adverse event that carries significant morbidity. Given that interventions after AKI occurrence have poor performance, there is substantial interest in prediction of AKI prior to its diagnosis. However, integration of real-time prognostic modeling into the electronic health record (EHR) has been challenging, as complex models increase the risk of error and complicate deployment. Our goal in this study was to create an implementable predictive model to accurately predict AKI in hospitalized patients and could be easily integrated within an existing EHR system. Methods and findings We performed a retrospective analysis looking at data of 169,859 hospitalized adults admitted to one of three study hospitals in the United States (in New Haven and Bridgeport, Connecticut) from December 2012 to February 2016. Demographics, medical comorbidities, hospital procedures, medications, and laboratory data were used to develop a model to predict AKI within 24 hours of a given observation. Outcomes of AKI severity, requirement for renal replacement therapy, and mortality were also measured and predicted. Models were trained using discrete-time logistic regression in a subset of Hospital 1, internally validated in the remainder of Hospital 1, and externally validated in Hospital 2 and Hospital 3. Model performance was assessed via the area under the receiver-operator characteristic (ROC) curve (AUC). The training set cohort contained 60,701 patients, and the internal validation set contained 30,599 patients. External validation data sets contained 43,534 and 35,025 patients. Patients in the overall cohort were generally older (median age ranging from 61 to 68 across hospitals); 44%–49% were male, 16%–20% were black, and 23%–29% were admitted to surgical wards. In the training set and external validation set, 19.1% and 18.9% of patients, respectively, developed AKI. The full model, including all covariates, had good ability to predict imminent AKI for the validation set, sustained AKI, dialysis, and death with AUCs of 0.74 (95% CI 0.73–0.74), 0.77 (95% CI 0.76–0.78), 0.79 (95% CI 0.73–0.85), and 0.69 (95% CI 0.67–0.72), respectively. A simple model using only readily available, time-updated laboratory values had very similar predictive performance to the complete model. The main limitation of this study is that it is observational in nature; thus, we are unable to conclude a causal relationship between covariates and AKI and do not provide an optimal treatment strategy for those predicted to develop AKI. Conclusions In this study, we observed that a simple model using readily available laboratory data could be developed to predict imminent AKI with good discrimination. This model may lend itself well to integration into the EHR without sacrificing the performance seen in more complex models.