Familial exudative vitreoretinopathy (FEVR) is a rare finding in patients with genetic forms of microcephaly. This study documents the detailed phenotype and expands the range of genetic ...heterogeneity.
Retrospective case series.
Twelve patients (10 families) with a diagnosis of FEVR and microcephaly were ascertained from pediatric genetic eye clinics and underwent full clinical assessment including retinal imaging. Molecular investigations included candidate gene Sanger sequencing, whole-exome sequencing (WES), and whole-genome sequencing (WGS).
All patients had reduced vision and nystagmus. Six were legally blind. Two probands carried bi-allelic LRP5 variants, both presenting with bilateral retinal folds. A novel homozygous splice variant, and 2 missense variants were identified. Subsequent bone density measurement identified osteoporosis in one proband. Four families had heterozygous KIF11 variants. Two probands had a retinal fold in one eye and chorioretinal atrophy in the other; the other 2 had bilateral retinal folds. Four heterozygous variants were found, including 2 large deletions not identified on Sanger sequencing or WES. Finally, a family of 2 children with learning difficulties, abnormal peripheral retinal vasculogenesis, and rod-cone dystrophy were investigated. They were found to have bi-allelic splicing variants in TUBGCP6. Three families remain unsolved following WES and WGS.
Molecular diagnosis has been achieved in 7 of 10 families investigated, including a previously unrecognized association with LRP5. WGS enabled molecular diagnosis in 3 families after prior negative Sanger sequencing of the causative gene. This has enabled patient-specific care with targeted investigations and accurate family counseling.
•All patients had reduced vision and nystagmus and half were legally blind.•Retinal findings ranged from peripheral non-perfusion to total retinal detachment.•Systemic associations included low bone density and learning difficulties.•Variants in LRP5, KIF11, and TUBGCP6 were identified in 7 of 10 families.
Stage 3 pancreatic ductal adenocarcinoma (PDAC) is defined by arterial involvement. This study objective was to evaluate outcomes for patients with stage 3 PDAC with potentially reconstructable ...arterial involvement, considered for neoadjuvant therapy (NAT) and pancreatic resection, and to compare outcomes following arterial (AR) and non-arterial resection (NAR).
This study included patients from 2009 to 2016 with biopsy-proven stage 3 PDAC who were offered NAT before surgical exploration. AR was performed if required to achieve R0 resection. Time to event outcomes were analysed from diagnosis date.
87/89 patients (97.8%) received NAT (chemotherapy 41.6%, chemotherapy/radiotherapy 56.2%). 46/89 (51.7%) underwent exploration; 31 underwent resection (AR n = 20, NAR n = 11). AR patients had longer operative time (681 vs. 563 min, p = 0.006) and more blood loss (1600 vs. 575 mL, p = 0.0004), with no difference for blood transfusion, pancreatic fistula, length of stay, reoperation, or mortality. R0 rate was 30/31. Post-resection 90-day mortality was 3.2%. Median overall survival was statistically comparable between the AR and NAR groups (19.7 vs. 28.4 months, p = 0.41).
AR had comparable clinical and oncologic outcomes to NAR. Following careful selection and non-progression after NAT, major AR may cautiously be considered if required to obtain a negative resection margin.
Background: The acquisition of microbial communities and the influence of delivery mode on the oral microbiota of the newborn infant remains poorly characterised. Methods: A cohort of pregnant women ...were enrolled in the study (n = 84). All infants were born full term, by Spontaneous vaginal delivery (SVD) or by Caesarean section (CS). At delivery a saliva sample along with a vaginal/skin sample from the mother. Saliva samples were the taken from the infant within one week of birth, and at week 4, week 8, 6 months and 1 year of age. We used high-throughput sequencing of V4-V5 region 16S rRNA amplicons to compare the microbiota of all samples. Results: The vaginal microbiota had a lower alpha diversity than the skin microbiota of the mother, while the infant oral microbiota diversity remained relatively stable from birth to 8 weeks of age. The oral microbiota of the neonate differed by birth modality up to 1 week of age (p < 0.05), but birth modality did not have any influence on the infant oral microbiota beyond this age. Conclusions: We conclude thatbirth mode does not have an effect on the infant oral microbiota beyond 4 weeks of age, and the oral microbiota of infants continues to develop until 1 year of age.
