tbuckley/cabot-search huggingface dataset:
Notice of Retraction: Ahimastos AA, et al. Effect of Ramipril on Walking Times and Quality of Life Among Patients With Peripheral Artery Disease and Intermittent Claudication: A Randomized Controlled Trial. JAMA. 2013;309(5):453-460.
Authors: Anna A. Ahimastos, Christopher Askew, Anthony Leicht, Elise Pappas, Peter Blombery, Christopher M. Reid, Jonathan Golledge, Bronwyn A. Kingwell
Journal: JAMA (2015)

In Reply We agree with Drs Redington and Caldarone that many animal and human studies have shown that a single or few (≤5) short episodes of remote ischemic preconditioning (typically 5 minutes of limb ischemia followed by 5 minutes of reperfusion) are protective for many organs (including the heart, brain, and kidney) with few reported adverse effects.However, few studies have examined the long-term effects of repeated episodes of remote ischemic preconditioning, and this is what we referred to in our Editorial that the effects of multiple episodes of remote ischemic preconditioning, which patients may be exposed to if remote ischemic preconditioning is widely used, are unclear.For example, the study by Meng et al 1 used remote ischemic preconditioning twice daily during 300 consecutive days to reduce stroke, but did not examine molecular mechanisms of brain protection or cardiovascular adverse effects.Similarly, a study by Shaked et al 2 that used intermittent cycles of remote ischemic preconditioning as adjunctive therapy for treatment of diabetic foot ulcers did not examine cardiovascular effects.Redington appeared to agree with our point of view as the coauthor of a review article, 3 which cautioned that "hyperconditioning (ie, an as-yet undefined, excessive number of conditioning episodes) may be deleterious."Another recent review article by Whittaker and Przyklenk 4 suggested that in addition to tachyphylaxis (ie, increased tolerance to the effect of an intervention), repeated episodes of limb ischemia may have unfavorable consequences for collagen and systemic effects mediated via matrix metalloproteinases.The authors concluded that the benefits of protection against ischemia may be found at low doses (ie, low number and duration of preconditioning episodes), but these benefits may be lost and adverse effects may occur (collagen damage) at high doses.In addition, remote ischemic preconditioning may have limited utility for cardioprotection in 2 large populations (elderly patients and those with diabetes) at high risk for cardiovascular diseases, 5 and may be associated with higher risk for atrial fibrillation, even when used at the conventional dose (5-minute episodes of ischemia/reperfusion repeated 5 times) before coronary artery bypass graft surgery. 6 Therefore, even though we share the enthusiasm of Redington and Caldarone for the promise of remote ischemic preconditioning for organ protection, investigators in the field should examine potential long-term harmful effects to various organs, including the heart, particularly when hyperconditioning is used.
Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11 (vol 39, pg 1434, 2007)
Authors: H Houlden, J Johnson, C Gardner-Thorpe, T Lashley, D Hernandez, P Worth, AB Singleton, DA Hilton, J Holton, T Revesz, MB Davis, P Giunti, NW Wood
Journal: Nature Genetics (2008)
LP34 : Ex vivo liver resection and autotransplantation: A feasible and highly effective procedure for patients with end-stage alveolar echinococcosis – 15 cases experience
Authors: H. Wen, J.-H. Dong, J.-H. Zhang, W.-D. Duan, J.-M. Zhao, Y.-R. Liang, Y.-M. Shao, X.-W. Ji, Q.-W. Tai, T. Li, H. Gu, T. Tuxun, Y.-B. He, J.-F. Huang
Journal: Journal of Hepatology (2015)
Targeting of phosphatidylserine by monoclonal antibodies augments the activity of paclitaxel and anti-PD1/PD-L1 therapy in the murine breast model E0771
Authors: Michael Gray, Jian Gong, Van Nguyen, Takuya Osada, Zachary Hartman, Jeff Hutchins, Bruce Freimark, Kim Lyerly
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The phospholipid lipid phosphatidylserine (PS) normally resides in the inner plasma membrane leaflet in most mammalian cells, including tumor and tumor associated vascular cells. Inducers of cellular stress, such as hypoxia and oxygen radicals encountered in tumors, and treatments
A comparison of metabolic control by continuous and intermittent therapies in acute renal failure.
Authors: W R Clark, B A Mueller, K J Alaka, W L Macias
Journal: Journal of the American Society of Nephrology (1994)

