tbuckley/cabot-search huggingface dataset:
Exercise capacity in long-term survivors of pediatric cancer
Authors: T. L. Miller, A. M. Miller, G. Lopez-Mitnik, G. Somarriba, S. R. Lipsitz, A. S. Hinkle, L. S. Constine, S. E. Lipshultz
Journal: Journal of Clinical Oncology (2009)

10026 Background: Childhood cancer survivors may have premature symptomatic cardiovascular and noncardiovascular diseases that contribute to reduced capacity for physical activity. Controlled assessments of exercise capacity and identification of risk factors for reduced capacity in survivors are lacking. Methods: We assessed maximal myocardial oxygen consumption (VO 2max ; measure of exercise capacity) in survivors at least 4 years after diagnosis and sibling controls. We evaluated associations between VO 2max and age, sex, treatments, cardiac structure and function, biomarkers, endocrine function, and physical activity. Results: Of 72 survivors (mean age, 22 y; range, 8.0 to 40 y) and 32 siblings (mean age, 20.2 y; range, 8 to 46 y), about half were male. The mean time since cancer diagnosis was 13.4 y (range, 4.5 to 31.6 y). In age- and sibling-pair adjusted analyses, VO 2max was lower in survivors than siblings (males, 28.53 vs. 30.90 mL/kg/min, P = 0.08; females, 19.81 vs. 23.40 mL/kg/min, P = 0.03). In male survivors, older age (P = 0.01), higher percent body fat (P &lt; 0.001) and high or low left ventricular (LV) mass Z-scores (P = 0.03) predicted lower VO 2max . In females, older age (P &lt; 0.001), methotrexate exposure (P = 0.01), and higher, but normal, LV load-dependent contractility (P = 0.02) predicted lower VO 2max . Conclusions: Physical fitness for most participants in each group was poor, and was generally lower in survivors, particularly females. Older age, higher body fat, methotrexate exposure, and extremes of LV mass/function were associated with lower VO 2max in survivors. Because physical activity can improve nutritional and cardiac conditions, survivors should be encouraged to engage in regular exercise with close medical monitoring. No significant financial relationships to disclose.
Is aortoiliac calcification linked to colorectal anastomotic leakage? A case-control study
Authors: G.S.A. Boersema, K.A. Vakalopoulos, M.C.J.M. Kock, P.M.A. van Ooijen, K. Havenga, G.J. Kleinrensink, J. Jeekel, J.F. Lange
Journal: International Journal of Surgery (2015)
Analysis of metabolic and ventilatory demands during activities of daily living in patients with non-cystic fibrosis bronchiectasis
Authors: Carina Silveira Mariano Nunes, Jacqueline Cristina Boldorini, Anderson Alves de Camargo, Samia Zahi Rached, Rodrigo Abensur Athanazio, Fernanda de Cordoba Lanza, Alberto Cukier, Rafael Stelmach, Simone Dal Corso
Journal: European Respiratory Journal (2014)

Introduction: Task-related oxygen uptake (VO 2 ), ventilation (VE), and heart rate (HR) during activities of daily living (ADL) have never been studied before in patients with non-cystic fibrosis bronchiectasis.  Aim: To determine metabolic and ventilatory demands during five ADLs.  Methods: Fifteen subjects (8 women; FEV 1  52±24 %pred, MRC 2.0±0.9) performed the following ADLs, five minutes apart: (1) putting on socks, shoes, and vest; (2) putting away different weights on a rack; (3) sweeping a floor; (4) carrying a 5Kg weight while walking; and (5) climbing stairs for a minute. During the tests, pulmonary gas exchange was measured (VO2000; Medical Graphics Corporation, St. Paul, MN).  Results: See Table 1.  Conclusions: Simple everyday activities such as walking, carrying weights, and climbing flights of stairs require a high metabolic demand with low ventilatory requirement and perception of effort.
Hippocalcin‐like 1 suppresses hepatocellular carcinoma progression by promoting p21Waf/Cip1 stabilization by activating the ERK1/2‐MAPK pathway
Authors: Yonglong Zhang, Yanfeng Liu, Jinlin Duan, Haibo Yan, Jun Zhang, Huilu Zhang, Qi Fan, Feifei Luo, Guoquan Yan, Ke Qiao, Jie Liu
Journal: Hepatology (2015)

