bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mortality of patients infected with HIV in the intensive care unit (2005 through 2010): significant role of chronic hepatitis C and severe sepsis
Authors: Medrano José , Álvaro-Meca Alejando , Boyer Alexandre , Jiménez-Sousa María A , Resino Salvador 
Published: August 2014

Abstract
Introduction
The combination antiretroviral therapy (cART) has led to decreased opportunistic infections and hospital admissions in human immunodeficiency virus (HIV)-infected patients, but the intensive care unit (ICU) admission rate remains constant (or even increased in some instances) during the cART era. Hepatitis C virus (HCV) infection is associated with an increased risk for hospital admission and/or mortality (particularly those related to severe liver disease) compared with the general population. The aim of this study was to assess the mortality among HIV-infected patients in ICU, and to evaluate the impact of HIV/HCV coinfection and severe sepsis on ICU mortality.

Methods
We carried out a retrospective study based on patients admitted to ICU who were recorded in the Minimum Basic Data Set (2005 through 2010) in Spain. HIV-infected patients (All-HIV-group (n = 1,891)) were divided into two groups: HIV-monoinfected patients (HIV group (n = 1,191)) and HIV/HCV-coinfected patients (HIV/HCV group (n = 700)). A control group (HIV(-)/HCV(-)) was also included (n = 7,496).

Results
All-HIV group had higher frequencies of severe sepsis (57.7% versus 39.4%; P < 0.001) than did the control group. Overall, ICU mortality in patients with severe sepsis was much more frequent than that in patients without severe sepsis (other causes) at days 30 and 90 in HIV-infected patients and the control group (P < 0.001). Moreover, the all-HIV group in the presence or absence of severe sepsis had a higher percentage of death than did the control group at days 7 (P < 0.001), 30 (P < 0.001) and 90 (P < 0.001). Besides, the HIV/HCV group had a higher percentage of death, both in patients with severe sepsis and in patients without severe sepsis compared with the HIV group at days 7 (P < 0.001) and 30 (P < 0.001), whereas no differences were found at day 90. In a bayesian competing-risk model, the HIV/HCV group had a higher mortality risk (adjusted hazard ratio (aHR) = 1.44 (95% CI = 1.30 to 1.59) and aHR = 1.57 (95% CI = 1.38 to 1.78) for patients with and without severe sepsis, respectively).

Conclusions
HIV infection was related to a higher frequency of severe sepsis and death among patients admitted to the ICU. Besides, HIV/HCV coinfection contributed to an increased risk of death in both the presence and the absence of severe sepsis.
Deciphering intratumor heterogeneity and temporal acquisition of driver events to refine precision medicine
Authors: Hiley Crispin , de Bruin Elza C , McGranahan Nicholas , Swanton Charles 
Published: August 2014

AbstractThe presence of multiple subclones within tumors mandates understanding of longitudinal and spatial subclonal dynamics. Resolving the spatial and temporal heterogeneity of subclones with cancer driver events may offer insight into therapy response, tumor evolutionary histories and clinical trial design.
Technical Advance: Ascorbic acid induces development of double-positive T cells from human hematopoietic stem cells in the absence of stromal cells
Authors: Huijskens Mirelle J A J , Walczak Mateusz , Koller Nicole , Briedé Jacob J , Senden-Gijsbers Birgit L M G , Schnijderberg Melanie C , Bos Gerard M J , Germeraad Wilfred T V 
Published: August 2014

AbstractThe efficacy of donor HSCT is partly reduced as a result of slow post-transplantation immune recovery. In particular, T cell regeneration is generally delayed, resulting in high infection-related mortality in the first years post-transplantation. Adoptive transfer of in vitro-generated human T cell progenitors seems a promising approach to accelerate T cell recovery in immunocompromised patients. AA may enhance T cell proliferation and differentiation in a controlled, feeder-free environment containing Notch ligands and defined growth factors. Our experiments show a pivotal role for AA during human in vitro T cell development. The blocking of NOS diminished this effect, indicating a role for the citrulline/NO cycle. AA promotes the transition of proT1 to proT2 cells and of preT to DP T cells. Furthermore, the addition of AA to feeder cocultures resulted in development of DP and SP T cells, whereas without AA, a preT cell-stage arrest occurred. We conclude that neither DLL4-expressing feeder cells nor feeder cell conditioned media are required for generating DP T cells from CB and G-CSF-mobilized HSCs and that generation and proliferation of proT and DP T cells are greatly improved by AA. This technology could potentially be used to generate T cell progenitors for adoptive therapy.
High IP-10 levels decrease T cell function in HIV-1-infected individuals on ART
Authors: Ramirez L A , Arango T A , Thompson E , Naji M , Tebas P , Boyer J D 
Published: August 2014