Azotemia control provided by blood pump-assisted continuous hemofiltration has not been rigorously compared with that provided by intermittent hemodialysis (IHD) for critically ill patients with acute renal failure (ARF). The metabolic control achieved by continuous venovenous hemofiltration (CVVH) and IHD was compared. In ARF patients treated with CVVH (N = 11), the normalized daily dose of therapy was 0.59 +/- 0.23 (mean +/- SD) and the normalized protein catabolic rate was 1.82 +/- 0.95 g/kg per day. The serum urea nitrogen concentration (SUN) declined with CVVH from an initial value of 114 +/- 32 to 79 +/- 17 mg/dL at steady state (SUNs). The initial analysis was a theoretical comparison between CVVH azotemia control and the control that would have been provided by IHD. Simulated IHD data were generated by conventional urea kinetic methods. The peak concentration hypothesis was invoked to compare CVVH SUNs and the peak IHD SUN (SUNp). A simulated IHD frequency of five times or more weekly was required to achieve a SUNp that did not differ from the CVVH SUNs. A similar comparison between the CVVH group and a separate group of ARF patients (N = 11) who received IHD was also performed. In the latter group, the normalized protein catabolic rate and the normalized daily dose of therapy were similar to those of the CVVH group. The SUNp (101 +/- 12 mg/dL) in the IHD group was significantly higher than the mean CVVH SUNs (P < 0.05). These data suggest that intensive hemodialysis is required to provide azotemia control similar to that provided by CVVH.(ABSTRACT TRUNCATED AT 250 WORDS)
Does having an asthmatic sibling affect the quality of life in children
Authors: Ozge Yilmaz, Ahmet Turkeli, Ozlem Karaca, Hasan Yuksel
Journal: European Respiratory Journal (2014)

Aim:  We aimed to investigate the influence of having an asthmatic sibling on a child9s quality of life.   Methods:  We enrolled 2-12 year aged children with an asthmatic sibling in the study group (n=114) and 2-12 year old children with a healthy sibling in the control group (n=114) of this case-control study. Sociodemographic characteristics, age and education of the children and disease severity characteristics of the asthmatic siblings were recorded. All parents filled in the Turkish generic PedsQL TM  short form appropriate for the child9s age group (2-4 years, 5-7 years and 8-12 years old).   Results:  Total PedsQL TM  scores were not significantly different in any of the age groups (p=0.23, p=0.13 and 0.11 in the increasing age groups respectively). Emotional PedsQL TM  subscores in children with an asthmatic sibling were significantly worse ( 83.0 vs 91.6 in the 2-4 year age group, 72.0 vs 92.2 in the 5-7 year age group, 73.7 vs 88.7 in the 8-12 year age group respectively, p≤0.002 for all). Similarly, psychosocial score of the scale was significantly impaired in the 2-4 and 5-7 year old groups but not the 8-12 year old group (p=0.01 in the first two groups, p=0.08 in the last group).   Conclusions:  Children with an asthmatic sibling have significantly impaired emotional QoL which implies the need for pscyhological assessment of these children and provide support if required.
ATF4 plays a pivotal role in the development of functional hematopoietic stem cells in mouse fetal liver
Authors: Yunze Zhao, Jie Zhou, Dan Liu, Fang Dong, Hui Cheng, Weili Wang, Yakun Pang, Yajie Wang, Xiaohuan Mu, Yanli Ni, Zhuan Li, Huiyu Xu, Sha Hao, Xiaochen Wang, Shihui Ma, Qian-fei Wang, Guozhi Xiao, Weiping Yuan, Bing Liu, Tao Cheng
Journal: Blood (2015)
Epoetin alfa 60,000 U QW followed by 80,000 U Q3W maintenance in patients with anemia and cancer receiving chemotherapy
Authors: A. Grosbach, C. J. Langer, V. Montoya, D. Williams
Journal: Journal of Clinical Oncology (2004)

