Objective:Contemporary prostate cancer(PCa)screening modalities such as prostate specific antigen(PSA)and digital rectal examination(DRE)are limited in their ability to predict the detection of clinically significant ...Objective:Contemporary prostate cancer(PCa)screening modalities such as prostate specific antigen(PSA)and digital rectal examination(DRE)are limited in their ability to predict the detection of clinically significant disease.Multi-parametric magnetic resonance imaging(mpMRI)of the prostate has been explored as a staging modality for PCa.Less is known regarding its utility as a primary screening modality.We examined our experience with mpMRI as both a screening and staging instrument.Methods:mpMRI studies performed between 2012 and 2014 in patients without PCa were cross-referenced with transrectal ultrasonography(TRUS)biopsy findings.Statistical analyses were performed to determine association of mpMRI findings with overall cancer diagnoses and clinically significant(Gleason score≥7)disease.Subgroup analyses were then performed on patients with a history of prior negative biopsy and those without a history of TRUS biopsy.mpMRI studies were also cross-referenced with RP specimens.Statistical analyses determined predictive ability of extracapsular extension(ECE),seminal vesicle involvement(SVI),and pathologic evidence of clinically significant disease(Gleason score7).Results:Four hundred biopsy naive or prior negative biopsy patients had positive mpMRI studies.Overall sensitivity,specificity,positive and negative predictive values were 94%,37%,58%,and 87%,respectively and 95%,31%,42%,and 93%,respectively for overall cancer detection and Gleason score≥7 disease.In patients with no prior biopsy history,mpMRI sensitivity,specificity,positive and negative predictive values were 94%,36%,65%,and 82%,for all cancers,and 95%,30%,50%,and 89%for Gleason score7 lesions,respectively.In those with prior negative biopsy sensitivity,specificity,positive and negative predictive values were 94%,37%,52%,and 90% for all cancers,and 96%,32%,36%,and 96% for Gleason score7 lesions,respectively.Seventy-four patients underwent radical prostatectomy(RP)after mpMRI.Lesion size on mpMRI correlated with the presence of Gleason score7 cancers(p Z 0.005).mpMRI sensitivity,specificity,positive and negative predictive values were 84%,39%,81%,and 44% respectively,for Gleason7 cancer.For ECE and SVI,sensitivity and specificity were 58% and 98% and 44% and 97%,respectively.Conclusion:mpMRI is an accurate predictor of TRUS biopsy and RP outcomes.mpMRI has significant potential to change PCa management,particularly in the screening population,in whom a significant proportion may avoid TRUS biopsy.Further studies are necessary to determine how mpMRI should be incorporated into the current PCa screening and staging paradigms.展开更多
Atopic dermatitis(AD)and narcolepsy type 1(NT1)are two distinct diseases that have not been classically shown to be related.The potential connection between the known immunological aetiology of AD and the proposed aut...Atopic dermatitis(AD)and narcolepsy type 1(NT1)are two distinct diseases that have not been classically shown to be related.The potential connection between the known immunological aetiology of AD and the proposed autoimmune pathophysiology of dysregulation in NT1;however,is the subject of ongoing speculation and debate with advances in gene sequencing and technology.Here,we present a case of a patient with concomitant refractory AD and NT1 and review the current research on their immunological relationship and the challenges in management relative to disease burden and psychiatric comorbidities.展开更多
Prolonged extra-oral period in dental avulsion is often associated with loss of viability of Periodontal fibroblasts (PDLF) and increased risk of ankylosis. Root surface treatment with bioactive agents to reduce the r...Prolonged extra-oral period in dental avulsion is often associated with loss of viability of Periodontal fibroblasts (PDLF) and increased risk of ankylosis. Root surface treatment with bioactive agents to reduce the risk of ankylosis can be a potential strategy. The objective of the study was to investigate the impact of an engineered chitosan nanoparticles (CSNP), photosensitizer Rose Bengal (RB) functionalized CSNP (CSRB) and sustained dexamethasone (CSDEX) releasing CSNP for application in management of delayed replantation of avulsed teeth. The 3D PDLF-macrophage (Mϕ) collagen model was developed and exposed to LPS, MCSF, RANKL