Small intestinal polyp burden in pediatric Peutz–Jeghers syndrome assessed through capsule endoscopy: a longitudinal study

The management of pediatric Peutz–Jeghers Syndrome (PJS) focuses on the prevention of intussusception complicating small intestinal (SI) polyposis. This hinges on the accurate appraisal of the polyp burden to tailor therapeutic interventions. Video Capsule Endoscopy (VCE) is an established tool to study SI polyps in children, but an in-depth characterization of polyp burden in this population is lacking. Methods: We performed a retrospective longitudinal cross-sectional analysis of VCE studies in pediatric PJS patients at our institution (CMKC) from 2010 to 2020. Demographic, clinical, and VCE findings reported by three reviewers in tandem were accrued. Polyp burden variables were modeled as functions of patient and study characteristics using linear mixed models adjusted for clustering. Results: The cohort included 15 patients. The total small bowel polyp count and largest polyp size clustered under 30 polyps and <20 mm in size. Luminal occlusion correlated closely with the estimated polyp size. Polyp distribution favored proximal (77%) over distal (66%) small bowel involvement. The adjusted largest polyp size was greater in males. Double Balloon Enteroscopy was associated with a decreased polyp burden. Conclusions: The polyp burden in pediatric PJS patients favors the proximal third of the small intestine, with relatively small numbers and a polyp size amenable to resection through enteroscopy. Male gender and older age were related to an increased polyp burden

Exchange Anisotropy in Epitaxial and Polycrystalline NiO/NiFe Bilayers

(001) oriented NiO/NiFe bilayers were grown on single crystal MgO (001) substrates by ion beam sputtering in order to determine the effect that the crystalline orientation of the NiO antiferromagnetic layer has on the magnetization curve of the NiFe ferromagnetic layer. Simple models predict no exchange anisotropy for the (001)-oriented surface, which in its bulk termination is magnetically compensated. Nonetheless exchange anisotropy is present in the epitaxial films, although it is approximately half as large as in polycrystalline films that were grown simultaneously. Experiments show that differences in exchange field and coercivity between polycrystalline and epitaxial NiFe/NiO bilayers couples arise due to variations in induced surface anisotropy and not from differences in the degree of compensation of the terminating NiO plane. Implications of these observations for models of induced exchange anisotropy in NiO/NiFe bilayer couples will be discussed.Comment: 23 pages in RevTex format, submitted to Phys Rev B

Quantitative High-Resolution Genomic Analysis of Single Cancer Cells

During cancer progression, specific genomic aberrations arise that can determine the scope of the disease and can be used as predictive or prognostic markers. The detection of specific gene amplifications or deletions in single blood-borne or disseminated tumour cells that may give rise to the development of metastases is of great clinical interest but technically challenging. In this study, we present a method for quantitative high-resolution genomic analysis of single cells. Cells were isolated under permanent microscopic control followed by high-fidelity whole genome amplification and subsequent analyses by fine tiling array-CGH and qPCR. The assay was applied to single breast cancer cells to analyze the chromosomal region centred by the therapeutical relevant EGFR gene. This method allows precise quantitative analysis of copy number variations in single cell diagnostics

Resting-State Network Alterations Differ between Alzheimer's Disease Atrophy Subtypes

Several Alzheimer's disease (AD) atrophy subtypes were identified, but their brain network properties are unclear. We analyzed data from two independent datasets, including 166 participants (103 AD/63 controls) from the DZNE-longitudinal cognitive impairment and dementia study and 151 participants (121 AD/30 controls) from the AD neuroimaging initiative cohorts, aiming to identify differences between AD atrophy subtypes in resting-state functional magnetic resonance imaging intra-network connectivity (INC) and global and nodal network properties. Using a data-driven clustering approach, we identified four AD atrophy subtypes with differences in functional connectivity, accompanied by clinical and biomarker alterations, including a medio-temporal-predominant (S-MT), a limbic-predominant (S-L), a diffuse (S-D), and a mild-atrophy (S-MA) subtype. S-MT and S-D showed INC reduction in the default mode, dorsal attention, visual and limbic network, and a pronounced reduction of "global efficiency" and decrease of the "clustering coefficient" in parietal and temporal lobes. Despite severe atrophy in limbic areas, the S-L exhibited only marginal global network but substantial nodal network failure. S-MA, in contrast, showed limited impairment in clinical and cognitive scores but pronounced global network failure. Our results contribute toward a better understanding of heterogeneity in AD with the detection of distinct differences in functional connectivity networks accompanied by CSF biomarker and cognitive differences in AD subtypes

