tbuckley/cabot-search huggingface dataset:
PITX2 Expression in Non-functional Pituitary Neuroendocrine Tumor with Cavernous Sinus Invasion
Authors: Ryota Tamura, Kentaro Ohara, Yukina Morimoto, Kenzo Kosugi, Yumiko Oishi, Mizuto Sato, Kazunari Yoshida, Masahiro Toda
Journal: Endocrine Pathology (2019)
Role of occlusion in periodontal disease
Authors: Euloir Passanezi, Adriana Campos Passanezi Sant'Ana
Journal: Periodontology 2000 (2019)

Abstract This article deals with establishing a new link between trauma from occlusion and periodontal pockets based on the know‐how and background gradually developed. To provide a better understanding to the reader, a historical perspective is firstly presented. The main features on the controversy of the role played by trauma from occlusion on the physiologic behavior of the periodontal structures are shown, together with how deviations from the normal characteristics of this relationship itself affect the integrity of the periodontal tissues when or associated with dental biofilm in the presence or not of periodontal pockets have arisen. The literature provides evidence showing that the very first publication to establish a strong correlation between trauma from occlusion and periodontal pockets in humans was of Latin‐American origin. However, subsequently, trauma from occlusion was mostly evaluated by an American group, followed by a Scandinavian group, yet with some contributions from the Latin‐American group. Basically trauma from occlusion has been correlated with periodontal pockets in view of the fact that these would render the periodontal supporting tissues more amenable to the spread of inflammation of biofilm‐related periodontal pockets. This would facilitate the fast deepening of periodontal pockets, influencing the generation of infrabony periodontal pockets or suprabony periodontal pockets that are deeper than in areas without trauma from occlusion. The factors related to these different behaviors are discussed. Several clinical cases are presented showing evidence that corroborates the possibility of an actual interrelationship between trauma from occlusion and periodontitis. Theoretical evaluations based on recent advances of the mechanisms involving molecular modulation in physiological and altered occlusal functions, as well as on research data, and evaluations from data of clinical cases, support the assumption that trauma from occlusion and periodontitis may embrace the unique pathologic condition of the associated lesion trauma from occlusion plus periodontitis or act independently even if both co‐exist simultaneously in a particular case. The link between both conditions that was emphasized as definitively necessary in order for an associated lesion to develop is that both lesions, namely trauma from occlusion and periodontitis, occur in their destructive stage at exactly the same time. This involvement would explain why so many different data are presented in the literature and hopefully will shed some light for development of new methodologies of research. Clinical cases were selected to present a treatment philosophy on the subject.
Increased intratumoral mast cells foster immune suppression and gastric cancer progression through TNF-α-PD-L1 pathway
Authors: Yipin Lv, Yongliang Zhao, Xianhua Wang, Na Chen, Fangyuan Mao, Yongsheng Teng, Tingting Wang, Liusheng Peng, Jinyu Zhang, Ping Cheng, Yugang Liu, Hui Kong, Weisan Chen, Chuanjie Hao, Bin Han, Qiang Ma, Quanming Zou, Jun Chen, Yuan Zhuang
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Mast cells are prominent components of solid tumors and exhibit distinct phenotypes in different tumor microenvironments. However, the nature, regulation, function, and clinical relevance of mast cells in human gastric cancer (GC) are presently unknown. <h3>Methods</h3> Flow cytometry analyses were performed to examine level and phenotype of mast cells in samples from 114 patients with GC. Multivariate analysis of prognostic factors for overall survival was performed using the Cox proportional hazards model. Kaplan-Meier plots for patient survival were performed using the log-rank test. Mast cells, T cells and tumor cells were isolated or generated, stimulated and/or cultured for in vitro and in vivo function assays. <h3>Results</h3> Patients with GC showed a significantly higher mast cell infiltration in tumors. Mast cell levels increased with tumor progression and independently predicted reduced overall survival. These tumor-infiltrating mast cells accumulated in tumors by CXCL12-CXCR4 chemotaxis. Intratumoral mast cells expressed higher immunosuppressive molecule programmed death-ligand 1 (PD-L1), and mast cells induced by tumors strongly express PD-L1 proteins in both time-dependent and dose-dependent manners. Significant correlations were found between the levels of PD-L1<sup>+</sup> mast cells and pro-inflammatory cytokine TNF-α in GC tumors, and tumor-derived TNF-α activated NF-κB signaling pathway to induce mast cell expression of PD-L1. The tumor-infiltrating and tumor-conditioned mast cells effectively suppressed normal T-cell immunity through PD-L1 in vitro, and tumor-conditioned mast cells contributed to the suppression of T-cell immunity and the growth of human GC tumors in vivo; the effect could be reversed by blocking PD-L1 on these mast cells. <h3>Conclusion</h3> Thus, our results illuminate novel immunosuppressive and protumorigenic roles of mast cells in GC, and also present a novel mechanism in which PD-L1 expressing mast cells link the proinflammatory response to immune tolerance in the GC tumor milieu.
Collagen gel droplet embedded culture drug sensitivity test (CD-DST) for esophageal cancers
Authors: Hiroshi Makino, Masao Miyashita, Tsutomu Nomura, Kiyohiko Yamashita, Ken Takahashi, Ichiro Akagi, Koji Sasajima, Takashi Tajiri
Journal: Cancer Research (2006)

