Multicenter Evaluation of Circulating Cell-Free DNA Extraction and Downstream Analyses for the Development of Standardized (Pre)analytical Work Flows.

BACKGROUND: In cancer patients, circulating cell-free DNA (ccfDNA) can contain tumor-derived DNA (ctDNA), which enables noninvasive diagnosis, real-time monitoring, and treatment susceptibility testing. However, ctDNA fractions are highly variable, which challenges downstream applications. Therefore, established preanalytical work flows in combination with cost-efficient and reproducible reference materials for ccfDNA analyses are crucial for analytical validity and subsequently for clinical decision-making. METHODS: We describe the efforts of the Innovative Medicines Initiative consortium CANCER-ID (http://www.cancer-id.eu) for comparing different technologies for ccfDNA purification, quantification, and characterization in a multicenter setting. To this end, in-house generated mononucleosomal DNA (mnDNA) from lung cancer cell lines carrying known TP53 mutations was spiked in pools of plasma from healthy donors generated from 2 different blood collection tubes (BCTs). ccfDNA extraction was performed at 15 partner sites according to their respective routine practice. Downstream analysis of ccfDNA with respect to recovery, integrity, and mutation analysis was performed centralized at 4 different sites. RESULTS: We demonstrate suitability of mnDNA as a surrogate for ccfDNA as a process quality control from nucleic acid extraction to mutation detection. Although automated extraction protocols and quantitative PCR-based quantification methods yielded the most consistent and precise results, some kits preferentially recovered spiked mnDNA over endogenous ccfDNA. Mutated TP53 fragments derived from mnDNA were consistently detected using both next-generation sequencing-based deep sequencing and droplet digital PCR independently of BCT. CONCLUSIONS: This comprehensive multicenter comparison of ccfDNA preanalytical and analytical work flows is an important contribution to establishing evidence-based guidelines for clinically feasible (pre)analytical work flows.

Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial.

A global phase 3 study evaluated the pharmacokinetics, efficacy, and safety of recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 63 previously treated male patients (12-61 years) with severe hemophilia B (factor IX [FIX] activity ≤2%). The study included 2 groups: group 1 patients received routine prophylaxis once every 7 days for 26 weeks, followed by either 7-, 10-, or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively; group 2 patients received on-demand treatment of bleeding episodes for 26 weeks and then switched to a 7-day prophylaxis regimen for a mean of 45 weeks. The mean terminal half-life of rIX-FP was 102 hours, 4.3-fold longer than previous FIX treatment. Patients maintained a mean trough of 20 and 12 IU/dL FIX activity on prophylaxis with rIX-FP 40 IU/kg weekly and 75 IU/kg every 2 weeks, respectively. There was 100% reduction in median annualized spontaneous bleeding rate (AsBR) and 100% resolution of target joints when subjects switched from on-demand to prophylaxis treatment with rIX-FP (P< .0001). The median AsBR was 0.00 for all prophylaxis regimens. Overall, 98.6% of bleeding episodes were treated successfully, including 93.6% that were treated with a single injection. No patient developed an inhibitor, and no safety concerns were identified. These results indicate rIX-FP is safe and effective for preventing and treating bleeding episodes in patients with hemophilia B at dosing regimens of 40 IU/kg weekly and 75 IU/kg every 2 weeks. This trial was registered at www.clinicaltrials.gov as #NCT0101496274.

Outcomes of proximal humeral fracture fixation with locked CFR-PEEK plating.

PURPOSE: To investigate the outcomes of proximal humeral fracture (PHF) fixation with a novel carbon-fiber-reinforced (CFR)-PEEK plate and to compare results with outcomes after conventional locked titanium plating. METHODS: Twenty-one patients (7 male, 14 female) with operative treatment of unilateral displaced PHFs (mean age, 66.8 ± 9.9 years) with a novel CRF-PEEK plate were prospectively enrolled. Patients were followed up clinically (Constant Score, Simple Shoulder Test and Simple Shoulder Value) and radiologically 3 months postoperative and again clinically 12 months postoperative. Implant-related complications were evaluated after 3 and 12 months. Results at 1-year follow-up were compared with results of 21 patients (7 male, 14 female; mean age, 67.4 ± 9.7 years) with conventional titanium locked plating by matched case-control analysis. RESULTS: All functional outcomes improved after CFR-PEEK plating (p < 0.05). Twelve months postoperatively, the mean age- and gender-related Constant Score was 99.8 ± 21.2%. All fractures healed by the 3-month follow-up without evidence of secondary screw perforation, fragment displacement or loss of fixation. There were no significant differences between the functional outcomes of patients with the CF-PEEK plate and patients with locked titanium plating (p > 0.05). Patients with locked titanium plating were significantly more likely to require revision surgery related to articular screw perforations (p = 0.048). CONCLUSIONS: Fracture fixation of displaced PHFs with a novel CFR-PEEK plate resulted in good to excellent 1-year functional outcomes which were similar to outcomes of conventional locked titanium plating. The stiffer locked titanium plating was associated with a higher risk of articular screw perforations than the more elastic CFR-PEEK plate.

