tbuckley/cabot-search huggingface dataset:
Abstract 19709: Lower Ankle-Brachial Index Within the Normal Range is Associated With Reduced Mitochondrial Energy Production, Explaining the Accompanying Poor Walking Endurance
Authors: Majd AlGhatrif, Ariel Zane, Matt Oberdier, Stephanie Studenski, Eleanor Simonsick, Ken Fishbein, David Reiter, Richard Spencer
Journal: Circulation (2016)

Introduction: Reduced walking endurance in peripheral arterial disease, defined as ABI <0.9, has been attributed to impaired muscle mitochondrial energetics. Individuals with borderline ABI between 0.9 and 1.0, or low normal ABI between 1.0 and 1.1 also have been found to have worse walking endurance than those with higher ABI.

Hypothesis: Poor walking endurance in individuals with lower ABI in borderline and normal ranges is mediated by impaired mitochondrial energy production.

Methods: We examined 382 men and women participating in the Baltimore Longitudinal Study of Aging, who were free of PAD. Walking endurance was assessed by 400 meter rapid gate speed (RGS-400). Muscle mitochondrial energy production was assessed by post-exercise phosphocreatine recovery rate constant ( K PCr) measured by phosphorus magnetic resonance spectroscopy (31P-MRS) of the left thigh; reduced K PCr reflects decreased mitochondria energy production. Ipsilateral ABI was measured by the Colin system. Multivariate models were adjusted for age, sex, glucose, and smoking status.

Results: The sample mean age was 71 ± 12 years; about 18% of the participants had diabetes; 4% were current and 40% were former smokers. There were significant associations between K PCr and each of ABI and RGS-400 (Figure 1); these remained significant after adjustment. Lower ABI was independently associated with slower RGS-400 (β=-0.60, P=0.0339). Adding K PCr to the model weakened the association between RGS-400 and ABI by 15%, rendering it statistically insignificant (β=-0.51, P=0.09.)

Conclusion: The association between lower ABI in the normal range and poorer walking endurance is mediated by lower mitochondrial energy production. Hence, even within the normal range, lower ABI could represent a preclinical reduction in lower extremity perfusion negatively affecting energy production. Prospective studies are needed to confirm these association and their long terms effects.

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Association of the Modified Frailty Index With 30-Day Surgical Readmission
Authors: Tyler S. Wahl, Laura A. Graham, Mary T. Hawn, Joshua Richman, Robert H. Hollis, Caroline E. Jones, Laurel A. Copeland, Edith A. Burns, Kamal M. Itani, Melanie S. Morris
Journal: JAMA Surgery (2017)