The optimal treatment for small, asymptomatic, nonfunctioning pancreatic neuroendocrine neoplasms (NF-PanNEN) is still controversial. European Neuroendocrine Tumor Society (ENETS) guidelines ...recommend a watchful strategy for asymptomatic NF-PanNEN <2 cm of diameter. Several retrospective series demonstrated that a non-operative management is safe and feasible, but no prospective studies are available. Aim of the ASPEN study is to evaluate the optimal management of asymptomatic NF-PanNEN ≤2 cm comparing active surveillance and surgery.
ASPEN is a prospective international observational multicentric cohort study supported by ENETS. The study is registered in ClinicalTrials.gov with the identification code NCT03084770. Based on the incidence of NF-PanNEN the number of expected patients to be enrolled in the ASPEN study is 1,000 during the study period (2017-2022). Primary endpoint is disease/progression-free survival, defined as the time from study enrolment to the first evidence of progression (active surveillance group) or recurrence of disease (surgery group) or death from disease. Inclusion criteria are: age >18 years, the presence of asymptomatic sporadic NF-PanNEN ≤2 cm proven by a positive fine-needle aspiration (FNA) or by the presence of a measurable nodule on high-quality imaging techniques that is positive at
Gallium DOTATOC-PET scan.
The ASPEN study is designed to investigate if an active surveillance of asymptomatic NF-PanNEN ≤2 cm is safe as compared to surgical approach.
The left renal vein (LRV) may be used for venous reconstruction during hepato-pancreato-biliary (HPB) surgery, although concerns exist about compromising renal function. This study aimed to determine ...renal outcomes following LRV harvest during HPB resections.
Circumferential PV/SMV resections from 2008 to 2014 were included within two groups (LRV harvest, Control). Absolute and change in Creatinine (Cr) and estimated GFR (eGFR), and rates of acute kidney injury (AKI) and chronic kidney disease (CKD), were compared. Multivariate logistic regression analyses were performed.
76 patients were included (LRV n = 17, Control n = 59). Median Cr and eGFR did not change within groups, although change in eGFR differed between groups at postoperative day (POD) 3 (−4.3 vs. 12.8, p = 0.0035) and 7 (−1.8 vs. 12.4, p = 0.0074). AKI occurred more frequently in the LRV group at POD1 (5/17 vs. 4/59, p = 0.023) and POD3 (5/17 vs. 3/59, p = 0012), with no difference in CKD between groups (2/11 vs. 5/33 at 3 months, p = 0.99). LRV harvest was an independent risk factor for AKI at POD1 and POD3, but not thereafter.
Patients who undergo LRV harvest experience a higher rate of AKI in the first three post-operative days. LRV harvest during pancreas resection does not impact on long-term renal function.
We aimed to assess osteogenesis in osteoprogenitor cells by nanopits and to assess optimal feature depth. Topographies of depth 80, 220 and 333 nm were embossed onto polycaprolactone discs. Bone ...marrow–derived mesenchymal stromal cells were seeded onto polycaprolactone discs, suspended in media and incubated. Samples were fixed after 3 and 28 days. Cells were stained for the adhesion molecule vinculin and the osteogenic transcription factor RUNX2 after 3 days. Adhesion was lowest on planar controls and it was the shallowest, and 80-nm-deep pits supported optimal adhesion formation. Deep pits (80 and 220 nm) induced most RUNX2 accumulation. After 28 days, osteocalcin and osteopontin expression were used as markers of osteoblastic differentiation. Deep pits (220 nm) produced cells with the highest concentrations of osteopontin and osteocalcin. All topographies induced higher expression levels than controls. We demonstrated stimulation of osteogenesis in a heterogeneous population of mesenchymal stromal cells. All nanopit depths gave promising results with an optimum depth of 220 nm after 28 days. Nanoscale modification of implant surfaces could optimise fracture union or osteointegration.
