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关键词： Pelvic exenteration   Recurrent disease   Gynecologic malignancy  

摘要： Objectives. To explore pre-operative factors and their impact on overall survival (OS) in a modern cohort of patients who underwent pelvic exenteration (PE) for gynecologic malignancies. Methods. A retrospective review was performed for all patients who underwent a PE from 1/1/2010 through 12/31/2018 at our institution. Inclusion criteria were exenteration due to recurrent or progressive carcinoma of the uterus, cervix, vagina or vulva, with histologically confirmed complete surgical resection of the malignancy. Exclusion criteria included PE for palliation of symptoms without recurrence, and for ovarian or rare histologic malignancies. Univariable and multivariable analysis were performed to identify factors predicting prolonged survival. Results. Overall, 71 patients met the inclusion criteria. Median age at time of exenteration was 62 years (range, 28-86 years). Vulvar cancer was the most common primary diagnosis (32%);30% had cervical cancer;23%, uterine cancer;15%, vaginal cancer. Median OS was 55.1 months (95% confidence interval (CI): 36-not estimable) with a median follow-up time of 40.8 months (95% CI: 1-116.1). On univariable analysis, age > 62 years (hazard ratio (HR) 2.71, 95% CI 1.27-5.79), American Society of Anesthesia (ASA) 3-4 (HR: 3.41 (95% CI 1.03-11.29), and vulvar cancer (HR 4.19 (95% CI 1.17-14.96) predicted worse OS. Tumor size and prior progression-free interval (PFI) did not meet statistical significance in OS analyses. On multivariable analysis, there were no significant factors associated with worse OS. Conclusions. PE performed with curative intent may be considered a treatment option in well-counseled, carefully selected patients, irrespective of tumor size and PFI before exenteration. (c) 2021 Elsevier Inc. All rights reserved.

摘要： Background: Fine-needle aspiration combined with the Bethesda System for Reporting Thyroid Cyto-pathology is indispensable in the diagnostic evaluation of thyroid nodules. Their increased detection over the last few decades mandates the determination of which thyroid nodules require surgical management for malignancy. This study examines the correlation of fine-needle aspiration to final histopathology of dominant thyroid nodules in a large series of surgical patients undergoing thyroidectomy at a single academic institution. Methods: A retrospective review of prospectively collected data of 1,228 patients who underwent fine-needle aspiration for a dominant thyroid nodule and thyroidectomy from a single institution between 2010 and 2019 was performed. The cases were stratified into all 6 Bethesda categories. Fine-needle aspiration results were compared to index thyroid nodule malignancy on final histopathology. Results: Of 1,228 patients who underwent thyroidectomy, the overall malignancy rate was 53%. When fine-needle aspiration was stratified by the Bethesda System for Reporting Thyroid Cytopathology, ma-lignancy rate was 29% for nondiagnostic;11% for benign;51% for atypia of undetermined significance/ follicular lesion of undetermined significance (AUS/FLUS);47% for follicular neoplasm/suspicious for follicular neoplasm (FN/SFN);84% for suspicious for malignancy (SFM);and 98% for malignant results on final histopathology. There was a false positive rate of 1% and false negative rate ranging from 7 to 11%. Conclusion: Fine-needle aspiration of a dominant thyroid nodule in patients who underwent thyroid-ectomy had an overall malignancy rate of 53%. False negative and false positive rates are within the reported range in surgical patient populations. The majority of patients with AUS/FLUS, FN/SFN and SFM results with underlying malignancy received the appropriate surgical resection. (c) 2021 Elsevier Inc. All rights reserved.

关键词： ZnONPs   Mosquito larvicidal   Antibacterial   Antioxidant   A549 cell line  

摘要： The present study pertained to biosynthesis, characterization and biomedical application (larvicidal, histopathology, antibacterial, antioxidant and anticancer activity) of Zinc oxide nanoparticles (ZnONPs) from Pleurotus djamor. The synthesized NPs were characterized using spectral and microscopic analyses and further confirmed by UV-Visible spectrophotometer with apeak of 350 nm. The ZnONPs showed strong antioxidant property (DPPH, H2O2 and ABTS(+) radical assay) and expressed good larval toxicity against Ae. aegypti and Cx. quinquefasciatus (IVth instar larvae) with the least LC50 and LC90 values (10.1, 25.6 and 14.4, 31.7 mg/l) after 24 h treatment, respectively. We noticed the morphological changes (damaged anal papillae area and the cuticle layers) in the treated larvae. For the antibacterial assay, the highest growth inhibition zone was recorded in C. diphteriae (28.6 +/- 0.3 mm), followed by P. fluorescens (27 +/- 0.5 mm) and S. aureus (26.6 +/- 1.5 mm). The in vitro cytotoxicity assay depicted a significant level of cytotoxic effects (LC50 values 42.26 mu g/ml) of ZnONPs against the A549 lung cancer cells, even at low dose. The overall findings of the study suggest that P. djamor had the ability for the biosynthesis of ZnONPs and could act as an alternative biomedical agent for future therapeutic applications in medical avenues.