Frail patients are known to have poor perioperative outcomes. There is a paucity of literature investigating how the Modified Frailty Index (mFI), a validated measure of frailty, is associated with unplanned readmission among military veterans following surgery.To understand the association between frailty and 30-day postoperative unplanned readmission.A retrospective cohort study was conducted among adult patients who underwent surgery and were discharged alive from Veterans Affairs hospitals for orthopedic, general, and vascular conditions between October 1, 2007, and September 30, 2014, with a postoperative length of stay between 2 and 30 days.Frailty, as calculated by the 11 variables on the mFI.The primary outcome of interest is 30-day unplanned readmission. Secondary outcomes included any 30-day predischarge or postdischarge complication, 30-day postdischarge mortality, and 30-day emergency department visit.The study sample included 236 957 surgical procedures (among 223 877 men and 13 080 women; mean [SD] age, 64.0 [11.3] years) from high-volume surgical specialties: 101 348 procedures (42.8%) in orthopedic surgery, 92 808 procedures (39.2%) in general surgery, and 42 801 procedures (18.1%) in vascular surgery. The mFI was associated with readmission (odds ratio [OR], 1.11; 95% CI, 1.10-1.12; R2 = 10.3%; C statistic, 0.71). Unadjusted rates of overall 30-day readmission (26 262 [11.1%]), postdischarge emergency department visit (34 204 [14.4%]), any predischarge (13 855 [5.9%]) or postdischarge (14 836 [6.3%]) complication, and postdischarge mortality (1985 [0.8%]) varied by frailty in a dose-dependent fashion. In analysis by individual mFI components using Harrell ranking, impaired functional status, identified as nonindependent functional status (OR, 1.16; 95% CI, 1.11-1.21; P < .01) or having a residual deficit from a prior cerebrovascular accident (OR, 1.17; 95% CI, 1.11-1.22; P < .01), contributed most to the ability of the mFI to anticipate readmission compared with the other components. Acutely impaired sensorium (OR, 1.12; 95% CI, 0.99-1.27; P = .08) and history of a myocardial infarction within 6 months (OR, 0.93; 95% CI, 0.81-1.06; P = .28) were not significantly associated with readmission.The mFI is associated with poor surgical outcomes, including readmission, primarily due to impaired functional status. Targeting potentially modifiable aspects of frailty preoperatively, such as improving functional status, may improve perioperative outcomes and decrease readmissions.
Tumor-triggered drug release from calcium carbonate-encapsulated gold nanostars for near-infrared photodynamic/photothermal combination antitumor therapy
Authors: Yanlei Liu, Xiao Zhi, Meng Yang, Jingpu Zhang, Lingnan Lin, Xin Zhao, Wenxiu Hou, Chunlei Zhang, Qian Zhang, Fei Pan, Gabriel Alfranca, Yuming Yang, Jesús M. de la Fuente, Jian Ni, Daxiang Cui
Journal: Theranostics (2017)

Different stimulus including pH, light and temperature have been used for controlled drug release to prevent drug inactivation and minimize side-effects.Herein a novel nano-platform (GNS@CaCO3/ICG) consisting of calcium carbonate-encapsulated gold nanostars loaded with ICG was established to couple the photothermal properties of gold nanostars (GNSs) and the photodynamic properties of indocyanine green (ICG) in the photodynamic/photothermal combination therapy (PDT/PTT).In this study, the calcium carbonate worked not only a drug keeper to entrap ICG on the surface of GNSs in the form of a stable aggregate which was protected from blood clearance, but also as the a pH-responder to achieve highly effective tumor-triggered drug release locally.The application of GNS@CaCO3/ICG for in vitro and in vivo therapy achieved the combined antitumor effects upon the NIR irradiation, which was superior to the single PDT or PTT.Meanwhile, the distinct pH-triggered drug release performance of GNS@CaCO3/ICG implemented the tumor-targeted NIR fluorescence imaging.In addition, we monitored the bio-distribution and excretion pathway of GNS@CaCO3/ICG based on the NIR fluorescence from ICG and two-photon fluorescence and photoacoustic signal from GNSs, and the results proved that GNS@CaCO3/ICG had a great ability for tumor-specific and tumor-triggered drug release.We therefore conclude that the GNS@CaCO3/ICG holds great promise for clinical applications in anti-tumor therapy with tumor imaging or drug tracing.
A phase II trial of combination irinotecan and oral etoposide chemotherapy in recurrent ovarian cancer: A Tohoku Gynecologic Cancer Unit (TGCU) study
Authors: S. Kumagai, T. Shoji, Y. Yokoyama, T. Takano, H. Mizunuma, N. Yaegashi, T. Sugiyama
Journal: Journal of Clinical Oncology (2009)

