tbuckley/cabot-search huggingface dataset:
Which is the best sperm retrieval technique for non-obstructive azoospermia? A systematic review
Authors: P. Donoso, H. Tournaye, P. Devroey
Journal: Human Reproduction Update (2007)

Our objective was to establish which is the best sperm retrieval technique in non-obstructive azoospermia based on the available evidence. To date, no randomized controlled trial has compared the efficiency of these strategies and thus current recommendations are based on cumulative evidence provided by descriptive, observational and controlled studies. Three outcome measures were assessed for the sperm retrieval techniques: sperm retrieval rate (SRR), complications and live birth rate. Twenty-four descriptive studies reporting on the results of testicular sperm extraction (TESE) were encountered. Seven controlled studies that compared microdissection (MD) TESE with conventional TESE and seven controlled studies comparing fine needle testicular aspiration (FNA) with TESE were identified. The mean SRR for TESE was 49.5% (95% CI 49.0–49.9). TESE with multiple biopsies results in a higher SRR than FNA especially in cases of Sertoli-cell-only (SCO) syndrome and maturation arrest. Current evidence suggests that MD performs better than conventional TESE only in cases of SCO where tubules containing active focus of spermatogenesis can be identified. MD appears to be the safest technique regarding post-operative complications followed by FNA. Only three studies could be identified concerning the influence of the sperm retrieval technique on clinical pregnancy and live birth rate, hence no definitive conclusions can be made. However, so far there appears to be no impact of the technique itself on success rates.
Douleurs d'origine vertebrale et traitements par manipulations
Authors: D. Brewerton
Journal: Annals of the Rheumatic Diseases (1973)

complement and lysosomes, Selye's Adaptation Syn- drome is described, details of the mechansim by which probenecid produces its uricosuric effect are given, an honourable mention is made of intravenous nitrogen mustard in the treatment of rheumatoid disease, and chondrocalcinosis receives its acknowledgement.It is probably true that American patients are more medically sophisticated than English medical students.But one winces to read that 'fibrositis is an inflammation in the
High Levels of Circulating VEGFR2+ Bone Marrow–Derived Progenitor Cells Correlate with Metastatic Disease in Patients with Pediatric Solid Malignancies
Authors: Melissa Taylor, Jochen Rössler, Birgit Geoerger, Agnès Laplanche, Olivier Hartmann, Gilles Vassal, Françoise Farace
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Pediatric solid malignancies display important angiogenic potential, and blocking tumor angiogenesis represents a new therapeutic approach for these patients. Recent studies have evidenced rare circulating cells with endothelial features contributing to tumor neovascularization and have shown the pivotal role of bone marrow–derived (BMD) progenitor cells in metastatic disease progression. We measured these cells in patients with pediatric solid malignancies as a prerequisite to clinical trials with antiangiogenic therapy. Patients and Methods: Peripheral blood was drawn from 45 patients with localized (n = 23) or metastatic (n = 22) disease, and 20 healthy subjects. Subsets of circulating vascular endothelial growth factor receptor (VEGFR)2+-BMD progenitor cells, defined as CD45−CD34+VEGFR2(KDR)+7AAD− and CD45dimCD34+VEGFR2+7AAD− events, were measured in progenitor-enriched fractions by flow cytometry. Mature circulating endothelial cells (CEC) were measured in whole blood as CD31+CD146+CD45−7AAD− viable events. Data were correlated with VEGF and sVEGFR2 plasma levels. Results: The CD45−CD34+VEGFR2(KDR)+7AAD− subset represented &amp;lt;0.003% of circulating BMD progenitor cells (≤0.05 cells/mL). However, the median level (range) of the CD45dimCD34+VEGFR2+7AAD− subset was higher in patients compared with healthy subjects, 1.5% (0%-10.3%) versus 0.3% (0%-1.6%) of circulating BMD progenitors (P &amp;lt; 0.0001), and differed significantly between patients with localized and metastatic disease, 0.7% (0%-8.6%) versus 2.9% (0.6%-10.3%) of circulating BMD progenitors (P &amp;lt; 0.001). Median CEC value was 7 cells/mL (0-152 cells/mL) and similar in all groups. Unlike VEGFR2+-BMD progenitors, neither CECs, VEGF, or sVEGFR2 plasma levels correlated with disease status. Conclusion: High levels of circulating VEGFR2+-BMD progenitor cells correlated with metastatic disease. Our study provides novel insights for angiogenesis mechanisms in pediatric solid malignancies for which antiangiogenic targeting of VEGFR2+-BMD progenitors could be of interest.
Comparison of the efficacy of the tumour necrosis factor blocking agents adalimumab, etanercept, and infliximab when added to methotrexate in patients with active rheumatoid arthritis
Authors: M C Hochberg
Journal: Annals of the Rheumatic Diseases (2003)

