CRP Predicts Safe Patient Discharge after Colorectal Surgery. Reply

Reply: We would like to thank Aurelie´n Dupre`, Johan Gagnie´r, Heloı¨se Samba, Michel Rivoire, and Karem Slim for their comments about our article ‘‘Procalcitonin Reveals Early Dehiscence in Colorectal Surgery: The PREDICS Study.’’1 It is very rewarding to realize that this paper is stimulating so many observations, this means thatwe are talking about an interesting topic

Assessment of plaque morphology in alzheimer’s mouse cerebellum using three-dimensional X-ray phase-based virtual histology

Visualization and characterization of beta -amyloid deposits is a fundamental task in pre-clinical study of Alzheimer's disease (AD) to assess its evolution and monitor the efficiency of new therapeutic strategies. While the cerebellum is one of the brain areas most underestimated in the context of AD, renewed interest in cerebellar lesions has recently arisen as they may link to motor and cognitive alterations. Thus, we quantitatively investigated three-dimensional plaque morphology in the cerebellum in APP/PS1 transgenic mouse, as a model of AD. In order to obtain a complete high-resolution three-dimensional view of the investigated tissue, we exploited synchrotron X-ray phase contrast tomography (XPCT), providing virtual slices with histology-matching resolution. We found the formation of plaques elongated in shape, and with a specific orientation in space depending on the investigated region of the cerebellar cortex. Remarkably, a similar shape is observed in human cerebellum from demented patients. Our findings demonstrate the capability of XPCT in volumetric quantification, supporting the current knowledge about plaque morphology in the cerebellum and the fundamental role of the surrounding tissue in driving their evolution. A good correlation with the human neuropathology is also reported

Procalcitonin Reveals Early Dehiscence in Colorectal Surgery: The PREDICS Study

Objectives: We designed a multicentric, observational study to test if Procalcitonin (PCT) might be an early and reliable marker of anastomotic leak (AL) after colorectal surgery (ClinicalTrials.govIdentifier:NCT01817647). Background: Procalcitonin is a biomarker used to monitor bacterial infections and guide antibiotic therapy. Anastomotic leak after colorectal surgery is a severe complication associated with relevant short and long-term sequelae. Methods: Between January 2013 and September 2014, 504 patients underwent colorectal surgery, for malignant colorectal diseases, in elective setting. White blood count (WBC), C-reactive protein (CRP) and PCT levels were measured in 3rd and 5th postoperative day (POD). AL and all postoperative complications were recorded. Results: We registered 28 (5.6%) anastomotic leaks. Specificity and negative predictive value for AL with PCT less than 2.7 and 2.3 ng/mL were, respectively, 91.7% and 96.9% in 3rd POD and 93% and 98.3% in 5th POD. Receiver operating characteristic curve for biomarkers shows that in 3rd POD, PCTand CRP have similar area under the curve (AUC) (0.775 vs 0.772), both better than WBC (0.601); in 5th POD, PCT has a better AUC than CRP and WBC (0.862 vs 0.806 vs 0.611). Measuring together PCT and CRP significantly improves AL diagnosis in 5th POD (AUC: 0.901). Conclusions: PCTand CRP demonstrated to have a good negative predictive value for AL, both in 3rd and in 5th POD. Low levels of PCT, together with low CRP values, seem to be early and reliable markers of AL after colorectal surgery. These biomarkers might be safely added as additional criteria of discharge protocols after colorectal surgery

Moderate and Severe Congenital Heart Diseases Adversely Affect the Growth of Children in Italy: A Retrospective Monocentric Study

: Children with congenital heart disease (CHD) are at increased risk for undernutrition. The aim of our study was to describe the growth parameters of Italian children with CHD compared to healthy children. We performed a cross-sectional study collecting the anthropometric data of pediatric patients with CHD and healthy controls. WHO and Italian z-scores for weight for age (WZ), length/height for age (HZ), weight for height (WHZ) and body mass index (BMIZ) were collected. A total of 657 patients (566 with CHD and 91 healthy controls) were enrolled: 255 had mild CHD, 223 had moderate CHD and 88 had severe CHD. Compared to CHD patients, healthy children were younger (age: 7.5 ± 5.4 vs. 5.6 ± 4.3 years, p = 0.0009), taller/longer (HZ: 0.14 ± 1.41 vs. 0.62 ± 1.20, p < 0.002) and heavier (WZ: -0,07 ± 1.32 vs. 0.31 ± 1.13, p = 0.009) with no significant differences in BMIZ (-0,14 ± 1.24 vs. -0.07 ± 1.13, p = 0.64) and WHZ (0.05 ± 1.47 vs. 0.43 ± 1.07, p = 0.1187). Moderate and severe CHD patients presented lower z-scores at any age, with a more remarkable difference in children younger than 2 years (WZ) and older than 5 years (HZ, WZ and BMIZ). Stunting and underweight were significantly more present in children affected by CHD (p < 0.01). In conclusion, CHD negatively affects the growth of children based on the severity of the disease, even in a high-income country, resulting in a significant percentage of undernutrition in this population

