Impact of left ventricular assist device therapy on the cardiac proteome and metabolome composition in ischemic cardiomyopathy

The changes in the myocardial proteome and metabolome associated with left ventricular assist device (LVAD) therapy in patients with ischemic cardiomyopathy (ICM) are poorly characterized. We investigated the impact of mechanical unloading following LVAD therapy on the myocardial proteome and metabolome. Matched samples of 5 patients’ myocardial tissue, harvested at the time of LVAD implant (“pre-LVAD”) or heart transplant (“post-LVAD”), were studied by quantitative proteomics and metabolomics as well as being probed for T-tubule structure and connexin-43 distribution. Moreover, pre-LVAD proteome profiles of ICM context were bioinformatically compared to pre-LVAD proteome profiles of dilated cardiac myopathy (DCM). More than 2120 proteins were reliably identified and quantified in paired patient samples. LVAD therapy led to proteomic remodeling, including reduced levels of α-1-antichymotrypsin together with an overall decrease of immune response proteins and an increase of proteins involved in membrane biology. Metabolomics highlighted increased glucose and glucose-6-phosphate levels in the left ventricle upon LVAD therapy. Wheat germ agglutinin staining demonstrated improved T-tubule structure. Connexin-43 displayed a trend for more pronounced intercalated disc localization. In comparing pre-LVAD proteome profiles of ICM context with pre-LVAD proteome profiles of dilated cardiac myopathy (DCM), we noticed an overrepresentation in ICM of proteins associated with humoral immune response. Our findings underline an impact of LVAD therapy on left ventricular biology in ICM. The proteomic, metabolomic, and structural alterations described here are typically associated with cardiac recovery. On the molecular level, our findings indicate the possibility of cardiac remodeling under LVAD therapy in ICM.     

Digital templating in total knee and hip replacement: an analysis of planning accuracy

Purpose

The aim of this study was to determine how well pre-operative size selection for total knee and hip arthroplasties based on the digital imaging with and without additional referencing correlated with the size actually implanted.

Methods

Size selection planning of total knee arthroplasty by digital templating was documented in 46 cases with reference ball (group A) and in 48 cases without ball (group B). In addition, prospective analysis of pre-operative planning was conducted for 52 acetabular components with reference ball (group C) and 69 without ball (group D) as well as stem planning in 38 cases with ball (group E) and 54 cases without ball (group F). The data were analysed and compared with the size of the final component selected during surgery.

Results

The correlation between planned and implanted size for total knee arthroplasty in group A resulted in femoral anteroposterior (AP) r = 0.8622 and lateral r = 0.8333 and in group B AP r = 0.4552 and lateral r = 0.6950. Tibial in group A was AP r = 0.9030 and lateral r = 0.9074 and in group B AP r = 0.7000 and lateral r = 0.6376. For the acetabular components, the results in group C were r = 0.5998 and group D r = 0.6923. For stems, group E was r = 0.5306 and group F r = 0.5786. No correlation between BMI and the difference between planned and implanted size was found in any of the groups.

Conclusion

In the case of total hip arthroplasty there was a relatively low correlation between planned and implanted sizes with or without reference ball. For total knee arthroplasties the already high precision of size planning was further improved by the additional referencing with a reference ball.     

Preparing for Prospective Clinical Trials: A National Initiative of an Excellence Registry for Consecutive Pancreatic Cancer Resections

Background

Despite significant improvements in perioperative mortality as well as response rates to multimodality treatment, results after surgical resection of pancreatic adenocarcinoma with respect to long-term outcomes remain disappointing. Patient recruitment for prospective international trials on adjuvant and neoadjuvant regimens is challenging for various reasons. We set out to assess the preconditions and potential to perform perioperative trials for pancreatic cancer within a well-established Austrian nationwide network of surgical and medical oncologists (Austrian Breast & Colorectal Cancer Study Group).

Methods

From 2005 to 2010 five high-volume centers and one medium-volume center completed standardized data entry forms with 33 parameters (history and patient related data, preoperative clinical staging and work-up, surgical details and intraoperative findings, postoperative complications, reinterventions, reoperations, 30-day mortality, histology, and timing of multimodality treatment). Outside of the study group, in Austria pancreatic resections are performed in three “high-volume” centers (>10 pancreatic resections per year), three “medium-volume” centers (5–10 pancreatic resections per year), and the rest in various low-volume centers (<5 pancreatic resections per year) in Austria. Nationwide data for prevalence of and surgical resections for pancreatic adenocarcinoma were contributed by the National Cancer Registry of Statistics of Austria and the Austrian Health Institute.

