Objective To compare the 1-year results after aortic valve-sparing (AVS) or valve-replacing (AVR) aortic root replacement from a prospective, international registry of 316 patients with Marfan ...syndrome (MFS). Methods Patients underwent AVS (n = 239, 76%) or AVR (n = 77, 24%) aortic root replacement at 19 participating centers from 2005 to 2010. One-year follow-up data were complete for 312 patients (99%), with imaging findings available for 293 (94%). The time-to-events were compared between groups using Kaplan-Meier curves and Cox proportional hazards models. Results Two patients (0.6%)—1 in each group—died within 30 days. No significant differences were found in early major adverse valve-related events (MAVRE; P = .6). Two AVS patients required early reoperation for coronary artery complications. The 1-year survival rates were similar in the AVR (97%) and AVS (98%) groups; the procedure type was not significantly associated with any valve-related events. At 1 year and beyond, aortic regurgitation of at least moderate severity (≥2+) was present in 16 patients in the AVS group (7%) but in no patients in the AVR group ( P = .02). One AVS patient required late AVR. Conclusions AVS aortic root replacement was not associated with greater 30-day mortality or morbidity rates than AVR root replacement. At 1 year, no differences were found in survival, valve-related morbidity, or MAVRE between the AVS and AVR groups. Of concern, 7% of AVS patients developed grade ≥2+ aortic regurgitation, emphasizing the importance of 5 to 10 years of follow-up to learn the long-term durability of AVS versus AVR root replacement in patients with MFS.
Abstract Background Few studies have focussed on the prognosis of young women with local recurrence (LR) after breast-conserving therapy and the factors that can be used to predict their prognosis. ...Methods We studied the outcome and related prognostic factors in 124 patients with an isolated local recurrence in the breast following breast-conserving surgery and radiotherapy for early stage breast cancer diagnosed at the age of 40 years or younger. Results The median follow-up of the patients after diagnosis of LR was 7.0 years. At 10 years from the date of salvage treatment, the overall survival rate was 73% (95% CI, 63–83), the distant recurrence-free survival rate was 61% (95% CI, 53–73), and the local control rate (i.e. survival without subsequent LR or local progression) was 95% (95% CI, 91–99). In the multivariate analysis, the risk of distant metastases also tended to be higher for patients with LR occurring within 5 years after BCT, as compared to patients with LR more than 5 years after BCT (Hazard ratio HR, 1.89; p = 0.09). A worse distant recurrence-free survival was also observed for patients with a LR measuring more than 2 cm in diameter, compared to those with a LR of 2 cm or smaller (HR, 2.88; p = 0.007), and for patients with a LR causing symptoms or suspicious findings at clinical breast examination, compared to those with a LR detected by breast imaging only (HR 3.70; p = 0.03). Conclusions These results suggest that early detection of LR after BCT in young women can improve treatment outcome.
Background
IL28B polymorphisms are predictors of therapy response in hepatitis C virus (HCV) patients. We do not know whether they are markers of treatment response in admixed populations or not.
...Aims
To determine whether IL28B polymorphisms are predictors of therapy response in patients with HCV from an admixed population and are influenced by genetic ancestry.
Methods
rs12979860 and rs8099917 were genotyped in 222 HCV patients treated with pegylated interferon and ribavirin. Ancestry was determined using genetic markers.
Results
IL28B rs12979860 C/C was associated with sustained virological response (SVR), whereas C/T and T/T were associated with failure to therapy (P = 1.12 × 10−5). IL28B rs8099917 T/T was associated with SVR, and G/G and G/T were associated with nonresponse/relapse (NR/R) (P = 8.00 × 10−3). Among HCV genotype 1 patients with C/C genotype, genomic ancestry did not interfere with therapy response. Among patients with rs12979860 T/T genotype, African genetic contribution was greater in the NR/R group (P = 1.51 × 10−3), whereas Amerindian and European genetic ancestry contribution were higher in the SVR group (P = 3.77 × 10−3 and P = 2.16 × 10−2 respectively). Among HCV type 1 patients with rs8099917 T/T, African genetic contribution was significantly greater in the NR/R group (P = 5.0 × 10−3); Amerindian and European ancestry genetic contribution were greater in the SVR group.