5558 Background: Various problems still exist in the management of recurrent ovarian cancer and there are limited treatment options especially for the platinum resistant patients (pts). We conducted a phase II study to evaluate the efficacy and safety of the combination irinotecan/oral etoposide chemotherapy. Methods: Eligibility criteria included recurrent ovarian cancer with measurable disease or positive CA125, preserved organ function, and aged 20–75. Treatment was conducted with irinotecan (60 mg/m2 iv, day 1, 15) and oral etoposide (50 mg/body day 1–21), q 28 days until disease progression or unacceptable toxicity. Primary endpoint was response rate (RR) and secondary endpoints included toxicity, progression-free survival (PFS), and overall survival (OS). Results: 38pts were enrolled on this study from May 2003 to April 2007, and all pts were eligible. Median age was 57 yrs (range 37–74). PS 0 in 24 pts, 1 in 10 pts, and 2 in 4 pts. Median number of previous regimen was 2 (range 1–4). Median treatment cycles were 6 (range 2–27). RR (CR+PR) was 18/38 (47.4%), and CR+PR+SD rate was 31/38 (81.6%). Grade 3/4 adverse effect included leukopenia (50.0%), neutropenia (52.6%), anemia (18.4%) and thrombocytopenia (2.6%), nausea/vomiting (7.9%) and diarrhea (2.6%). Treatment-related death was not observed. Median PFS was 7 months (range 1–33) and OS was 19 months (range 4–60). Among 20 pts with platinum resistant cases, RR was 6/20 (30.0%), CR+PR+SD rate was 14/20 (70.0%), median PFS was 6 months (range 1–33), and OS was 24 months (range 5–60). Conclusions: Combination irinotecan/oral etoposide chemotherapy can achieve a superior management for the recurrent ovarian cancer without declining QOL, and also has the possibility to be one of the most effective regimens as second-line chemotherapy. No significant financial relationships to disclose.
Effect of a multifaceted educational intervention for anti-infectious measures on sepsis mortality: a cluster randomized trial
Authors: Frank Bloos, Hendrik Rüddel, Daniel Thomas-Rüddel, Daniel Schwarzkopf, Christine Pausch, Stephan Harbarth, Torsten Schreiber, Matthias Gründling, John Marshall, Philipp Simon, Mitchell M. Levy, Manfred Weiss, Andreas Weyland, Herwig Gerlach, Tobias Schürholz, Christoph Engel, Claudia Matthäus-Krämer, Christian Scheer, Friedhelm Bach, Reimer Riessen, Bernhard Poidinger, Karin Dey, Norbert Weiler, Andreas Meier-Hellmann, Helene H. Häberle, Gabriele Wöbker, Udo X. Kaisers, Konrad Reinhart
Journal: Intensive Care Medicine (2017)
A Plasma Biomarker Panel to Identify Surgically Resectable Early-Stage Pancreatic Cancer
Authors: Seetharaman Balasenthil, Ying Huang, Suyu Liu, Tracey Marsh, Jinyun Chen, Sanford A. Stass, Debra KuKuruga, Randall Brand, Nanyue Chen, Marsha L. Frazier, J. Jack Lee, Sudhir Srivastava, Subrata Sen, Ann McNeill Killary
Journal: JNCI Journal of the National Cancer Institute (2017)

