bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary central nervous system plasmablastic lymphoma presenting in human immunodeficiency virus-negative but Epstein-Barr virus-positive patient: A case report
Authors: Zhang Li Ying , Lin Hui Yun , Gao Lan Xiang , Li Lin , Tian Yu Wang , Liu Zhi Qin , Shi Xiao Hua , Liang Zhi Yong 
Published: May 2012

Abstract

Abstract
We report a 32-year-old Outer Mongolian man, with plasmablastic lymphoma (PBL) primarily occured in the central nervous system and diagnosed by surgical resection. This patient appeared headache and Magnetic resonance imaging (MRI) showed multiple lesions in the right cerebral hemisphere including the right frontal-parietal lobe and right basal ganglia and the left cerebellum, he was diagnosed as lymphoma by stereotactic biopsy in January 2009 in local hospital, and was given radiotherapy 33 times after the biopsy. The patient was admitted to The Military General Hospital of Beijing PLA., Beijing, P.R. China on March 9th, 2011, with chief complaints of right limbs convulsioned suddenly, then fell down and lose of his consciousness, then awoke after 4 to 5 minutes, with symptoms of angulus oris numbness and the right upper limb powerless ten days ago.
MRI of the brain revealed a well-defined hyperdense and enhancing mass in the left frontal-parietal lobe, the meninges are closely related, there was extensive peritumoural edema noted with pressure effects, as evident by effacement of the left lateral ventricles and a 0.5 cm shift of the midline to the right side.
Surgical resection showed markedly atypical, large singly dispersed or cohesive proliferation of plasmacytoid cells with frequent abnormal mitoses and binucleation, some neoplastic cells were large with round or oval nuclei and showed coarse chromatin and smaller or unapparent nucleoli, some neoplastic cells with prominent nucleoli, apoptosis and necrosis were often presented. Immunohistochemistry staining and gene rearrangement together with other supportive investigation confirmed the diagnosis of primary central nervous system plasmablastic lymphoma. A month later, he was started on chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, leurocristime and prednisone) for a week. Other supportive treatment was provided for symptomatic epilepsy. The patient regained muscle strength in both upper limbs and right lower limb and the symptomatic epilepsy was controlled after two weeks. Then the patient was discharged. Follow-up data shows the patient to be alive eleven months after discharge.

Virtual Slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1649317674697046.
Near infrared spectroscopy (NIRS) of the thenar eminence in anesthesia and intensive care
Authors: Lipcsey Miklos , Woinarski Nicholas CZ , Bellomo Rinaldo 
Published: May 2012

AbstractNear infrared spectroscopy of the thenar eminence (NIRSth) is a noninvasive bedside method for assessing tissue oxygenation. The NIRS probe emits light with several wavelengths in the 700- to 850-nm interval and measures the reflected light mainly from a predefined depth. Complex physical models then allow the measurement of the relative concentrations of oxy and deoxyhemoglobin, and thus tissue saturation (StO2), as well as an approximation of the tissue hemoglobin, given as tissue hemoglobin index.Here we review of current knowledge of the application of NIRSthin anesthesia and intensive care.We performed an analytical and descriptive review of the literature using the terms “near-infrared spectroscopy” combined with “anesthesia,” “anesthesiology,” “intensive care,” “critical care,” “sepsis,” “bleeding,” “hemorrhage,” “surgery,” and “trauma” with particular focus on all NIRS studies involving measurement at the thenar eminence.We found that NIRSthhas been applied as clinical research tool to perform both static and dynamic assessment of StO2. Specifically, a vascular occlusion test (VOT) with a pressure cuff can be used to provide a dynamic assessment of the tissue oxygenation response to ischemia. StO2changes during such induced ischemia-reperfusion yield information on oxygen consumption and microvasculatory reactivity. Some evidence suggests that StO2during VOT can detect fluid responsiveness during surgery. In hypovolemic shock, StO2can help to predict outcome, but not in septic shock. In contrast, NIRS parameters during VOT increase the diagnostic and prognostic accuracy in both hypovolemic and septic shock. Minimal data are available on static or dynamic StO2used to guide therapy.Although the available data are promising, further studies are necessary before NIRSthcan become part of routine clinical practice.
Crk adaptor proteins act as key signaling integrators for breast tumorigenesis
Authors: Fathers Kelly E , Bell Emily S , Rajadurai Charles V , Cory Sean , Zhao Hong , Mourskaia Anna , Zuo Dongmei , Madore Jason , Monast Anie , Mes-Masson Anne-Marie , Grosset Andree-Anne , Gaboury Louis , Hallet Michael , Siegel Peter , Park Morag 
Published: May 2012