AbstractHIV-1-infected subjects, despite control of viral replication with ART, have an altered immune cytokine/chemokine milieu. Changes in systemic cytokines and chemokines can alter immune responses. IP-10, in particular, has been associated with pathogenesis in a number of conditions, and we found that IP-10 is increased in serum in subjects who are HIV-1 infected and on stable ART compared with HIV-1-uninfected individuals. In a series of in vitro studies, we found that PBMCs exposed to IP-10 showed a significant decrease in the number of cells capable of secreting IFN-γ, as well as other cytokines, when stimulated with recall antigens. Furthermore, treatment with IP-10 led to decreased antigen-specific calcium signaling and MAPK38 phosphorylation. Importantly, the cytokines, as well as proliferative responses, could be enhanced with an IP-10 Nab. Our findings suggest that IP-10-modulating drugs may potentially enhance T cell responses to vaccination and HIV-1 in HIV+ subjects on ART.
Comorbidity-Age Index: A Clinical Measure of Biologic Age Before Allogeneic Hematopoietic Cell Transplantation
Authors: Sorror Mohamed L. , Storb Rainer F. , Sandmaier Brenda M. , Maziarz Richard T. , Pulsipher Michael A. , Maris Michael B. , Bhatia Smita , Ostronoff Fabiana , Deeg H. Joachim , Syrjala Karen L. , Estey Elihu , Maloney David G. , Appelbaum Frederick R. , Martin Paul J. , Storer Barry E. 
Published: August 2014

Purpose Age has long been used as a major factor for assessing suitability for allogeneic hematopoietic cell transplantation (HCT). The HCT-comorbidity index (HCT-CI) was developed as a measure of health status to predict mortality risk after HCT. Whether age, comorbidities, or both should guide decision making for HCT is unknown. Patients and Methods Data from 3,033 consecutive recipients of HLA-matched grafts from five institutions contributed to this analysis. Patients were randomly divided into a training set to develop weights for age intervals and a validation set to assess the performance of prognostic models. Results In the training set, patients age 20 to 39 years, 40 to 49 years, 50 to 59 years, and ≥ 60 years had hazard ratios for nonrelapse mortality (NRM) of 1.21 (P = .29), 1.48 (P = .04), 1.75 (P = .004), and 1.84 (P = .005), respectively, compared with those age younger than 20 years. Consequently, age ≥ 40 years was assigned a weight of 1 to be added to the HCT-CI to constitute a composite comorbidity/age index. In the validation set, the composite comorbidity/age score had statistically significantly higher c-statistic estimates for prediction of NRM (0.664 v 0.556; P < .001) and survival (0.682 v 0.560; P < .001) compared with age, respectively. Patients with comorbidity/age scores of 0 to 2 had comparable mortality risks regardless of conditioning regimens. Patients with scores of 3 to 4 and ≥ 5 had statistically significant higher mortality risks after high-dose versus nonmyeloablative regimens. Conclusion Age is a poor prognostic factor. The proposed composite measure allows integration of both comorbidities and age into clinical decision making and comparative-effectiveness research of HCT.
There Is a Mismatch Between the Medicare Benefit Package and the Preferences of Patients With Cancer and Their Caregivers
Authors: Taylor Donald H. , Danis Marion , Zafar S. Yousuf , Howie Lynn J. , Samsa Gregory P. , Wolf Steven P. , Abernethy Amy P. 
Published: August 2014

Purpose To identify insured services that are most important to Medicare beneficiaries with cancer and their family caregivers when coverage is limited. Methods A total of 440 participants (patients, n = 246; caregivers, n = 194) were enrolled onto the CHAT (Choosing Health Plans All Together) study from August 2010 to March 2013. The exercise elicited preferences about what benefits Medicare should cover for patients with cancer in their last 6 months of life. Facilitated sessions lasted 2.5 hours, included 8 to 10 participants, and focused on choices about Medicare health benefits within the context of a resource-constrained environment. Results Six of 15 benefit categories were selected by > 80% of participants: cancer care, prescription drugs, primary care, home care, palliative care, and nursing home coverage. Only 12% of participants chose the maximum level of cancer benefits, a level of care commonly financed in the Medicare program. Between 40% and 50% of participants chose benefits not currently covered by Medicare: unrestricted cash, concurrent palliative care, and home-based long-term care. Nearly one in five participants picked some level of each of these three benefit categories and allocated on average 30% of their resources toward them. Conclusion The mismatch between covered benefits and participant preferences shows that addressing quality of life and the financial burden of care is a priority for a substantial subset of patients with cancer in the Medicare program. Patient and caregiver preferences can be elicited, and the choices they express could suggest potential for Medicare benefit package reform and flexibility.
Subclinical Peripheral Neuropathy in Patients With Multiple Myeloma Before Chemotherapy Is Correlated With Decreased Fingertip Innervation Density
Authors: Kosturakis Alyssa K. , He Zijing , Li Yan , Boyette-Davis Jessica A. , Shah Nina , Thomas Sheeba K. , Zhang Haijun , Vichaya Elisabeth G. , Wang Xin Shelley , Wendelschafer-Crabb Gwen , Kennedy William R. , Simone Donald A. , Cleeland Charles S. , Dougherty Patrick M. 
Published: August 2014

