Multimodal Hippocampal Subfield Grading For Alzheimer’s Disease Classification

Numerous studies have proposed biomarkers based on magnetic resonance imaging (MRI) to detect and predict the risk of evolution toward Alzheimer’s disease (AD). Most of these methods have focused on the hippocampus, which is known to be one of the earliest structures impacted by the disease. To date, patch-based grading approaches provide among the best biomarkers based on the hippocampus. However, this structure is complex and is divided into different subfields, not equally impacted by AD. Former in-vivo imaging studies mainly investigated structural alterations of these subfields using volumetric measurements and microstructural modifications with mean diffusivity measurements. The aim of our work is to improve the current classification performances based on the hippocampus with a new multimodal patch-based framework combining structural and diffusivity MRI. The combination of these two MRI modalities enables the capture of subtle structural and microstructural alterations. Moreover, we propose to study the efficiency of this new framework applied to the hippocampal subfields. To this end, we compare the classification accuracy provided by the different hippocampal subfields using volume, mean diffusivity, and our novel multimodal patch-based grading framework combining structural and diffusion MRI. The experiments conducted in this work show that our new multimodal patch-based method applied to the whole hippocampus provides the most discriminating biomarker for advanced AD detection while our new framework applied into subiculum obtains the best results for AD prediction, improving by two percentage points the accuracy compared to the whole hippocampus

Clinical Study Weight Loss after Sleeve Gastrectomy in Super Superobesity

Objective. This prospective study evaluated laparoscopic sleeve gastrectomy for its safety and efficiency in excess weight loss (%EWL) in super superobese patients (BMI > 60 Kg/m 2 ). Results. Thirty patients (33 women and 7 men) were included, with mean age of 35 years (range 18 to 59). Mean preoperative BMI was 66 Kg/m 2 (range 60 to 85). The study included one patient with complete situs inversus and 4 (14%) with previous restrictive gastric banding. The mean operative time was 120 minutes (range 80 to 220 min) and the mean hospital stay was 7.5 days (4 to 28 days). There was no postoperative mortality or need for a laparotomy conversion. Two subphrenic hematomas, one gastric fistula, and one pulmonary embolism, were the major complications. After 18 months 17 (77%) had sufficient weight loss and six had insufficient results, leading to either re-sleeve gastrectomy (3), or gastric bypass (2). Three years after the initial laparoscopic sleeve gastrectomy, the mean EWL was 51% (range 21 to 82). Conclusion. The laparoscopic sleeve gastrectomy is a safe and efficient operating procedure for treating super superobesity. In the case of insufficient weight loss, a second-stage operation like resleeve gastrectomy or gastric bypass can be proposed

Submucosal Tunnel Endoscopic Resection of Gastric Lesion Before Obesity Surgery: a Case Series

Background: Submucosal tumors (SMTs) of the gastrointestinal tract are a rare pathological entity comprising a wide variety of neoplastic and non-neoplastic lesions. Even if most SMTs are benign tumors (e.g., leiomyomas), a smaller portion may have a malignant potential (e.g., gastrointestinal stromal tumor (GIST)). Preoperative diagnosis of SMT in bariatric patients may arise challenging clinical dilemmas. Long-term surveillance may be difficult after bariatric surgery. Moreover, according to SMT location, its presence may interfere with planned surgery. Submucosal tunneling endoscopic resection (STER) has emerged as an effective approach for minimally invasive en bloc excision of SMTs. This is the first case series of STER for SMTs before bariatric surgery. Methods: Seven female patients underwent STER for removal of SMTs before bariatric surgery. All lesions were incidentally diagnosed at preoperative endoscopy. STER procedural steps comprised mucosal incision, submucosal tunneling, lesion enucleation, and closure of mucosal defect. Results: En bloc removal of SMT was achieved in all cases. Mean procedural time was of 45 min (SD 18.6). No adverse event occurred. Mean size of the lesions was 20.6 mm (SD 5.8). Histological diagnoses were 5 leyomiomas, 1 lipoma, and 1 low grade GIST. Bariatric procedure was performed after a mean period of 4.1 months (SD 1.6) from endoscopic resection. Conclusion: STER is a safe and effective treatment for the management of SMT even in bariatric patients awaiting surgery. Preoperative endoscopic resection of SMTs has the advantages of reducing the need for surveillance and removing lesions that could interfere with planned surgery. STER did not altered accomplishment of bariatric procedures