Abstract
Introduction
CT10 regulator of kinase (Crk) adaptor proteins (CrkI, CrkII and CrkL) play a role in integrating signals for migration and invasion of highly malignant breast cancer cell lines. This has important implications, as elevated CrkI/II protein levels were observed in a small cohort of breast cancer patients, which identified a potential role for Crk proteins in breast cancer progression. Numerous in vitro studies identified a role for Crk proteins in cell motility, but little is known about how Crk proteins contribute to breast cancer progression in vivo.

Methods
The clinical significance of Crk proteins in human breast cancer was assessed by analyzing published breast cancer datasets using a gene expression signature that was generated following CrkII over-expression and by examining Crk protein expression in tissue microarrays of breast tumors (n = 254). Stable knockdown of Crk (CrkI/CrkII/CrkL) proteins was accomplished using a short hairpin RNA (shRNA)-mediated approach in two basal breast cancer cell lines, MDA-231 1833TR and SUM1315, where the former have a high affinity to form bone metastases. Both in vitro assays (cell migration, invasion, soft agar growth) and in vivo experiments (intra-cardiac, tibial and mammary fat pad injections) were performed to assess the functional significance of Crk proteins in breast cancer.

Results
A gene signature derived following CrkII over-expression correlated significantly with basal breast cancers and with high grade and poor outcome in general. Moreover, elevated Crk immunostaining on tissue microarrays revealed a significant association with highly proliferative tumors within the basal subtype. RNAi-mediated knockdown of all three Crk proteins in metastatic basal breast cancer cells established a continued requirement for Crk in cell migration and invasion in vitro and metastatic growth in vivo. Furthermore, Crk ablation suppressed anchorage independent growth and in vivo orthotopic tumor growth. This was associated with diminished cell proliferation and was rescued by expression of non-shRNA targeted CrkI/II. Perturbations in tumor progression correlated with altered integrin signaling, including decreased cell spreading, diminished p130Cas phosphorylation, and Cdc42 activation.

Conclusions
These data highlight the physiological importance of Crk proteins in regulating growth of aggressive basal breast cancer cells and identify Crk-dependent signaling networks as promising therapeutic targets.
Metformin overdose, but not lactic acidosis per se, inhibits oxygen consumption in pigs
Authors: Protti Alessandro , Fortunato Francesco , Monti Massimo , Vecchio Sarah , Gatti Stefano , Comi Giacomo P , Giuseppe Rachele De , Gattinoni Luciano 
Published: May 2012

Abstract
Introduction
Hepatic mitochondrial dysfunction may play a critical role in the pathogenesis of metformin-induced lactic acidosis. However, patients with severe metformin intoxication may have a 30 to 60% decrease in their global oxygen consumption, as for generalized inhibition of mitochondrial respiration. We developed a pig model of severe metformin intoxication to validate this clinical finding and assess mitochondrial function in liver and other tissues.

Methods
Twenty healthy pigs were sedated and mechanically ventilated. Ten were infused with a large dose of metformin (4 to 8 g) and five were not (sham controls). Five others were infused with lactic acid to clarify whether lactic acidosis per se diminishes global oxygen use. Arterial pH, lactatemia, global oxygen consumption (VO2) (metabolic module) and delivery (DO2) (cardiac output by thermodilution) were monitored for nine hours. Oxygen extraction was computed as VO2/DO2. Activities of the main components of the mitochondrial respiratory chain (complex I, II and III, and IV) were measured with spectrophotometry (and expressed relative to citrate synthase activity) in heart, kidney, liver, skeletal muscle and platelets taken at the end of the study.

Results
Pigs infused with metformin (6 ± 2 g; final serum drug level 77 ± 45 mg/L) progressively developed lactic acidosis (final arterial pH 6.93 ± 0.24 and lactate 18 ± 7 mmol/L, P < 0.001 for both). Their VO2 declined over time (from 115 ± 34 to 71 ± 30 ml/min, P < 0.001) despite grossly preserved DO2 (from 269 ± 68 to 239 ± 51 ml/min, P = 0.58). Oxygen extraction accordingly fell from 43 ± 10 to 30 ± 10% (P = 0.008). None of these changes occurred in either sham controls or pigs infused with lactic acid (final arterial pH 6.86 ± 0.16 and lactate 22 ± 3 mmol/L). Metformin intoxication was associated with inhibition of complex I in the liver (P < 0.001), heart (P < 0.001), kidney (P = 0.003), skeletal muscle (P = 0.012) and platelets (P = 0.053). The activity of complex II and III diminished in the liver (P < 0.001), heart (P < 0.001) and kidney (P < 0.005) while that of complex IV declined in the heart (P < 0.001).