Evidence for sub-haplogroup h5 of mitochondrial DNA as a risk factor for late onset Alzheimer's disease

BACKGROUND: Alzheimer's Disease (AD) is the most common neurodegenerative disease and the leading cause of dementia among senile subjects. It has been proposed that AD can be caused by defects in mitochondrial oxidative phosphorylation. Given the fundamental contribution of the mitochondrial genome (mtDNA) for the respiratory chain, there have been a number of studies investigating the association between mtDNA inherited variants and multifactorial diseases, however no general consensus has been reached yet on the correlation between mtDNA haplogroups and AD. METHODOLOGY/PRINCIPAL FINDINGS: We applied for the first time a high resolution analysis (sequencing of displacement loop and restriction analysis of specific markers in the coding region of mtDNA) to investigate the possible association between mtDNA-inherited sequence variation and AD in 936 AD patients and 776 cognitively assessed normal controls from central and northern Italy. Among over 40 mtDNA sub-haplogroups analysed, we found that sub-haplogroup H5 is a risk factor for AD (OR=1.85, 95% CI:1.04-3.23) in particular for females (OR=2.19, 95% CI:1.06-4.51) and independently from the APOE genotype. Multivariate logistic regression revealed an interaction between H5 and age. When the whole sample is considered, the H5a subgroup of molecules, harboring the 4336 transition in the tRNAGln gene, already associated to AD in early studies, was about threefold more represented in AD patients than in controls (2.0% vs 0.8%; p=0.031), and it might account for the increased frequency of H5 in AD patients (4.2% vs 2.3%). The complete re-sequencing of the 56 mtDNAs belonging to H5 revealed that AD patients showed a trend towards a higher number (p=0.052) of sporadic mutations in tRNA and rRNA genes when compared with controls. CONCLUSIONS: Our results indicate that high resolution analysis of inherited mtDNA sequence variation can help in identifying both ancient polymorphisms defining sub-haplogroups and the accumulation of sporadic mutations associated with complex traits such as AD

The Molecular Assembly of Amyloid Aβ Controls Its Neurotoxicity and Binding to Cellular Proteins

Accumulation of β-sheet-rich peptide (Aβ) is strongly associated with Alzheimer's disease, characterized by reduction in synapse density, structural alterations of dendritic spines, modification of synaptic protein expression, loss of long-term potentiation and neuronal cell death. Aβ species are potent neurotoxins, however the molecular mechanism responsible for Aβ toxicity is still unknown. Numerous mechanisms of toxicity were proposed, although there is no agreement about their relative importance in disease pathogenesis. Here, the toxicity of Aβ 1–40 and Aβ 1–42 monomers, oligomers or fibrils, was evaluated using the N2a cell line. A structure-function relationship between peptide aggregation state and toxic properties was established. Moreover, we demonstrated that Aβ toxic species cross the plasma membrane, accumulate in cells and bind to a variety of internal proteins, especially on the cytoskeleton and in the endoplasmatic reticulum (ER). Based on these data we suggest that numerous proteins act as Aβ receptors in N2a cells, triggering a multi factorial toxicity

Evidence for Sub-Haplogroup H5 of Mitochondrial DNA as a Risk Factor for Late Onset Alzheimer's Disease

BACKGROUND: Alzheimer's Disease (AD) is the most common neurodegenerative disease and the leading cause of dementia among senile subjects. It has been proposed that AD can be caused by defects in mitochondrial oxidative phosphorylation. Given the fundamental contribution of the mitochondrial genome (mtDNA) for the respiratory chain, there have been a number of studies investigating the association between mtDNA inherited variants and multifactorial diseases, however no general consensus has been reached yet on the correlation between mtDNA haplogroups and AD. METHODOLOGY/PRINCIPAL FINDINGS: We applied for the first time a high resolution analysis (sequencing of displacement loop and restriction analysis of specific markers in the coding region of mtDNA) to investigate the possible association between mtDNA-inherited sequence variation and AD in 936 AD patients and 776 cognitively assessed normal controls from central and northern Italy. Among over 40 mtDNA sub-haplogroups analysed, we found that sub-haplogroup H5 is a risk factor for AD (OR=1.85, 95% CI:1.04-3.23) in particular for females (OR=2.19, 95% CI:1.06-4.51) and independently from the APOE genotype. Multivariate logistic regression revealed an interaction between H5 and age. When the whole sample is considered, the H5a subgroup of molecules, harboring the 4336 transition in the tRNAGln gene, already associated to AD in early studies, was about threefold more represented in AD patients than in controls (2.0% vs 0.8%; p=0.031), and it might account for the increased frequency of H5 in AD patients (4.2% vs 2.3%). The complete re-sequencing of the 56 mtDNAs belonging to H5 revealed that AD patients showed a trend towards a higher number (p=0.052) of sporadic mutations in tRNA and rRNA genes when compared with controls. CONCLUSIONS: Our results indicate that high resolution analysis of inherited mtDNA sequence variation can help in identifying both ancient polymorphisms defining sub-haplogroups and the accumulation of sporadic mutations associated with complex traits such as AD