3617  Cisplatin (CDDP) and 5-fluorouracil (5-FU) are usually combined for treating esophageal squamous cell carcinoma (ESCC). Standard chemotherapy using CDDP and 5-FU was effective for ESCC and also established for neoadjuvant chemotherapy. Recently chemotherapy protocols using docetaxel (DOC) for ESCC also have been reported. But we cannot know whether chemotherapy is sensitive or not until the patient is treated with CDDP, 5-FU or DOC, and the patients have to waste time and suffer from side effect of chemotherapy if the chemotherapy is not sensitive. To evaluate chemotherapy sensitivity, collagen gel droplet embedded culture drug sensitivity test(CD-DST) for esophageal cancer was applied. This method consists of a collagen gel droplet embedded culture step, exposure and washout of anticancer drug, a serum-free culture step, and evaluation of anticancer effect, using small quantities of cells. CD-DST has many advantages including high primary culture success rates, the original growth characteristics of the cultured cells, easy quantification of the anticancer effects without contamination with fibroblasts by using an image analysis system. Our research subjects were 20 patients with esophageal cancer who had undergone operations between August 2004 and October 2005 in our department. CD-DST test was applied to 21 specimens including 20 patients with (19 ESCCs, 1 small cell carcinoma,1 adenocarcinoma). Interpretable results using CD-DST test were obtained from 55% (11/20) of tumor specimens studied. Chemosensitivities to CDDP, 5-FU or DOC of tumors were 75% (6/8): 5-FU 80%(8/10), CDDP 33%(2/6), 5-FU+CDDP 100%(1/1), DOC67%(2/3). Many investigators reported that using CD-DST, sensitivity based induction chemotherapy was successful in the patients. This method has an advantage of a good correlation between in vitro and in vivo results, and simplicity and speed. We therefore consider that the CD-DST can be used to predict the response to anti-cancer drugs, and may also provide important information by contributing to the development of new chemotherapy regimens and tailor-made therapy for neoadjuvant chemotherapy. Analysis of immunohistochemistry or mRNA expression levels of molecular markers associated with chemotherapy sensitivity were perfomed by CD-DST test, and there is a report of a good correlation between immunohistochemistry or cDNA mocroarray and CD-DST test. These results suggest that we can predict more available chemotherapy sensitivity by combined tests.
Oncogenic Addiction to ERBB2 Signaling Predicts Response to Trastuzumab in Urothelial Cancer
Authors: Michael Karass, Rohan Bareja, Ethan Shelkey, Panagiotis J. Vlachostergios, Brian D. Robinson, Francesca Khani, Juan Miguel Mosquera, Douglas S. Scherr, Andrea Sboner, Scott T. Tagawa, Ana M. Molina, Olivier Elemento, David M. Nanus, Bishoy M. Faltas
Journal: Journal of the National Comprehensive Cancer Network (2019)

