tbuckley/cabot-search huggingface dataset:
A study of denileukin diftitox to treat refractory ovarian cancer.
Authors: Cheryl M. Czerlanis, Maureen Drakes, Amira Elmishad, Kelly Kosik, Mala Parthasarathy, Ronald Potkul, Donna M. Smith, Zheng Yu, Sandra Zakrzewski, Patrick J. Stiff
Journal: Journal of Clinical Oncology (2012)

e13121 Background: The number of circulating CD4+ regulatory T-cells (Tregs) has been correlated with outcome in advanced ovarian cancer. A prior report (Barnett, et al; AACR Abstracts 2006: 1148) suggested that denileukin diftitox, a fusion toxin containing interleukin-2 fused to diphtheria toxin, may be of therapeutic value in this disease acting via Treg depletion. As part of a larger study of denileukin diftitox with dendritic cell-based vaccination, we treated patients with the agent alone to determine if it depletes circulating CD4 + CD25 Hi FoxP3 + CD127 Low Tregs and induces clinical responses. Methods: Patients with relapsed/refractory ovarian or primary peritoneal carcinoma were eligible. No chemotherapy or immunotherapy was allowed for the preceding 4 weeks. Denileukin diftitox 18 μg/kg IV was given every 28 days for up to 4 cycles. Weekly monitoring of CD4 Tregs and CD8+CD28- Tregs was done by monoclonal antibody labeling of PBMC and flow cytometry studies. Clinical responses were measured by standard methods of disease assessment including CA125 testing. Results: Seven women were treated, of whom 3 had minimal residual disease (MRD). No Grade III-IV toxicities were seen. Unlike the prior report, no clinical responses were seen in 4 patients with bulky measurable disease. Median progression free survival was 5.5 months (range 0.5-20.5) and median overall survival will exceed 21.6 months (range 1.4-26.5+) with MRD a marker for prolonged remissions and survival. We saw no Treg depletion after the 1 st cycle; i.e., no patient had ≥25% reduction in Tregs at the expected nadir at day 14. Mean CD4+CD25 Hi FoxP3 + CD127 Low Tregs/CD4 cells for controls was 1.16% (range .35-2.13) at baseline, with no significant temporal variation. Mean Tregs/CD4 cells for treated subjects was 2.89% (range 1.06-5.40) at baseline and 3.11% (range .81-5.13) at day 14. For 6 patients who received ≥2 cycles, mean Tregs/CD4 cells dropped to 1.95% (range .71-3.74) at day 42 and 1.65% (range .78-2.36) at day 70. CD8+CD28- Tregs were only increased (&gt;50% of CD8 T-cells) in 2 patients and not correlated with remission duration. Conclusions: These data suggest that denileukin diftitox depletes Tregs in relapsed ovarian cancer only with repeated dosing and may be of clinical value in MRD.
Monoclonal Gammopathy May Be of Unpredictable Significance
Authors: Nikhil C. Munshi, Sundar Jagannath, Herve Avet-Loiseau
Journal: JAMA Oncology (2019)

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The Right and Left Hands of the State — Two Patients at Risk of Deportation
Authors: Anita Berlin, Victoria Koski-Karell, Kathleen R. Page, Sarah Polk
Journal: New England Journal of Medicine (2019)

Interview with Dr. Anita Berlin on the relationship between the state and medical care and maintaining the integrity of the medical code of ethics. (14:10)Download A woman escapes a violent homeland and a rapist-captor in the country where she seeks refuge, only to have an ED nurse turn her over to the police as an undocumented immigrant. How can clinicians negotiate between governmental expectations and their duty to patients?
Guided geriatric interventions (GI) in older adults with cancer: What, how, and for whom? The French PACA EST Cohort Experience.
Authors: Rabia Boulahssass, Sebastien Gonfrier, Jean-Marc Ferrero, Noemie Champigny, Cyrielle Rambaud, Remy Largillier, Damien Chauviere, Emmanuel Barranger, Jean Marc Bereder, Emmanuel Benizri, Delphine Borchiellini, Matthieu Durand, Patrick Baque, Jerome Delotte, Jerome Barriere, Jean-Michel Hannoun-Levi, Joel Guigay, Thierry Piche, Eric FRANCOIS, Olivier Guerin
Journal: Journal of Clinical Oncology (2019)

