Abstract Background The 4Kscore combines measurement of four kallikreins in blood with clinical information as a measure of the probability of significant (Gleason ≥7) prostate cancer (PCa) before ...prostate biopsy. Objective To perform the first prospective evaluation of the 4Kscore in predicting Gleason ≥7 PCa in the USA. Design, setting, and participants Prospective enrollment of 1012 men scheduled for prostate biopsy, regardless of prostate-specific antigen level or clinical findings, was conducted at 26 US urology centers between October 2013 and April 2014. Intervention The 4Kscore. Outcome measurements and statistical analysis The primary outcome was Gleason ≥7 PCa on prostate biopsy. The area under the receiver operating characteristic curve, risk calibration, and decision curve analysis (DCA) were determined, along with comparisons of probability cutoffs for reducing the number of biopsies and their impact on delaying diagnosis. Results and limitations Gleason ≥7 PCa was found in 231 (23%) of the 1012 patients. The 4Kscore showed excellent calibration and demonstrated higher discrimination (AUC 0.82) and net benefit compared to a modified Prostate Cancer Prevention Trial Risk Calculator 2.0 model and standard of care (biopsy for all men) according to DCA. A possible reduction of 30–58% in the number biopsies was identified with delayed diagnosis in only 1.3–4.7% of Gleason ≥7 PCa cases, depending on the threshold used for biopsy. Pathological assessment was performed according to the standard of care at each site without centralized review. Conclusion The 4Kscore showed excellent diagnostic performance in detecting significant PCa. It is a useful tool in selecting men who have significant disease and are most likely to benefit from a prostate biopsy from men with no cancer or indolent cancer. Patient summary The 4Kscore provides each patient with an accurate and personalized measure of the risk of Gleason ≥7 cancer to aid in decision-making regarding the need for prostate biopsy.
Abstract In order to improve our understanding of the evidence-based literature supporting temperature management during adult cardiopulmonary bypass, The Society of Thoracic Surgeons, the Society of ...Cardiovascular Anesthesiology and the American Society of ExtraCorporeal Technology tasked the authors to conduct a review of the peer-reviewed literature, including: 1) optimal site for temperature monitoring, 2) avoidance of hyperthermia, 3) peak cooling temperature gradient and cooling rate, and 4) peak warming temperature gradient and rewarming rate. Authors adopted the American College of Cardiology/American Heart Association method for development clinical practice guidelines, and arrived at the following recommendations: Class I Recommendations a) The oxygenator arterial outlet blood temperature is recommended to be utilized as a surrogate for cerebral temperature measurement during CPB. (Class I, Level C) b) To monitor cerebral perfusate temperature during warming, it should be assumed that the oxygenator arterial outlet blood temperature under-estimates cerebral perfusate temperature. (Class I, Level C) c) Surgical teams should limit arterial outlet blood temperature to <37o C to avoid cerebral hyperthermia. (Class 1, Level C) d) Temperature gradients between the arterial outlet and venous inflow on the oxygenator during CPB cooling should not exceed 10°C to avoid generation of gaseous emboli. (Class 1, Level C) e) Temperature gradients between the arterial outlet and venous inflow on the oxygenator during CPB rewarming should not exceed 10°C to avoid outgassing when blood is returned to the patient. (Class 1, Level C) Class IIa Recommendations a) Pulmonary artery or nasopharyngeal temperature recording is reasonable for weaning and immediate post-bypass temperature measurement. (Class IIa, Level C) b) Rewarming when arterial blood outlet temperature ≥30°C: i. To achieve the desired temperature for separation from bypass, it is reasonable to maintain a temperature gradient between arterial outlet temperature and the venous inflow of ≤4°C. (Class IIa, Level B) ii. To achieve the desired temperature for separation from bypass, it is reasonable to maintain a rewarming rate ≤0.5°C/min. (Class IIa, Level B) c) Rewarming when arterial blood outlet temperature <30°C: To achieve the desired temperature for separation from bypass, it is reasonable to maintain a maximal gradient of 10°C between arterial outlet temperature and venous inflow. (Class IIa, Level C) No Recommendation No recommendation for a guideline is provided concerning optimal temperature for weaning from CPB due to insufficient published evidence.