PLoS One

Diffusion MRI is extensively used to investigate changes in white matter microstructure. However, diffusion measures within white matter tissue can be affected by partial volume effects due to cerebrospinal fluid and white matter hyperintensities, especially in the aging brain. In previous aging studies, the cingulum bundle that plays a central role in the architecture of the brain networks supporting cognitive functions has been associated with cognitive deficits. However, most of these studies did not consider the partial volume effects on diffusion measures. The aim of this study was to evaluate the effect of free water elimination on diffusion measures of the cingulum in a group of 68 healthy elderly individuals. We first determined the effect of free water elimination on conventional DTI measures and then examined the effect of free water elimination on verbal fluency performance over 12 years. The cingulum bundle was reconstructed with a tractography pipeline including a white matter hyperintensities mask to limit the negative impact of hyperintensities on fiber tracking algorithms. We observed that free water elimination increased the ability of conventional DTI measures to detect associations between tissue diffusion measures of the cingulum and changes in verbal fluency in older individuals. Moreover, free water content and mean diffusivity measured along the cingulum were independently associated with changes in verbal fluency. This suggests that both tissue modifications and an increase in interstitial isotropic water would contribute to cognitive decline. These observations reinforce the importance of using free water elimination when studying brain aging and indicate that free water itself could be a relevant marker for age-related cingulum white matter modifications and cognitive decline

Endoscopic internal drainage for the management of leak, fistula, and collection after sleeve gastrectomy: our experience in 617 consecutive patients

Background: Endoscopy plays a pivotal role in the management of adverse events (AE) following bariatric surgery. Leaks, fistulae, and post-operative collection after sleeve gastrectomy (SG) may occur in up to 10% of cases. Objectives: To evaluate the efficacy and safety of endoscopic internal drainage (EID) for the management of leak, fistula, and collection following SG. Setting: Retrospective, observational, single center study on patients referred from several bariatric surgery departments to an endoscopic referral center. Methods: EID was used as first-line treatment for the management of leaks, fistulae, and collections. Leaks and fistulae were treated with double pigtail stent (DPS) deployment in order to guarantee internal drainage and second intention cavity obliteration. Collections were treated with endoscropic ultrasound (EUS)–guided deployment of DPS or lumen apposing metal stents. Results: A total of 617 patients (83.3% female; mean age, 43.1 yr) were enrolled in the study for leak (n = 300, 48.6%), fistula (n = 285, 46.2%), and collection (n = 32, 5.2%). Median follow-up was 19.5 months. Overall clinical success was 84.7% whereas 15.3% of cases required revisional surgery after EID failure. Clinical success according to type of AE was 89.5%, 78.5%, and 90% for leak, fistula, and collection, respectively. A total of 10 of 547 (1.8%) presented a recurrence during follow-up. A total of 28 (4.5%) AE related to the endoscopic treatment occurred. At univariate logistic regression predictors of failure were: fistula (OR 2.012), combined endoscopic approach (OR 2.319), need for emergency surgery (OR 1.755), and previous endoscopic treatment (OR 4.818). Conclusion: Early EID for the management of leak, fistula, and post-operative collection after SG seems a safe and effective first-line approach with good long-term results

Intraoperative assessment of biliary anatomy for prevention of bile duct injury: a review of current and future patient safety interventions

Background Bile duct injury (BDI) is a dreaded complication of cholecystectomy, often caused by misinterpretation of biliary anatomy. To prevent BDI, techniques have been developed for intraoperative assessment of bile duct anatomy. This article reviews the evidence for the different techniques and discusses their strengths and weaknesses in terms of efficacy, ease, and cost-effectiveness. Method PubMed was searched from January 1980 through December 2009 for articles concerning bile duct visualization techniques for prevention of BDI during laparoscopic cholecystectomy. Results Nine techniques were identified. The critical-view-of-safety approach, indirectly establishing biliary anatomy, is accepted by most guidelines and commentaries as the surgical technique of choice to minimize BDI risk. Intraoperative cholangiography is associated with lower BDI risk (OR 0.67, CI 0.61-0.75). However, it incurs extra costs, prolongs the operative procedure, and may be experienced as cumbersome. An established reliable alternative is laparoscopic ultrasound, but its longer learning curve limits widespread implementation. Easier to perform are cholecystocholangiography and dye cholangiography, but these yield poor-quality images. Light cholangiography, requiring retrograde insertion of an optical fiber into the common bile duct, is too unwieldy for routine use. Experimental techniques are passive infrared cholangiography, hyperspectral cholangiography, and near-infrared fluorescence cholangiography. The latter two are performed noninvasively and provide real-time images. Quantitative data in patients are necessary to further evaluate these techniques. Conclusions The critical-view-of-safety approach should be used during laparoscopic cholecystectomy. Intraoperative cholangiography or laparoscopic ultrasound is recommended to be performed routinely. Hyperspectral cholangiography and near-infrared fluorescence cholangiography are promising novel techniques to prevent BDI and thus increase patient safety

Xenon and Sevoflurane Provide Analgesia during Labor and Fetal Brain Protection in a Perinatal Rat Model of Hypoxia-Ischemia