Purpose The goal in this study was to determine the incidence of subclinical neuropathy in treatment-naive patients with multiple myeloma (MM) with no history of peripheral neuropathy using quantitative sensory tests (QSTs) and its correlation with innervation density of the extremities using noninvasive laser reflectance confocal microscopy. Patients and Methods QST results were collected for 27 patients with a diagnosis of MM and compared with data collected from 30 age- and sex-matched healthy volunteers. Skin temperature, sensorimotor function (grooved pegboard test), and detection thresholds for temperature, sharpness, and low-threshold mechanical stimuli (von Frey monofilaments and bumps detection test) were measured. Meissner's corpuscle (MC) density in the fingertips was assessed using in vivo laser reflectance confocal microscopy. Results Patients showed a high incidence (> 80%) of ≥ one subclinical QST deficit. These included increased von Frey, bumps, and warmth detection thresholds as compared with healthy volunteers. Patients also showed increases in cold pain, sensorimotor deficits (grooved pegboard test), and higher overall neuropathy scores. MC density was significantly lower in patients than controls and showed significant inverse correlation with bumps detection threshold. Conclusion Patients with MM commonly present with sensory and sensorimotor deficits before undergoing treatment, and these deficits seem to result from disease-related decreases in peripheral innervation density.
Efficacy of Skin-Directed Therapy for Cutaneous Metastases From Advanced Cancer: A Meta-Analysis
Authors: Spratt Daniel E. , Gordon Spratt Elizabeth A. , Wu Shenhong , DeRosa Antonio , Lee Nancy Y. , Lacouture Mario E. , Barker Christopher A. 
Published: August 2014

Purpose To perform the first meta-analysis of the efficacy of skin-directed therapies for cutaneous metastases. Methods MEDLINE, EMBASE, The Cochrane Library, and ClinicalTrials.gov databases were searched for reports of prospective clinical studies published between 1960 and 2013 that assessed the response of skin-directed therapy for cutaneous metastases (47 of 2,955 unique studies were selected). Primary end points of the study were complete and objective response rates. Secondary analyses were preplanned and included subgroup analyses by skin-directed therapy, histology, and recurrence rates. Meta-analyses were performed with random-effect modeling, and extent of heterogeneity between studies was determined with the Cochran Q and I2 tests. Results After applying exclusion criteria, 47 prospective studies of 4,313 cutaneous metastases were assessed. Five skin-directed therapies were identified: electrochemotherapy, photodynamic therapy, radiotherapy, intralesional therapy, and topical therapy. Among all cutaneous metastases, complete response rate was 35.5% (95% CI, 27.6% to 44.3%) and objective response rate was 60.2% (95% CI, 50.6% to 69.0%). Overall recurrence rate was estimated to be 9.2% (95% CI, 3.7% to 21.2%). Melanoma and breast carcinoma comprised 96.8% of all cutaneous metastases studied and had similar objective response rates (54.5% [95% CI, 48.3% to 60.7%] and 54.0% [95% CI, 48.3% to 59.7%], respectively). Grade ≥ 3 toxicity was reported in less than 6% of patients. Conclusion Response to skin-directed therapy for cutaneous metastases is high but heterogeneous across treatment modalities, with low rates of recurrence post-treatment. Treatment was generally well tolerated and conferred improvements in quality of life. Standardization of response criteria for cutaneous metastases and treatment algorithms to optimally use the available skin-directed therapies are needed.
Chemotherapy-Refractory Diffuse Large B-Cell Lymphoma and Indolent B-Cell Malignancies Can Be Effectively Treated With Autologous T Cells Expressing an Anti-CD19 Chimeric Antigen Receptor
Authors: Kochenderfer James N. , Dudley Mark E. , Kassim Sadik H. , Somerville Robert P.T. , Carpenter Robert O. , Stetler-Stevenson Maryalice , Yang James C. , Phan Giao Q. , Hughes Marybeth S. , Sherry Richard M. , Raffeld Mark , Feldman Steven , Lu Lily , Li Yong F. , Ngo Lien T. , Goy Andre , Feldman Tatyana , Spaner David E. , Wang Michael L. , Chen Clara C. , Kranick Sarah M. , Nath Avindra , Nathan Debbie-Ann N. , Morton Kathleen E. , Toomey Mary Ann , Rosenberg Steven A. 
Published: August 2014