11548 Background: Some previous studies in geriatric oncology have described the GI and their adherence. Today’s challenge is to screen patients needing specific GI and repeated Comprehensive Geriatric Assessments (CGA). We recently analyzed a phenotype of patients requiring more GI (Boulahssass et al, Cancers 2019). The main purpose of the present study is to compare types of GI implemented, according to patient frailty levels, in order to better understand the necessary care plan. Methods: Between April 2012 and May 2018, 3530 consecutive patients with solid tumors were enrolled in this multicentric, prospective cohort. 3140 patients (mean age:82y) were finally included and a CGA was performed at Baseline. Twelve GI were standardized, individualized or based on experience if no guidelines were available. Within 1 month, geriatricians including patients in the cohort received standardized training. Logistic regression was performed to compare types of GI in the 3 groups using the Balducci Score (B1/B2/B3). Results: 8819 GI were implemented for the 3140 patients. On average, fit patients had 1.5 GI (n = 146), vulnerable patients 2.4 GI (n = 1568) and frail patients 3.3 GI (n = 1426). We observed no significant differences between the 3 groups concerning specific pain management (Fit vs B2: p = 0.19; Fit vs B3: p = 0.57) and psychological care (Fit vs B2:p = 0.03; Fit vs B3:p = 0.24). In vulnerable and frail patients, we recorded more significant GI for nutritional care, delirium prevention, comorbidity management, nursing interventions, social worker interventions, treatment modifications for optimization or iatrogenic disorders and physiotherapy, with the highest Odds Ratio for nursing interventions (Fit vs B2 OR:2.9 p = 0.011; Fit vs B3 OR:9 P &lt; 0.001) and physiotherapy (Fit vs B2:OR 4.3 p &lt; 0.001; Fit vs B3:OR:9 p &lt; 0.001). B3 patients had significantly more GI on care pathways modifications (OR:3.1, p = 0.002) and caregiver care (OR:2, p = 0.049). Conclusions: Fit patients also needed GI. We observed differences in types of GI between the groups. However, the aims and levels also seemed to differ and need further studies to analyze their impact.
Актуальні питання діагностики та корекції лактазної недостатності в дітей та дорослих
Authors: Yu.I. Reshetilov, I.I. Redko, N.N. Protsenko, L.F. Kuznetsova, O.Yu. Vasilchenko, T.V. Bogoslav
Journal: GASTROENTEROLOGY (2014)

У статті обговорюються особливості клінічного перебігу та проблеми лікування лактазної недостатності в дітей та дорослих. Доведена терапевтична ефективність застосування замісної ферментотерапії при лікуванні первинної та вторинної лактазної недостатності в новонароджених та дітей раннього віку як на грудному, так і на штучному вигодовуванні та в дітей старшого віку й дорослих, що дозволяє зберегти споживання лактози та зменшити обсяг медикаментозної терапії.
A Prospective Head-to-Head Comparison of 18F-Fluciclovine With 68Ga-PSMA-11 in Biochemical Recurrence of Prostate Cancer in PET/CT
Authors: Birgit Pernthaler, Roman Kulnik, Christian Gstettner, Spela Salamon, Reingard M. Aigner, Herbert Kvaternik
Journal: Clinical Nuclear Medicine (2019)

Purpose One of the major challenges for all imaging modalities is accurate detection of prostate cancer (PCa) recurrence. Beyond the established 68 Ga-PSMA, a novel promising PET tracer in PCa imaging is 18 F-fluciclovine. For evaluating the advantages and disadvantages and the comparability, we conducted a prospective head-to-head comparison on 18 F-fluciclovine and 68 Ga-PSMA-11 in patients with biochemical recurrence of PCa. Methods 58 patients with biochemical recurrence of PCa after definitive primary therapy were included. Both scans were performed within a time window of mean 9.4 days. All scans were visually analyzed independently on a patient-, region- and lesion-based analysis. All the examinations were performed in the same medical department using identical scanners at any time. Results The overall detection rate for PCa recurrence was 79.3% in 18 F-fluciclovine and 82.8% in 68 Ga-PSMA-11 ( P = 0.64). Local recurrence was detected in 37.9% on 18 F-fluciclovine and in 27.6% on 68 Ga-PSMA-11 ( P = 0.03). Local pelvic lymph node recurrence was detected on 18 F-fluciclovine versus 68 Ga-PSMA-11 in 46.6% versus 50%, in extrapelvic lymph node metastases in 41.4% versus 51.7% and in bone metastases in 25.9% versus 36.2%. Lesion-based analysis showed identical findings in local pelvic lymph nodes in 39.7%, in extrapelvic lymph nodes in 22.4%, and in bone metastases in 13.8%. Conclusions The advantage of 18 F-fluciclovine is detecting curable localized disease in close anatomical relation to the urinary bladder, whereas 68 Ga-PSMA-11 fails because of accumulation of activity in the urinary bladder. 18 F-fluciclovine is almost equivalent to 68 Ga-PSMA-11 in detecting distant metastases of PCa recurrence.
Abstract 294: Mitochondrial Inner Membrane Protein Plays a Critical Role in the Ischemic Myocardial Dysfunction and Determines the Outcome of Cardiac Recovery
Authors: Jean C Bopassa
Journal: Circulation Research (2017)