关键词： active inflammation   appendix   chronic inflammation   microscopic colitis   ulcerative colitis  

摘要： Aims Appendiceal orifice mucosa often appears inflamed endoscopically, even when other colonic segments appear normal. Histological findings in biopsy samples taken from endoscopically abnormal mucosa may simulate a variety of inflammatory colitides. We performed this study to evaluate the clinical implications of inflammatory changes isolated to the appendiceal orifice. Methods and results In this double cohort study, biopsy samples from 26 histologically abnormal appendiceal orifices were reviewed. Twenty-five control cases were culled from endoscopically normal (n = 11) and abnormal (n = 14) appendiceal orifices that were histologically normal. Histological findings were correlated with presentation, medication history, findings at other colonic sites and clinical outcomes. Study cases displayed active inflammation (n = 12), chronic active inflammation (n = 13) or features simulating collagenous colitis (n = 1). Eighteen patients had biopsies taken from other colonic sites;these revealed benign polyps (n = 10) or displayed active (n = 4) or chronic active (n = 4) inflammation. All patients with findings isolated to the appendiceal orifice were asymptomatic at most recent clinical follow-up. Four of eight (50%) of the patients with inflammation in other biopsy samples were ultimately diagnosed with ulcerative colitis, in keeping with the well-established role of the appendix as a 'skip lesion' in that disorder. Control patients presented for screening colonoscopy (n = 19), iron deficiency anaemia (n = 3) or change in bowel habits (n = 3) and none reported gastrointestinal symptoms upon follow-up, regardless of the endoscopic appearance of the appendiceal orifice. Conclusion Isolated inflammation of the appendiceal orifice mucosa should not be regarded as a feature of evolving inflammatory bowel disease or other types of chronic colitis.

关键词： RNA modification   m6A   Tumor   Melanoma  

摘要： Methylation of N6-adenosine (m6A) is the most prevalent internal RNA modification and is especially common among the messenger RNAs. These m6A modifications regulate splicing, translocation, stability and translation of RNA through dynamic and reversible interactions with m6A-binding proteins, namely the writers, erasers and readers. RNA methyltransferases catalyze the m6A modifications, while demethylases reverse this methylation. Deregulation of the m6A modification process has been implicated in human carcinogenesis, including melanoma-which carries one of the highest mutant rates. In this review, we provide an up-to-date summary of m6A regulation and its biological impacts on normal and cancer cells, with emphasis on the deregulation of m6A modification and m6A regulators in melanoma. In addition, we highlight the prospective potential of exploiting m6A modification in the treatment of melanoma and non-cancer diseases.

关键词： Prostate cancer   Active surveillance   Radical prostatectomy   Upgrading  

摘要： Introduction: Current guidelines support active surveillance (AS) for select patients with favorable intermediate risk (FIR) prostate cancer (CaP). A significant proportion of FIR CaP patients undergoing surgical treatment are found to have evidence of adverse pathology. Our objective was to determine the incidence and predictors of pathologic upgrading in FIR AS patients undergoing radical prostatectomy. Materials and methods: The Surveillance, Epidemiology, and End Results Prostate with Watchful Waiting (WW) database was used to identify men younger than 80 years with National Comprehensive Cancer Network FIR CaP initially opting for AS and/or WW between 2010 and 2015 and subsequently underwent radical prostatectomy at least one year following diagnosis. Patients were assigned into one of three subgroups based on their intermediate risk factor: Gleason Score 7(3 + 4) (Group 1), prostate specific antigen level of 10-20 ng/ml (Group 2), and cT2b-c (Group 3). Pathologic upgrading was present in Group 1 if pathologic GS was 7 (4 + 3) or worse. For patients in Groups 2 and 3, upgrading occurred if pathologic GS was 7 (3 + 4) or worse. Oncologic and sociodemographic predictors of pathologic upgrading were evaluated univariable and multivariable logistic regression analysis. Results: 18,760 patients were identified. Pathologic upgrading occurred in 138 (13.3%), 59 (25.0%), and 8,011 (45.8%) patients in groups 1, 2, and 3 respectively. Pathologic downgrading occurred in 226 (21.7%) patients in group 1. Significant predictors of pathologic upgrading on multivariable analysis included older age at diagnosis: 70 to 79 vs. 40 to 49 years (Groups 1 and 3, P < 0.05), a more recent diagnosis: 2014 to2015 vs. 2010-2011 (Groups 2 and 3, P < 0.005), higher volume disease: 37.5% to 49.9% vs. 0% to 12.4% (Groups 2 and 3, P < 0.005), and clinically palpable disease (Groups 1 and 2, P < 0.05). Additional risk factors for upgrading included uninsured or Medicaid status, diagnosis in a W

