Outcome of valve sparing root replacement for diverse indications

Objectives We report the mid-term outcomes of valve-sparing aortic root replacement (VSRR) in a cohort including patients with bicuspid aortic valve (BAV), connective tissue disorder (CTD), aortic dissection (AD), and congenital heart disease (CHD). Design. From 2005 to 2017, 174 patients underwent VSRR with the reimplantation technique. The mean age was 46 +/- 14 years. The mean follow-up time was 4.8 +/- 2.8 years. The indication for operation was aortic aneurysm for 127 (73%), aortic insufficiency (AI) for 38 (22%), and AD for 9 patients (5%). Preoperatively, 53 patients (31%) had >= moderate AI. BAV, CTD (Marfan or Loyes-Dietz), previous Ross procedure, or CHD was present in 57 (33%), 28 (16%), 7 (4%) and 12 patients (7%), respectively. Concomitant aortic valve repair was performed for 103 patients (59%). Results. Thirty-day mortality was zero. Four patients underwent aortic valve replacement (AVR) during follow-up. Kaplan-Meier estimates for survival, freedom from AVR, and freedom from >= moderate AI or reoperation were 96, 98, and 97% at 5 years. There was no difference in survival, freedom from AVR, or freedom from >= moderate AI or reoperation in patients with and without BAV, CTD, leaflet repair, or preoperative >= moderate AI. In Cox regression analysis, BAV, CTD, aortic valve repair, preoperative >= moderate AI, or aortic dimension were not risk factors for reoperation or valve dysfunction. Conclusions. Mid-term outcomes of VSRR for patients with diverse indications in terms of survival, reoperation rate, and valve dysfunction rate were excellent in a center with a limited annual volume of VSSR.Peer reviewe

AI Model for Prostate Biopsies Predicts Cancer Survival

An artificial intelligence (AI) algorithm for prostate cancer detection and grading was developed for clinical diagnostics on biopsies. The study cohort included 4221 scanned slides from 872 biopsy sessions at the HUS Helsinki University Hospital during 2016–2017 and a subcohort of 126 patients treated by robot-assisted radical prostatectomy (RALP) during 2016–2019. In the validation cohort (n = 391), the model detected cancer with a sensitivity of 98% and specificity of 98% (weighted kappa 0.96 compared with the pathologist’s diagnosis). Algorithm-based detection of the grade area recapitulated the pathologist’s grade group. The area of AI-detected cancer was associated with extra-prostatic extension (G5 OR: 48.52; 95% CI 1.11–8.33), seminal vesicle invasion (cribriform G4 OR: 2.46; 95% CI 0.15–1.7; G5 OR: 5.58; 95% CI 0.45–3.42), and lymph node involvement (cribriform G4 OR: 2.66; 95% CI 0.2–1.8; G5 OR: 4.09; 95% CI 0.22–3). Algorithm-detected grade group 3–5 prostate cancer depicted increased risk for biochemical recurrence compared with grade groups 1–2 (HR: 5.91; 95% CI 1.96–17.83). This study showed that a deep learning model not only can find and grade prostate cancer on biopsies comparably with pathologists but also can predict adverse staging and probability for recurrence after surgical treatment

AI Model for Prostate Biopsies Predicts Cancer Survival

An artificial intelligence (AI) algorithm for prostate cancer detection and grading was developed for clinical diagnostics on biopsies. The study cohort included 4221 scanned slides from 872 biopsy sessions at the HUS Helsinki University Hospital during 2016–2017 and a subcohort of 126 patients treated by robot-assisted radical prostatectomy (RALP) during 2016–2019. In the validation cohort (n = 391), the model detected cancer with a sensitivity of 98% and specificity of 98% (weighted kappa 0.96 compared with the pathologist’s diagnosis). Algorithm-based detection of the grade area recapitulated the pathologist’s grade group. The area of AI-detected cancer was associated with extra-prostatic extension (G5 OR: 48.52; 95% CI 1.11–8.33), seminal vesicle invasion (cribriform G4 OR: 2.46; 95% CI 0.15–1.7; G5 OR: 5.58; 95% CI 0.45–3.42), and lymph node involvement (cribriform G4 OR: 2.66; 95% CI 0.2–1.8; G5 OR: 4.09; 95% CI 0.22–3). Algorithm-detected grade group 3–5 prostate cancer depicted increased risk for biochemical recurrence compared with grade groups 1–2 (HR: 5.91; 95% CI 1.96–17.83). This study showed that a deep learning model not only can find and grade prostate cancer on biopsies comparably with pathologists but also can predict adverse staging and probability for recurrence after surgical treatment