8215 Background: Epoetin alfa (EPO) at a starting dose of 40,000 U SC once weekly (QW) has been shown to be effective in the treatment of chemotherapy-induced anemia in cancer patients (pts). It is hypothesized that higher starting doses followed by less frequent maintenance dosing may shorten time to Hb response and increase response rates. Methods: In this ongoing open-label, multicenter, pilot study in 130 anemic pts with cancer receiving CT, EPO 60,000 U SC was administered QW for up to 12 weeks (wks) until a target Hb ≥12 g/dL was reached (initiation phase [IP]). Pts then received EPO 80,000 U SC every 3 weeks (Q3W; maintenance phase [MP]) to maintain Hb 11.5 g/dL to 12.5 g/dL. Primary end point was proportion of pts with Hb ≥12 g/dL or Hb increase ≥2 g/dL from baseline in the IP. Eligible pts were ≥18 y with nonmyeloid malignancy, baseline Hb ≤11 g/dL, and scheduled to receive CT Q3W for ≥15 wks. Pts were followed for up to 24 wks and received 1 dose of EPO after last CT cycle. Pts with Hb ≥12 g/dL during IP continued QW dosing until the start of next CT cycle, then began Q3W MP. Pts were withdrawn for missed doses or Hb <11 g/dL during MP. Results: Thirty-six pts are evaluable for analysis (mean baseline Hb 10.2 ± 0.9 g/dL). Nineteen pts entered the MP after a median of 5 wks; mean Hb was 12.0 ± 0.9 g/dL at start of MP therapy and has been maintained for a median of 7 wks. The proportion of pts with Hb ≥12 g/dL or Hb increase ≥2 g/dL from baseline in the IP was 61%. Seventeen (55%) of 31 pts had Hb increase ≥1 g/dL after 4 wks. EPO dose was reduced to 40,000 U QW in 9 (25%) pts in IP and 60,000 U Q3W in 7 (37%) pts in MP due to Hb>13 g/dL or Hb increase >1.3-g/dL in 2 wks. Seventeen pts were withdrawn (8 in IP, 9 in MP) due to MP Hb <11 g/dL (n = 4), loss to follow-up (n = 3), not reaching target Hb ≥12 g/dL in the IP (n = 2), death (n = 1), AE (n = 1), and other/missing (n = 6). Conclusions: These preliminary data suggest that EPO 60,000 U QW increases Hb and that 60,000–80,000 U Q3W can maintain Hb in the majority of pts entering maintenance. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ortho Biotech Products, L.P. Aventis; Johnson & Johnson; Ortho Biotech Products, L.P. Johnson & Johnson Novartis
Chemo-radiation protocol for locally advanced (LA) squamous cell carcinoma (SCC) of the larynx (L) and oropharynx (OP): Organ-preservation and short term mortality
Authors: D. Herchenhorn, F. L. Dias, L. M. Moraes, C. G. Ferreira, R. A. Lima, J. Kligerman, C. M. Araujo
Journal: Journal of Clinical Oncology (2004)

5606 Background: LA SCC of the head and neck compromise 50% of patients(pts) diagnosed at our Institution. Surgical resection is not a curative option in most of the pts. with LA disease. Methods: From Dec 2000 to Nov 2003, 57 pts with L and OP carcinoma were treated with the combination of Cisplatin (C) 100mg/m2 days1,22,43 with standard Radiotherapy (RT), and evaluated for response, toxicity, survival and quality of life in a single institution in Brasil. Results: Median age 55y(25–72), 47 pts with L(82,5%)and 10 pts OP(17,5%), 26 pts were stageIII 45,6%, IVA 42,1% and IVB12,3%, all pts had PS 0–1. 89,4% completed RT with doses 66–70,2Gy (180fr), all pts had at least a 1 week delay after 45Gy; 43 pts received 3 cycles of C(75,4%).Reasons for C interruption: drop in PS 4, nefrotoxicity, ototoxicity, dermatitis, bleeding. Delay of C in 12 pts(21%) and 5pts (8,8%) reduced C dose. GradeIII/IV NCI toxicity include: skin 28%, gastro-intestinal 23%, hematological 5,3%, renal 7%. Median weight loss was 10% of the initial weight, traqueostomy was necessary in 26pts(45,6%) but in 12 pts before and 02 during therapy, 26pts needed enteral feeding(45,6%). Complete response in the primary tumor occurred in 39 pts(68,4%), 02 of this pts had residual lymph nodes, and 16 pts(28,1%) had residual tumor, 2 are not available. Cervical dissection in 4 pts(2 in CR) and salvage laryngectomy in 6pts. 6 pts in CR relapsed, median time to recurrence was 11,2 months(6–19).With a follow-up of 13,7 months(2–35) 17 pts are dead(29,8%) and 35 are alive free of disease(61,4%), 80% of the stage IVB are dead. Median survival for this group is only 6 months (Kaplan-Meier 95% CI 3,4–8,7). There was no statistical survival difference between L and OP pts or N0 and N positive pts p=0,44, 22% and 34% of N0 and N1 patients are dead. In a mutlivariate analysis there was a correlation between age and interruption of RT p=0,004 and of C p=0,04, PS1 pts also had more interruptions of RT then PS0 p=0,0001. Conclusions: Combined therapy with C and RT was feasible and toxicity was similar to previous published series. Although 12% of the pts had previous traqueostomy, 49% of the pts achieved organ preservation and 30% are dead with a short follow-up; stage IVB pts were not good candidates for combine treatment and Rt delays could contribute to short term mortality. No significant financial relationships to disclose.
Risk factors for tuberculosis relapse in Polish patients
Authors: Izabela Siemion-Szczesniak, Maria Korzeniewska-Kosela, Jan Kus
Journal: European Respiratory Journal (2013)

Background: Recurrent tuberculosis is unfavorable epidemiological phenomenon because it can be associated with resistance to drugs.

