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121.
Roberto V.P. Ribeiro Mitesh V. Badiwala Danny Ramzy Laura C. Tumiati Vivek Rao 《The Journal of thoracic and cardiovascular surgery》2019,157(2):615-625.e1
Objective
Hypertonic saline (HTS) has potent immune and vascular effects. We assessed recipient pretreatment with HTS on allograft function in a porcine model of heart transplantation and hypothesized that HTS infusion would limit endothelial and left ventricular (LV) dysfunction following transplantation.Methods
Heart transplants were performed after 6 hours of cold ischemic storage. Recipient pigs were randomized to treatment with or without HTS (7.5% NaCl) before cardiopulmonary bypass (CPB). Using a myograft apparatus, coronary artery endothelial-dependent (Edep) and -independent (Eind) relaxation was assessed. LV performance was determined using pressure-volume loop analysis. Pulmonary interleukin (IL)-2, IL-6, and tumor necrosis factor (TNF)-α expression was measured.Results
Weaning from CPB and LV performance after transplantation were improved in HTS-treated animals. Successful weaning from CPB was greater in the HTS-treated hearts (8 of 8 vs 2 of 8; P < .05). Mean LV functional recovery was improved in the HTS-treated animals, as assessed by preload recruitable stroke work (65 ± 10% vs 27 ± 10%; P < .001) and end-systolic elastance (55 ± 7% vs 37 ± 4%; P < .001). Treatment with HTS resulted in improved Edep (mean maximum elastance [Emax], 56 ± 5% vs 37 ± 7%; P < .001) and Eind (mean Emax%, 77 ± 6% vs 52 ± 4%; P < .001) vasorelaxation compared with control. Pulmonary expression of IL-2, IL-6, and TNF-α increased following transplantation, whereas HTS therapy attenuated IL production (P < .001). Transplantation increased plasma TNF-α levels and LV TNF-α expression, whereas HTS prevented this up-regulation (P < .001).Conclusions
Recipient HTS pretreatment preserves allograft vasomotor and LV function, and HTS therapy limits CPB-induced injury. HTS may be a novel recipient intervention to prevent graft dysfunction. 相似文献122.
123.
Bimal Bhindi Christine M. Lohse Phillip J. Schulte Ross J. Mason John C. Cheville Stephen A. Boorjian Bradley C. Leibovich R. Houston Thompson 《European urology》2019,75(5):766-772
Background
Partial nephrectomy (PN) is generally favored for cT1 tumors over radical nephrectomy (RN) when technically feasible. However, it can be unclear whether the additional risks of PN are worth the magnitude of renal function benefit.Objective
To develop preoperative tools to predict long-term estimated glomerular filtration rate (eGFR) beyond 30 d following PN and RN, separately.Design, setting, and participants
In this retrospective cohort study, patients who underwent RN or PN for a single nonmetastatic renal tumor between 1997 and 2014 at our institution were identified. Exclusion criteria were venous tumor thrombus and preoperative eGFR <15 ml/min/1.73 m2.Intervention
RN and PN.Outcome measurements and statistical analysis
Hierarchical generalized linear mixed-effect models with backward selection of candidate preoperative features were used to predict long-term eGFR following RN and PN, separately. Predictive ability was summarized using marginal , which ranges from 0 to 1, with higher values indicating increased predictive ability.Results and limitations
The analysis included 1152 patients (13 206 eGFR observations) who underwent RN and 1920 patients (18 652 eGFR observations) who underwent PN, with mean preoperative eGFRs of 66 ml/min/1.73 m2 (standard deviation [SD] = 18) and 72 ml/min/1.73 m2 (SD = 20), respectively. The model to predict eGFR after RN included age, diabetes, preoperative eGFR, preoperative proteinuria, tumor size, time from surgery, and an interaction between time from surgery and age (marginal ). The model to predict eGFR after PN included age, presence of a solitary kidney, diabetes, hypertension, preoperative eGFR, preoperative proteinuria, surgical approach, time from surgery, and interaction terms between time from surgery and age, diabetes, preoperative eGFR, and preoperative proteinuria (marginal ). Limitations include the lack of data on renal tumor complexity and the single-center design; generalizability needs to be confirmed in external cohorts.Conclusions
We developed preoperative tools to predict renal function outcomes following RN and PN. Pending validation, these tools should be helpful for patient counseling and clinical decision-making.Patient summary
We developed models to predict kidney function outcomes after partial and radical nephrectomy based on preoperative features. This should help clinicians during patient counseling and decision-making in the management of kidney tumors. 相似文献124.
125.
Lara Feulner Hamed S. Najafabadi Simon Tanguay Janusz Rak Yasser Riazalhosseini 《Urologic oncology》2019,37(2):166-175
Background
Clear cell renal cell carcinoma (ccRCC) is known to occur across the adult lifetime traversing the spectrum of age-related organismal changes. Little is known as to how the aging process may affect the course of renal cell carcinoma (RCC) and the repertoire of genes involved.Methods
Using The Cancer Genome Atlas (n?=?436) and Cancer Genomics of the Kidney (n?=?89) datasets, we applied regression analysis to examine associations between patient age and gene expression profiles in ccRCC tumors and normal kidney tissues. Pathway enrichment analysis was performed to identify cellular process that is affected by aging in ccRCC. Moreover, connectivity mapping analysis was used to predict age-dependent response to drug treatments.Results
Our analysis revealed different age-dependent gene expression spectra in ccRCC and normal kidney tissues. These findings were significant and independently reproducible in both datasets examined. Age up-regulated genes, showing higher expression in older patients, were significantly enriched (false discovery rate <0.05) in normal tissues for pathways associated with immune response and extracellular matrix organization, whereas age up-regulated genes in tumors were enriched for metabolism and oxidation pathways. Strikingly, age down-regulated genes in normal cells were also enriched for metabolism and oxidation, while those in tumors were enriched for extracellular matrix organization. Further in silico analysis of potential drug targets predicted preferential efficacy of Phosphoinositide 3-kinase inhibitor or immunotherapy in association with age.Conclusion
We report on previously unrecognized associations between age and molecular underpinnings of RCC, including age-associated expression of genes implicated in RCC development or treatment. 相似文献126.