Purpose T cells can be genetically modified to express an anti-CD19 chimeric antigen receptor (CAR). We assessed the safety and efficacy of administering autologous anti-CD19 CAR T cells to patients with advanced CD19+ B-cell malignancies. Patients and Methods We treated 15 patients with advanced B-cell malignancies. Nine patients had diffuse large B-cell lymphoma (DLBCL), two had indolent lymphomas, and four had chronic lymphocytic leukemia. Patients received a conditioning chemotherapy regimen of cyclophosphamide and fludarabine followed by a single infusion of anti-CD19 CAR T cells. Results Of 15 patients, eight achieved complete remissions (CRs), four achieved partial remissions, one had stable lymphoma, and two were not evaluable for response. CRs were obtained by four of seven evaluable patients with chemotherapy-refractory DLBCL; three of these four CRs are ongoing, with durations ranging from 9 to 22 months. Acute toxicities including fever, hypotension, delirium, and other neurologic toxicities occurred in some patients after infusion of anti-CD19 CAR T cells; these toxicities resolved within 3 weeks after cell infusion. One patient died suddenly as a result of an unknown cause 16 days after cell infusion. CAR T cells were detected in the blood of patients at peak levels, ranging from nine to 777 CAR-positive T cells/μL. Conclusion This is the first report to our knowledge of successful treatment of DLBCL with anti-CD19 CAR T cells. These results demonstrate the feasibility and effectiveness of treating chemotherapy-refractory B-cell malignancies with anti-CD19 CAR T cells. The numerous remissions obtained provide strong support for further development of this approach.
Rituximab Extended Schedule or Re-Treatment Trial for Low–Tumor Burden Follicular Lymphoma: Eastern Cooperative Oncology Group Protocol E4402
Authors: Kahl Brad S. , Hong Fangxin , Williams Michael E. , Gascoyne Randy D. , Wagner Lynne I. , Krauss John C. , Habermann Thomas M. , Swinnen Lode J. , Schuster Stephen J. , Peterson Christopher G. , Sborov Mark D. , Martin S. Eric , Weiss Matthias , Ehmann W. Christopher , Horning Sandra J. 
Published: August 2014

Purpose In low–tumor burden follicular lymphoma (FL), maintenance rituximab (MR) has been shown to improve progression-free survival when compared with observation. It is not known whether MR provides superior long-term disease control compared with re-treatment rituximab (RR) administered on an as-needed basis. E4402 (RESORT) was a randomized clinical trial designed to compare MR against RR. Patients and Methods Eligible patients with previously untreated low–tumor burden FL received four doses of rituximab, and responding patients were randomly assigned to either RR or MR. Patients receiving RR were eligible for re-treatment at each disease progression until treatment failure. Patients assigned to MR received a single dose of rituximab every 3 months until treatment failure. The primary end point was time to treatment failure. Secondary end points included time to first cytotoxic therapy, toxicity, and health-related quality of life (HRQOL). Results A total of 289 patients were randomly assigned to RR or MR. With a median follow-up of 4.5 years, the estimated median time to treatment failure was 3.9 years for patients receiving RR and 4.3 years for those receiving MR (P = .54). Three-year freedom from cytotoxic therapy was 84% for those receiving RR and 95% for those receiving MR (P = .03). The median number of rituximab doses was four patients receiving RR and 18 for those receiving MR. There was no difference in HRQOL. Grade 3 to 4 toxicities were infrequent in both arms. Conclusion In low–tumor burden FL, a re-treatment strategy uses less rituximab while providing disease control comparable to that achieved with a maintenance strategy.
Apelin Counteracts Vasopressin-Induced Water Reabsorption via Cross Talk Between Apelin and Vasopressin Receptor Signaling Pathways in the Rat Collecting Duct
Authors: Hus-Citharel Annette , Bodineau Laurence , Frugière Alain , Joubert Fanny , Bouby Nadine , Llorens-Cortes Catherine 
Published: August 2014