Blood-based biomarkers for early detection of pancreatic ductal adenocarcinoma (PDAC) are urgently needed. Current biomarkers lack high sensitivity and specificity for population screening. The gold-standard biomarker, CA 19-9, also fails to demonstrate the predictive value necessary for early detection.To validate a functional genomics-based plasma migration signature biomarker panel, plasma tissue factor pathway inhibitor (TFPI), tenascin C (TNC-FN III-C), and CA 19-9 levels were measured by enzyme-linked immunosorbent assays in three early-stage PDAC plasma cohorts, including two independent blinded validation cohorts containing a total of 43 stage I, 163 stage II, 86 chronic pancreatitis, 31 acute biliary obstruction, and 108 controls. Logistic regression models developed classification rules combining TFPI and/or TNC-FN III-C with CA 19-9 for patient cases and control subjects, with or without adjustment for age and diabetes status. Model classification performance was evaluated and analyses repeated among subpopulations without diabetes and pancreatitis history. Two-sided P values were calculated using bootstrap method.The TFPI/TNC-FN III-C/CA 19-9 panel improved CA 19-9 performance in all early-stage cohorts, including discriminating stage IA/IB/IIA, stage IIB, and all early-stage cancer from healthy controls. Statistical significance was reached for a number of subcohorts, including for all early-stage cancer vs healthy controls (cohort 1 AUC = 0.92, 95% CI = 0.86 to 0.96, P = .04; cohort 3 AUC = 0.83, 95% CI = 0.76 to 0.89, P = .045). Among subcohorts without diabetes and pancreatitis history, the panel approaches potential clinical utility for early detection to discriminate early-stage PDAC from healthy controls including an area under the curve (AUC) of 0.87 (95% CI = 0.77 to 0.95) for stage I/IIA, an AUC of 0.93 (95% CI = 0.87 to 0.98) for stage IIB, and a statistically significant AUC of 0.89 (95% CI = 0.82 to 0.95) for all early-stage cancer ( P = .03).TFPI/TNC-FN III-C migration signature adds statistically significantly to CA 19-9's predictive power to detect early-stage PDAC and may have clinical utility for early detection of surgically resectable PDAC, as well as for enhanced survival from this routinely lethal cancer.
KCNQ-Encoded Potassium Channels as Therapeutic Targets
Authors: Vincenzo Barrese, Jennifer B. Stott, Iain A. Greenwood
Journal: The Annual Review of Pharmacology and Toxicology (2017)

Kv7 channels are voltage-gated potassium channels encoded by KCNQ genes that have a considerable physiological impact in many cell types. This reliance upon Kv7 channels for normal cellular function, as well as the existence of hereditary disorders caused by mutations to KCNQ genes, means that pharmacological targeting of these channels has broad appeal. Consequently, a plethora of chemical entities that modulate Kv7 channel activity have been developed. Moreover, Kv7 channels are influenced by many disparate intracellular mediators and trafficking processes, making upstream targeting an appealing prospect for therapeutic development. This review covers the main characteristics of these multifunctional and versatile channels with the aim of providing insight into the therapeutic value of targeting these channels.
Early Post Transplant Organ Toxicity after Allogeneic One-Haplotype Mismatch (Haplo) Hematopoietic Stem Cell Transplant (HSCT)
Authors: Didier Blaise, Clemence Mediavilla, Amir Meskine, Stéfania Bramanti, Samia Harbi, Sabine Furst, Catherine Faucher, Angela Granata, Faezeh Legrand, Djamel Mokart, Pierre Jean Weiller, Christian Chabannon, Jérome Rey, Diane Coso, Luca Castagna, Raynier Devillier
Journal: Blood (2016)
A foot tumour as late cutaneous Lyme borreliosis: a new entity?
Authors: O. Bauvin, J.-L. Schmutz, S. De Martino, T. Busato, B. Cribier, A. Barbaud, D. Wahl, A.-C. Bursztejn
Journal: British Journal of Dermatology (2017)

Acrodermatitis chronica atrophicans (ACA) is the late cutaneous form of Lyme borreliosis. The early inflammatory phase manifests with a bluish‐red discoloration and doughy swelling of the skin. The atrophic phase represents a late‐phase process with red discoloration, and a thin and wrinkled appearance of the skin. We present a patient who exhibited a previously undescribed form of late cutaneous Lyme borreliosis (LCLB) with a foot tumour. A 64‐year‐old woman had a large tumorous lesion on the right sole. The tumour size and deformation of the feet made wearing shoes difficult. On skin histology, a granulomatous lymphohistiocytic infiltrate with plasma cells was noticed. In fact, the patient recalled tick bites 2 or 3 years before. Borrelia burgdorferi (Bb) serology was highly positive and a polymerase chain reaction analysis on the skin biopsy detected Bb sensu lato, genospecies B. afzelii. We diagnosed LCLB and antibiotics were prescribed. On the more recent examination, the tumour had totally disappeared; the skin was atrophic and dry with only few scales. We report an atypical case of European LCLB, suggesting that ACA is not the only possible presentation of LCLB. The diagnosis of ACA is often clinically missed for months or years, and may be mistaken at the inflammation phase for vascular disorders, erysipelas or bursitis/arthritis, and at the atrophic phase for lichen sclerosus atrophicus, morphoea or anetoderma. To our knowledge, no such tumorous LCLB has previously been described.
FES PET/CT analysis to evaluate the impact of localization of breast cancer metastases on ER expression.
Authors: Hilde H. Nienhuis, Michel van Kruchten, Andor W. J. M. Glaudemans, Alfons H. H. Bongaerts, Erik F. J. De Vries, Carolina Pia Schroder, Elisabeth G. E. de Vries, Geke Hospers
Journal: Journal of Clinical Oncology (2015)