Objective The purpose of this study was to capture the preoperative plans of expert hepato-pancreato-biliary (HPB) surgeons with the goal of finding consistent aspects of the preoperative planning ...process. Design HPB surgeons were asked to think aloud when reviewing 4 preoperative computed tomography scans of patients with distal pancreatic tumors. The imaging features they identified and the planned actions they proposed were tabulated. Surgeons viewed the tabulated list of imaging features for each case and rated the relevance of each feature for their subsequent preoperative plan. Average rater intraclass correlation coefficients were calculated for each type of data collected (imaging features detected, planned actions reported, and relevance of each feature) to establish whether the surgeons were consistent with one another in their responses. Average rater intraclass correlation coefficient values greater than 0.7 were considered indicative of consistency. Setting Division of General Surgery, University of Toronto. Participants HPB surgeons affiliated with the University of Toronto. Results A total of 11 HPB surgeons thought aloud when reviewing 4 computed tomography scans. Surgeons were consistent in the imaging features they detected but inconsistent in the planned actions they reported. Of the HPB surgeons, 8 completed the assessment of feature relevance. For 3 of the 4 cases, the surgeons were consistent in rating the relevance of specific imaging features on their preoperative plans. Conclusion These results suggest that HPB surgeons are consistent in some aspects of the preoperative planning process but not others. The findings further our understanding of the preoperative planning process and will guide future research on the best ways to incorporate the teaching and evaluation of preoperative planning into surgical training.
Surgical judgment has been an elusive construct to define, let alone teach or assess. A recent study has characterized a phenomenon called slowing down when you should, and suggests it is a hallmark ...for operative judgment. This research highlights areas where surgical judgment can be identified and therefore taught more explicitly in the operating room. Through the identification of these slowing-down moments and an understanding of how control is negotiated between surgeon and trainee during these moments, this article uses several theoretic frameworks to understand how teaching judgment in the operating room can be optimized.
Meeting report - building a centrosome Baffet, Alexandre D; Martin, Carol-Anne; Scarfone, Ilaria ...
Journal of cell science,
08/2013, Letnik:
126, Številka:
Pt 15
Journal Article
Recenzirano
Odprti dostop
Located in the 16th century Wiston House in West Sussex, UK, the 'Building a Centrosome' Workshop was organised by The Company of Biologists and chaired by Fanni Gergely and David Glover (University ...of Cambridge). Held in March 2013, the Workshop gathered together many of the leaders in the field of centrosome biology, as well as postdocs and students who were given the opportunity to meet and interact with many of the scientists who inspired their early careers. The diverse range of speakers provided a multi-disciplinary forum for the exchange of ideas, and gave fresh impetus to tackling outstanding questions related to centrosome biology. Here, we provide an overview of the meeting and highlight the main themes that were discussed.
Pathophysiology of hypertension secondary to obesity García Casilimas, Guihovany Alberto; Martin, Daniel Augusto; Martínez, María Alejandra ...
Archivos de cardiología de México,
2017 Oct - Dec, 20171001, Letnik:
87, Številka:
4
Journal Article
Recenzirano
Odprti dostop
The obesity is a problem with a high morbidity and mortality all over the world. It has now been designated as a cardiovascular risk factor. It often predisposes the development of many diseases that ...reduce quality of life, such as hypertension, dyslipidaemia, and diabetes. These diseases are associated with some of the criteria that should be considered in the diagnosis of metabolic syndrome. During this review, explanations will be presented on the relationship between obesity, metabolic syndrome, and the development of hypertension from neurohumoral, biochemical and mechanical concepts.
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