with and without CSDEX/CSNP. Immunofluorescence and cytokine analysis was done at 2 and 7 days to assess cellular interactions. Maxillary right incisors in male Wistar rats were extracted, exposed to extraoral dry or LPS for 1 h and treated with or without CSDEX/CSRB for 1 min before replantation. Rats were euthanized after 21 days for micro-CT, TRAP, and immunofluorescence analysis. CSDEX/CSNP treatment in 3D model significantly reduced CD80, NFATc1, STAT6 and increased CD206 and periostin expression (p < 0.05). TNFα, MMP9 was downregulated and IL10, TGFβ1, MMP2 upregulated with CSDEX/CSNP (p < 0.05). CSDEX/CSRB in animal study significantly reduced resorption, ankylosis, TRAP activity and osteocalcin expression and increased periostin (p<0.05). CSDEX demonstrated higher anti-inflammatory activity by downregulating TNFα, while CSNP upregulated TGFβ1, periostin, and downregulated MMP9. The combination of matrix stabilization with CSRB with periostin upregulation and sustained releasing CSDEX showed potential for hampering root resorption and ankylosis in dental avulsion.展开更多
Review articles can be extremely valuable.They synthesize information for readers,often provide clarity and valuable insights into a topic;and good review articles tend to be cited frequently.Review articles do not re...Review articles can be extremely valuable.They synthesize information for readers,often provide clarity and valuable insights into a topic;and good review articles tend to be cited frequently.Review articles do not require Institutional Review Board(IRB)approval if the data reviewed are public(including private and government databases)and if the articles reviewed have received IRB approval previously.展开更多
Complete intracorporeal urinar y diversion(ICUD)with an orthotopic neobladder is an emerging procedure.The objective of this article was to assess retrospectively the urodynamic and continence results after robot-assi...Complete intracorporeal urinar y diversion(ICUD)with an orthotopic neobladder is an emerging procedure.The objective of this article was to assess retrospectively the urodynamic and continence results after robot-assisted radical cystectomy(RARC)and ICUD with a modified orthotopic Studer neobladder.After a median follow-up time of 11 months,all patients were socially continent(≤1 pad)at daytime.Median Pouch capacity was 404 ml with a median postvoid residual volume of 0 ml.All patients stated that they would choose the same type of urinary diversion again.RARC and ICUD with orthotopic neobladder provides promising functional and urodynamic results with high patient satisfaction.展开更多
Macrophages(MQ)are major constituents of chronically inflamed periapical tissues in apical periodontitis.This study aimed to investigate the immunomodulatory effect of engineered bioactive chitosan-based nanoparticles...Macrophages(MQ)are major constituents of chronically inflamed periapical tissues in apical periodontitis.This study aimed to investigate the immunomodulatory effect of engineered bioactive chitosan-based nanoparticles(CSnp)antibiofilm medication on MQ cocultured with periodontal ligament fibroblasts(PdLF).Cells viability,spreading,PdLF migration,and intracellular CSnp uptake were characterized.Tandem Mass Tag-based proteomics was applied to analyze MQ global protein expression profiles after interaction with Enterococcus faecalis biofilm,CSnp-treated biofilm,and CSnp.Secreted inflammatory mediators were analyzed.Following bioinformatics analyses,candidate proteins were validated via targeted proteomics.CSnp maintained cells viability,increased MQ spreading,and PdLF migration(p<0.05).Transmission electron micrographs demonstrated CSnp internalization via macropinocytosis,clathrin-mediated endocytosis,and phagocytosis.Proteomic analysis revealed that CSnp-treated biofilm upregulated proteins(>1.5-folds,p<0.05)showed functional enrichment in the pathway of metal sequestration by antimicrobial proteins,while downregulated proteins showed enrichment in ferroptosis.CSnp upregulated proteins exhibiting antioxidant and immunoregulatory properties.Upregulation of SERPINB1 by CSnp(>1.5-folds,p<0.05)was validated.CSnp-treated biofilm reduced pro-inflammatory IL-1β and nitric oxide but enhanced anti-inflammatory IL-10 and TGF-β1(p<0.05).Internalized engineered bioactive CSnp reprogrammed MQ proteomic and cytokine profiles to modulate biofilm-mediated inflammation,and prompted PdLF migration,emphasizing its potential to regulate healing process in the treatment of apical periodontitis.展开更多