Conclusions
Metformin intoxication induces lactic acidosis, inhibits global oxygen consumption and causes mitochondrial dysfunction in liver and other tissues. Lactic acidosis per se does not decrease whole-body respiration.
Higher vs. lower fluid volume for septic shock: clinical characteristics and outcome in unselected patients in a prospective, multicenter cohort
Authors: Smith Søren H , Perner Anders 
Published: May 2012

Abstract
Introduction
Patients with septic shock require fluid, but the optimum amount is unknown. Therefore we assessed patient characteristics and outcome associated with fluid volume in unselected patients with septic shock including those with three days of shock.

Methods
We conducted a prospective, multicenter, observational study of all adult patients with septic shock during a 3-month study period at six general ICUs: three in university hospitals and three in regional hospitals. After day 1 and 3 of shock, patients were divided into two groups according to the overall median fluid volumes. Characteristics between these groups were compared using non-parametric and Chi-square statistics.

Results
The 164 included patients received median 4.0 l (IQR 2.3-6.3) of fluid during the first day of septic shock. Patients receiving higher volumes (> 4.0 l) on day 1 had higher p-lactate (3.4 (2.2-5.5) vs. 2.0 (1.6-3.0) mmol l-1, P < 0.0001) compared to those receiving lower volumes. In contrast simplified acute physiology score (SAPS) II (54 (45-64) vs. 54 (45-67), P = 0.73), sequential organ failure assessment (SOFA) score (11 (9-13) vs. 11 (9-13), P = 0.78) and 90-day mortality (48 vs. 53%, P = 0.27) did not differ between groups. The 95 patients who still had shock on day 3 had received 7.5 l (4.3 - 10.8) of fluid by the end of day 3. Patients receiving higher volumes (> 7.5 l) had higher p-lactate (2.6 (1.7-3.4) vs. 1.9 (1.6-2.4) mmol l-1, P < 0.01) on day 3 and lower 90-day mortality (40 vs. 62%, P = 0.03) than those receiving lower volumes in spite of comparable admission SAPS II (53 (46-67) vs. 55 (49-62), P = 0.47) and SOFA scores on day 3 (10 (8-13) vs. 11 (10-14), P = 0.33).

Conclusions
In this cohort of unselected ICU patients with septic shock, initial fluid volume was not associated with mortality. In patients with shock for three days or more, higher fluid volumes including crystalloids, colloids and blood products were associated with reduced mortality.
Prospective Study of Health-Related Quality of Life for Children With Brain Tumors Treated With Proton Radiotherapy
Authors: Kuhlthau Karen A. , Pulsifer Margaret B. , Yeap Beow Y. , Rivera Morales Dianali , Delahaye Jennifer , Hill Kristen S. , Ebb David , Abrams Annah N. , MacDonald Shannon M. , Tarbell Nancy J. , Yock Torunn I. 
Published: May 2012

Purpose We describe the health-related quality of life (HRQoL) of a cohort of children with brain tumors treated with proton radiotherapy. Patients and Methods We recruited 142 pediatric patients with brain tumors (age 2 to 18 years) and parents of such patients treated with proton radiation at Massachusetts General Hospital from 2004 to 2010. HRQoL was assessed using the PedsQL core, brain tumor, and cancer modules (range, 0 to 100). Assessments took place during radiation and annually thereafter. We examined correlations of HRQoL with disease, treatment, and cognitive and behavioral data. Results Overall reports of HRQoL during treatment were 74.8 and 78.1 for child self-report (CSR) and 67.0 and 74.8 for parent proxy report (PPR) for the core and brain tumor modules, respectively. PPR demonstrated lower HRQoL scores than CSR, but the two were highly correlated. Higher HRQoL scores were significantly associated with Wechsler Full Scale Intelligence Quotient scores (administered via the age-appropriate version) and better scores on two behavioral measures. Disease type also correlated with PPR core total HRQoL score at the beginning of treatment: medulloblastoma or primitive neuroectodermal tumors, 57.8; germ cell tumors, 63.5; ependymoma or high-grade glioma, 69.8; low-grade glioma, 71.5; and other low-grade neoplasms, 78.0 (P = .001). Craniospinal irradiation and chemotherapy were negatively correlated with HRQoL. Conclusion This is the first study to our knowledge of HRQoL in a cohort of children with brain tumors treated with proton radiation. This prospective study demonstrates the effect of disease type and intensity of treatment on HRQoL. It further suggests that where CSR is not possible, PPR is appropriate in most circumstances.
Tobacco Smoking and Increased Risk of Death and Progression for Patients With p16-Positive and p16-Negative Oropharyngeal Cancer
Authors: Gillison Maura L. , Zhang Qiang , Jordan Richard , Xiao Weihong , Westra William H. , Trotti Andy , Spencer Sharon , Harris Jonathan , Chung Christine H. , Ang K. Kian 
Published: May 2012