Recovery of subscapularis and shoulder function following arthroscopic treatment of isolated anterior and combined anterosuperior rotator cuff lesions.

BACKGROUND: The purpose of the study was to evaluate the recovery of the subscapularis and shoulder function dependent on the type of lesion and type of surgical treatment, when compared to the non-affected contralateral shoulder. We hypothesized that regardless of type of lesion and performed surgical intervention, a significant muscle insufficiency as compared to the healthy contralateral side will remain. PATIENTS AND METHODS: Sixty-eight patients (14 females and 54 males) with an anterior or anterosuperior cuff lesion at an average age of 55.7 ± 11.7 years (range 20-80 years) were prospectively evaluated up to 24 months. Intraoperatively, the lesions were classified according to current systems and treated by debridement or reconstruction. Pre- and postoperatively, the Constant Score (CS) as well as the belly-press angle (BPA) and back-to-hand distance (BHD) on the affected and on the contralateral shoulder was noted. RESULTS: 29.4% had an isolated subscapularis lesion whereas 69.1% had concomitant supraspinatus pathology. In 17 patients an arthroscopic debridement and in 51 patients an arthroscopic repair were performed. Postoperatively, all patients revealed a significant improvement of the CS, BPA and BHD (p < 0.05) independent of the type of lesion or the surgical intervention. However, reconstruction of the subscapularis tendon resulted in significant differences of CS, BPA and BHD (p < 0.05) compared to the contralateral shoulder. CONCLUSION: Reconstruction of subscapularis lesions cannot provide full subscapularis function since a residual subscapularis insufficiency remains, other than in patients with small partial tears treated with debridement alone.

Arthroplasty compared to internal fixation by locking plate osteosynthesis in comminuted fractures of the distal humerus.

PURPOSE: The purpose of this study was to evaluate and compare the results after double locking plate osteosynthesis (ORIF) and total elbow arthroplasty (TEA) in AO type C fractures of the distal humerus. METHODS: This retrospective study includes clinical results of 29 patients (9xTEA, 20xORIF) with a mean age of 62 years. The male to female ratio was 8:21. Range of motion, MEPS, DASH and complications were evaluated. Patients older than 60 years (n = 19) were filtered and compared statistically. RESULTS: After a mean follow-up of 25 months the ORIF-group reached an extension-flexion of 99°±23° and the TEA-group of 111°±13°. The ORIF-group vs. the TEA-group had a mean MEPS of 85±17 vs. 94±11 and DASH of 34±24 vs. 24±12. In patients older than 60 years extension-flexion was 97°±23° after ORIF and 110°±14 after TEA (p = 0.237). The ORIF-group vs. the TEA-group had a mean MEPS of 82±21 vs. 94±11 (p = 0.078) and DASH of 45±18 vs. 26±11 (p = 0.023). The ORIF-group had a 4.4 times higher risk for major complications. CONCLUSION: TEA and ORIF lead to comparable functional results, but major complications are more common after ORIF. Despite this, ORIF remains the gold standard for younger and older patients because of the lifelong loading limitation after TEA, unknown implant survival and problematic revision surgery. For patients older than 60 years a primary TEA can be recommended in exceptional cases, if the loading limitation is acceptable for the individual or the fracture is not reconstructable.

Safety and pharmacokinetics of a novel recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in hemophilia B patients.

