HAROW: the first comprehensive prospective observational study comparing treatment options in localized prostate cancer

Purpose

To collect data on primary treatment decision and follow-up in patients with diagnosed, histologically confirmed localized (T1a–T2c/N0/M0) prostate cancer (PCa) for up to 5 years in a prospective observational non-interventional study.

Methods

Patients were non-randomly allocated to one of the five treatment strategies: hormone therapy, active surveillance, radiation, operation, or watchful waiting.

Results

A total of 3169 patients were included by 259 participating sites; 2957 patients had at least one follow-up visit. 54.8 % of tumors at baseline were staged as T1c, 38 % as T2a–T2c, and 7.1 % as T1a or T1b (missing: 0.2 %). 38.9, 32.6 and 26.6 % of patients were classified as low risk, intermediate risk, and high risk according to d’Amico, respectively (missing: 1.8 %). 56.6 % of patients underwent prostatectomy as primary therapy, 16.4 % received radiation, 6.9 % HT, 15.8 and 4.3 % decided for AS or WW. Mean follow-up was 28.4 months. Progression rates were between 8.6 % (RT) and 33.1 % (AS).

Conclusion

Whereas RP remains the main treatment option of localized PCa, active surveillance appears to become an accepted and selectively employed treatment option. Careful selection of patients is documented by the highest proportion of patients with low risk (82.5 %), PSA density <0.2 ng/ml/ml (77.5 %), T1 staging (83.6 %), Gleason score ≤6 (92.5 %), ≤2 positive biopsies (79.4 %), and lowest mean PSA (5.8 ng/ml) in the AS group. The relatively high progression rate in the AS group has to be considered in the context of treatment changes; 71/155 patients had a documented change of treatment and 62 of them with a follow-up period of >3 months.

     

Evaluation of stair motion contributes to new insights into hip osteoarthritis‐related motion pathomechanics

Stair motion in the presence of hip osteoarthritis (OA) has received less attention than level walking. Its more strenuous aspect may shed the light on different locomotor strategies when compared to walking. We, therefore, aimed to define stair motion features associated to hip OA and to evaluate whether these specific features would differ from level walking and better characterize the hip pathological condition. Principal component and linear discriminant analyses were, respectively, used as data reduction and classification techniques. Our study highlighted that most of stair motion features associated to hip OA were similar to the ones of walking. Stair descent presented with the lowest misclassification error rate, ranging from 12% to 19% (estimated by cross‐validation). But, features that may be considered as a mechanism to reduce demand on the hip abductors were found to be more important in the stair ascent condition. This was reflected by both, greater importance in the classification rule and variance compared with walking, that is, decreased hip internal rotation moment at mid‐stance (72.50% vs. 57.63%) and increased trunk lateroflexion toward affected side (56.43% vs. 29.37%). This study emphasized the importance of investigating stair motion in hip osteoarthritic population by highlighting specific locomotor strategies. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:187–196, 2016.     

Oxidatively damaged DNA in aging dyslipidemic ApoE-/- and wild-type mice

The free radical theory of aging depicts an accumulation of cellular oxidatively damaged DNA. In this study, we investigated this theory in mice with knocked-out apolipoprotein E gene (ApoE(-/-)), which develops atherosclerosis and wild-type counterparts. The level of oxidatively damaged DNA was investigated as strand breaks, endonuclease III- and formamidopyrimidine DNA glycosylase-sensitive sites by the comet assay. The level of DNA damage was mainly increased with age in the liver of ApoE(-/-) mice, whereas no increase was observed in the aorta or lung of the mice. This suggests that the accumulation of oxidized DNA in the liver of dyslipidemic ApoE(-/-) mice could be secondary to dysfunction of the lipid metabolism. Visually, the aortas of the ApoE(-/-) mice were clearly atherosclerotic as indicated by rigid texture and yellowish in color. However, the unaltered levels of oxidized DNA in severely atherosclerotic aortas of old ( approximately 70 weeks) ApoE(-/-) mice indicate that oxidative stress may not be a generalized phenomenon, but rather related locally to the individual plaques. In conclusion, the results of this study suggest that dyslipidemic ApoE(-/-) mice suffer from hepatic oxidative stress in terms of oxidized DNA, and this effect could be due to the dysfunction of lipid metabolism.     

Epidemiologie und Behandlungsmanagement bei Schockraumpatienten mit Gesichtsschädelverletzungen

Objective

To minimize overall mortality and optimise reconstructive and cosmetic outcome in severely injured patients with maxillofacial injuries the interdisciplinary coordination of several surgical disciplines is required. It is still discussed controversy whether patients with maxillofacial fractures benefit from early fracture repair or if delayed operative management also yields in good results.

Methods

Herein we analysed the data of 1252 severely injured patients between May 1998 through June 2002 in our trauma department regarding fractures of the maxillofacial region, injury severity, length of ICU stay and postoperative complications in patients with either early (within 72?hours) or delayed (>?3?days) facial fracture repair.

Results

147 patients had severe facial fractures. Average age was 39.8 years (3–87 years), mean ICU was 25 (+/– 16) and the overall mortality 12% (n?=?18). The most common cause for the injuries were traffic accidents in 45%. 78 patients (53%) underwent surgical repair of the maxillofacial fractures; 18 patients had early fracture repair and 60 patients had delayed operative repair. We found 4 complications (22%) in the early repair group and 13 local complications (21%) in the group with delayed surgical repair.

Conclusion

Delayed repair of maxillofacial injuries in severely injured patients is feasible and yields in good results compared to early fracture repair.     

Monocytes give rise to mucosal, but not splenic, conventional dendritic cells

The mononuclear phagocyte (MP) system is a body-wide macrophage (MPhi) and dendritic cell (DC) network, which contributes to tissue homeostasis, inflammation, and immune defense. The in vivo origins of MPs remain poorly understood. Here, we use an adoptive precursor cell transfer strategy into MP-depleted mice to establish the in vivo differentiation sequence from a recently identified MPhi/DC-restricted bone marrow (BM) precursor (MDP) via BM and blood intermediates to peripheral MPhis and DCs. We show that MDPs are in vivo precursors of BM and blood monocytes. Interestingly, grafted Gr1high "inflammatory" blood monocytes shuttle back to the BM in the absence of inflammation, convert into Gr1low monocytes, and contribute further to MP generation. The grafted monocytes give rise to DCs in the intestinal lamina propria and lung, but not to conventional CD11chigh DCs in the spleen, which develop during homeostasis from MDPs without a monocytic intermediate.     

Pineal cysts without hydrocephalus: microsurgical resection via an infratentorial-supracerebellar approach—surgical strategies,complications, and their avoidance

Neurosurgical Review - Indications for surgery of pineal cysts without ventriculomegaly are still under debate. In view of the limited data for pineal cyst resection in the absence of...