Hepatocellular carcinoma (HCC) is the third leading cause of cancer‐related death. However, the underlying mechanism during hepatocarcinogenesis remains unclarified. Stable isotope labeling by amino acids in cell culture (SILAC) is a powerful quantitative strategy for proteome‐wide discovery of novel biomarkers in cancers. Hippocalcin‐like 1 (HPCAL1) is a calcium sensor protein. However, the biological function of HPCAL1 is poorly understood in cancers, including HCC. Herein, HPCAL1 was identified by SILAC as a novel hepatocarcinogenesis suppressor down‐regulated in HCC cell lines and tissues. Importantly, lost expression of HPCAL1 was associated with worse prognosis of HCC patients. Interestingly, secreted HPCAL1 protein in the plasma dropped dramatically in HCC patients compared with healthy donors. Receiver operating characteristic curve analysis showed that serum HPCAL1 at a concentration of 8.654 ng/mL could better predict HCC. Furthermore, ectopic expression of HPCAL1 suppresses cell proliferation, while depletion of HPCAL1 led to increased cell growth both in vitro and in vivo . Mechanistically, HPCAL1 directly interacted with p21 Waf/Cip1 in the nucleus, which requires the EF‐hand 4 motif of HPCAL1 and the Cy1 domain of p21. This interaction stabilized p21 Waf/Cip1 in an extracellular signal‐regulated kinase 1/2‐mitogen‐activated protein kinase‐dependent manner, which subsequently prevented p21 Waf/Cip1 proteasomal degradation by disrupting SCF Skp2 and CRL4 Cdt2 E3 ligase complexes, resulting in increased protein stability and inhibitory effect of p21 Waf/Cip1 . Notably, the tumor suppressive function of HPCAL1 was dependent on p21 in vitro and in vivo . Consistent with this observation, expression of HPCAL1 and p21 Waf/Cip1 was positively correlated in HCC tissues. Conclusion: These findings highlight a novel tumor suppressor upstream of p21 Waf/Cip1 in attenuating cell cycle progression and provide a promising diagnostic and prognostic factor, as well as a potential therapeutic target for HCC. (H epatology 2016;63:880–897)
A review of the the clinico-pathological presentation of cervical cancer in Ilorin, Nigeria.
Authors: R. Saidu, K. O. O. Ibrahim, K. Adesina
Journal: Journal of Clinical Oncology (2011)

e15516 Background: Cervical cancer is a public health problem in developing countries. The aim of this study is to review the clinical and histopathological presentation of cervical cancer in Ilorin, Nigeria. Methods: The medical records of all histologically confirmed cervical cancer managed at the University of Ilorin Teaching Hospital from January 2000 to December 2009 were retrieved and analyzed. Results: There were 213 cases of cervical cancer managed in the hospital over this period. Their mean age was 55.2 years (±13.8; range 23-92). More than half of them (63%) were more than 50 years of age and the highest prevalence was in the age group 50-57 (26.8%). The mean parity was 6.7 (±2.4; range 0-13). Most of the women (87.9%) were grandmultiparous and 98.8% were currently married. The main clinical symptoms were irregular vaginal bleeding (76.7%,) vaginal discharge (36.5%) and post coital bleeding (23.3%). About 32.4% had more than 1 symptom. About 15.6% reported to the hospital within the first month of onset of symptoms. While 88.6% presented with advanced stage disease, stage IIIB was the most common stage (54.3%) of the disease at presentation. Squamous cell carcinoma was the commonest type of malignancy found in this study 196 (92%) while adenocarcinoma formed only 2.8%. The Large cell Keratinised histologic variant is the commonest squamous cell carcinoma type (45.2%) closely followed by the Large cell non-keratinized. All the patients were referred to a center that could offer radiotherapy. Conclusions: Cervical cancer is still a very serious problem in developing countries including Nigeria. The importance of this review cannot be overemphasized because it serves as a reminder to all stakeholders in cervical cancer prevention that this disease is still killing women in the developing countries. It also serves as an advocacy tool to all that making cervical cancer prevention strategies available and affordable to the developing countries is a top priority issues. And to the scientific community, it is still a challenge that a simple and affordable method of preventing cervical cancer must be made available as soon as possible.
Reducing hospital admission in COPD exacerbation by urgent oxygen provision and home monitoring of capillary blood gases
Authors: Howell Clague, Marie Herring, Paul Frear
Journal: European Respiratory Journal (2012)