Despite more than a half century of “safe” cardiopulmonary bypass (CPB), the evidence base surrounding the conduct of anticoagulation therapy for CPB has not been organized into a succinct guideline. ...For this and other reasons, there is enormous practice variability relating to the use and dosing of heparin, monitoring heparin anticoagulation, reversal of anticoagulation, and the use of alternative anticoagulants. To address this and other gaps, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiologists, and the American Society of Extracorporeal Technology developed an Evidence Based Workgroup. This was a group of interdisciplinary professionals gathered to summarize the evidence and create practice recommendations for various aspects of CPB. To date, anticoagulation practices in CPB have not been standardized in accordance with the evidence base. This clinical practice guideline was written with the intent to fill the evidence gap and to establish best practices in anticoagulation therapy for CPB using the available evidence.
To identify relevant evidence, a systematic review was outlined and literature searches were conducted in PubMed using standardized medical subject heading (MeSH) terms from the National Library of Medicine list of search terms. Search dates were inclusive of January 2000 to December 2015. The search yielded 833 abstracts, which were reviewed by two independent reviewers. Once accepted into the full manuscript review stage, two members of the writing group evaluated each of 286 full papers for inclusion eligibility into the guideline document. Ninety-six manuscripts were included in the final review. In addition, 17 manuscripts published before 2000 were included to provide method, context, or additional supporting evidence for the recommendations as these papers were considered sentinel publications.
Members of the writing group wrote and developed recommendations based on review of the articles obtained and achieved more than two thirds agreement on each recommendation. The quality of information for a given recommendation allowed assessment of the level of evidence as recommended by the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Recommendations were written in the three following areas: (1) heparin dosing and monitoring for initiation and maintenance of CPB; (2) heparin contraindications and heparin alternatives; and (3) reversal of anticoagulation during cardiac operations. It is hoped that this guideline will serve as a resource and will stimulate investigators to conduct more research and to expand on the evidence base on the topic of anticoagulation therapy for CPB.
Background
With depression predicted to contribute to an increased disease burden in coming decades, prevention efforts have become increasingly important. In order to prevent depression it is ...valuable to identify and classify longitudinal patterns of depressive symptoms across development, ideally beginning early in childhood. To achieve this, longitudinal studies are increasingly using person‐centered data‐analytic methods to model subgroups with similar developmental patterns (trajectories) of depressive symptoms.
Method
A search was completed for English language studies that longitudinally modeled depressive symptom trajectories in nonclinical populations with a baseline age of <19 years. Study characteristics were extracted, prevalence rates and risk factors were summarized, a random‐effect meta‐analysis was undertaken, and risk of bias analysis completed.
Results
Twenty studies published between 2002 and 2015 were included. Participants were recruited at ages 4 through 17 (average age 12.34) and followed longitudinally for an average of 7.45 years. Between 3 and 11 trajectory subgroups were identified. A random pooled effect estimate identified 56% 95% Confidence Interval (CI) 46–65% of the sampled study populations (N = 41,236) on ‘No or low’ depressive symptom trajectories and 26% (CI 14–40%) on a ‘Moderate’ trajectory. ‘High’, ‘Increasing’, and ‘Decreasing’ depressive symptom subgroups were evident for 12% (CI 8–17%). Moderate symptoms were associated with poorer adjustment and outcomes relative to low symptom groups. ‘High’ or ‘Increasing’ trajectories were predominantly predicted by: female gender, low socioeconomic status, higher stress reactivity; conduct issues; substance misuse, and problems in peer and parental relationships.
Conclusions
The review highlighted consistent evidence of subgroups of children and adolescents who differ in their depressive symptom development over time. The findings suggest preventative interventions should evaluate the longer term benefits of increasing membership in low and moderate trajectories, while also targeting reductions in high‐risk subgroups. Considerable between‐study method and measurement variation indicate the need for future trajectory studies to use standardized methods.
