Robleswinther0461
Microsurgical procedures for reconstruction after resection of head and neck tumours have become standardised and reliable. Among them, the scapular free flap is used less often, mostly to avoid excessive operating times. We hypothesise that complex reconstructions after resection of oral squamous cell carcinoma (OSCC) are successful even with time-consuming free flaps such as the scapular free flap. In this retrospective, single-centre study, we used the evaluation of medical records to investigate the postoperative outcome of microvascular reconstruction after ablative surgery of OSCC. Associations among the categorical variables were analysed using Pearson's chi squared test or Fisher´s exact test. Among the continuous variables, the t test or Mann-Whitney U test were used as appropriate. For multivariate analysis, the logistic regression model was calculated. In the sample of 280 free flap reconstructions, we performed 142 radial forearm and 119 scapular free flaps. The American Society of Anesthesiology (ASA) score (p=0.006) and the duration of the operation (p=0.010) are independent factors which influence the need for operative revisions. The type of free flap is irrelevant for that. With 4.2% flap losses, scapular free flaps were successful; even in patients ≥ 70 years old (0 flap losses). Complex reconstructions after surgical resection of OSCC are successful even in aged patients. The scapular free flap is a good choice for mandibular reconstruction despite the time-consuming intraoperative repositioning of the patient. Quinoline-Val-Asp-Difluorophenoxymethylketone In an increasingly ageing group of patients, who have more vascular diseases, scapular free flaps could be a very successful alternative after ablative surgery of oral squamous cell carcinoma. Congenital midline nasal lesions are extremely rare, and nasal dermoids are their most common presentation. To the best of our knowledge, only two cases of a philtrum sinus with skull base extension have been reported previously. A 3-year-old boy presented to the maxillofacial department with a discharging upper lip sinus that had been present from birth. No other congenital abnormalities were reported. Initially this sinus was assumed to be blind-ended and excised under general anaesthetic, but the area then failed to heal. Radiological work-up showed a patent dermal sinus that extended from the infranasal region through the nasal septum into the basal aspect of the anterior cranial fossa. The patient was referred for multidisciplinary management. A high index of suspicion of nasofrontal dermoid should be exercised when a patient presents with an upper lip sinus and recurrent discharge, until it is proven otherwise. Brain aging is a complex process that includes atrophy, vascular injury, and a variety of age-associated neurodegenerative pathologies, together determining an individual's course of cognitive decline. While Alzheimer's disease and related dementias contribute to the heterogeneity of brain aging, these conditions themselves are also heterogeneous in their clinical presentation, progression, and pattern of neural injury. We reviewed studies that leveraged data-driven approaches to examining heterogeneity in Alzheimer's disease and related dementias, with a principal focus on neuroimaging studies exploring subtypes of regional neurodegeneration patterns. Over the past decade, the steadily increasing wealth of clinical, neuroimaging, and molecular biomarker information collected within large-scale observational cohort studies has allowed for a richer understanding of the variability of disease expression within the aging and Alzheimer's disease and related dementias continuum. Moreover, the availability of these large-scale datasets has supported the development and increasing application of clustering techniques for studying disease heterogeneity in a data-driven manner. In particular, data-driven studies have led to new discoveries of previously unappreciated disease subtypes characterized by distinct neuroimaging patterns of regional neurodegeneration, which are paralleled by heterogeneous profiles of pathological, clinical, and molecular biomarker characteristics. Incorporating these findings into novel frameworks for more differentiated disease stratification holds great promise for improving individualized diagnosis and prognosis of expected clinical progression, and provides opportunities for development of precision medicine approaches for therapeutic intervention. We conclude with an account of the principal challenges associated with data-driven heterogeneity analyses and outline avenues for future developments in the field. BACKGROUND Parkinson's disease (PD) and schizophrenia (SCZ) are heritable brain disorders that involve dysregulation of the dopaminergic system. Epidemiological studies have reported potential comorbidity between the disorders, and movement disturbances are common in patients with SCZ before treatment with antipsychotic drugs. Despite this, little is known about shared genetic etiology between the disorders. METHODS We analyzed recent large genome-wide association studies on patients with SCZ (N = 77,096) and PD (N = 417,508) using a conditional/conjunctional false discovery rate (FDR) approach to evaluate overlap in common genetic variants and improve statistical power for genetic discovery. Using a variety of biological resources, we functionally characterized the identified genomic loci. RESULTS We observed genetic enrichment in PD conditional on associations with SCZ and vice versa, indicating polygenic overlap. We then leveraged this cross-trait enrichment using conditional FDR analysis and identified 9 novel PD risk loci and 1 novel SCZ locus at conditional FDR less then .01. Furthermore, we identified 9 genomic loci jointly associated with PD and SCZ at conjunctional FDR less then .05. There was an even distribution of antagonistic and agonistic effect directions among the shared loci, in line with the insignificant genetic correlation between the disorders. Of 67 genes mapped to the shared loci, 65 are expressed in the human brain and show cell type-specific expression profiles. CONCLUSIONS Altogether, the study increases understanding of the genetic architectures underlying SCZ and PD, indicating that common molecular genetic mechanisms may contribute to overlapping pathophysiological and clinical features between the disorders.