A recombinant fusion protein linking coagulation factor IX (FIX) with human albumin (rIX-FP) has been developed to facilitate hemophilia B treatment by less frequent FIX dosing. This first-in-human dose-escalation trial in 25 previously treated subjects with hemophilia B (FIX ≤ 2 IU/dL) examined the safety and pharmacokinetics of 25, 50, and 75 IU/kg rIX-FP. Patients in the 50-IU/kg cohort underwent a comparative pharmacokinetics assessment with their previous FIX product (plasma-derived or recombinant). No allergic reactions or inhibitors were observed. Four mild, possibly treatment-related adverse events were reported. In the 50-IU/kg cohort (13 subjects), the mean half-life of rIX-FP was 92 hours, more than 5 times longer than the subjects' previous FIX product. After 25 or 50 IU/kg rIX-FP administration, the baseline-corrected mean FIX activity remained elevated at day 7 (7.4 IU/dL and 13.4 IU/dL, respectively) and day 14 (2.5 IU/dL and 5.5 IU/dL, respectively). The incremental recovery of rIX-FP was higher than both recombinant and plasma-derived FIX (1.4 vs 0.95 and 1.1 IU/dL per IU/kg, respectively). These results demonstrated both the safety and improved pharmacokinetics of rIX-FP, thus indicating this new product with extended half-life as possibly able to control and prevent bleeding with less frequent injection.

Identification of PTS(Fru) as the major fructose uptake system of Clostridium acetobutylicum.

As a member of the saccharolytic clostridia, a variety of different carbohydrates like glucose, fructose, or mannose can be used as carbon and energy source by Clostridium acetobutylicum ATCC 824. Thirteen phosphoenolpyruvate-dependent phosphotransferase systems (PTS) have been identified in C. acetobutylicum, which are likely to be responsible for the uptake of hexoses, hexitols, or disaccharides. Here, we focus on three PTS which are expected to be involved in the uptake of fructose, PTS(Fru), PTS(ManI), and PTS(ManII). To analyze their individual functions, each PTS was inactivated via homologous recombination or insertional mutagenesis. Standardized comparative batch fermentations in a synthetic medium with glucose, fructose, or mannose as sole carbon source identified PTS(Fru) as primary uptake system for fructose, whereas growth with fructose was not impaired in PTS(ManI) and slightly altered in PTS(ManII)-deficient strains of C. acetobutylicum. The inactivation of PTS(ManI) resulted in slower growth on mannose whereas the loss of PTS(ManII) revealed no phenotype during growth on mannose. This is the first time that it has been shown that PTS(Fru) and PTS(ManI) of C. acetobutylicum are directly involved in fructose and mannose uptake, respectively. Moreover, comprehensive comparison of the fermentation products revealed that the loss of PTS(Fru) prevents the solvent shift as no butanol and only basic levels of acetone and ethanol could be determined.

Coenzyme A-transferase-independent butyrate re-assimilation in Clostridium acetobutylicum-evidence from a mathematical model.

The hetero-dimeric CoA-transferase CtfA/B is believed to be crucial for the metabolic transition from acidogenesis to solventogenesis in Clostridium acetobutylicum as part of the industrial-relevant acetone-butanol-ethanol (ABE) fermentation. Here, the enzyme is assumed to mediate re-assimilation of acetate and butyrate during a pH-induced metabolic shift and to faciliate the first step of acetone formation from acetoacetyl-CoA. However, recent investigations using phosphate-limited continuous cultures have questioned this common dogma. To address the emerging experimental discrepancies, we investigated the mutant strain Cac-ctfA398s::CT using chemostat cultures. As a consequence of this mutation, the cells are unable to express functional ctfA and are thus lacking CoA-transferase activity. A mathematical model of the pH-induced metabolic shift, which was recently developed for the wild type, is used to analyse the observed behaviour of the mutant strain with a focus on re-assimilation activities for the two produced acids. Our theoretical analysis reveals that the ctfA mutant still re-assimilates butyrate, but not acetate. Based upon this finding, we conclude that C. acetobutylicum possesses a CoA-tranferase-independent butyrate uptake mechanism that is activated by decreasing pH levels. Furthermore, we observe that butanol formation is not inhibited under our experimental conditions, as suggested by previous batch culture experiments. In concordance with recent batch experiments, acetone formation is abolished in chemostat cultures using the ctfa mutant.

Arthroscopy after locked plating of proximal humeral fractures: implant removal, capsular release, and intra-articular findings.