Workplace ostracism is a prevalent and detrimental type of mistreatment. To curtail this harmful behavior, researchers need to identify who is more likely to intentionally ostracize others at work ...and the motives that drive them to do so. Past reviews of workplace ostracism focus primarily on the outcomes of ostracism, and the few that address the antecedents often examine a limited set of variables. We examined themes in the ostracism literature and determined that employees intentionally ostracize others due to either punitive or defensive motives. Punitive motives are focused on protecting the interests of the group, whereas defensive motives pertain to defending the interests of the self. We present a model of the ostracizer based on these motives and the associated perceptions of threat and negative emotions that precipitate ostracism. Our model provides an extension of the workplace ostracism literature by presenting a testable theoretical framework, rooted in appraisal theory, to explain why and when employees are likely to ostracize others at work. We also provided suggestions for an expansion of the ostracizer motives literature, with the goal of encouraging research that provides greater understanding of the perspective of the ostracizer.
Despite more than a half century of “safe” cardiopulmonary bypass (CPB), the evidence base surrounding the conduct of anticoagulation therapy for CPB has not been organized into a succinct guideline. ...For this and other reasons, there is enormous practice variability relating to the use and dosing of heparin, monitoring heparin anticoagulation, reversal of anticoagulation, and the use of alternative anticoagulants. To address this and other gaps, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiologists, and the American Society of Extracorporeal Technology developed an Evidence Based Workgroup. This was a group of interdisciplinary professionals gathered to summarize the evidence and create practice recommendations for various aspects of CPB. To date, anticoagulation practices in CPB have not been standardized in accordance with the evidence base. This clinical practice guideline was written with the intent to fill the evidence gap and to establish best practices in anticoagulation therapy for CPB using the available evidence. To identify relevant evidence, a systematic review was outlined and literature searches were conducted in PubMed using standardized medical subject heading (MeSH) terms from the National Library of Medicine list of search terms. Search dates were inclusive of January 2000 to December 2015. The search yielded 833 abstracts, which were reviewed by two independent reviewers. Once accepted into the full manuscript review stage, two members of the writing group evaluated each of 286 full papers for inclusion eligibility into the guideline document. Ninety-six manuscripts were included in the final review. In addition, 17 manuscripts published before 2000 were included to provide method, context, or additional supporting evidence for the recommendations as these papers were considered sentinel publications. Members of the writing group wrote and developed recommendations based on review of the articles obtained and achieved more than two thirds agreement on each recommendation. The quality of information for a given recommendation allowed assessment of the level of evidence as recommended by the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Recommendations were written in the three following areas(1) heparin dosing and monitoring for initiation and maintenance of CPB; (2) heparin contraindications and heparin alternatives; and (3) reversal of anticoagulation during cardiac operations. It is hoped that this guideline will serve as a resource and will stimulate investigators to conduct more research and to expand on the evidence base on the topic of anticoagulation therapy for CPB.
In March 2020, the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) advised the suspension of all non-emergent oculofacial patient care, imparting unprecedented ...interruptions in fellowship training.
ASOPRS fellows and program directors were asked to complete an anonymous survey regarding their perceived impact of the COVID-19 crisis.
Forty ASOPRS fellows (70.2%) participated, including 20 first-year and 20 second-year trainees, from all country regions. During the social distancing restrictions, 100% of fellows continued to participate in surgical procedures, including orbital biopsy (77.5%), abscess drainage (55.0%), fracture repair (45.6%), eyelid lesion excision (70.0%) and temporal artery biopsy (57.5%). ASOPRS fellows evaluated patients, including in emergency room (84.6%) and inpatient hospital (76.9%) settings, wearing surgical (85.0%) or N-95 (40.0%) masks, gloves (80.0%) and eye protection (62.5%).
Most ASOPRS fellows (87.5%) participated in virtual interinstitutional education sessions and indicated a desire to continue this curriculum. Fellows also used available time for research (85.0%), independent study (77.5%), personal health (70.0%) and social interaction (60.0%).
ASOPRS fellows reported COVID-19 restrictions to have a mild (72.5%) to moderate (27.5%) impact on their overall training, and most (75.0%) felt their surgical confidence to decline. Fellowship program directors also asserted a mild (72.2%), moderate (19.4%) or significant (5.6%) impact on subspecialty training, and 94.4% predict adverse effects on graduation case logs.
