• Caspersen Potter posted an update 1 month, 3 weeks ago

    Mutations in genes directly implicated in mitochondrial functioning (like Parkin and PINK1) are responsible for rare genetic forms of the disease. A close connection between alpha-synuclein accumulation and mitochondrial dysfunction has been observed. Finally, mitochondria are involved also in atypical parkinsonisms, in particular multiple system atrophy. The available knowledge is still not sufficient to clearly state whether mitochondrial dysfunction plays a primary role in the very initial stages of these diseases or is secondary to other phenomena. However, the presented data strongly support the hypothesis that whatever the initial cause of neurodegeneration is, mitochondrial impairment has a critical role in maintaining and fostering the neurodegenerative process.Purpose Non-invasive high-grade (HG) bladder cancer is a heterogeneous disease that is characterized insufficiently. First-line Bacillus Calmette-Guérin instillation fails in a substantial amount of cases and alternative bladder-preserving treatments are limited, underlining the need to promote a further molecular understanding of non-invasive HG lesions. Here, we characterized pure HG papillary urothelial bladder cancer (pure pTa HG), a potential subgroup of non-invasive HG bladder carcinomas, with regard to molecular subtype affiliation and potential for targeted therapy. Methods An immunohistochemistry panel comprising luminal (KRT20, ERBB2, ESR2, GATA3) and basal (KRT5/6, KRT14) markers as well as p53 and FGFR3 was used to analyze molecular subtype affiliations of 78 pure pTa HG/papillary pT1(a) HG samples. In 66 of these, ERBB2 fluorescence in situ hybridization was performed. Additionally, targeted sequencing (31 genes) of 19 pTa HG cases was conducted, focusing on known therapeutic targets or those described to predict response to targeted therapies noted in registered clinical trials or that are already approved. Results We found that pure pTa HG/papillary pT1(a) HG lesions were characterized by a luminal-like phenotype associated with frequent (58% of samples) moderate to high ERBB2 protein expression, rare FGFR3 alterations on genomic and protein levels, and a high frequency (89% of samples) of chromatin-modifying gene alterations. Of note, 95% of pTa HG/papillary pT1 HG cases harbored at least one potential druggable genomic alteration. Conclusions Our data should help guiding the selection of targeted therapies for investigation in future clinical trials and, additionally, may provide a basis for prospective mechanistic studies of pTa HG pathogenesis.The coronavirus SARS-CoV-2 (COVID-19) outbreak is having a profound impact on the management of patients with cancer. In this review, we comprehensively investigate the various aspects of cancer care during the pandemic, taking advantage of data generated in Asia and Europe at the frontline of the COVID-19 pandemic spread. Cancer wards have been subjected to several modifications to protect patients and healthcare professionals from COVID-19 infection, while attempting to maintain cancer diagnosis, therapy, and research. In this setting, the management of COVID-19 infected patients with cancer is particularly challenging. We also discuss the direct and potential remote impacts of the global pandemic on the mortality of patients with cancer. As such, the indirect impact of the pandemic on the global economy and the potential consequences in terms of cancer mortality are discussed. As the infection is spreading worldwide, we are obtaining more knowledge on the COVID-19 pandemic consequences that are currently impacting and may continue to further challenge cancer care in several countries.Background Epidermal growth factor receptor (EGFR) mutation testing is recommended for selecting patients with non-squamous non-small cell lung cancer (NSCLC) for EGFR tyrosine kinase inhibitor drug treatment. Objective The objective of this article was to systematically review available evidence on the utilisation and determinants of EGFR mutation testing of patients with NSCLC in routine clinical practice. Patients and methods Searches were made of five electronic databases (Web of Science, MEDLINE [Ovid], Science Direct, EMBASE and Scopus), bibliographies of relevant articles, studies that cited included studies and relevant cancer websites. Studies were included if they (1) reported the rate of uptake of EGFR testing in patients with NSCLC; (2) were conducted in routine clinical practice settings; (3) were published in English prior to July 2017; and (4) had full text available. Studies were appraised using the STROBE and the National Institutes of Health (National Heart, Lung and Blood Institute) checklirmer/no smoking; advanced stage of lung cancer; adenocarcinoma histology; better mobility; radiation therapy; available tissue specimen; and private insurance. Among 16,146 tested patients, EGFR mutations were detected in 4328 patients (26.8%). However, estimates of mutation prevalence were biased by incomplete and selective testing in many studies. Conclusions The uptake of EGFR mutation testing of patients with NSCLC is suboptimal in many parts of the world. Incomplete uptake of testing is fuelled by selective testing referral practices, sample limitations, and funding constraints.Purpose The implantation of non-absorbable meshes is the gold standard technique for ventral hernia (VH) repairs. However, emergency surgeries are often related to contaminated/infected fields, where the implantation of prosthetic materials may not be recommendable. Our aim was to evaluate the results of polyvinylidene fluoride (PVDF) meshes used for contaminated and/or complicated VH repairs in the acute setting. Methods We conducted a retrospective analysis of patients with VH who underwent emergency surgery involving PVDF meshes, in a tertiary hospital (from November 2013 to September 2019). We analyzed postoperative complications and 1-year recurrence rates. We evaluated the relationships between contamination grade, mesh placement, infectious complications, and recurrences. Results We gathered data on 123 patients; their mean age was 62.3 years, their mean BMI was 31.1 kg/m2, and their mean CeDAR index was 51.6. 