527 Background: Recent data suggests that differences in locations of metastases could have implications for tumor characteristics and thus for therapy response. Limited knowledge is available in this respect about heterogeneity of the estrogen receptor (ER). 18F-fluoro-17β-estradiol (FES) uptake on positron emission tomography (PET), reflects ER expression. We aimed to analyze FES uptake in tumor lesions at different sites in metastatic breast cancer patients. Methods: Eligible patients: biopsy proven ER positive breast cancer, post-menopausal, metastases outside the liver, no history of another metastatic malignancy, no use of ER antagonists for ≥ 5 weeks prior to FES PET. They had undergone FES PET with 64-slice mCT within the UMCG (Jan 2009 - Sept 2014). We re-analyzed FES PET and CT scans for metastases. A lesion with maximum absolute standardized uptake value (SUVmax) ≥ 1.5 was considered ER positive. Background tracer uptake was measured for normal tissues. CT lesions with diameter ≥ 10 mm were included. Liver lesions were not evaluated on PET given high background signal. Results: In 67 patients, 1,338 lesions were identified by CT (120 patients), PET (913 patients) or both (305 patients) in bone (79%), lymph nodes (15%), lungs (3%) and liver (2%). SUVmax of FES positive lesions varied maximally 10-fold between patients (median 1.61-15.61), and up to 11-fold within individual patients (range 1.8-19.4). Median SUVmax of bone, lymph nodes and lung lesions were respectively 3.21 (range 0.44-24.3); 3.26 (0.75-19.4) and 2.41 (0.54-6.46). For bone metastases median SUVmax varied for the sites with highest uptake in cervical spine (4.17) and lowest in sternum (2.55). Also background SUVmaxlevels differed per location with highest level in lumbal spine (1.46) and lowest in fat tissue (0.65). Lung metastases were more frequently FES negative (20%) than bone (7%, p < 0.01) and lymph nodes metastases (5%, p < 0.01). Conclusions: FES uptake in breast cancer metastases is heterogeneous within and between patients and differs per localization in the body, indicating the need for whole body metastases evaluation for precision medicine. Supported by Dutch Cancer Society grants RUG 2010-4739 and 2012-5565 and ERC Advanced grant 293445.
Ex Vivo Evaluation of VLA-4 Expression in Primary Human Multiple Myeloma Bone Marrow Samples and In Vivo Mobilization of Murine Multiple Myeloma Cells with Small Molecule VLA-4 Inhibitors
Authors: Chantiya Chanswangphuwana, Michael P. Rettig, Walter Akers, Deep Hathi, Matthew Holt, Julie O'Neal, Julie Ritchey, Danny Kohnen, Justin A King, Michael H. Tomasson, Ravi Vij, Monica Shokeen, John F DiPersio
Journal: Blood (2016)
Lymph node ratio, adjuvant chemotherapy and survival in resected non-small cell lung cancer and pN1 disease: A Brown University experience.
Authors: Kalyan C. Mantripragada, Thomas Ollila, Humera Khurshid
Journal: Journal of Clinical Oncology (2015)

