Risk score predicts high‐grade prostate cancer in DNA‐methylation positive,histopathologically negative biopsies

BACKGROUND

Prostate cancer (PCa) diagnosis is challenging because efforts for effective, timely treatment of men with significant cancer typically result in over‐diagnosis and repeat biopsies. The presence or absence of epigenetic aberrations, more specifically DNA‐methylation of GSTP1, RASSF1, and APC in histopathologically negative prostate core biopsies has resulted in an increased negative predictive value (NPV) of ～90% and thus could lead to a reduction of unnecessary repeat biopsies. Here, it is investigated whether, in methylation‐positive men, DNA‐methylation intensities could help to identify those men harboring high‐grade (Gleason score ≥7) PCa, resulting in an improved positive predictive value.

METHODS

Two cohorts, consisting of men with histopathologically negative index biopsies, followed by a positive or negative repeat biopsy, were combined. EpiScore, a methylation intensity algorithm was developed in methylation‐positive men, using area under the curve of the receiver operating characteristic as metric for performance. Next, a risk score was developed combining EpiScore with traditional clinical risk factors to further improve the identification of high‐grade (Gleason Score ≥7) cancer.

RESULTS

Compared to other risk factors, detection of DNA‐methylation in histopathologically negative biopsies was the most significant and important predictor of high‐grade cancer, resulting in a NPV of 96%. In methylation‐positive men, EpiScore was significantly higher for those with high‐grade cancer detected upon repeat biopsy, compared to those with either no or low‐grade cancer. The risk score resulted in further improvement of patient risk stratification and was a significantly better predictor compared to currently used metrics as PSA and the prostate cancer prevention trial (PCPT) risk calculator (RC). A decision curve analysis indicated strong clinical utility for the risk score as decision‐making tool for repeat biopsy.

CONCLUSIONS

Low DNA‐methylation levels in PCa‐negative biopsies led to a NPV of 96% for high‐grade cancer. The risk score, comprising DNA‐methylation intensity and traditional clinical risk factors, improved the identification of men with high‐grade cancer, with a maximum avoidance of unnecessary repeat biopsies. This risk score resulted in better patient risk stratification and significantly outperformed current risk prediction models such as PCPTRC and PSA. The risk score could help to identify patients with histopathologically negative biopsies harboring high‐grade PCa. Prostate 76:1078–1087, 2016. © 2016 The Authors. The Prostate Published by Wiley Periodicals, Inc.     

Reporting of neuropsychological dysfunction remains discrepant between individuals with traumatic brain injury and their close others up to five years post-injury

Purpose: The degree to which individuals with traumatic brain injury (TBI) and their close others share a common understanding and experience of post-injury neuropsychological changes is currently unclear. The aim of this preliminary study was to longitudinally examine levels of agreement between self and close other reports of neuropsychological dysfunction following TBI and explore factors associated with these agreement levels. Method: Sixty-three people with TBI and their nominated close others independently completed the Structured Outcome Questionnaire at 1- and 5-years post-injury, reporting whether the person with TBI was experiencing any negative cognitive, behavioural or emotional changes compared to pre-injury. Results: Agreement levels between pair members ranged from chance to approximately 75% across neuropsychological domains and did not significantly change over 1- and 5-year time points. In the case of pair disagreement, close others were generally more likely to report difficulties. Pair disagreement was significantly associated with close other anxiety. Conclusions: Agreement between self and close others remains limited up to 5-years post-injury which questions the practice of using these reports interchangeably in research and clinical practice. Preliminary findings suggest some association between pair disagreement and close other psychological function; however, further research is warranted.

• Implications for Rehabilitation

• Reporting of neuropsychological dysfunction between individuals with TBI and their close others is not sufficiently reliable to warrant interchangeable use within research or clinical practice.

• Including both individuals with TBI and their close others in clinical assessments will facilitate a more holistic understanding of the client’s difficulties and their relationships with those close to them.

• Preliminary findings indicate that disagreement between individuals with TBI and their close others may be associated with close other anxiety. Clinicians should be aware of the potential for disagreement to impact on the psychological health of close others.

     

中老年患者无明确诊断意义的鳞状上皮细胞病变以上宫颈病变临床处理方法研究

目的 探讨中老年患者性质不明不典型鳞状上皮细胞（ASCUS）及ASCUS以上宫颈病变的临床处理方法.方法 根据临床对中老年患者ASCUS宫颈病变不同处理方法分组,观察1组（348例）行阴道镜检查;观察2组（316例）行高危型人乳头瘤病毒（HPV）检测,HPV阳性行阴道镜检查;观察3组（129例）定期宫颈细胞学复检,鳞状上皮内病变行阴道镜检查,比较三组临床处理情况.结果 三组574例患者同时行液基薄层细胞学检查（TCT）及阴道镜宫颈活检病理检查,结果上皮内瘤变（CIN）以上宫颈病变223例（38.9%）,其中CIN Ⅰ 136例（23.7%）、CINⅡ64例（11.2%）、CINⅢ20例（3.5%）、原位癌3例（0.5%）;观察1组348例中,行阴道镜检查348例（100.0%）,活检CINⅡ以上的患者36例（10.3%）;观察2组转阴道镜检查213例（67.4%）,活检CINⅡ以上的患者38例（12.0%）;观察3组转阴道镜检查13例（10.1%）,活检CINⅡ以上的患者3例（2.3%）.活检CINⅡ以上检出率,观察1组、观察2组差异无统计学意义（P＞0.05）,与观察3组比较差异均有统计学意义（x2 =7.014、9.156,均P＜0.05）.结论 高危型HPV检测分流ASCUS,可减少宫颈病变处理过程中误诊、漏诊及过度治疗的问题.     