PURPOSE: The purpose of this study was to determine the outcomes of arthroscopy after proximal humeral plating and the occurrence of concomitant pathology and avascular necrosis. METHODS: Forty-five patients (28 women; median age, 58.5 years [range, 30 to 82 years]) underwent arthroscopies of 46 shoulders because of unsatisfactory results after locked plating of proximal humeral fractures. They were prospectively followed up for 3, 12, and 24 months postoperatively. Relevant intra-articular lesions were documented. The patients were assigned to 1 of the following groups: (1) articular screw perforation, (2) subacromial plate impingement, or (3) post-traumatic/postoperative shoulder stiffness. Shoulder range of motion and function as measured with the age- and gender-adjusted Constant-Murley score, as well as the Simple Shoulder Test, were compared among the groups. RESULTS: Concomitant lesions of the articular cartilage, long head of the biceps tendon, tuberosities, and rotator cuff were found in 34 patients (75%). Two-thirds of patients (n = 31) had a partial or complete 270° capsular release. Of the patients, 84% (n = 38) underwent 3 and 12 months' follow-up and 82% (n = 37) underwent 24 months' follow-up. The active range of abduction (P = .029), flexion (P = .048), and internal rotation (P = .0005) had improved significantly at 24 months' follow-up compared with the preoperative status. The mean adjusted Constant-Murley score of patients with post-traumatic shoulder stiffness (n = 15, 64.2% ± 7.9%) and articular screw perforation (n = 19, 73.3% ± 8.4%) was significantly lower (P = .0089 and P = .042, respectively) than that of patients with subacromial plate impingement (n = 12, 93.4% ± 4.3%). CONCLUSIONS: High rates of relevant articular pathologies and the necessity of capsular release in a majority of patients with unsatisfactory results after locked plating of proximal humeral fractures make arthroscopy a valuable revision tool with promising results in cases of high plate positioning, screw perforation, and postoperative/post-traumatic shoulder stiffness. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Has the arthroscopically assisted reduction of acute AC joint separations with the double tight-rope technique advantages over the clavicular hook plate fixation?

PURPOSE: The purpose of this study was to compare the results after arthroscopically assisted double TightRope(®)-(TR) reduction with results after clavicular hook plate (HP) fixation in acute high-grade acromioclavicular (AC) joint separations. METHODS: Between 2004 and 2010, 69 consecutive patients with acute AC joint separations type Rockwood III and V were subjected to surgical reconstruction. 56 patients (81 %) were available for evaluation. Thereof, 30 (median age: 39 years; n = 12 acute Rockwood III and n = 18 Rockwood V injuries) were treated by a clavicular HP and 26 (median age: 39 years; n = 10 acute Rockwood III and n = 16 Rockwood V injuries) using the double TR technique. Group HP was evaluated at a median of 48 (7-77) months after surgery and the TR group 17 (7-29) months after stabilization. Visual Analogue Scale (VAS) for Pain, Simple Shoulder Test (SST), Constant Score (CS) and Taft Score (TS) were assessed. Sonographic measurements were performed to evaluate recurrent instability. RESULTS: Clinical examination demonstrated comparable results without significant differences. In the groups HP and TR, the VAS was median 0.8 (range, 0.0-7.5) and 0.4 (range, 0.0-5.7), the SST reached median 11 (range, 0-12 points) and 12 points (range, 8-12 points). The CS was median 92.4 % (range, 21.5-105.4 %) and 94.0 % (range, 54.6-105.3 %) and the TS median 10 (range, 3-12 points) and 10 points (range, 5-12 points). Sonographic measurements showed a mean coracoclavicular (CC) distance of 25.3 ± 4.5 (HP) and 25.5 ± 4.3 mm (TR) (n.s.). In both groups, CC distance of the operated side was significantly higher compared to the uninjured side. The complication rate was 13 % in group HP and 12 % in group TR. CONCLUSIONS: In acute high-grade AC joint instabilities, both techniques lead to mostly good and excellent clinical results, although comparable partial recurrent vertical instability could be observed. Diagnosis and therapy of concomitant glenohumeral injuries and no obligatory implant removal are advantages of the arthroscopic procedure.

Monobloc radial head prostheses in complex elbow injuries: results after primary and secondary implantation.

PURPOSE: Dislocations of components, loosening of the stem, overstuffing and removal in up to 24 % of common radial head prostheses (RHP) after implantation in complex elbow injuries signal the need for improvement. The latest biomechanical evidence shows advantages for monopolar designs. Clinical results after primary and secondary implantation of the newly designed press-fit monobloc monopolar RHP in cases of complex elbow injury are evaluated. METHODS: Twenty-nine patients [median age 60 years (29-86)] were followed up retrospectively for a median of 25 months (7-54) post-operatively. Subjective parameters, the Mayo Elbow Performance Score (MEPS), the Broberg and Morrey score (BMS), latest radiographs and complications were evaluated. RESULTS: MEPS and BMS averaged 87.2 ± 12.9 and 81.1 ± 11.9 points, respectively. No case of implant loosening was observed; the RHP had to be removed in one case (3 %). The overall complication and revision rate was higher after secondary (53 %) than after primary (19 %) implantation. CONCLUSIONS: Satisfactory clinical results and low short-term removal rates emphasise the practicality of monobloc monopolar RHP. Differentiated treatment of complex elbow fracture-dislocations is compulsory to avoid the need for secondary RHP implantation which carries a higher complication rate.

