Validation and Performance Comparison of Two Scoring Systems Created Specifically to Predict the Risk of Deep Sternal Wound Infection after Bilateral Internal Thoracic Artery Grafting

Background: The Gatti and the bilateral internal mammary artery (BIMA) scores were created to predict the risk of deep sternal wound infection (DSWI) after bilateral internal thoracic artery (BITA) grafting. Methods: Both scores were evaluated retrospectively in two consecutive series of patients undergoing isolated multi-vessel coronary surgical procedures - i.e., the Trieste (n = 1,122; BITA use, 52.1%; rate of DSWI, 5.7%) and the Besan\ue7on cohort (n = 721; BITA use, 100%; rate of DSWI, 2.5%). Baseline patient characteristics were compared between the two validation samples. For each score, the accuracy of prediction and predictive power were assessed by the area under the receiver-operating characteristic curve (AUC) and the Goodman-Kruskal gamma coefficient, respectively. Results: There were significant differences between the two series in terms of age, gender, New York Heart Association functional class, chronic lung disease, left ventricular function, surgical priority, and the surgical techniques used. In the Trieste series, accuracy of prediction of the Gatti score for DSWI was higher than that of the BIMA score (AUC, 0.729 vs. 0.620, p = 0.0033). The difference was not significant, however, in the Besan\ue7on series (AUC, 0.845 vs. 0.853, p = 0.880) and when only BITA patients of the Trieste series were considered for analysis (AUC, 0.738 vs. 0.665, p = 0.157). In both series, predictive power was at least moderate for the Gatti score and low for the BIMA score. Conclusions: The Gatti and the BIMA scores seem to be useful for pre-operative evaluation of the risk of DSWI after BITA grafting. Further validation studies should be performed

Dementia, infections and vaccines: 30 years of controversy

This paper reports the proceedings of a virtual meeting convened by the European Interdisciplinary Council on Ageing (EICA), to discuss the involvement of infectious disorders in the pathogenesis of dementia and neurological disorders leading to dementia. We recap how our view of the infectious etiology of dementia has changed over the last 30 years in light of emerging evidence, and we present evidence in support of the implication of infection in dementia, notably Alzheimer’s disease (AD). The bacteria and viruses thought to be responsible for neuroinflammation and neurological damage are reviewed. We then review the genetic basis for neuroinflammation and dementia, highlighting the genes that are currently the focus of investigation as potential targets for therapy. Next, we describe the antimicrobial hypothesis of dementia, notably the intriguing possibility that amyloid beta may itself possess antimicrobial properties. We further describe the clinical relevance of the gut–brain axis in dementia, the mechanisms by which infection can move from the intestine to the brain, and recent findings regarding dysbiosis patterns in patients with AD. We review the involvement of specific pathogens in neurological disorders, i.e. SARS-CoV-2, human immunodeficiency virus (HIV), herpes simplex virus type 1 (HSV1), and influenza. Finally, we look at the role of vaccination to prevent dementia. In conclusion, there is a large body of evidence supporting the involvement of various infectious pathogens in the pathogenesis of dementia, but large-scale studies with long-term follow-up are needed to elucidate the role that infection may play, especially before subclinical or clinical disease is present

Pericardiectomy for constrictive pericarditis: a risk factor analysis for early and late failure