96.4% of patients had a grade 2-3 ventral hernia according to the Rosen index. The mean defect width was 8 cm (IQR 2-18). 93 cases (75.6%) were described as contaminated or dirty surgeries. A PVDF mesh was placed using an IPOM technique in 56.3% of cases, and via interposition location in 39.9%. The one-month recurrence rate was 5.7% and recurrence after one year was 19.1%. The overall mortality rate was 27.6%. Risk of recurrence was related to patients with a Rosen score over 2 (p less then 0.001), as well as with postoperative SSI (p = 0.045). Higher recurrence rates were not related to PVDF mesh placement. Conclusion The use of PVDF meshes for emergency VH repairs in contaminated surgeries seems safe and useful, with reasonable recurrence rates, and acceptable infectious complication rates, similar to those published in the literature.The most frequent pancreatic cysts in patients of developmental age are pseudocysts, neoplastic cysts, posttraumatic cysts, and parasitic cysts. Retention cysts, duplication cysts, and congenital cysts are called true cysts. Among the true cysts, congenital cysts are very rare and include 1% of all pancreatic cysts. The finding of true congenital pancreatic cysts in children under 3 years represents a very rare event; less than 30 have been described in the literature. We describe the case of a 3-year-old male who came to our observation for abdominal pain and underwent an abdomen ultrasound examination. The ultrasound examination showed unilocular sub-centimeter cystic lesions, distributed throughout the pancreatic parenchyma. The patient was, therefore, not subjected to any treatment, and after a few days, the symptoms regressed spontaneously. This description probably represents the first case in the literature of “congenital multicystic disease” of the pancreas.Fluctuating viscoelasticity for conformation-tensor-based models is studied at equilibrium, in simple-shear deformation, and in uniaxial extension. 4-Aminobutyric price The models studied are the upper-convected Maxwell model, the FENE-P model with finite chain-extensibility, and the Giesekus model with anisotropic drag. Using numerical simulations, the models are compared in detail both with each other and with analytical predictions for the Maxwell model. At equilibrium, the models differ only marginally, both in terms of static and dynamic characteristics. When deformed, the average mechanical response of the Maxwell model is unaffected by the strength of thermal fluctuations, while the mechanical response of the FENE-P and Giesekus models show a slight decrease the stronger the fluctuations in simple shear, whereas the decrease in uniaxial extension is marginal. For all models, the standard deviation of the mechanical response increases with increasing strength of fluctuations, and the magnitude of the standard deviation relative to the average for given fluctuation strength generally decreases the stronger the deformation, this effect being stronger for uniaxial extension than for simple-shear deformation.Purpose Local subacromial infiltration with steroids is a common method of treatment of subacromial impingement syndrome. However, the use of steroids has concerns like tendon rupture, articular cartilage changes and infections. Local NSAIDs infiltration has recently been tried in literature. This study compares the effect of subacromial injections of ketorolac with steroids. Methods A randomized controlled study was planned with 35 patients in each group. Patients in group-1 were infiltrated with subacromial ketorolac (60 mg with 2% lignocaine) and in group-2 with a steroid (methylprednisolone-40 mg with 2% lignocaine). A similar rehabilitation protocol was followed, and clinical outcomes were analyzed using visual analog scale (VAS) for pain and shoulder pain and disability score (SPADI) and range of motion at one-month and three-months follow-up. Results Total data of 67 patients were analyzed, as three patients were lost to follow-up. In group 1, mean VAS improved from 7.9 [Formula see text] 0.95 to 3.19 [Formula see text] 0.81 (p less then 0.001) and SPADI improved from 61.41 [Formula see text] 11.86 to 28.91 [Formula see text] 9.06 (p less then 0.001) at three months, respectively. In group 2, mean VAS improved from 8.05 [Formula see text] 0.94 to 2.9 [Formula see text] 0.64 (p less then 0.001) and SPADI improved from 63.45 [Formula see text] 9.64 to 25.32 [Formula see text] 6.87 (p less then 0.001) at three months, respectively. However, there were no differences in functional outcomes between the groups (p = 0.21 for VAS, p = 0.16 for SPADI). Conclusion Subacromial ketorolac infiltration has an equivalent outcome as that of steroid infiltration. Ketorolac could be considered as a reasonable alternative to steroids in cases where it is contraindicated.Context A substantial number of patients undergoing bariatric surgery are prescribed psychopharmacological medication. However, the impact of concomitant psychopharmacological medication on the frequency of relevant vitamin deficiencies in postoperative follow-up is not known. Methods Five hundred twenty-four patients with obesity who underwent bariatric surgery (January 2004 to September 2018) with follow-up of at least 12 months, were included in retrospective analysis. Postoperative follow-up visits between January 2015 and September 2019 were analyzed. Anthropometric and laboratory data were analyzed at the first documented follow-up visit after on average 39.5 ± 37.3 months and at every following visit during the observation period. Patients with prescribed psychopharmacological drugs (PD) were compared with patients without (control group, CON). Results Psychopharmacological medication was documented in 25% (132) of patients. In 59 patients documented prescription of more than one psychiatric drug was found, whereas psychopharmacological monotherapy was found in 73 patients.