To determine, using the method of adjusted indirect comparisons, whether there are differences in efficacy of tumour necrosis factor (TNF alpha) blocking agents, as measured by the rate ratios for American College of Rheumatology (ACR) 20, 50, and 70 responses, in patients with rheumatoid arthritis with an incomplete response to methotrexate.A systematic review was performed to identify placebo controlled trials of 24-30 weeks' duration of combination therapy that used a step-up approach with the addition of TNF alpha blocking agents to methotrexate. The method of "adjusted indirect comparisons" was used to compare results across trials to determine the relative risk for an ACR20 or 50 response.Placebo controlled trials for adalimumab, etanercept, and infliximab provided data on ACR20 and 50 responses. Both the similarity of demographic and disease characteristics of patients at entry, and the homogeneity of response rates in the placebo groups across trials, suggested that comparing results across trials was valid. The relative risk for obtaining an ACR20 and 50 response derived from the adjusted indirect comparisons of the TNF alpha blocking agents did not significantly differ from unity.The analysis showed that the three currently marketed TNF alpha blocking agents have similarly efficacy when added to methotrexate in the treatment of patients with rheumatoid arthritis with active disease.
Effect of Hospital Safety-Net Burden on Cost and Outcomes After Surgery
Authors: Richard S. Hoehn, Koffi Wima, Matthew A. Vestal, Drew J. Weilage, Dennis J. Hanseman, Daniel E. Abbott, Shimul A. Shah
Journal: JAMA Surgery (2015)

Safety-net hospitals provide broad services for a vulnerable population of patients and are financially at risk owing to impending reimbursement penalties and policy changes.To determine the effect of patient and hospital factors on surgical outcomes and cost at safety-net hospitals.Hospitals in the University HealthSystem Consortium database from January 1, 2009, through December 31, 2012 (n = 31), were grouped according to their safety-net burden, defined as the proportion of Medicaid and uninsured patient charges for all hospitalizations during that time (n = 12,638,166). Nine cohorts, based on a variety of surgical procedures, were created and examined with regard to preoperative characteristics, postoperative outcomes, and resource utilization. Multiple logistic regression was performed to analyze the effect of patient and center factors on outcomes. Hospital Compare data from the Centers for Medicare & Medicaid Services were linked and used to characterize and compare the groups of hospitals.Postoperative mortality, 30-day readmissions, and total direct cost.For all 9 procedures examined in 231 hospitals comprising 12,638,166 patient encounters, patients at hospitals with high safety-net burden (HBHs) (vs hospitals with low and medium safety-net burdens) were most likely to be young, to be black, to be of the lowest socioeconomic status, and to have the highest severity of illness and the highest cost for surgical care (P < .01 for all). For 7 of 9 procedures, HBHs had the highest proportion of emergent cases and longest length of stay (P < .01 for all). After adjusting for patient characteristics and center volume, HBHs still had higher odds of mortality for 3 procedures (odds ratios [ORs], 1.81-2.08; P < .05), readmission for 2 procedures (ORs, 1.19-1.30; P < .05), and the highest cost of care associated with 7 of 9 procedures (risk ratios, 1.23-1.35; P < .05). Analysis of Hospital Compare data found that HBHs had inferior performance on Surgical Care Improvement Project measures, higher rates of surgical complications, and inferior markers of emergency department timeliness and efficiency (all P < .05).These data suggest that intrinsic qualities of safety-net hospitals lead to inferior surgical outcomes and increased cost across 9 elective surgical procedures. These outcomes are likely owing to hospital resources and not necessarily patient factors. In addition, impending changes to reimbursement may have a negative effect on the surgical care at these centers.
29. In Vivo Imaging and Therapy of Breast Cancer Xenografts Following MUC1 Promoter-Driven Expression of the Sodium Iodide Symporter (NIS)
Journal: Molecular Therapy (2004)