Predictors of early and late failure of pericardiectomy for constrictive pericarditis (CP) have not been established. Early and late outcomes of a cumulative series of 81 (mean age 60\ua0years; mean EuroSCORE II, 3.3%) consecutive patients from three European cardiac surgery centers were reviewed. Predictors of a combined endpoint comprising in-hospital death or major complications (including multiple transfusion) were identified with binary logistic regression. Non-parametric estimates of survival were obtained with the Kaplan\u2013Meier method. Predictors of poor late outcomes were established using Cox proportional hazard regression. There were 4 (4.9%) in-hospital deaths. Preoperative central venous pressure > 15\ua0mmHg (p = 0.005) and the use of cardiopulmonary bypass (p = 0.016) were independent predictors of complicated in-hospital course, which occurred in 29 (35.8%) patients. During follow-up (median, 5.4\ua0years), preoperative renal impairment was a predictor of all-cause death (p = 0.0041), cardiac death (p = 0.0008), as well as hospital readmission due to congestive heart failure (p = 0.0037); while partial pericardiectomy predicted all-cause death (p = 0.028) and concomitant cardiac operation predicted cardiac death (p = 0.026), postoperative central venous pressure < 10\ua0mmHg was associated with a low risk both of all-cause and cardiac death (p < 0.0001 for both). Ten-year adjusted survival free of all-cause death, cardiac death, and hospital readmission were 76.9%, 94.7%, and 90.6%, respectively. In high-risk patients with CP, performing pericardiectomy before severe constriction develops and avoiding cardiopulmonary bypass (when possible) could contribute to improving immediate outcomes post-surgery. Complete removal of cardiac constriction could enhance long-term outcomes

Microsatellite instability and intratumoural heterogeneity in 100 right-sided sporadic colon carcinomas

Microsatellite instability has been proposed as an alternative pathway of colorectal carcinogenesis. The aim of this study was to evaluate the interest of immunohistochemistry as a new tool for highlighting mismatch repair deficiency and to compare the results with a PCR-based microsatellite assay. A total of 100 sporadic proximal colon adenocarcinomas were analysed. The expression of hMLH1, hMSH2 and hMSH6 proteins evaluated by immunohistochemistry was altered in 39% of the cancers, whereas microsatellite instability assessed by PCR was detected in 43%. There was discordance between the two methods in eight cases. After further analyses performed on other tumoural areas for these eight cases, total concordance between the two techniques was observed (Kappa=100%). Our results demonstrate that immunohistochemistry may be as efficient as microsatellite amplification in the detection of unstable phenotype provided that at least two samples of each carcinoma are screened, because of intratumoural heterogeneity

Pressure Load: The Main Factor for Altered Gene Expression in Right Ventricular Hypertrophy in Chronic Hypoxic Rats

BACKGROUND: The present study investigated whether changes in gene expression in the right ventricle following pulmonary hypertension can be attributed to hypoxia or pressure loading. METHODOLOGY/PRINCIPAL FINDINGS: To distinguish hypoxia from pressure-induced alterations, a group of rats underwent banding of the pulmonary trunk (PTB), sham operation, or the rats were exposed to normoxia or chronic, hypobaric hypoxia. Pressure measurements were performed and the right ventricle was analyzed by Affymetrix GeneChip, and selected genes were confirmed by quantitative PCR and immunoblotting. Right ventricular systolic blood pressure and right ventricle to body weight ratio were elevated in the PTB and the hypoxic rats. Expression of the same 172 genes was altered in the chronic hypoxic and PTB rats. Thus, gene expression of enzymes participating in fatty acid oxidation and the glycerol channel were downregulated. mRNA expression of aquaporin 7 was downregulated, but this was not the case for the protein expression. In contrast, monoamine oxidase A and tissue transglutaminase were upregulated both at gene and protein levels. 11 genes (e.g. insulin-like growth factor binding protein) were upregulated in the PTB experiment and downregulated in the hypoxic experiment, and 3 genes (e.g. c-kit tyrosine kinase) were downregulated in the PTB and upregulated in the hypoxic experiment. CONCLUSION/SIGNIFICANCE: Pressure load of the right ventricle induces a marked shift in the gene expression, which in case of the metabolic genes appears compensated at the protein level, while both expression of genes and proteins of importance for myocardial function and remodelling are altered by the increased pressure load of the right ventricle. These findings imply that treatment of pulmonary hypertension should also aim at reducing right ventricular pressure