Disorders characterized by ischemia/reperfusion (I/R), such as myocardial infarction and stroke, is the leading cause of death in the US. Indeed, reoxygenation of cardiomyocytes after an ischemic insult leads to mitochondrial Ca 2+ overload and increase in ROS generation that triggers the opening of mitochondrial permeability transition pore (mPTP), making this event crucial in the mechanism of cell death after I/R. Several proteins have been proposed contributing to formation and function of mPTP, but its exact molecular identity and mechanism still need to be elucidated. Cyclophylin D (CypD) deleted mice displayed a marked desensitization of the mPTP to Ca 2+ overload and oxidative stress establishing it as a key component of mPTP. However, CypD null mitochondria still exhibit mPTP activity. Using 2D-DIGE and mass spectrometry, we identified mitofilin, which plays an important role of maintaining mitochondrial cristae morphology, as a protein that the expression is reduced after I/R versus sham. We thus investigated the impact of mitofilin regulation in the mPTP formation. We found that: i) mitofilin -/- mice subjected to I/R exhibited an increase in myocardial infarct size, a reduced cardiac functional recovery, a reduced mitochondrial Ca 2+ retention capacity required to induce the mPTP opening and an increase in mitophagy compared to WT; ii) Knockdown of mitofilin in H9c2 myoblasts with siRNA led to: increase in apoptosis via activation of AIF-PARP1 pathway that is associated with S phase arrest of the cell cycle and nuclear fragmentation, increase in mitochondrial cristae disorganization, in ROS production and Calpain activity, as well as decrease in intracellular ATP production and mitochondrial membrane potential versus scramble siRNA; iii) mitofilin structurally bound to CypD and this interaction is abridged after the mPTP opening triggered by Ca 2+ overload after I/R. These results indicate that mitofilin plays an essential role in the mechanism of mPTP formation and cardiomyocyte death.
Oesophageal cancer: risks, prevention, and diagnosis
Authors: Sri G Thrumurthy, M Asif Chaudry, Sasha S D Thrumurthy, Muntzer Mughal
Journal: BMJ (2019)

### What you need to know

Oesophageal cancer is currently the sixth commonest source of cancer-associated death across the world: 572 034 new cases and 508 585 mortalities were reported in 2018.1 Global disease incidence has increased significantly in the past four decades.23 Recent data from the World Health Organization suggest that age-standardised incidence is higher across eastern Asia than any other region, but the UK continues to harbour the highest incidence among individual countries.1 In this review, “oesophageal cancer” refers to adenocarcinoma of the oesophagus and that of the gastro-oesophageal junction, because their pathophysiological and clinical similarities allow them to be staged and managed as similar entities (gastric cancer is staged differently).4

Over the past decade, the increased uptake of early referral schemes across the UK, North America, and Western Europe has improved detection of early stage, curable disease.567 Coupled with novel endoscopic therapies and perioperative treatment strategies, overall survival rates have also improved.8

This review aims to guide generalists through the referral and early diagnosis processes of oesophageal cancer, as well as highlighting risk and current preventive strategies.

Oesophageal cancer refers to tumours originating from the oesophageal mucosa that may progress locally to involve the underlying submucosa and muscular layer, eventually invading adjacent structures such as the tracheobronchial tree, recurrent laryngeal nerve, thoracic aorta, or diaphragm (fig 1).