Current NICE guidance recommends hospital admission when SpO2   As part of the NHS Lung Improvement Programme, Sunderland Urgent Care Team (South Tyneside NHS Foundation Trust) set up a six month Pilot to reduce emergency hospital admission by introducing measurement of capillary blood gases (TcABGs) and the urgent provision of oxygen to manage what would have been an admission into a treatable condition at home. Following a clinical assessment, a team of advanced nurse practitioners guided by an operational protocol measured TcABGs in a group of patients with AECOPD who9s SpO2 was in the range 85 -89%. Suitable patients were provided with oxygen cylinders delivering oxygen in the range of 2-6 L/min and monitored until oxygenation improved (SpO2 > 90%) and there was clinical recovery. Initially, urgent oxygen provision and ABG measurement proved problematic but 25 patients were recruited. 4 were excluded for breaching protocol (2 TcABGs failed, 1 was acidotic (pH 7.29) and chose to remain at home, 1 had no follow up data). 4 were admitted (2 acidotic, 2 hypoxic on LTOT). The remaining 16 hypoxic (SpO2 86% ± 1) patients improved (SpO2 93% ± 2) with urgent oxygen provision and were managed safely at home but 1 became non compliant. Initial visit times lasted 186.2 ± 80.7 mins with between four and twelve follow up visits until recovery. With urgent oxygen provision, careful selection and monitoring, hospital admission can be avoided even in moderately hypoxic patients with exacerbations of COPD.
Esophageal Complications in Patients with Ankylosing Spondylitis: Endoscopic and Histomorphological Features
Authors: A.A. Zazdravnov
Journal: GASTROENTEROLOGY (2020)

On the basis of clinical and endoscopic examination of 31 patients with ankylosing spondylitis (AS) with clinical signs of esophageal lesions, we have found that in these patients erosive lesions of the esophagus occur much more often than in simple gastroesophageal reflux disease (GERD). Esophageal lesions in patients with AS are more severe than in simple GERD — severe erosive esophagitis (of C and D grade) is detected in 43.8 % of patients with erosive and ulcerative lesions of the esophagus against AS. Microscopic examination of biopsy material taken from esophageal mucosa suggests multifactorial mechanism of esophageal lesions in AS, including systemic and local immune inflammation, abnormal microvasculature, excessive proliferation of connective tissue, disseminated sclerotic processes in the wall of the esophagus, reduced number of esophageal glands.
Reply
Authors: Siddharth Singh, Rohan Khera, M. Hassan Murad, Rohit Loomba
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. We thank Wei and colleagues for their interest in our evidence synthesis.1 In general, most of our analyses were associated with low heterogeneity; therefore, we believe that there is no significant impact of heterogeneity on our certainty in the estimates or conclusions. We do not believe this affected the applicability or generalizability of our results. We agree with Wei and colleagues that further knowledge about subgroup interactions and effect modifiers like duration of treatment, dose, and associated morbidities will be helpful. However, such analyses require individual patient data. Because there is only a small number of available trials, performing such exploration using meta‐regression techniques is not feasible and can potentially lead to misleading and spurious findings if performed using aggregate estimates.2 We also certainly would not recommend pursuing post hoc sensitivity analyses without a clear rationale. Unfortunately, we do not believe that there is a particular "model" or statistical technique that can remedy this issue.
Civil Defense Agency
Authors: Thomas F. Maher
Journal: New England Journal of Medicine (1955)