Conclusion
IL28B rs12979860 and rs8099917 polymorphisms were predictors of therapy response in HCV genotypes 1, 2 and 3 subjects from an admixed population. Genomic ancestry did not interfere with response to therapy in patients with rs12979860 C/C, whereas it interfered in patients with C/T and T/T genotypes. Among HCV genotype 1 rs8099917 T/T patients, genomic ancestry interfered with response to therapy.
The quality of the preoperative assessment clinic (PAC) is determined by many factors. Patients’ experiences are important indicators, but often overlooked. We prepare to set priorities to improve ...the PAC by obtaining detailed patients’ feedback on the quality of the PAC, and establishing the value patients and professionals attach to different care aspects, using the Patient Experiences with the Preoperative Assessment Clinic questionnaire.
The PAC's standard of service was determined for five care aspects (dimensions), using patients’ feedback. The importance of a dimension to patients was determined by calculating the effects of the dimensions on patients’ overall appraisal. In addition, professionals were asked to rate the importance of the different care aspects.
Patients had the most positive experiences with the nurse, and the least positive experiences with waiting. However, waiting was least important to patients. When combining the PAC's standard of service with the value given to the dimensions by patients and professionals separately, we found in both instances that waiting was in greatest need of improvement. This was followed by reception, the anaesthetist, remaining experiences, and finally the nurse.
Quality improvement of the PAC can be achieved by obtaining patients’ feedback on the quality, determine a PAC's standard of service, recognize service areas that require improvement, and identify actions appropriate to bring about improvement. The value patients and professionals attach to different aspects of care can then be used to prioritize improvements.
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•The methylation of amines is performed with paraformaldehyde, CaH2 and Pd/C.•An easy-to-handle procedure applied to aniline and primary alkylamines.•In situ hydrogen production from ...calcium hydride and water.
The methylation of amines by paraformaldehyde in the presence of calcium hydride as a source of hydrogen and palladium on charcoal as catalyst was studied. Depending on the quantity of paraformaldehyde, monomethylated and dimethylated amines were selectively and efficiently prepared in one pot with good yields.
Background Cerebrospinal fluid drainage, a well-established means of preventing paraplegia after thoracic aortic aneurysm surgery, can result in serious, sometimes lethal complications. In a large ...group of patients who underwent surgical thoracic aortic aneurysm repair with cerebrospinal fluid drainage, we examined the incidences of and potential risk factors for these outcomes. Methods The records were reviewed of 504 patients who underwent surgical thoracic aortic aneurysm repair with cerebrospinal fluid drainage at the Texas Heart Institute at St. Luke's Episcopal Hospital between February 2005 and December 2009. All historical data, inpatient records, and billing data were searched for evidence of complications. Results Of the 504 patients, 14 (2.8%) had intracranial hemorrhage, of whom 10 (72%) had subdural hematoma. Postdural puncture headache developed in 49 patients (9.7%), of whom 17 (34.6%) required epidural blood patch placement for resolution. Multivariable analysis identified having a connective tissue disorder (odds ratio, 3.08; 95% confidence interval, 1.33-7.13) as an independent predictor of postdural puncture headache, but not age less than 40 years (odds ratio, 0.97; 95% confidence interval, 0.94-0.99). Conclusions Cerebrospinal fluid drainage, as performed by our method, seems to be associated with a modest rate of intracranial bleeding in patients who undergo surgical thoracic aortic aneurysm repair. In contrast, postdural puncture headache is not uncommon, particularly in patients with connective tissue disease. Clinicians caring for these patients should consider the likelihood of postdural puncture headache, and any such patient with postoperative headache should be assessed for epidural blood patch placement.
BACKGROUNDLipopolysaccharide (LPS), the major glycolipid component of Gram-negative bacterial outer membranes, is a potent endotoxin responsible for many of the directly or indirectly induced ...symptoms of infection. Lipoproteins (in particular, high-density lipoproteins) sequester LPS, thereby acting as a humoral detoxification mechanism.
PATIENTSDifferences in the lipoprotein composition in human plasma and lymph of a control patient group (n = 5) without systemic inflammatory response syndrome (non-SIRS/MOF) and patients with SIRS and multiple organ failure (MOF, n = 9) were studied. The LPS binding capacity of the lipoproteins in SIRS/MOF and non-SIRS/MOF patients was investigated by rechallenge of the plasma and lymph with fluorescently labeled LPS ex vivo. The lipoprotein composition was analyzed using immunochemical techniques and high-performance gel permeation chromatography.