PurposeTobacco smoking is associated with oropharynx cancer survival, but to what extent cancer progression or death increases with increasing tobacco exposure is unknown.Patients and MethodsPatients with oropharynx cancer enrolled onto a phase III trial of radiotherapy from 1991 to 1997 (Radiation Therapy Oncology Group [RTOG] 9003) or of chemoradiotherapy from 2002 to 2005 (RTOG 0129) were evaluated for tumor human papillomavirus status by a surrogate, p16 immunohistochemistry, and for tobacco exposure by a standardized questionnaire. Associations between tobacco exposure and overall survival (OS) and progression-free survival (PFS) were estimated by Cox proportional hazards models.ResultsPrevalence of p16-positive cancer was 39.5% among patients in RTOG 9003 and 68.0% in RTOG 0129. Median pack-years of tobacco smoking were lower among p16-positive than p16-negative patients in both trials (RTOG 9003: 29 v 45.9 pack-years; P = .02; RTOG 0129: 10 v 40 pack-years; P < .001). After adjustment for p16 and other factors, risk of progression (PFS) or death (OS) increased by 1% per pack-year (for both, hazard ratio [HR], 1.01; 95% CI, 1.00 to 1.01; P = .002) or 2% per year of smoking (for both, HR, 1.02; 95% CI, 1.01 to 1.03; P < .001) in both trials. In RTOG 9003, risk of death doubled (HR, 2.19; 95% CI, 1.46 to 3.28) among those who smoked during radiotherapy after accounting for pack-years and other factors, and risk of second primary tumors increased by 1.5% per pack-year (HR, 1.015; 95% CI, 1.005 to 1.026).ConclusionRisk of oropharyngeal cancer progression and death increases directly as a function of tobacco exposure at diagnosis and during therapy and is independent of tumor p16 status and treatment.
Impact of Routine Pathology Review on Treatment for Node-Negative Breast Cancer
Authors: Kennecke Hagen F. , Speers Caroline H. , Ennis Catherine A. , Gelmon Karen , Olivotto Ivo A. , Hayes Malcolm 
Published: May 2012

Purpose Routine secondary pathology review influences diagnosis and treatment among patients diagnosed with breast cancer. The impact of review on patients with node-negative breast cancer and the nature of the pathology elements leading to management changes are not well described. Methods Patients with node-negative, invasive, or in situ breast cancer and evaluable nodes referred to the British Columbia Cancer Agency during two time periods between 2004 and 2007 were included. Pathologists with expertise in breast cancer reviewed the original reports and slides. Biomarker testing was not routinely repeated. Medical record review was conducted to determine whether original pathology was changed and whether recommended therapy was affected. Results Among 906 eligible patients, 405 (45%) received a pathology review. Univariate comparisons revealed that reviewed patients were younger (P < .001) and more likely to have close margins (P < .001), whereas other characteristics were similar. A total of 102 pathology changes were documented among 81 patients (20%). The most frequently changed elements were grade (40%) and lymphovascular (26%), nodal (15%), and margin (12%) status. These changes resulted in 27 treatment modifications among 25 patients (6%). Treatment changes were primarily related to nodal and margin status, and only two of 27 were related to measurement of tumor biology in women with estrogen receptor–positive, node-negative breast cancer. Conclusion Reported rates of change are significant and warrant routine secondary pathology review among patients with node-negative breast cancer or ductal carcinoma in situ before final treatment is recommended. Review remains relevant in the era of gene expression signatures to determine margin and nodal status.
Bevacizumab in Combination With Chemotherapy As First-Line Therapy in Advanced Gastric Cancer: A Biomarker Evaluation From the AVAGAST Randomized Phase III Trial
Authors: Van Cutsem Eric , de Haas Sanne , Kang Yoon-Koo , Ohtsu Atsushi , Tebbutt Niall C. , Ming Xu Jian , Peng Yong Wei , Langer Bernd , Delmar Paul , Scherer Stefan J. , Shah Manish A. 
Published: May 2012