Conditionally replicative viruses, based on tumor cell biology or tumor specific promoters, represent a powerful approach to treat cancer. However, several problems have been encountered including replication profiles which could not be explained by tumor cell biology and lack of specificity of the tumor specific promoters in viral context. As iv administrated viruses home to the liver, absence of aspecific replication is of crucial importance in clinical success of such agents. Animal studies still are the golden standard to study efficacy of this approach. However, replication of human (adeno)viruses is absent in non-human tissues. The use of animal models therefore does not provide information on the specificity of replication. Therefore the need for assays to determine lack of replication in healthy cells, especially liver cells, is obvious.
The 39th David A. Karnofsky Lecture: Bench-to-Bedside Translation of Targeted Therapies in Multiple Myeloma
Authors: Kenneth C. Anderson
Journal: Journal of Clinical Oncology (2012)

Multiple myeloma (MM) is a remarkable example of rapid bench-to-bedside translation in new drug development. The proteasome inhibitor bortezomib and immunomodulatory drug lenalidomide targeted MM cells in the bone marrow (BM) microenvironment to overcome conventional drug resistance in laboratory and animal models and were rapidly translated into clinical trials demonstrating their efficacy in patients with relapsed and then newly diagnosed MM, with a doubling of the median survival as a direct result. The future is even brighter. First, immune-based therapies are being developed (eg, elotuzumab monoclonal antibody [MoAb]; CD138DM immunotoxin; MM cell-dendritic cell vaccines; CD138, CS-1, and XBP-1 peptide vaccines; anti-17 MoAb; and other treatments to overcome causes of immune dysfunction). Second, promising next-generation agents target the MM cell in its microenvironment (eg, deubiquitinating enzyme inhibitors; chymotryptic [carfilzomib, Onyx 0912, MLN 9708] and broader [NPI-0052] proteasome inhibitors; immunoproteasome inhibitors; and pomalidamide). Moreover, agents targeting bone biology (eg, zoledronic acid, anti-DKK-1 MoAb, anti-B-cell activating factor MoAb and bortezomib, Btk inhibitor) show promise not only in preserving bone integrity but also against MM. Third, rationally based combination therapies, including bortezomib with Akt, mammalian target of rapamycin, or histone deacetylase inhibitors, are active even in bortezomib-refractory MM. Finally, genomics is currently being used in the definition of MM heterogeneity, new target discovery, and development of personalized therapy. Myeloma therefore represents a paradigm for targeting the tumor in its microenvironment, which has already markedly improved patient outcome in MM and has great potential in other hematologic malignancies and solid tumors as well.
The extent of the anti-citrullinated protein antibody repertoire is associated with arthritis development in patients with seropositive arthralgia
Authors: L. A. van de Stadt, A. R. van der Horst, M. H. M. T. de Koning, W. H. Bos, G. J. Wolbink, R. J. van de Stadt, G. J. M. Pruijn, B. A. C. Dijkmans, D. van Schaardenburg, D. Hamann
Journal: Annals of the Rheumatic Diseases (2010)

To determine the fine specificity of anti-citrullinated protein antibodies (ACPA) in the early phase of arthritis development, the ACPA repertoire in arthralgia patients and the association with arthritis development were studied.A total of 244 patients with arthralgia positive for anti-cyclic citrullinated peptide antibodies (aCCPs) and/or IgM rheumatoid factor (IgM-RF), without arthritis were included. Development of arthritis was defined as presence of one or more swollen joints at clinical examination during follow-up. Sera were tested at baseline for reactivity to five citrullinated peptides derived from fibrinogen (three), vimentin (one) and α-enolase (one) and five corresponding arginine peptides in an ELISA.In all, 69 patients (28%) developed arthritis in a median of 3 joints after a median follow-up of 11 (IQR 5-20) months. Reactivity to each peptide was significantly associated with arthritis development (p<0.001). The ACPA repertoire did not differ between patients who did or did not develop arthritis. Among aCCP-positive patients, patients recognising two or more additional citrullinated peptides developed arthritis more often (p=0.04). The number of recognised peptides was positively associated with the aCCP level (p<0.001). Crossreactivity between different peptides was minimal.Arthritis development is not associated with recognition of a specific citrullinated peptide once joint complaints are present. The ACPA repertoire in some patients with arthralgia is expanded. High aCCP levels are associated with a qualitatively broad ACPA repertoire. Patients with an extended ACPA repertoire have a higher risk of developing arthritis.
Arterial Paclitaxel Distribution and Deposition
Authors: Christopher J. Creel, Mark A. Lovich, Elazer R. Edelman
Journal: Circulation Research (2000)