Fig 1 
Layers of the oesophageal …
Health outcomes of young children born to mothers who received 2009 pandemic H1N1 influenza vaccination during pregnancy: retrospective cohort study
Authors: Laura K Walsh, Jessy Donelle, Linda Dodds, Steven Hawken, Kumanan Wilson, Eric I Benchimol, Pranesh Chakraborty, Astrid Guttmann, Jeffrey C Kwong, Noni E MacDonald, Justin R Ortiz, Ann E Sprague, Karina A Top, Mark C Walker, Shi Wu Wen, Deshayne B Fell
Journal: BMJ (2019)

Abstract Objective To determine whether any association exists between exposure to 2009 pandemic H1N1 (pH1N1) influenza vaccination during pregnancy and negative health outcomes in early childhood. Design Retrospective cohort study. Setting Population based birth registry linked with health administrative databases in the province of Ontario, Canada. Participants All live births from November 2009 through October 2010 (n=104 249) were included, and children were followed until 5 years of age to ascertain study outcomes. Main outcome measures Rates of immune related (infectious diseases, asthma), non-immune related (neoplasms, sensory disorders), and non-specific morbidity outcomes (urgent or inpatient health services use, pediatric complex chronic conditions) were evaluated from birth to 5 years of age; under-5 childhood mortality was also assessed. Propensity score weighting was used to adjust hazard ratios, incidence rate ratios, and risk ratios for potential confounding. Results Of 104 249 live births, 31 295 (30%) were exposed to pH1N1 influenza vaccination in utero. No significant associations were found with upper or lower respiratory infections, otitis media, any infectious diseases, neoplasms, sensory disorders, urgent and inpatient health services use, pediatric complex chronic conditions, or mortality. A weak association was observed between prenatal pH1N1 vaccination and increased risk of asthma (adjusted hazard ratio 1.05, 95% confidence interval 1.02 to 1.09) and decreased rates of gastrointestinal infections (adjusted incidence rate ratio 0.94, 0.91 to 0.98). These results were unchanged in sensitivity analyses accounting for any potential differential healthcare seeking behavior or access between exposure groups. Conclusions No associations were observed between exposure to pH1N1 influenza vaccine during pregnancy and most five year pediatric health outcomes. Residual confounding may explain the small associations observed with increased asthma and reduced gastrointestinal infections. These outcomes should be assessed in future studies.
Improving outcomes in patients with non-tuberculous mycobacterial disease: is there light at the end of the tunnel?
Authors: Keertan Dheda
Journal: European Respiratory Journal (2019)

This issue of the European Respiratory Journal presents a series of research papers, reviews and editorials on the emerging problem of non-tuberculous mycobacterial (NTM) disease, the burden of which is increasing in many parts of the world [1]. Thus, NTM-related disease is a burgeoning public health problem even in areas where tuberculosis is endemic. Non-tuberculous mycobacteria are hardy environmental saprophytes and opportunistic pathogens that usually afflict those with structural lung disease and/or a compromised immune system due to old age or other reasons, including poorly characterised hereditary or acquired defects in innate or adaptive immunity [2]. Although there many causes of NTM pulmonary disease (NTM-PD), Mycobacterium avium complex (MAC), Mycobacterium kansasii and Mycobacterium abscessus (MAB) are generally the most commonly seen causative agents in many parts of the world [1]. Improving outcomes in patients with non-tuberculous mycobacterial diseases <http://bit.ly/2ITj8O2>
EuroTag rugby league: a semi-contact version of the game
Authors: D. J. Foy
Journal: BMJ (2015)

<h3>Objectives</h3> Though mesenchymal stem cells (MSC) have been clinically used to repair a variety of damaged tissues, the underlying mechanisms remain elusive as the majority of the ex vivo expanded MSC die shortly after transplantation. The aim of the study was to explore the inconsistency of cell death and their therapeutic role in the process of tissue repair. <h3>Methods</h3> Apoptosis of rat MSC was elicited by maintaining cells in the conditions of hypoxia (1% O2, 5% CO2, 94% N2) or/and serum-free α modified eagle medium for 72 h, the sub-cellular substances were harvested by ultracentrifugation of the supernatants and analysed by flow cytometric techniques, surface markers like CD29, CD44A and phosphatidylserine were detected by cytofluorimetic analyses. <h3>Results</h3> MSC apoptosis occurred in the presence of either hypoxia or serum-free condition as well, and it reached up to its maximal under the combined treatment, to which the apoptotic proportion was 17.44±2.15% after the cells were exposed for 72 h. Substantial amount of membrane microparticles was released by the apoptotic MSC into the supernatants, which co-expressed MSC9s surface markers CD29 and CD44A, cells membrane Annexin-V-binding phosphatidylserine as well. The amount of microparticles was around 15-fold of that of the parent cell numbers. <h3>Conclusions</h3> Membrane microvesicles can be released from MSC under apoptosis process, which might serve as the mediators in the cross-talk between the transplanted cells and their surrounding tissues.
Abstract 17587: Coronary Artery Bypass Graft: Heart Surgery Center Performance in Contemporary China
Authors: Shengshou Hu, Zhe Zheng, Xin Yuan, Sharon L Normand, Yun Wang, Harlan M Krumholz
Journal: Circulation (2010)