Urothelial carcinoma (UC) is a common and frequently lethal cancer. Despite the presence of genomic alterations creating dependency on particular signaling pathways, the use of targeted therapies in advanced and metastatic UC has been limited. We performed an integrated analysis of whole-exome and RNA sequencing of primary and metastatic tumors in a patient with platinum-resistant UC. We found a strikingly high ERBB2 mRNA expression and enrichment of downstream oncogenic ERBB2 signaling in this patient's tumors compared with tumors from an unselected group of patients with UC (N=17). This patient had an exceptional sustained response to trastuzumab. Our findings show that oncogenic addiction to ERBB2 signaling potentially predicts response to ERBB2-directed therapy of UC.
Liquid biopsy assay for lung carcinoma using centrifuged supernatants from fine-needle aspiration specimens
Authors: B. Hannigan, W. Ye, M. Mehrotra, V. Lam, A. Bolivar, S. Zalles, B.A. Barkoh, D. Duose, P.C. Hu, R. Broaddus, J. Stewart, J. Heymach, L.J. Medeiros, I. Wistuba, R. Luthra, S. Roy-Chowdhuri
Journal: Annals of Oncology (2019)

IntroductionTumor mutation profiling is standard-of-care in lung carcinoma patients. However, comprehensive molecular profiling of small specimens, including core needle biopsy (CNB) and fine-needle aspiration (FNA) specimens, may often be inadequate due to limited tissue. Centrifuged FNA supernatants, which are typically discarded, have emerged recently as a novel liquid-based biopsy for molecular testing. In this study, we evaluate the use of lung carcinoma FNA supernatants for detecting clinically relevant mutations.MethodsSupernatants from lung carcinoma FNA samples (n = 150) were evaluated. Samples were further analyzed using next-generation sequencing (NGS) and ultrasensitive droplet digital PCR (ddPCR). Mutation profiles in a subset of samples were compared with results derived from paired tissue samples from the same patient (n = 67) and available plasma liquid biopsy assay (n = 45).ResultsAll 150 samples yielded adequate DNA and NGS were carried out successfully on 104 (90%) of 116 selected samples. Somatic mutations were detected in 82% of the samples and in 50% of these patients a clinically relevant mutation was identified that would qualify them for targeted therapy or a clinical trial. There was high overall concordance between the mutation profiles of supernatants and the corresponding tissue samples, with 100% concordance with concurrent FNA and 96% with concurrent CNB samples. Comparison of actionable driver mutations detected in supernatant versus plasma samples showed 84% concordance.ConclusionsFNA supernatants can provide a valuable specimen source for genotyping lung carcinoma especially in patients with insufficient tumor tissue, thereby reducing multigene mutation profiling failure rates, improving turnaround times, and avoiding repeat biopsies.
Postpartum depression: new drug will be monitored at approved sites
Authors: Owen Dyer
Journal: BMJ (2019)

The first drug approved by the US Food and Drug Administration for the treatment for postpartum depression will be administered only to short term inpatients at specially approved sites, as the FDA seeks to monitor risks of adverse events that emerged during clinical trials.1

Brexanolone (made by Sage Therapeutics and marketed as Zulresso), is an injected drug that has shown a much faster effect than oral treatments in ameliorating depressive symptoms, but the demands of infusion—and the risk identified in trials of patients fainting or having reduced consciousness—mean that patients will have to remain at designated treatment centres for 60 hours while the drug is infused.

Any adverse events will be carefully tracked as part of a risk evaluation and …
Abstract 19227: Results of an Implantable Cardioverter Defibrillator Screening Program Based on Transthoracic Echocardiography at a Tertiary Academic Medical Center
Authors: William F Dresen, Augustus E Mealor, Will Camnitz, Samuel Love, Neha Choubey, Rohit Malhotra, Andrew Darby, Pamela Mason, John Dent, J. Michael Mangrum, John P DiMarco, John D Ferguson, Kenneth C Bilchick
Journal: Circulation (2014)