Consensus Statement on Circulating Biomarkers for Advanced Prostate Cancer

Context: In advanced prostate cancer (PC), there is increasing investigation of circulating biomarkers, including quantitation and characterization of circulating tumour cells and cell-free nucleic acids, for therapeutic monitoring and as prognostic and predictive biomarkers. However, there is a lack of consensus and standardisation regarding analyses, reporting, and integration of results into specific clinical contexts. A consensus meeting on circulating biomarkers was held to address these topics. Objective: To present a report of the consensus statement on circulating biomarkers in advanced PC. Evidence acquisition: Four important areas of controversy in the field of circulating biomarkers in PC management were identified: known clinical utility of circulating biomarkers; unmet clinical needs for circulating biomarkers in PC care; most pressing blood-based molecular assays required; and essential steps for developing circulating biomarker assays. A panel of 18 international PC experts in the field of circulating biomarkers developed the programme and consensus questions. The panel voted publicly but anonymously on 50 predefined questions developed following a modified Delphi process. Evidence synthesis: Voting was based solely on panellist opinions of the predefined topics and therefore not on a standard literature review or meta-analysis. The outcomes of the voting had varying degrees of support, as reflected in the wording of this article and in the detailed voting results provided in the Supplementary material. Conclusions: The expert voting results presented can guide the future development of circulating biomarkers for PC care. Notably, the consensus meeting highlighted the importance of reproducibility and variability studies, among other significant areas in need of trials specifically designed to address them. Patient summary: A panel of international experts met to discuss and vote on the use of different blood-based prostate cancer tests, and how they can be used to guide treatment and disease monitoring to deliver more precise and better patient care

Evaluation of DNA ploidy in relation with established prognostic factors in patients with locally advanced (unresectable) or metastatic pancreatic adenocarcinoma: a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>Most patients with ductal pancreatic adenocarcinoma are diagnosed with locally advanced (unresectable) or metastatic disease. The aim of this study was to evaluate the prognostic significance of DNA ploidy in relation with established clinical and laboratory variables in such patients.</p> <p>Methods</p> <p>Two hundred and twenty six patients were studied retrospectively. Twenty two potential prognostic variables (demographics, clinical parameters, biochemical markers, treatment modality) were examined.</p> <p>Results</p> <p>Mean survival time was 38.41 weeks (95% c.i.: 33.17–43.65), median survival 27.00 weeks (95% c.i.: 23.18–30.82). On multivariate analysis, 10 factors had an independent effect on survival: performance status, local extension of tumor, distant metastases, ploidy score, anemia under epoetin therapy, weight loss, pain, steatorrhoea, CEA, and palliative surgery and chemotherapy. Patients managed with palliative surgery and chemotherapy had 6.7 times lower probability of death in comparison with patients without any treatment. Patients with ploidy score > 3.6 had 5.0 times higher probability of death in comparison with patients with ploidy score < 2.2 and these with ploidy score 2.2–3.6 had 6.3 times higher probability of death in comparison with patients with ploidy score < 2.2.</p> <p>Conclusion</p> <p>According to the significance of the examined factor, survival was improved mainly by the combination of surgery and chemotherapy, and the presence of low DNA ploidy score.</p

Consensus Statement on Circulating Biomarkers for Advanced Prostate Cancer

Context: In advanced prostate cancer (PC), there is increasing investigation of circulating biomarkers, including quantitation and characterization of circulating tumour cells and cell-free nucleic acids, for therapeutic monitoring and as prognostic and predictive biomarkers. However, there is a lack of consensus and standardisation regarding analyses, reporting, and integration of results into specific clinical contexts. A consensus meeting on circulating biomarkers was held to address these topics. Objective: To present a report of the consensus statement on circulating biomarkers in advanced PC. Evidence acquisition: Four important areas of controversy in the field of circulating biomarkers in PC management were identified: known clinical utility of circulating biomarkers; unmet clinical needs for circulating biomarkers in PC care; most pressing blood-based molecular assays required; and essential steps for developing circulating biomarker assays. A panel of 18 international PC experts in the field of circulating biomarkers developed the programme and consensus questions. The panel voted publicly but anonymously on 50 predefined questions developed following a modified Delphi process. Evidence synthesis: Voting was based solely on panellist opinions of the predefined topics and therefore not on a standard literature review or meta-analysis. The outcomes of the voting had varying degrees of support, as reflected in the wording of this article and in the detailed voting results provided in the Supplementary material. Conclusions: The expert voting results presented can guide the future development of circulating biomarkers for PC care. Notably, the consensus meeting highlighted the importance of reproducibility and variability studies, among other significant areas in need of trials specifically designed to address them. Patient summary: A panel of international experts met to discuss and vote on the use of different blood-based prostate cancer tests, and how they can be used to guide treatment and disease monitoring to deliver more precise and better patient car