Successful implementation of local arterial drug delivery requires transmural distribution of drug. The physicochemical properties of the applied compound, which govern its transport and tissue binding, become as important as the mode of delivery. Hydrophilic compounds distribute freely but are cleared rapidly. Hydrophobic drugs, insoluble in aqueous solutions, bind to fixed tissue elements, potentially prolonging tissue residence and biological effect. Paclitaxel is such a hydrophobic compound, with tremendous therapeutic potential against proliferative vascular disease. We hypothesized that the recent favorable preclinical data with this compound may derive in part from preferential tissue binding as a result of unique physicochemical properties. The arterial transport of paclitaxel was quantified through application ex vivo and measurement of the subsequent transmural distribution. Arterial paclitaxel deposition at equilibrium varied across the arterial wall and was everywhere greater in concentration than in the applied drug source. Permeation into the wall increased with time, from 15 minutes to 4 hours, and varied with the origin of delivery. In contrast to hydrophilic compounds, the concentration in tissue exceeds the applied concentration and the rate of transport was markedly slower. Furthermore, endovascular and perivascular paclitaxel application led to markedly differential deposition across the blood vessel wall. These data suggest that paclitaxel interacts with arterial tissue elements as it moves under the forces of diffusion and convection and can establish substantial partitioning and spatial gradients across the tissue. The complexity of paclitaxel pharmacokinetics requires in-depth investigation if this drug is to reach its full clinical potential in proliferative vascular diseases.
Perioperative therapy for locally advanced gastroesophageal cancer: current controversies and consensus of care
Authors: Amikar Sehdev, Daniel VT Catenacci
Journal: Journal of Hematology & Oncology (2013)

Gastroesophageal cancer (GEC) remains a challenging problem in oncology. Anatomically, GEC is comprised of distal gastric adenocarcinoma (GC), classically associated with Helicobacter Pylori, while proximal esophagogastric adenocarcinoma (EGJ AC) has increased significantly in incidence over the past years. Despite contrasting etiologies, histologies, and molecular phenotypes of distal and proximal GEC, in many cases perioperative (and metastatic) treatment strategies converge to similar approaches. For patients undergoing curative intent surgery, advances in perioperative chemotherapy and/or chemoradiotherapy, either before and/or after surgery, have demonstrated improved survivals compared to surgery alone. This review focuses on how the 'boundary' of the Z-line and/or the anatomical distinction of 'proximal' (EGJ) vs. 'distal' (GC) cancer has led to diverse inclusion/exclusion criteria for clinical trial enrollment, embodying various combinations of chemotherapy and radiation before and/or after surgery. Supporting evidence of each of these approaches consequently has led to a number of varying practices by geographical region and Institution/Physician, based on differing experience, preference, and clinical circumstance. Adequate direct comparison of these approaches is lacking currently, but data from a number of concerted efforts should be available in the next years to further direct best standards of care. Introduction of biologically targeted agents, namely anti-angiogenics and anti-HER family therapeutics are being evaluated to determine whether further therapeutic gains can be realized over classic cytotoxic chemotherapy alone (with/without radiotherapy). To date, novel molecularly targeted agents have yet to demonstrate benefit in this setting. In the following comprehensive review we will address the intricacies of perioperative treatment of locally advanced GEC, with focus on clinical trials supporting the diverse set of perioperative multidisciplinary approaches.
VHL regulates the effects of miR-23b on glioma survival and invasion via suppression of HIF-1α/VEGF and β-catenin/Tcf-4 signaling
Authors: Lingchao Chen, Lei Han, Kailiang Zhang, Zhendong Shi, Junxia Zhang, Anling Zhang, Yongzhi Wang, Yijun Song, Yongli Li, Tao Jiang, Peiyu Pu, Chuanlu Jiang, Chunsheng Kang
Journal: Neuro-Oncology (2012)