Objective: To identify risk factors associated with relapse in TB patients in Poland

Methods: Data of 45282 cases with culture confirmed tuberculosis registered in the Central TB Register from 2002 to 2012 were analyzed according to demographic, social and clinical factors that may determine the recurrence of tuberculosis. Chi-squared test was used to assess statistical significance (SS) of each factor and multivariate analyses (MVA) to identify the independent risk factors.

Results: There were 4271 relapsed cases of TB. The proportion of patients with relapse was significantly higher among: unmarried (11.8% vs. 10.7%, p<0.001), persons with lower education level (12.2% vs. 7.1%, p<0.0001), homeless (15.8% vs. 11.1%, p<0.0001), unemployed (12.8% vs. 10.7%, p<0.0001) and in men (12.8% vs. 8%, p<0.0001). Relapses were more common in patients with smear positive TB that in smear negative (12.7% vs. 9.5%, p<0.0001). Multidrug resistance (MDR) occured more frequently in previously treated cases (44.3% vs. 11.2%, p<0.0001) and patients with MDR-TB tended to relapse more frequently (44.3% vs. 11.2%, p<0.0001). Mean age of cases with relapse was 52.4 (±14 yrs), and of new cases 51.5 (±17.7) yrs, which was a statistically significant difference (p< 0.002). In MVA relapse remained significantly related to unemployment, low educational level and homelessness.

Conclusion: The results of our study indicate that socio-economic deprivation is very strongly associated with relapse in TB patients in Poland, so a special attention should be put to the direct observation of treatment in these patients.
Insulin-like growth factor receptor 1 (IGFR-1) and outcome measures in advanced non-small cell lung cancer (NSCLC) patients treated with gefitinib
Authors: M. J. Fidler, S. Basu, L. Buckingham, K. Kaiser, S. E. McCormack, J. S. Coon, P. D. Bonomi
Journal: Journal of Clinical Oncology (2008)

8036 Background: Increased expression of IGFR-1 has been hypothesized to impart resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Our objective was to associate clinical outcomes of advanced NSCLC gefitinib treated patients (pts) with IGFR-1 expression. Methods: Consecutive Expanded Access Trial pts with > 1 week gefitinib were included for analysis. Tissue was evaluated for IGFR-1 immunohistochemistry (IHC). IGFR-1 positivity was defined as any staining present. Results: The characteristics of the 83 pts with tumor available for IGFR-1 staining were: 38 male (45.8%), median age 66, 13 never- smokers (15.7%), 51 with adenocarcinoma histology (61.4%), 78 pts with ECOG performance status 0–1 (94.0%). For the entire group of 83 pts, the objective response rate (complete response (CR) + partial response (PR)) was 14.5 %, disease control rate (CR + PR+ stable disease) was 57.8%. The median progression free interval (PFI, censored at 1 yr) was 3.0 months (mo); the median overall survival (OS), 7.3 mo. Using landmark analysis in which 35 pts (42.2 %) with rapidly progressive disease (defined as progression free interval (PFI) ≤ 70 days) were excluded, a significant association between positive IGFR-1 expression and prolonged median PFI (5.7 mo vs. 4.0 mo, respectively, p < 0.05 from Gehan-Wilcoxon test) was seen. No significant association was found between IGFR-1 and response, rapid progression, or OS. Conclusions: Though counter-intuitive, our results suggest improved efficacy with increased IGFR-1 expression and gefitinib therapy in previously treated advanced NSCLC pts. Our results are similar to those of Cappuzzo et al. (Annals of Oncology, 2006) where longer median survival was seen in gefitinib treated pts whose tumors had high IGFR-1 expression. Further study of the relationship between IGFR and EGFR molecular markers and of combinations of EGFR and IGFR inhibitors in NSCLC should be considered. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca Oncology AstraZeneca Oncology
Natural killer cell hyporesponsiveness and impaired development in a CD247-deficient patient
Authors: Mar Valés-Gómez, Gloria Esteso, Cigdem Aydogmus, Alfonso Blázquez-Moreno, Ana V. Marín, Alejandro C. Briones, Beatriz Garcillán, Eva-María García-Cuesta, Sheila López Cobo, Sule Haskologlu, Manuela Moraru, Funda Cipe, Kerry Dobbs, Figen Dogu, Silvia Parolini, Luigi D. Notarangelo, Carlos Vilches, Maria J. Recio, José R. Regueiro, Aydan Ikinciogullari, Hugh T. Reyburn
Journal: Journal of Allergy and Clinical Immunology (2015)
Qualitative assessment of brain morphology in acute and chronic schizophrenia
Authors: J Lieberman, B Bogerts, G Degreef, M Ashtari, G Lantos, J Alvir
Journal: American Journal of Psychiatry (1992)