During the COVID-19 restrictions most ASOPRS fellows participated in emergent clinical activities and novel telemedicine curriculum. Most fellows and program directors expressed concern regarding a negative impact on overall subspecialty education and surgical confidence.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
A wide range of pharmacological, surgical, and mechanical pump approaches have been studied to attenuate the systemic inflammatory response to cardiopulmonary bypass, yet no systematically based ...review exists to cover the scope of anti-inflammatory interventions deployed. We therefore conducted an evidence-based review to capture "self-identified" anti-inflammatory interventions among adult cardiopulmonary bypass procedures. To be included, trials had to measure at least one inflammatory mediator and one clinical outcome, specified in the "Outcomes 2010" consensus statement. Ninety-eight papers satisfied inclusion criteria and formed the basis of the review. The review identified 33 different interventions and approaches to attenuate the systemic inflammatory response. However, only a minority of papers (35 of 98 35.7%) demonstrated any clinical improvement to one or more of the predefined outcome measures (most frequently myocardial protection or length of intensive care unit stay). No single intervention was supported by strong level A evidence (multiple randomized controlled trials RCTs or meta-analysis) for clinical benefit. Interventions at level A evidence included off-pump surgery, minimized circuits, biocompatible circuit coatings, leukocyte filtration, complement C5 inhibition, preoperative aspirin, and corticosteroid prophylaxis. Interventions at level B evidence (single RCT) for minimizing inflammation included nitric oxide donors, C1 esterase inhibition, neutrophil elastase inhibition, propofol, propionyl-L-carnitine, and intensive insulin therapy. A secondary analysis revealed that suppression of at least one inflammatory marker was necessary but not sufficient to confer clinical benefit. The most effective interventions were those that targeted multiple inflammatory pathways. These observations are consistent with a "multiple hit" hypothesis, whereby clinically effective suppression of the systemic inflammatory response requires hitting multiple inflammatory targets simultaneously. Further research is warranted to evaluate if combinations of interventions that target multiple inflammatory pathways are capable of synergistically reducing inflammation and improving outcomes after cardiopulmonary bypass.
Mucopolysaccharidosis (MPS) VII is a lysosomal storage disorder characterized by deficient activity of β-glucuronidase, leading to progressive accumulation of incompletely degraded heparan, dermatan, ...and chondroitin sulfate glycosaminoglycans (GAGs). Patients with MPS VII exhibit progressive skeletal deformity including kyphoscoliosis and joint dysplasia, which decrease quality of life and increase mortality. Previously, using the naturally-occurring canine model, we demonstrated that one of the earliest skeletal abnormalities to manifest in MPS VII is failed initiation of secondary ossification in vertebrae and long bones at the requisite postnatal developmental stage. The objective of this study was to obtain global insights into the molecular mechanisms underlying this failed initiation of secondary ossification. Epiphyseal tissue was isolated postmortem from the vertebrae of control and MPS VII-affected dogs at 9 and 14 days-of-age (n = 5 for each group). Differences in global gene expression across this developmental window for both cohorts were measured using whole-transcriptome sequencing (RNA-Seq). Principal Component Analysis revealed clustering of samples within each group, indicating clear effects of both age and disease state. At 9 days-of-age, 1375 genes were significantly differentially expressed between MPS VII and control, and by 14 days-of-age, this increased to 4719 genes. A targeted analysis focused on signaling pathways important in the regulation of endochondral ossification was performed, and a subset of gene expression differences were validated using qPCR. Osteoactivin (GPNMB) was the top upregulated gene in MPS VII at both ages. In control samples, temporal changes in gene expression from 9 to 14 days-of-age were consistent with chondrocyte maturation, cartilage resorption, and osteogenesis. In MPS VII samples, however, elements of key osteogenic pathways such as Wnt/β-catenin and BMP signaling were not upregulated during this same developmental window suggesting that important bone formation pathways are not activated. In conclusion, this study represents an important step towards identifying therapeutic targets and biomarkers for bone disease in MPS VII patients during postnatal growth.
•Failed endochondral ossification in MPS VII is associated with broad dysregulation of osteogenic signaling pathways.•Dysregulated gene expression precedes tissue level abnormalities in MPS VII secondary ossification centers.•Wnt and BMP signaling pathways may represent druggable targets for normalizing bone formation in MPS VII patients.•Glycoprotein non-metastatic melanoma B (osteoactivin) may represent a biomarker of skeletal disease severity in MPS VII.
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