Background During the COVID-19 pandemic,decreased volumes of stroke admissions and mechanical thrombectomy were reported.The study’s objective was to examine whether subarachnoid haemorrhage(SAH)hospitalisations and ...Background During the COVID-19 pandemic,decreased volumes of stroke admissions and mechanical thrombectomy were reported.The study’s objective was to examine whether subarachnoid haemorrhage(SAH)hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.Methods We conducted a cross-sectional,retrospective,observational study across 6 continents,37 countries and 140 comprehensive stroke centres.Patients with the diagnosis of SAH,aneurysmal SAH,ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases,10th Revision,codes.The 3-month cumulative volume,monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before(1 year and immediately before)and during the pandemic,defined as 1 March-31 May 2020.The prior 1-year control period(1 March-31 May 2019)was obtained to account for seasonal variation.Findings There was a significant decline in SAH hospitalisations,with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic,representing a relative decline of 22.5%(95%CI−24.3%to−20.7%,p<0.0001).Embolisation of ruptured aneurysms declined with 1170-1035 procedures,respectively,representing an 11.5%(95%CI−13.5%to−9.8%,p=0.002)relative drop.Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations,a 24.9%relative decline(95%CI−28.0%to−22.1%,p<0.0001).A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1%(95%CI 32.3%to 50.6%,p=0.008)despite a decrease in SAH admissions in this tertile.Interpretation There was a relative decrease in the volume of SAH hospitalisations,aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic.These findings in SAH are consistent with a decrease in other emergencies,such as stroke and myocardial infarction.展开更多
文摘Objective:Contemporary prostate cancer(PCa)screening modalities such as prostate specific antigen(PSA)and digital rectal examination(DRE)are limited in their ability to predict the detection of clinically significant disease.Multi-parametric magnetic resonance imaging(mpMRI)of the prostate has been explored as a staging modality for PCa.Less is known regarding its utility as a primary screening modality.We examined our experience with mpMRI as both a screening and staging instrument.Methods:mpMRI studies performed between 2012 and 2014 in patients without PCa were cross-referenced with transrectal ultrasonography(TRUS)biopsy findings.Statistical analyses were performed to determine association of mpMRI findings with overall cancer diagnoses and clinically significant(Gleason score≥7)disease.Subgroup analyses were then performed on patients with a history of prior negative biopsy and those without a history of TRUS biopsy.mpMRI studies were also cross-referenced with RP specimens.Statistical analyses determined predictive ability of extracapsular extension(ECE),seminal vesicle involvement(SVI),and pathologic evidence of clinically significant disease(Gleason score7).Results:Four hundred biopsy naive or prior negative biopsy patients had positive mpMRI studies.Overall sensitivity,specificity,positive and negative predictive values were 94%,37%,58%,and 87%,respectively and 95%,31%,42%,and 93%,respectively for overall cancer detection and Gleason score≥7 disease.In patients with no prior biopsy history,mpMRI sensitivity,specificity,positive and negative predictive values were 94%,36%,65%,and 82%,for all cancers,and 95%,30%,50%,and 89%for Gleason score7 lesions,respectively.In those with prior negative biopsy sensitivity,specificity,positive and negative predictive values were 94%,37%,52%,and 90% for all cancers,and 96%,32%,36%,and 96% for Gleason score7 lesions,respectively.Seventy-four patients underwent radical prostatectomy(RP)after mpMRI.Lesion size on mpMRI correlated with the presence of Gleason score7 cancers(p Z 0.005).mpMRI sensitivity,specificity,positive and negative predictive values were 84%,39%,81%,and 44% respectively,for Gleason7 cancer.For ECE and SVI,sensitivity and specificity were 58% and 98% and 44% and 97%,respectively.Conclusion:mpMRI is an accurate predictor of TRUS biopsy and RP outcomes.mpMRI has significant potential to change PCa management,particularly in the screening population,in whom a significant proportion may avoid TRUS biopsy.Further studies are necessary to determine how mpMRI should be incorporated into the current PCa screening and staging paradigms.