Purpose The AVAGAST study showed that adding bevacizumab to chemotherapy in patients with advanced gastric cancer improves progression-free survival and tumor response rate but not overall survival. To examine the hypothesis that angiogenic markers may have predictive value for bevacizumab efficacy in gastric cancer, AVAGAST included a prospective, mandatory biomarker program. Patients and Methods Patients with previously untreated, locally advanced or metastatic gastric cancer were randomly assigned to bevacizumab (n = 387) or placebo (n = 387) in combination with chemotherapy. Blood and tumor tissue samples were collected at baseline. Prespecified biomarkers included plasma vascular endothelial growth factor-A (VEGF-A), protein expression of neuropilin-1, and VEGF receptors-1 and -2 (VEGFR-1 and VEGFR-2). Correlations between biomarkers and clinical outcomes were assessed by using a Cox proportional hazards model. Results Plasma was available from 712 patients (92%), and tumor samples were available from 727 patients (94%). Baseline plasma VEGF-A levels and tumor neuropilin-1 expression were identified as potential predictors of bevacizumab efficacy. Patients with high baseline plasma VEGF-A levels showed a trend toward improved overall survival (hazard ratio [HR], 0.72; 95% CI, 0.57 to 0.93) versus patients with low VEGF-A levels (HR, 1.01; 95% CI, 0.77 to 1.31; interaction P = .07). Patients with low baseline expression of neuropilin-1 also showed a trend toward improved overall survival (HR, 0.75; 95% CI, 0.59 to 0.97) versus patients with high neuropilin-1 expression (HR, 1.07; 95% CI, 0.81 to 1.40; interaction P = .06). For both biomarkers, subgroup analyses demonstrated significance only in patients from non-Asian regions. Conclusion Plasma VEGF-A and tumor neuropilin-1 are strong biomarker candidates for predicting clinical outcome in patients with advanced gastric cancer treated with bevacizumab.
Mechanism of PKA-Dependent and Lipid-Raft Independent Stimulation of Connexin43 Expression by Oxytoxin in Mouse Embryonic Stem Cells
Authors: Yun Seung Pil , Park Su Shin , Ryu Jung Min , Park Jae Hong , Kim Mi Ok , Lee Jang-Hern , Han Ho Jae 
Published: May 2012

AbstractPrevious studies shows that connexins appear very early during murine embryo development, the gap junctional intercellular communication found in the inner cell mass of early embryo is also maintained in embryonic stem cells (ESC), and expression of oxytocin receptor (OTR) is developmentally regulated at early embryonic development. However, effect of oxytocin (OT) on the regulation of the connexin43 (Cx43) and maintenance of undifferentiation is not fully understood in stem cells. Therefore, we investigated the effect of OT on Cx43 expression and related signaling cascades in mouse ESC. OT increased Cx43 expression that was inhibited by the OTR inhibitor atosiban. In experiments to examine whether the effect of OT depends on lipid rafts, caveolin-1 (cav-1), cav-2, and flotillin-2, but not OTR, were detected in lipid raft fractions. Also, colocalization of OTR, cav-1, and cav-2 was not detected. Moreover, the lipid raft disruptor methyl-β-cyclodextrin did not attenuate OT-induced Cx43 expression. In experiments to examine related signaling pathways, OT activated cAMP/protein kinase A (PKA) which was inhibited by adenylyl cyclase inhibitor SQ 22536 and PKA inhibitor PKI. OT increased nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) phosphorylation which was inhibited by PKI. OT also increased cAMP response element-binding (CREB)/CREB-binding protein (CBP) expression in the nucleus and induced the formation of CREB1/NF-κB/CBP complexes, which was blocked by the NF-κB-specific small interfering RNA, NF-κB inhibitors, SN50, and bay11–7082. Complex disruption by NF-κB inhibitors decreased OT-induced Cx43 expression. In conclusion, OT stimulates Cx43 expression through the NF-κB/CREB/CBP complex via the lipid raft-independent OTR-mediated cAMP/PKA in mouse ESC.