Increased myeloid cell hypoxia-inducible factor-1 delays obliterative airway disease in the mouse

BACKGROUND: Obliterative bronchiolitis after lung transplantation is characterized by chronic airway inflammation leading to the obliteration of small airways. Hypoxia-inducible factor-1 (HIF-1) is a master regulator of cellular responses to hypoxia and inflammation. The Von Hippel-Lindau protein (pVHL) drives the degradation of oxygen-sensitive subunit HIF-1 alpha that controls the activity of HIF-1. We investigated the effect of myeloid cell targeted gene deletion of HIF-1 alpha or its negative regulator pVHL on the development of obliterative airway disease (OAD) in the recipients of tracheal allografts, a mouse model for obliterative bronchiolitis after lung transplantation. METHODS: Tracheal allografts were heterotopically transplanted from BALB/c donor mice to fully major histocompatibility complex mismatched recipient mice with HIF-1 alpha or VHL gene deletion in myeloid cells. The recipients were left non-immunosuppressed or received tacrolimus daily. Histologic, immunohistochemical, and real-time reverse transcription polymerase chain reaction analyses were performed at 3, 10, and 30 days. RESULTS: In the absence of immunosuppression, myeloid cell-specific VHL deficiency of the recipient mice improved epithelial recovery, decreased inflammatory cell infiltration and expression of pro-inflammatory cytokines, increased regulatory forkhead box P3 messenger RNA expression, and reduced OAD development in tracheal allografts. In the presence of tacrolimus immunosuppression, loss of HIF-1 alpha activity in myeloid cells of the recipient by HIF-1 alpha gene deletion accelerated OAD development in mouse tracheal allografts. CONCLUSIONS: Activity of the HIF-pathway affects the development of allograft rejection, and our results suggest that myeloid cell-specific VHL-deficiency that potentially increases HIF-activity decreases allograft inflammation and the subsequent development of OAD in mouse tracheal allografts. (C) 2016 International Society for Heart and Lung Transplantation. All rights reserved.Peer reviewe

Disability pension due to musculoskeletal diagnoses: importance of work-related factors in a prospective cohort study of Finnish twins

OBJECTIVES: The aim of this study was to investigate the impact of work-related risk factors for future disability pension (DP) due to musculoskeletal diagnoses and for a subgroup of these, namely, DP due to osteoarthritis. METHODS: For this prospective study of 16 028 Finnish twins born in 1911-1957 and employed at baseline, a postal questionnaire collected information in 1975 on work-related factors; follow-up data on DP was gathered through register linkages up to 2004. A series of proportional hazards (Cox) regression models were used to analyze the associations between work-related factors and the incidence of DP. RESULTS: During the 30-year follow-up, 1297 participants (8%) were granted DP due to musculoskeletal diagnoses, 376 of which were due to osteoarthritis. High stress of daily activities, monotonous work, physical workload (namely work including lifting and carrying or physically heavy work), several workplace changes, and unemployment displayed a strong association with DP due to musculoskeletal diagnoses that was not affected by familial factors, including genetics and shared environment. Additionally, standing work increased the risk for DP due to osteoarthritis. CONCLUSIONS: Uninfluenced by family background or other confounding factors, several work-related factors were identified as being strong and direct risk factors for DP due to musculoskeletal diagnoses.Peer reviewe

Self-Assembly of Amphiphilic Janus Dendrimers into Mechanically Robust Supramolecular Hydrogels for Sustained Drug Release

Peer reviewe

CD34+ cell mobilization, blood graft composition, and posttransplant recovery in myeloma patients compared to non-Hodgkinʼs lymphoma patients: results of the prospective multicenter Goa study

BACKGROUND Autologous stem cell transplantation is an established treatment option for patients with multiple myeloma (MM) or non-Hodgkin?s lymphoma (NHL). STUDY DESIGN AND METHODS In this prospective multicenter study, 147 patients with MM were compared with 136 patients with NHL regarding the mobilization and apheresis of blood CD34+ cells, cellular composition of infused blood grafts, posttransplant recovery, and outcome. RESULTS Multiple myeloma patients mobilized CD34+ cells more effectively (6.3???106/kg vs. 3.9???106/kg, p?=?0.001). The proportion of poor mobilizers (peak blood CD34+ cell count 100?days) nonrelapse mortality (NRM; 6% vs. 0%, p?=?0.003). CONCLUSIONS Non-Hodgkin?s lymphoma and MM patients differ in terms of mobilization of CD34+ cells, graft cellular composition, and posttransplant recovery. Thus, the optimal graft characteristics may also be different.Peer reviewe