文摘Atopic dermatitis(AD)and narcolepsy type 1(NT1)are two distinct diseases that have not been classically shown to be related.The potential connection between the known immunological aetiology of AD and the proposed autoimmune pathophysiology of dysregulation in NT1;however,is the subject of ongoing speculation and debate with advances in gene sequencing and technology.Here,we present a case of a patient with concomitant refractory AD and NT1 and review the current research on their immunological relationship and the challenges in management relative to disease burden and psychiatric comorbidities.
基金American Association of Endodontists Foundation(#1208771)Natural Sciences and Engineering Research Council of Canada(Discovery grant)(AK-RGPIN-2020-05844)Canada Research Chair Program,and Dr.Lloyd and Mrs.Kay Chapman Chairship.
文摘Prolonged extra-oral period in dental avulsion is often associated with loss of viability of Periodontal fibroblasts (PDLF) and increased risk of ankylosis. Root surface treatment with bioactive agents to reduce the risk of ankylosis can be a potential strategy. The objective of the study was to investigate the impact of an engineered chitosan nanoparticles (CSNP), photosensitizer Rose Bengal (RB) functionalized CSNP (CSRB) and sustained dexamethasone (CSDEX) releasing CSNP for application in management of delayed replantation of avulsed teeth. The 3D PDLF-macrophage (Mϕ) collagen model was developed and exposed to LPS, MCSF, RANKL with and without CSDEX/CSNP. Immunofluorescence and cytokine analysis was done at 2 and 7 days to assess cellular interactions. Maxillary right incisors in male Wistar rats were extracted, exposed to extraoral dry or LPS for 1 h and treated with or without CSDEX/CSRB for 1 min before replantation. Rats were euthanized after 21 days for micro-CT, TRAP, and immunofluorescence analysis. CSDEX/CSNP treatment in 3D model significantly reduced CD80, NFATc1, STAT6 and increased CD206 and periostin expression (p < 0.05). TNFα, MMP9 was downregulated and IL10, TGFβ1, MMP2 upregulated with CSDEX/CSNP (p < 0.05). CSDEX/CSRB in animal study significantly reduced resorption, ankylosis, TRAP activity and osteocalcin expression and increased periostin (p<0.05). CSDEX demonstrated higher anti-inflammatory activity by downregulating TNFα, while CSNP upregulated TGFβ1, periostin, and downregulated MMP9. The combination of matrix stabilization with CSRB with periostin upregulation and sustained releasing CSDEX showed potential for hampering root resorption and ankylosis in dental avulsion.
文摘Review articles can be extremely valuable.They synthesize information for readers,often provide clarity and valuable insights into a topic;and good review articles tend to be cited frequently.Review articles do not require Institutional Review Board(IRB)approval if the data reviewed are public(including private and government databases)and if the articles reviewed have received IRB approval previously.
文摘Complete intracorporeal urinar y diversion(ICUD)with an orthotopic neobladder is an emerging procedure.The objective of this article was to assess retrospectively the urodynamic and continence results after robot-assisted radical cystectomy(RARC)and ICUD with a modified orthotopic Studer neobladder.After a median follow-up time of 11 months,all patients were socially continent(≤1 pad)at daytime.Median Pouch capacity was 404 ml with a median postvoid residual volume of 0 ml.All patients stated that they would choose the same type of urinary diversion again.RARC and ICUD with orthotopic neobladder provides promising functional and urodynamic results with high patient satisfaction.