Detection of erbB2 copy number variations in plasma of patients with esophageal carcinoma

<p>Abstract</p> <p>Background</p> <p>Mortality is high in patients with esophageal carcinoma as tumors are rarely detected before the disease has progressed to an advanced stage. Here, we sought to isolate cell-free DNA released into the plasma of patients with esophageal carcinoma, to analyze copy number variations of marker genes in the search for early detection of tumor progression.</p> <p>Methods</p> <p>Plasma of 41 patients with esophageal carcinoma was prospectively collected before tumor resection and chemotherapy. Our dataset resulted heterogeneous for clinical data, resembling the characteristics of the tumor. DNA from the plasma was extracted to analyze copy number variations of the <it>erbB2 </it>gene using real-time PCR assays.</p> <p>Results</p> <p>The real-time PCR assays for <it>erbB2 </it>gene showed significant (<it>P </it>= 0.001) copy number variations in the plasma of patients with esophageal carcinoma, as compared to healthy controls with high sensitivity (80%) and specificity (95%). These variations in <it>erbB2 </it>were negatively correlated to the progression free survival of these patients (<it>P </it>= 0.03), and revealed a further risk category stratification of patients with low VEGF expression levels.</p> <p>Conclusion</p> <p>The copy number variation of <it>erbB2 </it>gene from plasma can be used as prognostic marker for early detection of patients at risk of worse clinical outcome in esophageal cancer.</p

Associations between sex, body mass index and the individual microglial response in Alzheimer’s disease

Background and objectives 18-kDa translocator protein position-emission-tomography (TSPO-PET) imaging emerged for in vivo assessment of neuroinflammation in Alzheimer’s disease (AD) research. Sex and obesity effects on TSPO-PET binding have been reported for cognitively normal humans (CN), but such effects have not yet been systematically evaluated in patients with AD. Thus, we aimed to investigate the impact of sex and obesity on the relationship between β-amyloid-accumulation and microglial activation in AD. Methods 49 patients with AD (29 females, all Aβ-positive) and 15 Aβ-negative CN (8 female) underwent TSPO-PET ([18F]GE-180) and β-amyloid-PET ([18F]flutemetamol) imaging. In 24 patients with AD (14 females), tau-PET ([18F]PI-2620) was additionally available. The brain was parcellated into 218 cortical regions and standardized-uptake-value-ratios (SUVr, cerebellar reference) were calculated. Per region and tracer, the regional increase of PET SUVr (z-score) was calculated for AD against CN. The regression derived linear effect of regional Aβ-PET on TSPO-PET was used to determine the Aβ-plaque-dependent microglial response (slope) and the Aβ-plaque-independent microglial response (intercept) at the individual patient level. All read-outs were compared between sexes and tested for a moderation effect of sex on associations with body mass index (BMI). Results In AD, females showed higher mean cortical TSPO-PET z-scores (0.91 ± 0.49; males 0.30 ± 0.75; p = 0.002), while Aβ-PET z-scores were similar. The Aβ-plaque-independent microglial response was stronger in females with AD (+ 0.37 ± 0.38; males with AD − 0.33 ± 0.87; p = 0.006), pronounced at the prodromal stage. On the contrary, the Aβ-plaque-dependent microglial response was not different between sexes. The Aβ-plaque-independent microglial response was significantly associated with tau-PET in females (Braak-II regions: r = 0.757, p = 0.003), but not in males. BMI and the Aβ-plaque-independent microglial response were significantly associated in females (r = 0.44, p = 0.018) but not in males (BMI*sex interaction: F(3,52) = 3.077, p = 0.005). Conclusion While microglia response to fibrillar Aβ is similar between sexes, women with AD show a stronger Aβ-plaque-independent microglia response. This sex difference in Aβ-independent microglial activation may be associated with tau accumulation. BMI is positively associated with the Aβ-plaque-independent microglia response in females with AD but not in males, indicating that sex and obesity need to be considered when studying neuroinflammation in AD