Introduction: There has been interest in quality improvement programs based on screening of LV function in order to increase rates of adherence to guideline-based recommendations for implantable cardioverter defibrillators (ICDs) for primary prevention (PP) of sudden cardiac death. Methods: We queried the echocardiography database at a tertiary academic medical center for patients with LVEF ≤ 35% on a transthoracic echocardiogram (TTE) and analyzed clinical data from the electronic medical record. We then determined the proportion receiving ICDs, reasons ICDs were not implanted, mortality rates, and our risk score for death (JACC 2012; 60:1647-55). Results: Of the 406 patients reviewed with LVEF 35% or less, 22.9% had an ICD at the time of the TTE and 10.8% had an ICD implanted during a median follow-up of 4.0 years (ICD-DURING-FU). With respect to patients without ICDs, 6.2% (of total group) did not survive the index hospitalization, 16.4% did not meet primary prevention criteria due to life expectancy less than 1 year or other guideline-based criteria, and 23.4% had spontaneous LVEF improvement to above 35% (LVEF-SPONT-IMPROVED), while the remaining 20.0% met guideline-based criteria for a primary prevention ICD (NO-ICD-DESPITE-CRITERIA) (Table). The NO-ICD-DESPITE-CRITERIA group had a greater mortality (35.8%) than the LVEF-SPONT-IMPROVED group (21.1%; p=0.03) and the ICD-DURING-FU group (20.5%; trend with p=0.07). In a multivariable logistic model, LVEF-SPONT-IMPROVED (v. ICD-DURING-FU) patients had OR=0.50 for death (p=0.049) after adjustment for the risk score. Conclusions: In a large cross section of patients with TTEs and extended follow-up, 1 in 5 patients did not have ICDs implanted despite meeting standard PP criteria. Another significant group did not have ICDs implanted because they had improvement in LV function during follow-up, and these patients had a similar survival probability to patients who did have ICDs implanted during follow-up.
Percutaneous Transcatheter Mitral Valve Replacement
Authors: John G. Webb, Dale J. Murdoch, Robert H. Boone, Robert Moss, Adrian Attinger-Toller, Philipp Blanke, Anson Cheung, Mark Hensey, Jonathon Leipsic, Kevin Ong, Janarthanan Sathananthan, David A. Wood, Jian Ye, Paolo Tartara
Journal: Journal of the American College of Cardiology (2019)
Interhospital Transfer of Stroke Patients for Endovascular Treatment
Authors: James C. Grotta
Journal: Circulation (2019)

T2][3][4][5] These are the worst strokes that most often do not respond to systemic thrombolytics.The number needed to treat to result in one additional patient with no residual disability was only 4. Endovascular treatment was started within 6 hours of stroke symptom onset, but as with systemic thrombolysis and most reperfusion therapies, outcomes were better with faster achievement of successful reperfusion.Specialty societies and their guidelines almost immediately adopted EVT as standard of care. 6In 2018, additional studies showed that some patients with adequate collaterals as identified on tissue/perfusion computed tomography or magnetic resonance imaging can benefit from EVT up to 24 hours after stroke symptom onset. 7,8he dual accomplishment of establishing a powerful new treatment and expanding the time window for its application to more patients has galvanized the stroke community.However, it has also created some problems, the main one being that the interventionalists and hospitals trained and equipped to identify good candidates and carry out EVT are largely limited to tertiary centers in urban areas.This is important, as for example, almost half of the US population does not live within a 60-minute drive of such a tertiary center 9 and must be transferred from another center.This issue, ie, getting patients eligible for EVT to the right hospital, is the broad topic addressed by the important study by Shah et al 10 published in this issue of Circulation.Using the Get With The Guidelines database, the authors found that since 2012, 43% of patients receiving EVT arrived by transfer from another hospital, with a sharp increase after 2015 when results from the 5 trials demonstrating EVT effectiveness were first presented and published.Furthermore, patients who were transferred-in took over an hour longer to get treated by EVT as calculated from the time the patient was last known normal to EVT initiation.Although transferin patients were moved from the emergency department door to EVT faster than those arriving directly, the door-to-EVT initiation times for the 2 groups still exceeded an hour (68 minutes for transfer versus 128 minutes for direct).These data graphically illustrate a major problem with current stroke systems of care.Roughly half of patients who need the most effective stroke treatment available have to be moved from one hospital to another to receive it, resulting in substantial delay, not to mention cost and inconvenience.These findings are consistent with current trends in stroke management.Transfers for "higher level of care" (not just for EVT) have increased dramatically over
Liver fibrosis affects the targeting properties of drug delivery systems to macrophage subsets in vivo
Authors: Can Ergen, Patricia Maria Niemietz, Felix Heymann, Maike Baues, Felix Gremse, Robert Pola, Louis van Bloois, Gert Storm, Fabian Kiessling, Christian Trautwein, Tom Luedde, Twan Lammers, Frank Tacke
Journal: Biomaterials (2019)
Abstract 17423: Identifying Left Ventricular Origin of Premature Ventricular Contractions Based on a Characteristic "Teton Sign" QRS on Ambulatory Holter Monitoring
Authors: Sandeep S Sodhi, Curtis M Steyers, Praveen K Rao, Olusegun Olusesi, Phillip S Cuculich, Daniel H Cooper
Journal: Circulation (2017)