Abstract
Apelin receptors (ApelinRs) are expressed along an increasing cortico-medullary gradient in collecting ducts (CDs). We showed here that iv injection of apelin 17 (K17F) in lactating rats characterized by increases in both synthesis and release of arginine vasopressin (AVP) increased diuresis concomitantly with a significant decrease in urine osmolality and no change in Na+ and K+ excretion. Under these conditions, we also observed a significant decrease in apical aquaporin-2 immunolabeling in CD, with a cortico-medullary gradient, suggesting that K17F-induced diuresis could be linked to a direct action of apelin on CD. We then examined the potential cross talk between V1a AVP receptor (V1a-R), V2 AVP receptor (V2-R) and ApelinR signaling pathways in outer medullary CD (OMCD) and inner medullary CD microdissected rat CD. In OMCD, expressing the 3 receptors, K17F inhibited cAMP production and Ca2+ influx induced by 1-desamino-8-D-arginine vasopressin a V2-R agonist. Similar effects were observed in inner medullary CD expressing only V2-R and ApelinR. In contrast, in OMCD, K17F increased by 51% the Ca2+ influx induced by the stimulation of V1a-R by AVP in the presence of the V2-R antagonist SR121463B, possibly enhancing the physiological antagonist effect of V1a-R on V2-R. Thus, the diuretic effect of apelin is not only due to a central effect by inhibiting AVP release in the blood circulation as previously shown but also to a direct action of apelin on CD, by counteracting the antidiuretic effect of AVP occurring via V2-R.
Divergent Effects of Oxytocin Treatment of Obese Diabetic Mice on Adiposity and Diabetes
Authors: Altirriba Jordi , Poher Anne-Laure , Caillon Aurélie , Arsenijevic Denis , Veyrat-Durebex Christelle , Lyautey Jacqueline , Dulloo Abdul , Rohner-Jeanrenaud Françoise 
Published: August 2014

AbstractOxytocin has been suggested as a novel therapeutic against obesity, because it induces weight loss and improves glucose tolerance in diet-induced obese rodents. A recent clinical pilot study confirmed the oxytocin-induced weight-reducing effect in obese nondiabetic subjects. Nevertheless, the mechanisms involved and the impact on the main comorbidity associated with obesity, type 2 diabetes, are unknown. Lean and ob/ob mice (model of obesity, hyperinsulinemia, and diabetes) were treated for 2 weeks with different doses of oxytocin, analogues with longer half-life (carbetocin) or higher oxytocin receptor specificity ([Thr4,Gly7]-oxytocin). Food and water intake, body weight, and glycemia were measured daily. Glucose, insulin, and pyruvate tolerance, body composition, several hormones, metabolites, gene expression, as well as enzyme activities were determined. Although no effect of oxytocin on the main parameters was observed in lean mice, the treatment dose-dependently reduced food intake and body weight gain in ob/ob animals. Carbetocin behaved similarly to oxytocin, whereas [Thr4,Gly7]-oxytocin (TGOT) and a low oxytocin dose decreased body weight gain without affecting food intake. The body weight gain-reducing effect was limited to the fat mass only, with decreased lipid uptake, lipogenesis, and inflammation, combined with increased futile cycling in abdominal adipose tissue. Surprisingly, oxytocin treatment of ob/ob mice was accompanied by a worsening of basal glycemia and glucose tolerance, likely due to increased corticosterone levels and stimulation of hepatic gluconeogenesis. These results impose careful selection of the conditions in which oxytocin treatment should be beneficial for obesity and its comorbidities, and their relevance for human pathology needs to be determined.
Identifying and meeting people's post-stroke emotional needs: a service evaluation
Authors: Platten Melanie 
Published: August 2014

Background: Post-stroke emotional needs were highlighted as going unmet in a recent report by the Stroke Association. Aim: To determine local service provision of emotional support. Method: Questionnaires were distributed to 200 stroke patients and their carers. The survey aimed to gather information on emotional needs post-stroke and the service people had received. Results: A total of 88 sets of questionnaires were returned by post. Some 47% of patients and 35% of carers/relatives felt that their emotional needs had been met by the stroke team. Chi-squared analysis of the data revealed differences in the information, advice and support received by those who felt their emotional needs were met and those with unmet needs. Conclusions: Suggestions to improve the service are made, including more frequent use of standardised measures of emotional difficulties, providing more information about emotional impacts of stroke at an appropriate time in recovery and consistently providing service users with the opportunity to discuss emotional difficulties and support needs.