127.
Diego Adrianzen Herrera Nadia Ashai Roman Perez-Soler 《Expert opinion on pharmacotherapy》2019,20(1):95-102
Introduction: Nanoparticle albumin-bound paclitaxel (nab-paclitaxel), a microtubule inhibitor, has demonstrated clinical efficacy in the treatment of advanced non-small cell lung cancer (NSCLC) either as monotherapy or in combination. Nab-paclitaxel was developed to reduce the toxicities associated with solvent-bound paclitaxel (sb-paclitaxel).
Areas covered: This review first focuses on the clinical trials evaluating the efficacy and tolerability of nab-paclitaxel in NSCLC at different settings. The approval of nab-paclitaxel in combination with carboplatin at the front-line setting for advanced NSCLC was based on the key phase III study, which showed that nab-paclitaxel/carboplatin was associated with superior overall response rate and favorable toxicity profile compared to sb-paclitaxel/carboplatin. The review also addresses the nab-paclitaxel pharmacology, other combinations (e.g. immunotherapy with PD-1/PD-L1 inhibitors), potential biomarkers (e.g. caveolin-1), and special subgroups (e.g. the elderly, squamous histology).
Expert opinion: Existing data has established the role of nab-paclitaxel in the management of advanced NSCLC. Emerging evidence, such as preliminary results from Keynote-407 and IMpower 131 studies, indicates that novel combinations of nab-paclitaxel/carboplatin and PD-1/PD-L1 inhibitors could further improve clinical benefits with manageable toxicity. Nevertheless, in order to better position nab-paclitaxel and to improve patient selection, future studies are warranted to further understand its mechanism of action, predictive biomarkers, and potential synergism with other agents. 相似文献
128.
工作相关肌肉骨骼疾患(WMSDs)是常见的慢性非传染性疾病。WMSDs已成为影响工人健康、降低工人生命质量和造成经济损失的重要因素,可见于多个行业、工种。本文对WMSDs流行现状及人体工效学负荷相关研究进行综述,以期找到职业人群保护的可行方法。 相似文献
129.
Ewelina Kazimierczyk Andrzej Eljaszewicz Paula Zembko Ewa Tarasiuk Malgorzata Rusak Agnieszka Kulczynska-Przybik Marta Lukaszewicz-Zajac Karol Kaminski Barbara Mroczko Maciej Szmitkowski Milena Dabrowska Bozena Sobkowicz Marcin Moniuszko Agnieszka Tycinska 《Pharmacological reports : PR》2019,71(1):73-81
Background
Acute myocardial infarction (AMI) causes irreversible myocardial damage and release of inflammatory mediators, including cytokines, chemokines and miRNAs. We aimed to investigate changes in the levels of cytokines (IL-6, TNF-α and IL-10), miRNAs profiles (miR-146 and miR-155) and distribution of different monocyte subsets (CD14++CD16-, CD14++CD16+, CD14+CD16++) in the acute and post-healing phases of AMI.Methods
In eighteen consecutive AMI patients (mean age 56.78?±?12.4 years, mean left ventricle ejection fraction – LVEF: 41.9?±?9.8%), treated invasively, monocyte subsets frequencies were evaluated (flow cytometry), cytokine concentrations were analyzed (ELISA) as well as plasma miRNAs were isolated twice – on admission and after 19.2?±?5.9 weeks of follow-up. Measurements were also performed among healthy volunteers.Results
AMI patients presented significantly decreased frequencies of classical cells in comparison to healthy controls (median 71.22% [IQR: 64.4–79.04] vs. 84.35% [IQR: 81.2–86.7], p?=?0.001) and higher percent of both intermediate and non-classical cells, yet without statistical significance (median 6.54% [IQR: 5.14–16.64] vs. 5.87% [IQR: 4.48–8.6], p?=?0.37 and median 5.99% [IQR: 3.39–11.5] vs. 5.26% [IQR: 3.62–6.2], p?=?0.42, respectively). In AMI patients both, analyzed plasma miRNA concentrations were higher than in healthy subjects (miR-146: median 5.48 [IQR: 2.4–11.27] vs. 1.84 [IQR: 0.87–2.53], p?=?0.003; miR-155: median 25.35 [IQR: 8.17–43.15] vs. 8.4 [IQR: 0.08–16.9], p?=?0.027, respectively), and returned back to the values found in the control group in follow-up. miR-155/miR-146 ratio correlated with the frequencies of classical monocytes (r=0.6, p?=?0.01) and miR-155 correlated positively with the concentration of inflammatory cytokines ? IL-6 and TNF-α.Conclusions
These results may suggest cooperation of both pro-inflammatory and anti-inflammatory signals in AMI in order to promote appropriate healing of the infarcted myocardium. 相似文献130.
B. Davido R. Batista H. Fessi H. Michelon L. Escaut C. Lawrence M. Denis C. Perronne J. Salomon A. Dinh 《Médecine et maladies infectieuses》2019,49(3):214-218