It is not possible to identify all pregnancies at risk of neonatal hypoxic-ischemic encephalopathy (HIE). Many women use some form of analgesia during childbirth and some anesthetic agents have been shown to be neuroprotective when used as analgesics at subanesthetic concentrations. In this study we sought to understand the effects of two anesthetic agents with presumptive analgesic activity and known preconditioning-neuroprotective properties (sevoflurane or xenon), in reducing hypoxia-induced brain damage in a model of intrauterine perinatal asphyxia. The analgesic and neuroprotective effects at subanesthetic levels of sevoflurane (0.35%) or xenon (35%) were tested in a rat model of intrauterine perinatal asphyxia. Analgesic effects were measured by assessing maternal behavior and spinal cord dorsal horn neuronal activation using c-Fos. In separate experiments, intrauterine fetal asphyxia was induced four hours after gas exposure; on post-insult day 3 apoptotic cell death was measured by caspase-3 immunostaining in hippocampal neurons and correlated with the number of viable neurons on postnatal day (PND) 7. A separate cohort of pups was nurtured by a surrogate mother for 50 days when cognitive testing with Morris water maze was performed. Both anesthetic agents provided analgesia as reflected by a reduction in the number of stretching movements and decreased c-Fos expression in the dorsal horn of the spinal cord. Both agents also reduced the number of caspase-3 positive (apoptotic) neurons and increased cell viability in the hippocampus at PND7. These acute histological changes were mirrored by improved cognitive function measured remotely after birth on PND 50 compared to control group. Subanesthetic doses of sevoflurane or xenon provided both analgesia and neuroprotection in this model of intrauterine perinatal asphyxia. These data suggest that anesthetic agents with neuroprotective properties may be effective in preventing HIE and should be tested in clinical trials in the future

A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling

Chromatin remodeling complexes are known to modify chemical marks on histones or to induce conformational changes in the chromatin in order to regulate transcription. De novo dominant mutations in different members of the SWI/SNF chromatin remodeling complex have recently been described in individuals with Coffin-Siris (CSS) and Nicolaides-Baraitser (NCBRS) syndromes. Using a combination of whole-exome sequencing, NGS-based sequencing of 23 SWI/SNF complex genes, and molecular karyotyping in 46 previously undescribed individuals with CSS and NCBRS, we identified a de novo 1-bp deletion (c.677delG, p.Gly226Glufs*53) and a de novo missense mutation (c.914G>T, p.Cys305Phe) in PHF6 in two individuals diagnosed with CSS. PHF6 interacts with the nucleosome remodeling and deacetylation (NuRD) complex implicating dysfunction of a second chromatin remodeling complex in the pathogenesis of CSS-like phenotypes. Altogether, we identified mutations in 60% of the studied individuals (28/46), located in the genes ARID1A, ARID1B, SMARCB1, SMARCE1, SMARCA2, and PHF6. We show that mutations in ARID1B are the main cause of CSS, accounting for 76% of identified mutations. ARID1B and SMARCB1 mutations were also found in individuals with the initial diagnosis of NCBRS. These individuals apparently belong to a small subset who display an intermediate CSS/NCBRS phenotype. Our proposed genotype-phenotype correlations are important for molecular screening strategie

Variability of NT-proBNP and Its Relationship with Inflammatory Status in Patients with Stable Essential Hypertension: A 2-Year Follow-Up Study

The variability of NT-proBNP levels has been studied in heart failure, yet no data exist on these changes over time in hypertensive patients. Furthermore, studies on the relationship between natriuretic peptides and inflammatory status are limited.220 clinically and functionally asymptomatic stable patients (age 59 ± 13, 120 male) out of 252 patients with essential hypertension were followed up, and NT-proBNP was measured at baseline, 12 and 24 months. No differences in NT-proBNP were found with respect to the basal stage in the hypertrophic group, but significant changes were found in non-hypertrophic subjects. The reproducibility of NT-proBNP measurements was better in patients with hypertrophy than in the non-hypertrophic group for the three intervals (stage I-basal; stage II-stage I; stage II-basal) with a reference change value of 34%, 35% and 41%, respectively, in the hypertrophic group. A more elevated coefficient of correlation was obtained in the hypertrophic group than in patients without hypertrophy: basal versus stage I (r = 0.79, p < 0.0001 and r = 0.59, p < 0.0001) and stage I versus stage II (r = 0.86, p < 0.0001 and r = 0.56, p < 0.0001). Finally, levels of NT-proBNP significantly correlated with sTNF-R1 (p < 0.0001) and IL-6 (p < 0.01) during follow-up. A multivariate linear regression analysis showed that sTNF-R1 is an independent factor of NT-proBNP.This work shows that there is good stability in NT-proBNP levels in a follow-up study of asymptomatic patients with stable hypertension and left ventricular hypertrophy. As a consequence, assessment of NT-proBNP concentrations may be a useful tool for monitoring the follow-up of hypertensive patients with hypertrophy. Measured variations in peptide levels, exceeding 35% in a 12-month follow-up and 41% in a 24-month follow-up, may indicate an increase in cardiovascular risk, and therefore implies adjustment in the medical treatment. In addition, this study shows a link between neurohormonal and inflammatory activation in these patients