Neuroimaging studies of brain morphology in schizophrenia have used predominantly morphometric techniques to assess brain scans. However, as currently implemented, such methods are not particularly helpful in the routine assessment of individual patients. The purpose of this study was to evaluate brain morphology seen with magnetic resonance imaging (MRI) by qualitative assessment, the most frequently used method in clinical practice for evaluating brain scans.First-episode (N = 62) and chronic, multi-episode (N = 24) schizophrenic patients and healthy comparison subjects (N = 42) underwent MRI of the whole head in a sequence that provided 63 contiguous brain slice images. Each subject received a rating of normal, questionably abnormal, or definitely abnormal for four brain regions (lateral ventricles, third ventricle, medial temporal lobe structures, and frontal/parietal cortex) and a global rating.The schizophrenic patients had significantly higher global rates of abnormal morphology (first-episode group, 31%; chronic group, 42%) than the normal subjects (5%). The highest regional rates of abnormalities were seen in the lateral ventricles and the lowest in the frontal/parietal cortex. Although the chronic patients had generally higher abnormal rates than the first-episode patients, these differences were not statistically significant. The qualitative ratings of brain morphology were significantly correlated with quantitative assessments performed in separate studies.Despite its limits in sensitivity (and until quantitative morphometric techniques are made practical and more widely available), qualitative evaluation of MRI scans can be a useful technique in research and clinical evaluation of patients with schizophrenia.
Gemcitabine with or without cisplatin in patients (pts) with advanced or metastatic biliary tract cancer (ABC): Results of a multicenter, randomized phase III trial (the UK ABC-02 trial)
Authors: J. W. Valle, H. S. Wasan, D. D. Palmer, D. Cunningham, D. A. Anthoney, A. Maraveyas, S. K. Hughes, M. Roughton, J. A. Bridgewater
Journal: Journal of Clinical Oncology (2009)

4503 Background: There is no established standard chemotherapy for pts with inoperable ABC. We previously reported an improvement in progression-free survival (PFS) in a randomised phase II trial of 86 pts (ABC-01) using gemcitabine/cisplatin (GemCis) vs. gemcitabine (Gem) (Valle ASCO-GI 2006, abstr. 98). This study was extended into ABC-02, a phase III trial, to recruit a further 314 pts with overall survival (OS) as the primary end-point. Methods: Consenting pts with histologically/cytologically-confirmed ABC, aged ≥18 years, ECOG performance status 0 - 2, and adequate haematological, hepatic and renal function were randomised to receive either Cis (25 mg/m 2 ) followed by Gem (1000 mg/m 2 D1, 8 q21d) for 8 cycles, or Gem alone (1000 mg/m 2 on D1, 8, 15 q28d) for 6 cycles, stratified by extent of disease, site of primary tumour, ECOG score and centre. The trial had an 80% power to detect an OS hazard ratio of 0.73. Results: From May 2005 to October 2008, 324 pts were randomised to ABC- 02 from 34 UK centres. We report the pre-planned combined analysis of ABC-01 and ABC-02 based on 410 pts (GemCis=206/Gem=204). Patient characteristics: median age 64 yrs (range 23–85); male (47%); metastatic disease (75%), locally advanced (25%); gallbladder (36%), bile duct (59%), ampulla (5%); and ECOG 0–1 (87%), 2 (12%). With a median follow-up of 6.1 months and 263 deaths, the median OS was greater with GemCis than Gem, 11.7 vs. 8.2 months (log rank p=0.002), with hazard ratio 0.68 (95%-CI 0.53, 0.86). The median PFS was greater with GemCis than Gem, 8.5 vs. 6.5 months (log rank p=0.003), with hazard ratio 0.70 (95%-CI 0.56, 0.88).Toxicity was similar between the arms (by week 12, 57% had a grade 3/4 toxicity in each arm), though there was a slight excess of neutropenia using GemCis. Conclusions: This is the largest ever study in ABC and demonstrates a clear survival advantage for GemCis without added clinically significant toxicity, setting a new international standard of care. No significant financial relationships to disclose.