e18529 Background: Large retrospective analyses of the SEER database indicate that a higher lymph node ratio (LNR: The number of positive lymph nodes divided by the number of lymph nodes resected during surgery) is associated with poorer survival in resected non-small cell lung cancer (NSCLC). Most of these studies were conducted before adjuvant chemotherapy became standard of care. This study aims to analyze association between LNR and survival among patients with pN1 disease stratified by adjuvant chemotherapy use. Methods: Tumor registries of Rhode Island and Miriam Hospitals were used to identify 65 patients who underwent resection for N1 NSCLC between January 2007 and December 2013. Median follow up was 27 months. Patients were classified into two LNR groups ( ≤ 0.15, > 0.15). Unadjusted and adjusted survival analyses were used to evaluate the relationship between LNR and survival. Staging followed the AJCC cancer staging manual, 7thedition. Results: Overall, 41% of participants had an LNR of ≤ 0.15 and 59%, an LNR > 0.15 with median number of nodes resected being 10 (range 1-23). 70% of the ≤ 0.15 LNR group and 52% of > 0.15 LNR group received adjuvant chemotherapy (p = 0.15). There was no significant difference in baseline age, sex, histology, location, type of surgery, T stage and visceral pleural invasion between the LNR groups. Mean relapse free survival was 65 and 46 months in the ≤ 0.15/ > 0.15 LNR groups respectively. A higher LNR was associated with worse lung cancer recurrence (HR 1.85; 95% CI 0.78-4.5; p = 0.08) and all-cause mortality (HR 1.48; 95% CI 0.69-3.2; p = 0.15) that was not statistically significant. Stratified and adjusted analysis by adjuvant chemotherapy use again did not show a statistically significant association between LNR and survival though the trend of worse survival with higher LNR persisted (HR 1.86; 95% CI 0.76-4.55; p = 0.08). Conclusions: Higher pN1 LNR in NSCLC was associated with higher risk of recurrence and death even with adjuvant chemotherapy use but these associations were not statistically significant. We plan a larger study to address limitations of small data set, short follow up and fewer patients with LNR > 0.5 in this study.
Abstract P285: Small Dose of Medium Chain Fatty Acids From Coconut Oil Does Not Enhance Thermogenesis in Overweight Adolescents
Authors: Janna LaBarrie, Marie-Pierre St-Onge
Journal: Circulation (2017)

Background: Previous research has shown that consumption of medium chain triglycerides (MCT) in overweight adults can increase energy expenditure and improve weight management, but no research has been done in children. Our study tests the effects of a test oil enriched in MCT from coconut oil, on energy expenditure, satiety, and metabolic markers in overweight and obese adolescents. Methods: We conducted a randomized, double blind, crossover study in which 15 children, age 13-18 y, with a body mass index &gt;85 th percentile for age and sex, were enrolled. Two test meals were administered which contained 20 g of fat from either corn oil or an MCT-enriched baking fat (providing approximately 4.7 g of fatty acids with chain lengths ≤12C). A fasting blood sample was taken before breakfast and the thermic effect of food (TEF) was assessed using indirect calorimetry for 6 h. During the test, satiety was measured using visual analog scales (VAS) and additional blood samples were obtained from an intravenous catheter at times 30, 45, 60, 120, and 180 min post-meal for measurement of hormones and metabolites. Results: There was no significant effect of fat type, time, or fat type x time interaction on TEF, appetite and satiety, glucose, and insulin area under the curve (AUC). However, there was a significant effect of fat type on leptin (P = 0.027), triglycerides (P = 0.020), and peptide YY (P = 0.0085) whereby leptin and triglyceride concentrations were lower with corn oil consumption and peptide YY concentrations were higher. Conclusions: Our results do not suggest that this MCT-rich test oil enhances thermogenesis and satiety in children. Given that this is the only current study of its kind, more research is needed into the use of MCT as a tool in weight management in overweight and obese children.