Aberrant microRNA expression has been implicated in the development of human cancers. Here, we investigated the oncogenic significance and function of miR-23b in glioma. We identified that the expression of miR-23b was elevated in both glioma samples and glioma cells, indicated by real-time polymerase chain reaction analyses. Down-regulation of miR-23b triggered growth inhibition, induced apoptosis, and suppressed invasion of glioma in vitro. Luciferase assay and Western blot analysis revealed that VHL is a direct target of miR-23b. Restoring expression of VHL inhibited glioma proliferation and invasion. Mechanistic investigation revealed that miR-23b deletion decreased HIF-1α/VEGF expression and suppressed β-catenin/Tcf-4 transcription activity by targeting VHL. Furthermore, expression of VHL was inversely correlated with miR-23b in glioma samples and was predictive of patient survival in a retrospective analysis. Therefore, we demonstrated that downregulation of miR-23b suppressed tumor survival through targeting VHL, leading to the inhibition of β-catenin/Tcf-4 and HIF-1α/VEGF signaling pathways.
No difference in moxifloxacin penetration between infected and uninfected pleural fluid
Authors: Kalliopi Chatzika, Katerina Manika, Paschalina Kontou, Georgia Pitsiou, Konstantinos Zarogoulidis, Ioannis Kioumis
Journal: European Respiratory Journal (2013)

Introduction: Moxifloxacin (MXF) is often prescribed for the treatment of pleural space infections. However, there are no existing data on MXF penetration into pleural fluid (PF) in humans.

Aims: To compare the kinetics and penetration of MXF in patients with infected and uninfected pleural effusion.

Methods: Nine patients with infected effusion (51.8±19.3 years) and ten patients with uninfected effusion (70.9±11.8 years) enrolled the study. All patients received a single intravenous dose of 400 mg MXF. Serial plasma (PL) and PF samples were collected for a 24 hour interval. MXF concentration in PL and PF was determined by high-performance liquid chromatography. The maximum concentration (CmaxPF) was estimated by direct observation of determined values and TmaxPF was the time to reach that concentration. The area under concentration-time curve (AUC24PL and AUC24PF) was calculated by the trapezoidal rule.

Results:

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No statistically significant differences were observed between two groups in PF Cmax, AUC24 and MXF penetration. The time to reach maximum concentration of MXF in PF was statistically significantly longer in patients with infected effusion.

Conclusions: These data demonstrate an equal MXF penetration in both groups and also a remarkable delay in achievement of PF Cmax in patients with pleural space infection.The presence of infection did not affect the degree of MXF penetration and the on-site drug exposure as expressed by the AUC24PF.
A controlled, randomized trial of highly selective vagotomy versus selective vagotomy and pyloroplasty in the treatment of duodenal ulcer.
Authors: O Kronborg, P Madsen
Journal: Gut (1975)

The results of highly selective vagotomy without drainage and selective vagotomy with pyloroplasty for duodenal ulcer were compared in a randomized, controlled trial of a series of 100 patients. The frequency of dumping, diarrhoea, and epigastric fullness was significantly lower after highly selective (6, 6, and 8 percent) than after selective vagotomy (30, 20, and 28 percent) one year after the operations. Recurrent and persisting duodenal ulcers appearing from one to four years after the operations were significantly more frequent after highly selective (22 percent) than after selective vagotomy (8 percent). No significant relationships were found between recurrent ulceration and gastric acid secretion measurements after the two operations. The Hollander response was early positive in 28 percent and late positive in 30 percent of the patients subjected to highly selective vagotomy, while the corresponding figures after selective vagotomy were 26 and 32 percent. The overall clinical results of the two operations were not different according to the classification of Visick. Excluding the patients with recurrence resulted in significantly better clinical results after highly selective vagotomy.
How to Chew Up Cells
Authors: Göran K. Hansson
Journal: Circulation Research (2012)

D efective organelles as well as dead cells need to be taken care of.These are the tasks for 2 biological processes: autophagy and efferocytosis.Both occur in the atherosclerotic plaque, but their modus operandi and role in the disease process have remained unclear.Two recent studies show that efficient macrophage autophagy is needed for optimal efferocytosis and that defective autophagy leads to oxidative stress, inflammasome activation, and expansion of the plaque's necrotic core.Therefore, autophagy may play a crucial role in the resolution of vascular inflammation and prevent the progression of atherosclerosis.