Background: Little is known about the variation in performance of CABG in China. Our objective was to characterize the variation in performance by site across hospitals participating in a regional ...
Prevalence and prognostic value of D‐dimer elevation in patients with AL amyloidosis
Authors: Anita Pudusseri, Vaishali Sanchorawala, J. Mark Sloan, Katherine M. Bever, Gheorghe Doros, Shivangi Kataria, Shayna Sarosiek
Journal: American Journal of Hematology (2019)

Light chain (AL) amyloidosis is a protein folding disorder that can affect many different organ systems, in addition to the coagulation pathway. D-dimer, a measurement of fibrin degradation, is commonly elevated in hematologic malignancies, but the prevalence and significance of D-dimer elevation in AL amyloidosis is unknown. We conducted an analysis of 921 patients with AL amyloidosis that presented to the Boston University Amyloidosis Center. Baseline characteristics and laboratory data of the 897 patients included in the final cohort were analyzed. Four hundred twenty three patients (47%) had an elevated D-dimer (>0.5 μg/mL). Multivariate analysis demonstrated that a normal D-dimer level of ≤0.5 μg/mL, and a level of >0.5 μg/mL but <1 μg/mL, conferred a lower risk of mortality (HR 0.49 and 0.59, respectively) when compared to a D-dimer level ≥ 1 μg/mL. The increased risk of mortality in patients with a D-dimer level ≥ 1 μg/mL was present in all cardiac stages. The median overall survival based on D-dimer range of ≤0.5, >0.5 but <1, and ≥ 1 μg/mL was 5.86, 4.04, and 2.08 years, respectively (P < .001). This retrospective analysis demonstrates the high prevalence of D-dimer elevation in AL amyloidosis and confirms that this laboratory finding is independently associated with decreased survival.
Clinical and Genome-Wide Analysis of Serum Platinum Levels after Cisplatin-Based Chemotherapy
Authors: Matthew R. Trendowski, Omar El-Charif, Mark J. Ratain, Patrick Monahan, Zepeng Mu, Heather E. Wheeler, Paul C. Dinh, Darren R. Feldman, Shirin Ardeshir-Rouhani-Fard, Robert J. Hamilton, David J. Vaughn, Chunkit Fung, Christian Kollmannsberger, Taisei Mushiroda, Michiaki Kubo, Robyn Hannigan, Frederick Strathmann, Lawrence H. Einhorn, Sophie D. Fossa, Lois B. Travis, M. Eileen Dolan
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Serum platinum is measurable for years after completion of cisplatin-based chemotherapy (CBC). We report the largest investigation of serum platinum levels to date of 1,010 testicular cancer survivors (TCS) assessed 1–35 years after CBC and evaluate genetic contributions to these levels. Experimental Design: Eligible TCS given 300 or 400 (±15) mg/m2 cisplatin underwent extensive audiometric testing, clinical examination, completed questionnaires, and had crude serum platinum levels measured. Associations between serum platinum and various risk factors and toxicities were assessed after fitting a biexponential model adjusted for follow-up time and cumulative cisplatin dose. A genome-wide association study (GWAS) was performed using the serum platinum residuals of the dose and time-adjusted model. Results: Serum platinum levels exceeded the reference range for approximately 31 years, with a strong inverse relationship with creatinine clearance at follow-up (age-adjusted P = 2.13 × 10−3). We observed a significant, positive association between residual platinum values and luteinizing hormone (age-adjusted P = 6.58 × 10−3). Patients with high residual platinum levels experienced greater Raynaud phenomenon than those with medium or low levels (age-adjusted ORhigh/low = 1.46; P = 0.04), as well as a higher likelihood of developing tinnitus (age-adjusted ORhigh/low = 1.68, P = 0.07). GWAS identified one single-nucleotide polymorphism (SNP) meeting genome-wide significance, rs1377817 (P = 4.6 × 10−8, a SNP intronic to MYH14). Conclusions: This study indicates that residual platinum values are correlated with several cisplatin-related toxicities. One genetic variant is associated with these levels.