MLP (muscle LIM protein) as a stress sensor in the heart

Muscle LIM protein (MLP, also known as cysteine rich protein 3 (CSRP3, CRP3)) is a muscle-specific-expressed LIM-only protein. It consists of 194 amino-acids and has been described initially as a factor involved in myogenesis (Arber et al. Cell 79:221–231, 1994). MLP soon became an important model for experimental cardiology when it was first demonstrated that MLP deficiency leads to myocardial hypertrophy followed by a dilated cardiomyopathy and heart failure phenotype (Arber et al. Cell 88:393–403, 1997). At this time, this was the first genetically altered animal model to develop this devastating disease. Interestingly, MLP was also found to be down-regulated in humans with heart failure (Zolk et al. Circulation 101:2674–2677, 2000) and MLP mutations are able to cause hypertrophic and dilated forms of cardiomyopathy in humans (Bos et al. Mol Genet Metab 88:78–85, 2006; Geier et al. Circulation 107:1390–1395, 2003; Hershberger et al. Clin Transl Sci 1:21–26, 2008; Knöll et al. Cell 111:943–955, 2002; Knöll et al. Circ Res 106:695–704, 2010; Mohapatra et al. Mol Genet Metab 80:207–215, 2003). Although considerable efforts have been undertaken to unravel the underlying molecular mechanisms—how MLP mutations, either in model organisms or in the human setting cause these diseases are still unclear. In contrast, only precise knowledge of the underlying molecular mechanisms will allow the development of novel and innovative therapeutic strategies to combat this otherwise lethal condition. The focus of this review will be on the function of MLP in cardiac mechanosensation and we shall point to possible future directions in MLP research

Time course and mechanisms of left ventricular systolic and diastolic dysfunction in monocrotaline-induced pulmonary hypertension

Although pulmonary hypertension (PH) selectively overloads the right ventricle (RV), neuroendocrine activation and intrinsic myocardial dysfunction have been described in the left ventricle (LV). In order to establish the timing of LV dysfunction development in PH and to clarify underlying molecular changes, Wistar rats were studied 4 and 6 weeks after subcutaneous injection of monocrotaline (MCT) 60 mg/kg (MCT-4, n = 11; MCT-6, n = 11) or vehicle (Ctrl-4, n = 11; Ctrl-6, n = 11). Acute single beat stepwise increases of systolic pressure were performed from baseline to isovolumetric (LVPiso). This hemodynamic stress was used to detect early changes in LV performance. Neurohumoral activation was evaluated by measuring angiotensin-converting enzyme (ACE) and endothelin-1 (ET-1) LV mRNA levels. Cardiomyocyte apoptosis was evaluated by TUNEL assay. Extracellular matrix composition was evaluated by tenascin-C mRNA levels and interstitial collagen content. Myosin heavy chain (MHC) composition of the LV was studied by protein quantification. MCT treatment increased RV pressures and RV/LV weight ratio, without changing LV end-diastolic pressures or dimensions. Baseline LV dysfunction were present only in MCT-6 rats. Afterload elevations prolonged tau and upward-shifted end-diastolic pressure dimension relations in MCT-4 and even more in MCT-6. MHC-isoform switch, ACE upregulation and cardiomyocyte apoptosis were present in both MCT groups. Rats with severe PH develop LV dysfunction associated with ET-1 and tenascin-C overexpression. Diastolic dysfunction, however, could be elicited at earlier stages in response to hemodynamic stress, when only LV molecular changes, such as MHC isoform switch, ACE upregulation, and myocardial apoptosis were present.Supported by Portuguese grants from FCT (POCI/SAU-FCF/60803/2004 and POCI/SAU-MMO/61547/2004) through Cardiovascular R&D Unit (FCT No. 51/94)

Vaccines in older age: moving from current practice to optimal coverage—a multidisciplinary consensus conference

Vaccines are a key strategy to promote healthy aging, but vaccine coverage remains below target levels in at-risk adults and older individuals. We present here the results of a multidisciplinary consensus conference convened to perform a multidimensional assessment of vaccination in geriatric medicine, with a view to developing a well-defined strategy for the promotion of vaccines in older people. We discuss recommended vaccines in older individuals, and describe the wide regional heterogeneity between regions in the Italian context. The main obstacles to implementation of vaccines in practice are reviewed, as well as potential strategies to remove these barriers. Finally, the importance of including vaccines and vaccination in undergraduate and postgraduate medical education is underlined. The information summarized in this document is expected to help develop educational and promotional initiatives to achieve greater uptake of vaccines among older individuals, as a key means to promote healthy aging