Biomechanical testing of a new plate system for the distal humerus compared to two well-established implants.

PURPOSE: A biomechanical study was performed to test the hypothesis that a new anatomically preformed, thinner, soft-tissue protecting plate system for distal humeral fractures (Tifix®-hybridplate [HP]) would show comparable results in the quasi-static and dynamic testings compared to two conventional implants: The 3.5-mm reconstruction plate (RP) providing primary stability with normal bone mineral density (BMD), and a multidirectional locking plate (Tifix(®)-plate [P]) which can be used with poor bone quality. METHODS: The Tifix(®)-HP was developed by the working group. The biomechanical testing was performed on a C2-fracture-model in 24 synthetic humeri. Three groups, each with eight bone-implant-constructs, were analysed in quasi-static and dynamic tests. RESULTS: The quasi-static measurements showed that under extension loading both locking plates (Tifix(®)-P, Tifix(®)-HP) were significantly stiffer than the reconstruction plate, and that the Tifix(®)-HP had a significantly lower stiffness than the two other implants under flexion loading. In the dynamic tests the Tifix(®)-P allowed significantly less fracture motion compared to the Tifix(®)-HP and the reconstruction plate. In an osteopaenic bone model locking plates failed only under much higher dynamic force than the reconstruction plate. The reconstruction plate and the Tifix(®)-P always failed through screw loosening, whereas the newly developed Tifix(®)-HP showed screw loosening in only one third of cases. CONCLUSION: The hypothesis that the newly designed plate system showed comparable results in the quasi-static and dynamic tests compared to the conventional implants with a significantly lower implant volume and thickness was confirmed.

Treatment of osteochondral fractures of the knee: a meta-analysis of available scientific evidence.

PURPOSE: Although traumatic osteochondral fractures of the knee represent a common pathology of the knee joint, there is no general agreement concerning specific treatment of this entity. This meta-analysis was initiated in order to evaluate scientific evidence on different treatment options for acute osteochondral fractures of the knee. METHODS: For this purpose an OVID-based systematic literature search was performed including the following databases: MEDLINE, MEDLINE preprints, Embase, CINAHL, Life Science Citations, British National Library of Health and Cochrane Central Register of Controlled Trials. The literature search period was from 1946 to January 2012, which led to the identification of 1,226 articles. After applying study-specific inclusion criteria a total of 19 studies with clinical follow-up of 638 patients were included. The methodology of these studies was systematically analysed by means of the Coleman Methodology Score. Outcome and success rates were evaluated depending on treatment applied. RESULTS: All studies (n = 19) identified represent case series (evidence-based medicine level IV) and included a total of 638 patients. The average post-operative follow-up was 46 ± 27 months (range 3.75-108). The mean number of study subjects per study was 33 ± 44 patients (range 4-169). The average Coleman Methodology Score was 29 ± 17 points (range 5-72). Six different scoring systems were used for clinical assessment. The overall clinical success rate was 83% and varied between 45 and 100%. CONCLUSIONS: This meta-analysis reveals a significant lack of scientific evidence for treatment of osteochondral fractures of the knee. No valid conclusion can be drawn from this study concerning the recommendation of a specific treatment algorithm. Nevertheless, the overall failure rate of 17% underlines that an acute osteochondral fracture of the knee represents an important pathology which is not a self-limiting injury and needs further investigation.

Arthroscopically assisted stabilization of chronic AC-joint instabilities in GraftRope™ technique with an additive horizontal tendon augmentation.