文摘本文是由Robert T.Sataloff,Ehab Y.Hanna,李大庆教授等20余位耳鼻咽喉头颈外科领域知名期刊主编共同撰写的一篇针对系统评价等不同类型综述文章标准及复杂性分析的述评类文章。该文章将于2021年7月在包括《世界耳鼻咽喉头颈外科杂志(英文)》,Journal of Voice,Head&Neck,American Journal of Rhinology&Allergy,The Laryngoscope等20余本国际知名耳鼻咽喉头颈外科期刊同时以英文版本刊出,为了便于中国读者对该内容进行深入了解,在获得相应授权后,本刊特别邀请刘争教授团队对该文章进行翻译,同期在本刊以中文版本刊登。希望本文对广大读者在撰写综述类文章时有所裨益。
基金supported in part by a research grant from the American Association of Endodontists Foundation[#509641]the Natural Sciences and Engineering Research Council of Canada:Discovery Grant-AK[RGPIN-2020-05844]supported by a scholarship funded by the Egyptian Ministry of Higher Education.
文摘Macrophages(MQ)are major constituents of chronically inflamed periapical tissues in apical periodontitis.This study aimed to investigate the immunomodulatory effect of engineered bioactive chitosan-based nanoparticles(CSnp)antibiofilm medication on MQ cocultured with periodontal ligament fibroblasts(PdLF).Cells viability,spreading,PdLF migration,and intracellular CSnp uptake were characterized.Tandem Mass Tag-based proteomics was applied to analyze MQ global protein expression profiles after interaction with Enterococcus faecalis biofilm,CSnp-treated biofilm,and CSnp.Secreted inflammatory mediators were analyzed.Following bioinformatics analyses,candidate proteins were validated via targeted proteomics.CSnp maintained cells viability,increased MQ spreading,and PdLF migration(p<0.05).Transmission electron micrographs demonstrated CSnp internalization via macropinocytosis,clathrin-mediated endocytosis,and phagocytosis.Proteomic analysis revealed that CSnp-treated biofilm upregulated proteins(>1.5-folds,p<0.05)showed functional enrichment in the pathway of metal sequestration by antimicrobial proteins,while downregulated proteins showed enrichment in ferroptosis.CSnp upregulated proteins exhibiting antioxidant and immunoregulatory properties.Upregulation of SERPINB1 by CSnp(>1.5-folds,p<0.05)was validated.CSnp-treated biofilm reduced pro-inflammatory IL-1β and nitric oxide but enhanced anti-inflammatory IL-10 and TGF-β1(p<0.05).Internalized engineered bioactive CSnp reprogrammed MQ proteomic and cytokine profiles to modulate biofilm-mediated inflammation,and prompted PdLF migration,emphasizing its potential to regulate healing process in the treatment of apical periodontitis.
文摘Background During the COVID-19 pandemic,decreased volumes of stroke admissions and mechanical thrombectomy were reported.The study’s objective was to examine whether subarachnoid haemorrhage(SAH)hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.Methods We conducted a cross-sectional,retrospective,observational study across 6 continents,37 countries and 140 comprehensive stroke centres.Patients with the diagnosis of SAH,aneurysmal SAH,ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases,10th Revision,codes.The 3-month cumulative volume,monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before(1 year and immediately before)and during the pandemic,defined as 1 March-31 May 2020.The prior 1-year control period(1 March-31 May 2019)was obtained to account for seasonal variation.Findings There was a significant decline in SAH hospitalisations,with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic,representing a relative decline of 22.5%(95%CI−24.3%to−20.7%,p<0.0001).Embolisation of ruptured aneurysms declined with 1170-1035 procedures,respectively,representing an 11.5%(95%CI−13.5%to−9.8%,p=0.002)relative drop.Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations,a 24.9%relative decline(95%CI−28.0%to−22.1%,p<0.0001).A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1%(95%CI 32.3%to 50.6%,p=0.008)despite a decrease in SAH admissions in this tertile.Interpretation There was a relative decrease in the volume of SAH hospitalisations,aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic.These findings in SAH are consistent with a decrease in other emergencies,such as stroke and myocardial infarction.