RESULTSIn the non-SIRS/MOF patient group, plasma and lymph levels of apolipoprotein A-I (600 and 450 mg/L, respectively), apolipoprotein B (440 and 280 mg/L, respectively), total cholesterol (2.88 and 1.05 mM, respectively), and total triglycerides (0.67 and 0.97 mM, respectively) were observed. In the SIRS/MOF group, a decrease of apolipoprotein A-I (−55% in plasma and lymph), a decrease of apolipoprotein B (−43% in plasma and −38% in lymph), and a decrease of total cholesterol levels (−54% in plasma and −37% in lymph) were demonstrated. However, the triglyceride levels in the SIRS/MOF group showed a 30% increase in plasma and a 47% decrease in lymph compared with the non-SIRS/MOF patients. In SIRS/MOF patients, a 2.8-fold increase in plasma and a 1.8-fold increase in lymph of the LPS low-density lipoprotein/high-density lipoprotein ratio was observed, indicating that the relative LPS binding capacity of the lipoproteins in the SIRS/MOF patient group showed a trend to be shifted mainly toward low-density lipoproteins. Furthermore, in plasma and lymph of four SIRS/MOF patients, a novel cholesterol-containing high-density lipoprotein–like particle was found that barely had LPS binding capacity (<5%).
CONCLUSIONSIn the SIRS/MOF patients, the changes in lipoprotein composition in lymph are a reflection of those in plasma, except for the triglyceride levels. In comparison with the non-SIRS/MOF patients, the SIRS/MOF patients show a shifted LPS binding capacity of high-density lipoproteins toward low-density lipoproteins in plasma and in lymph. Moreover, in plasma and lymph, novel cholesterol-containing particles, resembling high-density lipoprotein, were identified in the SIRS/MOF patient group.
Abstract Background “Academic surgeon” describes a member of a medical school department of surgery, but this term does not fully define the important role of such physician-scientists in advancing ...surgical science through translational research and innovation. Methods The curriculum vitae and self-descriptive vignettes of the records of achievement of seven surgeons possessing documented records of academic leadership, innovation, and dissemination of knowledge were reviewed. Results Out analysis yielded seven attributes of the archetypal academic surgeon: 1) identifies complex clinical problems ignored or thought unsolvable by others, 2) becomes an expert, 3) innovates to advance treatment, 4) observes outcomes to further improve and innovate, 5) disseminates knowledge and expertise, 6) asks important questions to further improve care, and 7) trains the next generation of surgeons and scientists. Conclusion Although alternative pathways to innovation and academic contribution also exist, the academic surgeon typically devotes years of careful observation, analysis, and iterative investigation to identify and solve challenging or unexplored clinical problems, ideally leverages resources available in academic medical centers to support these endeavors.
Anthracyclines, such as doxorubicin (Dox), are widely used chemotherapeutic agents for the treatment of solid tumors and hematologic malignancies. However, they frequently induce cardiotoxicity ...leading to dilated cardiomyopathy and heart failure. This study sought to investigate the role of the Exchange Protein directly Activated by cAMP (EPAC) in Dox-induced cardiotoxicity and the potential cardioprotective effects of EPAC inhibition. We show that Dox induces DNA damage and cardiomyocyte cell death with apoptotic features. Dox also led to an increase in both cAMP concentration and EPAC1 activity. The pharmacological inhibition of EPAC1 (with CE3F4) but not EPAC2 alleviated the whole Dox-induced pattern of alterations. When administered
, Dox-treated WT mice developed a dilated cardiomyopathy which was totally prevented in EPAC1 KO mice. Moreover, EPAC1 inhibition potentiated Dox-induced cell death in several human cancer cell lines. Thus, EPAC1 inhibition appears as a potential therapeutic strategy to limit Dox-induced cardiomyopathy without interfering with its antitumoral activity.
Deuteron and anti-deuteron production in Z decays has been observed in the ALEPH experiment at LEP. The production rate of anti-deuterons is measured to be (5.9±1.8±0.5)×10−6 per hadronic Z decay in ...the anti-deuteron momentum range from 0.62 to 1.03 GeV/c. The coalescence parameter B2, which characterizes the likelihood of anti-deuteron production, is measured to be 0.0033±0.0013 GeV2 in Z decays. These measurements indicate that the production of anti-deuterons is suppressed in e+e− collisions compared to that in pp and photoproduction collisions.
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