Results

In total, 492 consecutive patients underwent pancreatic resection for ductal adenocarcinoma. All postoperative complications leading to hospital readmission were treated at the primary surgical department and documented in the database. Overall morbidity and pancreatic fistula rate were 45.5 % and 10.1 %, respectively. Within the entire cohort there were 9.8 % radiological reinterventions and 10.4 % reoperations. Length of stay was 16 days in median (0–209); 12 of 492 patients died within 30 days after operation, resulting in a 30-day mortality rate of 2.4 %. Seven of the total 19 deaths (36.8 %) occurred after 30 days, during hospitalization at the surgical department, resulting in a hospital mortality rate of 3.9 % (19/492). With a standardized histopathological protocol, there were 70 % (21/30) R0 resections, 30 % (9/30) R1 resections, and no R2 resections in Vienna and 62.7 % (32/51) R0 resections, 35.3 % (18/51) R1 resections, and 2 % (1/51) R2 resections in Salzburg. Resection margin status with nonstandardized protocols was classified as R0 in 82 % (339/411), R1 in 16 % (16/411), and R2 in 1.2 % (5/411). Perioperative chemotherapy was administered in 81.1 % of patients (8.3 % neoadjuvant; 68.5 % adjuvant; 4.3 % palliative); chemoradiotherapy (1.6 % neoadjuvant; 3 % adjuvant; 0.2 % palliative), in 4.9 % of patients. The six centers that contributed to this registry initiative provided surgical treatment to 40 % of all Austrian patients, resulting in a median annual recruitment of 85 (51–104) patients for the entire ABCSG-group and a median of 11.8 (0–38) surgeries for each individual department.

Conclusions

Surgical quality data of the ABCSG core pancreatic group are in line with international standards. With continuing centralization the essential potential to perform prospective clinical trials for pancreatic adenocarcinoma is given in Austria. Several protocol proposals aiming at surgical and multimodality research questions are currently being discussed.     

Application of the Pareto principle to identify and address drug-therapy safety issues

Purpose

Adverse drug events (ADE) and medication errors (ME) are common causes of morbidity in patients presenting at emergency departments (ED). Recognition of ADE as being drug related and prevention of ME are key to enhancing pharmacotherapy safety in ED. We assessed the applicability of the Pareto principle (～80 % of effects result from 20 % of causes) to address locally relevant problems of drug therapy.

Methods

In 752 cases consecutively admitted to the nontraumatic ED of a major regional hospital, ADE, ME, contributing drugs, preventability, and detection rates of ADE by ED staff were investigated. Symptoms, errors, and drugs were sorted by frequency in order to apply the Pareto principle.

Results

In total, 242 ADE were observed, and 148 (61.2 %) were assessed as preventable. ADE contributed to 110 inpatient hospitalizations. The ten most frequent symptoms were causally involved in 88 (80.0 %) inpatient hospitalizations. Only 45 (18.6 %) ADE were recognized as drug-related problems until discharge from the ED. A limited set of 33 drugs accounted for 184 (76.0 %) ADE; ME contributed to 57 ADE. Frequency-based listing of ADE, ME, and drugs involved allowed identification of the most relevant problems and development of easily to implement safety measures, such as wall and pocket charts.

Conclusions

The Pareto principle provides a method for identifying the locally most relevant ADE, ME, and involved drugs. This permits subsequent development of interventions to increase patient safety in the ED admission process that best suit local needs.     

Effect of ambulatory blood pressure measurement on sleep in patients with a major depressive episode

BACKGROUND: To assess the effects of ambulatory blood pressure measurement (ABPM) upon sleep in mentally depressed patients with near absence of deep (stage 3 and 4) sleep. METHODS: Twelve depressed patients aged 50.5+/-13.5 (21-item Hamilton Depression Rating Scale: 23.8+/-5.1) were studied on three consecutive nights in the sleep laboratory. In a random order, blood pressure was measured with a portable device over 24 h on either day 2 or 3. Polysomnographic data were analysed according to the criteria of Rechtschaffen and Kales. RESULTS: Compared to the control night, there was a significant increase of awakenings during the ABPM night. However, total sleeping time as well as sleep efficiency remained unchanged. Percentage of nocturnal decrease in both systolic and diastolic blood pressure was unrelated to the number of arousals. CONCLUSION: In depressed patients with severe disturbances of sleep architecture, ABPM did not lead to a prolongation of time awake or decrease in sleep efficiency.