THE NATURE AND SIGNIFICANCE OF RADIOACTIVE FALLOUTWith the detonation of a thermonuclear bomb such as the hydrogen bomb, four major effects are to be noted: blast, heat, instantaneous nuclear radiation and residual radioactivity. The first three occur at the time of detonation. With a 35-megaton hydrogen bomb immediate nuclear radiation does not present a serious hazard beyond a radius of approximately 18 miles from ground zero, where heat and blast are of great concern. The area of blast, heat and nuclear radiation varies according to the energy liberated at the time of explosion. In general an ordinary 1X atomic . . .
Introduction of antineoplastic drug NSC631570 in an inpatient and outpatient setting: Comparative evaluation of biological effects
Authors: Mariia Rudyk, Olexander Fedorchuk, Yaroslav Susak, Yaroslav Nowicky, Larysa Skivka
Journal: Asian Journal of Pharmaceutical Sciences (2016)

The aim of this study is to evaluate the effect of moderate physical exercise and treatment time on the organism's response to NSC631570. The sensitivity of circulating phagocytes to the drug at different times of day was estimated in in vitro experiments. NSC631570 was administered intravenously to healthy volunteers (eleven men, 23 ± 2 years) in a single therapeutic dose in an inpatient and an outpatient setting. Blood samples were obtained before the drug administration, 30 min after the drug injection and every fourth hour throughout the 24 hour period. Biochemical parameters were determined using the hematological analyzer. Flow cytometry was used to evaluate phagocyte metabolism. Treatment of circulating phagocytes with NSC631570 in vitro resulted in an increase in ROS production along with a decrease in their phagocytic activity, most expressed in the morning time. Drug injection to sedentary persons resulted in pro-inflammatory metabolic polarization of circulating phagocytes. Introduction of NSC631570 to active persons was accompanied by a significant increase in phagocyte endocytosis along with a decrease in the daily mean of ROS generation. Significant oscillation (but in the normal ranges) of urea, creatinine, alanine aminotransferase and aspartate aminotransferase after NSC631570 introduction in the outpatient setting was shown during the day. Physical activity interferes with immunomodulatory action of NSC631570 and abrogates pro-inflammatory shift of circulating phagocytes. Biochemical parameters of blood from patients treated with NSC631570 in the outpatient setting must be interpreted cautiously considering the effect of physical activity on some metabolic biomarkers.
Human epidermal growth factor receptor 2 (HER2) suppression with the addition of lapatinib to trastuzumab in HER2-positive metastatic breast cancer (HALT: LPT112515).
Authors: Nancy U. Lin, Michael A. Danso, Alice K. David, Joseph J. Muscato, Daniel Rayson, William A. Houck, Catherine Elizabeth Ellis, Michelle DeSilvio, Amanda Garofalo, Jeremy Levin, Eric P. Winer
Journal: Journal of Clinical Oncology (2013)

TPS664 Background: Evidence supports the concept of dual HER2 blockade as a treatment strategy for HER2+ breast cancer (BC). In patients with prior trastuzumab (T)-treated HER2+ metastatic BC (MBC), treatment with T plus lapatinib (L) was associated with longer progression-free survival (PFS) and overall survival (OS) compared with L alone, and had an acceptable safety and tolerability profile. In patients with stage II/III BC, preoperative treatment with T plus L plus paclitaxel (P) resulted in significantly higher pathologic complete response rates compared with P combined with either agent alone. This study is designed to evaluate whether the addition of L improves PFS among women with HER2+ MBC receiving T as maintenance therapy. Methods: In this open-label, Phase III study, 280 patients will be stratified by line of treatment (first/second) and hormone receptor status (positive/negative), then randomized 1:1 to receive maintenance treatment with either L (1000 mg qd, continuously) in combination with T (6 mg/kg once every 3 weeks [q3w]), or T (6 mg/kg q3w) alone until disease progression, death, discontinuation due to adverse events, or other reasons. The primary endpoint is PFS; secondary endpoints are OS, clinical benefit rate, and safety. Eligible patients are females, aged ≥18 years with HER2+ MBC who have completed 12-24 weeks of first-/second-line treatment with T plus chemotherapy with an objective response or stable disease at chemotherapy discontinuation. Patients with stable brain metastases are eligible if entering the study on second-line treatment. Efficacy endpoints will be analyzed in the intent-to-treat population. A total of 193 PFS events is required to detect a 50% increase in median PFS from 18 weeks (T alone) to 27 weeks (L+T) with an associated hazard ratio of 0.667, an 80% power and a 1-sided type I error of 0.025. One interim analysis is planned for futility when ~97 PFS events (50% of required events) have been observed. Safety endpoints will be analyzed in all randomized patients who receive ≥1 dose of study medication. The trial is currently open for accrual in the United States and Canada. Clinical trial information: NCT00968968.
Clinical findings and interventions in cancer patients referred to a cachexia clinic (CC)
Authors: Z. Nooruddin, D. Hui, S. Dalal, E. Bruera, E. Del Fabbro
Journal: Journal of Clinical Oncology (2009)