Introduction: Premature ventricular contractions (PVCs) frequently originate from the outflow tract of the right ventricle (RVOT) or left ventricle (LVOT). Catheter-based mapping and ablation of RV...
HSR19-095: Healthcare Resource Utilization and Costs in Patients Treated with Systemic Therapies in Metastatic Melanoma
Authors: Andrew J Klink, Bruce Feinberg, Frank Xiaoqing Liu, Sama Ahsan, Damion Nero, Bartosz Chmielowski
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: The treatment (tx) landscape for patients (pts) with metastatic melanoma (MM) has changed dramatically from systemic chemotherapy (chemo) to novel therapies, including targeted therapies (TT) and immunotherapies (IO mono- and combination therapy) in recent years. Healthcare resource utilization (HCRU) and cost data are needed to further evaluate tx in a value-based healthcare system. The study aimed to describe HCRU and total cost of care among first line (1L) US MM pts treated with IO, TT, or chemo. Methods: A retrospective observational study was conducted using a U.S. claims database. Adults with ≥2 claims for melanoma and ≥1 claim for metastasis between January 1, 2012 and June 30, 2017 were identified. Pts had pharmacy and medical enrollment ≥6 months pre and ≥3 months post 1L tx start. Per pt per month (PPPM) HCRU and costs were calculated by 1L tx drug class: PD-1, CTLA-4, CTLA-4+PD-1, mono-TT, combo-TT, and chemo. Adjusted odds ratios (OR) for HCRU were estimated by logistic regressions, and adjusted costs were estimated by generalized linear models to control for differences in pt characteristics across groups. Results: Among 1,599 MM pts (255 PD-1, 555 CTLA-4, 88 CTLA-4+PD-1, 210 mono-TT, 102 combo-TT, 389 chemo), mean age ranged from 59–68 years across tx groups, and the majority was male (62%). Any hospitalization during 1L was less frequent among PD-1 (26%) compared to 35%–46% of all other groups (all P &lt;.05). CTLA-4, CTLA-4+PD-1, and combo-TT had increased odds of hospitalization compared to PD-1 (adjusted ORs: 2.10, 2.35, 2.15, respectively; all P &lt;.05). Total adjusted PPPM costs were significantly lower for PD-1 compared to CTLA-4, CTLA-4+PD-1 and combo-TT and higher compared to mono-TT and chemo (Table 1). Conclusions: Hospitalizations represent an important healthcare resource for MM pts and were lowest among PD-1. Total monthly costs varied substantially across 1L regimens and were significantly lower in PD-1 compared to CTLA-4, CTLA-4+PD-1, and combo-TT. HCRU and costs differentiate 1L MM regimens.
Abstract 18689: Time of Day and Day of Week Variations in Chest Pain Encounters at the Prehospital Setting
Authors: Mohammad Alhamaydeh, Mohammad Alrawashdeh, Christian Martin-Gill, Clifton Callaway, Salah S Al-Zaiti
Journal: Circulation (2017)

Introduction: The onset of acute coronary syndrome (ACS) often shows time-of-day variation, which is usually attributed to the circadian pattern of neurohormonal activities, coagulation cascade, an...
Many private primary care services and slimming clinics flout regulations, finds regulator
Authors: Gareth Iacobucci
Journal: BMJ (2019)

Almost half of private primary care services and slimming clinics in England aren’t providing safe care, the country’s healthcare regulator has warned.

For its new report the Care Quality Commission analysed a sample of inspection reports of private primary medical care services, including general practice services and specialist clinics.1

Safety was identified as the biggest problem across the private primary care sector. In particular it noted concerns about the safety and efficacy of prescribing, poor record keeping, and clinicians not communicating their activity with the patient’s GP. This was often related to …
Infographic. 11 best practice recommendations for care in musculoskeletal pain
Authors: Ivan Lin, Alan Rankin, Louise Wiles, Rob Waller, Roger Goucke, Yusuf Nagree, Michael Gibberd, Leon Straker, Chris G Maher, Peter B O’Sullivan
Journal: British Journal of Sports Medicine (2019)

Musculoskeletal (MSK) pain disorders are a major societal burden1 and yet health care practices are not always concordant with recommended care.2 3 …