关键词： pathologic hip fracture   pathologic femoral neck fracture   hemiarthroplasty   total hip arthroplasty   pathologic proximal femur fracture  

摘要： ABSTR A C T Background: Hemiarthroplasty (HA) and total hip arthroplasty (THA) have been widely discussed as treatment options for displaced osteoporotic femoral neck fractures. Pathologic femoral neck fractures from primary or metastatic tumors are comparatively rare and poorly investigated. The purpose of this study was to compare outcomes, complications, and perioperative survival for HA and THA in the treatment of pathologic femoral neck fractures of neoplastic etiology. Methods: A multicenter retrospective cohort study identified patients with pathologic femoral neck fractures treated with HA or THA from 2005 to 2018. Demographics, American Society of Anesthesiol-ogists classification, Charlson comorbidity index, Dorr classification, histopathologic diagnosis, and surgical data were compared. The primary outcome was reoperation. Secondary outcomes included 90 -day mortality, estimated blood loss, length of stay, periprosthetic fracture, periprosthetic joint infection, and Eastern Cooperative Oncology Group performance status. Results: There were 116 patients with HA and 48 patients with THA, with no differences between groups with regard to American Society of Anesthesiologists classification, Charlson comorbidity index, or Dorr classification. There were no differences between HA and THA in the primary outcome of reoperation (5.2% vs 4.2%, P = 1.00) or secondary outcomes of perioperative 90-day overall mortality (30.2% vs 25.0%, P = .51), estimated blood loss, transfusion rates, length of stay, discharge location, periprosthetic joint infection, periprosthetic fracture, or preoperative or postoperative Eastern Cooperative Oncology Group performance status. Conclusions: Both HA and THA are viable options for the treatment of patients with pathologic femoral neck fractures and demonstrated no differences in reoperations, complications, perioperative 90-day mortality, or functional outcome scores. Level of Evidence: Level III. (c) 2021 Published by Elsevier Inc.

关键词： sharp waves   ripples   replay   Alzheimer's disease  

摘要： Synapse loss and altered synaptic strength are thought to underlie cognitive impairment in Alzheimer's disease (AD) by disrupting neural activity essential for memory. While synaptic dysfunction in AD has been well characterized in anesthetized animals and in vitro, it remains unknown how synaptic transmission is altered during behavior. By measuring synaptic efficacy as mice navigate in a virtual reality task, we find deficits in interneuron connection strength onto pyramidal cells in hippocampal CA1 in the 5 relevant human familial mutations (5XFAD) of the mouse model of AD. These inhibitory synaptic deficits are most pronounced during sharp-wave ripples (SWRs), network oscillations important for memory that require inhibition. Indeed, 5XFAD mice exhibit fewer and shorter SWRs with impaired place cell reactivation. By showing inhibitory synaptic dysfunction in 5XFAD mice during spatial navigation behavior and suggesting a synaptic mechanism underlying deficits in network activity essential for memory, this work bridges the gap between synaptic and neural activity deficits in AD.

关键词： Temporal lobe epilepsy   Hippocampal sclerosis   Hippocampal subfield   Histopathology   Automated hippocampal volumetry  

摘要： The objectives of this study were 1) to histologically validate the hippocampal subfield volumetry based on T2weighted MRI, and 2) to explore its clinical impact on postsurgical memory function and seizure outcome in temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS). We analyzed the cases of 24 patients with medial TLE (12 left, 12 right) and HS who were preoperatively examined with T2-weighted high-resolution MRI. The volume of each hippocampal subfield was calculated with an automatic segmentation of hippocampal subfields (ASHS) program. Hippocampal sclerosis patterns were determined pathologically, and the cross-sectional area and neuronal cell density of the CA1 and CA4 subfields were calculated using tissue specimens. Pre- and postoperative memory evaluations based on the Wechsler Memory Scale-Revised (WMS-R) were performed. We compared the presurgical MRI-based volumes with the pathological measurements in each subfield and then compared them with the change in the patients' neurocognitive function. As a result, there was a significant relationship between the presurgical MRI-based volume of CA4/dentate gyrus (DG) and the cross-sectional area of CA4 calculated with tissue specimens (Spearman's rs = 0.482, p = 0.023), and a similar trend-level correlation was observed in CA1 (rs = 0.455, p = 0.058). Some of MRI-based or pathology-based parameters in the subfields preliminarily showed relationships with the postsurgical memory changes. In conclusion, automated subfield volumetry for patients with hippocampal sclerosis moderately reflects their subfield atrophy and might be useful to predict the postsurgical change of memory function in these patients.