Injuries from firearms in hunting activities

Background

Recreational hunting is a very popular sport, and frequently involves firearms. Few studies address the pattern of firearm injuries occurring with hunting and how they differ from firearm injuries not associated with hunting.

Purpose

A nation wide database will provide an overall perspective of the scope of the problem and types of injuries.

Methods

Our data were obtained from the Inter-University Consortium for Political and Social Research Firearm Injury Surveillance Study 1993–2008 (ICPSR 30543). It was statistically analyzed for demographic and injury patterns using SUDAAN 10™ software. A p < 0.05 was considered to be statistically significant.

Results

There were 1,841,269 ED visits for firearm related injuries 1993–2008; 35,970 were involved in hunting (1.95%). Hunters were older than non-hunters (34.5 vs. 26.7 years, p < 0.0001). Handguns were involved in 48% of the non-hunters and 5.3% of the hunters (p < 0.0001). The injury was unintentional in 99.4% of hunters; for non-hunters 32.1% were unintentional and 60.7% assaults. The majority of the hunting injuries presented to small hospitals (65.9%) while the majority of non-hunting injuries presented to the large (27.0%) and very large (35.0%) hospitals. Hunters were nearly all Caucasian (92%). In hunters, 57% were shot compared to 77% in non-hunters. The most common diagnosis in hunters was a laceration (42%) compared to a puncture in non-hunters (41%). The head and neck accounted for nearly one-half of the injuries in hunters (47%); for non-hunters it was the head and neck (29%) and the leg/foot (24%). Mortality was 0.6% for hunters and 5.3% for non-hunters. The use of alcohol and being involved in antisocial behaviours was much higher in the non-hunters. The estimated incidence of a firearm injury associated with hunting activities was 9 per 1 million hunting days.

Conclusion

Hunters injured by firearms were nearly all Caucasian, older than non-hunters, did not involve handguns, presented to small hospitals, often sustained unintentional injuries and were not shot; most commonly injured in the head and neck, and had an overall mortality of 0.6%. These data can be a reference for future studies regarding hunting injuries associated with firearms.     

The accuracy of diagnostic tests for adenoid hypertrophy: A systematic review

BackgroundAdenoid hypertrophy may cause sleep-disordered breathing and altered craniofacial growth. The authors conducted a study to gauge the accuracy of alternative tests compared with nasoendoscopy (reference standard) for screening adenoid hypertrophy.MethodsThe authors conducted a systematic review that included searches of electronic databases, hand searches of bibliographies of relevant articles and gray literature searches. They included all articles in which an alternative test was compared with nasoendoscopy in children with suspected nasal or nasopharyngeal airway obstruction.ResultsThe authors identified seven articles that were of poor to good quality. They identified the following alternative tests: multirow detector computed tomography (sensitivity, 92 percent; specificity, 97 percent), videofluoroscopy (sensitivity, 100 percent; specificity, 90 percent), rhinomanometry with decongestant (sensitivity, 83 percent; specificity, 83 percent) and clinical examination (sensitivity, 22 percent; specificity, 88 percent). Lateral cephalograms tended to have good to fair sensitivity (typically 61-75 percent) and poor specificity (41-55 percent) when adenoid size was evaluated but excellent to good specificity when airway patency was evaluated (68-96 percent).ConclusionsNo ideal tool exists for dentists to screen adenoid hypertrophy, owing to access constraints, radiation concerns and suboptimal diagnostic accuracy. Research is needed to identify a low-risk, easily acceptable, highly valid diagnostic screening tool.Practical ImplicationsAlthough lateral cephalograms (which have good to fair sensitivity) and a thorough medical history (which has good specificity) are imperfect individually, when they are used together, they can compensate for each other's weaknesses. This combined approach is the best tool available to dentists for screening adenoid hypertrophy.     

A Prospective Observational Study on Short-Term Functional Outcome of Arthroscopic Anterior Cruciate Ligament Repair of Proximal Tears Using Knotless Single Suture Anchor Technique

PurposeTo assess the clinical outcomes in patients with anterior cruciate ligament (ACL) proximal tears undergoing arthroscopic primary repair with knotless single suture anchor technique.MethodsThe first twenty-two consecutive patients with proximal ACL tears (Sherman types I and II and high-grade partial tears) treated with arthroscopic primary repair with single suture anchor technique were evaluated until 6 months post-operatively. Patients were evaluated with validated functional outcome measures (IKDC and Lysholm scores) and clinical tests for ACL stability.ResultsAt 6-month follow-up, 91% of patients (n = 20) achieved excellent outcome measures for IKDC and Lysholm scores and had complete stability of the ACL to clinical testing. Two patients with poor outcomes at six weeks; one with subjective instability and the other underwent revision surgery represented a failure rate of 9%. The median Lysholm score was 96 (IQ range, 96–100) and median IKDC subjective score was 87.40 (IQ range, 78.20–88.50) at 6-month follow-up. The improvement in Lysholm and IKDC scores over a period of six months post-operatively was statistically significant when compared to preoperative scores (p ≪ 0.0001). Maximum improvement in clinical outcomes is achieved in the first 6 weeks post-surgery with a slower increase thereafter, a time interval which may be considered as a figurative yield point for future work in this field.ConclusionArthroscopic ACL primary repair with knotless single suture anchor technique provides excellent short-term clinical outcomes in a carefully selected subset of patients with proximal ACL tears. More powered and longer duration studies are needed to understand longer term outcomes.Level of EvidenceLevel IV, therapeutic case series.