e20551 Background: The cancer-related anorexia/cachexia syndrome is primarily caused by an aberrant inflammatory response and neurohormonal dysfunction. Secondary causes that contribute to diminished nutrient intake include early satiety, constipation, nausea, vomiting, mood alterations, dysgeusia, and dysphagia. We determined the frequency and management of both secondary cachexia causes and metabolic/endocrine alterations in a new CC at a Comprehensive Cancer Center. Methods: We conducted a retrospective chart review of 159 consecutive patients who underwent structured assessments at the CC. Demographics, weight loss, secondary causes and specific treatments were analyzed. Results: The patients had the following characteristics: median age 59, females 39%, median body mass index 20.3, median weight loss over the preceding 3 months 7%, and hypoalbuminemia 76%. At consultation, 102 (64%) were on chemotherapy/radiation and 13 (8%) were on enteral or parenteral nutrition. Appetite stimulants prior to consult included megestrol (n=36, 22%), corticosteroids (n=21, 13%) and dronabinol (n=10, 6%). The median number of secondary causes was 3 (Q1-Q3 2–4), with a median of 2 (Q1-Q3 1–3) interventions per patient. 22 (14%), 105 (66%) and 32 (20%) patients had 0–1, 2–4 and 5–8 secondary cachexia causes, respectively. The table lists the significant findings and corresponding interventions. 52 (33%) were enrolled onto clinical trials for primary cachexia. Conclusions: A total of 411 treatable secondary cachexia causes and 89 endocrine/metabolic alterations were identified in our cohort. Low cost effective interventions were available for most of the common findings. [Table: see text] No significant financial relationships to disclose.
The influence of triple-negative status on survival of patients with early-stage breast cancer treated in a Brazilian outpatient cancer center.
Authors: F. M. Vieira, J. H. Salem, L. H. De Lima Araujo, R. C. Helal, M. Zukin, T. S. Gomes, C. C. Silva, M. G. Lima, A. Boukai, C. G. M. Ferreira, N. Teich
Journal: Journal of Clinical Oncology (2011)

e11539 Background: Triple-negative (TN) breast cancer is an aggressive disease with intrinsic poor prognosis. This breast cancer subtype is defined as negative expression for estrogen/progesterone receptors and HER2, and it is managed with standard chemotherapy - including anthracycline and taxanes. The objective of this study was to evaluate, in a real world perspective, the impact of TN status on survival among early-stage breast cancer patients treated in a private oncologic center in Brazil. Methods: We retrospectively studied 721 patients with early-stage breast cancer between 1999 and 2009. Clinical characteristics and outcomes were described and compared for TN and non-TN patients. Variables were compared using Mann-Whitney test, and survival curves were estimated with Kaplan-Meier method, and compared with log-rank (SPSS v 17.0 software). Results: 102 (14%) patients were classified as TN and showed less differentiated and more advanced tumors. The rate of grade 3 tumors was 55% and 22% for TN and non-TN groups (P<.0001), while the rate of stage II-III was 65% and 55% (P=.07). Accordingly, the survival was considerably worst among TN patients, with 5-year overall survival of 79% vs 92% (P<.001). Of note, no difference was detected regarding median age (54 vs 53 years; P=.99), median tumor size (2 cm for both; P=.25), and nodal positivity (64% vs 62%; P=.75) for TN and non-TN, respectively. The rate of adjuvant/neoadjuvant treatment was 98% for TN and 100% for non-TN patients, and taxanes were used in 55% in both situations. Conclusions: Our findings are consistent with current worldwide literature, and confirm that TN status is associated with shorter survival among early-stage breast cancer patients in a Brazilian cancer registry. Moreover, our group identified significantly worst tumor features among TN patients, including undifferentiated and advanced tumors.