PURPOSE: A chronic symptomatic acromioclavicular joint (ACJ) instability is a possible consequence of an acute ACJ separation. Besides vertical instability a horizontal component of the instability is common in high-grade ACJ separation and clinically relevant; especially, in chronic cases. A new technique of horizontal biologic ACJ augmentation with a transacromial gracilis tendon loop as an addition to the arthroscopically assisted stabilization with the GraftRope™ device is described and first clinical and sonographical results are shown. HYPOTHESIS: The results after arthroscopically assisted single bundle reconstruction of the coracoclavicular (CC) ligaments with an additional horizontal tendon augmentation are comparable to the results of other stabilizing techniques in chronic ACJ instabilities. METHODS: A consecutive series of 20 patients with chronic symptomatic ACJ instability was stabilized with this new technique. 16 patients were followed-up clinically and sonographically. Patient satisfaction, visual analogue scale (VAS), simple shoulder test (SST), Constant score (CS) and Taft score (TS) were assessed. Bilateral sonographic measurements were performed to evaluate recurrent instabilities. Complications and concomitant glenohumeral injuries were analyzed. RESULTS: Sixteen patients (n = 2 female, n = 14 male, median age 40 (21-61) years, follow-up rate 84 %) were evaluated median 13 months (range 4-27 months) after indexed operation. 11 patients had a chronic ACJ instability after Rockwood type III, and 5 patients after Rockwood type V lesion. 6 patients suffered a recurrent symptomatic instability after operative treatment. 10 patients of the group were primary stabilized with the new technique. 15 of 16 patients were satisfied with the result of the operation at the follow-up examination. The VAS was median 4.6 of 10 points (range 1.1-7.4 points). The SST reached 9 points (range 5-12 points). The adjusted CS was median 84 % (range 46-93 %) and TS median 9 points (range 5-12 points). The sonographic measurements showed a significant difference in the CC distance between the unaffected and the affected side (21.7 vs. 24.8 mm, p = 0.009). The acromioclavicular distance was median 11 mm (range 7-17 mm) after resection of the lateral clavicle. Concomitant glenohumeral injuries were arthroscopically detected in seven patients. Postoperative complications occurred in one patient (wound infection). In one case, the clavicular washer was removed due to local paresthesia after healing of the graft. CONCLUSIONS: The arthroscopically assisted stabilization of chronic ACJ instabilities with the GraftRope™ device and an additive horizontal tendon augmentation technique leads to good short-term results with a supplementary horizontal stabilization.

All-arthroscopic intramedullary nailing of 2- and 3-part proximal humeral fractures: a new arthroscopic technique and preliminary results.

PURPOSE: The most criticism of antegrade humeral nailing is the potentially deleterious effect on the shoulder function, which is caused by the trauma to the M. supraspinatus (SSP) at the nail insertion site. We describe a new technique of all-arthroscopical intramedullary nailing, which preserves the rotator cuff, and compare it with the conventional open procedure. METHODS: From 11/2009 to 12/2010 82 patients with unstable, displaced proximal humeral fractures were treated surgically. Twenty-one of these patients received an intramedullary nailing. Sixteen of 21 met the inclusion criteria. Based on the surgeon's arthroscopic experience, patients were assigned to the arthroscopic (group I, n = 8) or open group (group II, n = 8). Both groups were compared due to the replacement results, complications, time of surgery and fluoroscopy. Concomitant intraarticular pathologies were assessed (group I). First clinical results after a median follow-up of 13 months (group I) and 14 months (group II) were reported. RESULTS: Between group I and II, no significant differences were seen in patients age [77 years (range 45-90 years) vs. 76 years (range 65-92 years)], gender (6 female/2 male vs. 5 female/3 male) and fracture pattern (six 2-/two 3-part fractures vs. five 2-/three 3-part fractures). The reduction was evaluated by the caput-diaphysis-angle, which was median 137° (range 120-147°) in group I and 132° (range 120-158°) in group II (p = 0.959). Postoperatively, group I showed one varus-, group II two varus- and valgus deformities. Median time of surgery was 75 min (range 45-182 min) versus 70 min (range 40-146 min) (p = 0.442), fluoroscopy time 1.5 min (range, 0.6-3.7 min) versus 1.2 min (range 0.3-2.2 min) in group I and II (p = 0.336). Concomitant pathologies like one traumatic bicipital tendon-lesion and three partial lesions of the SSP were observed and treated in group I. Constant Scores and Visual Analogue Scale did not differ significantly between both groups at the time of follow-up. CONCLUSIONS: All-arthroscopical humeral nailing is possible, preserves the rotator cuff and provides equal replacement and functional results like the open technique. An arthroscopically visualized optimal nail insertion point provides less frequent head deformities. Level of evidence Level III.

Outcomes and risks of operative treatment of rupture of the anterior cruciate ligament in children and adolescents.

PURPOSE: The aim of this meta-analysis was to evaluate the clinical outcomes and risks of anterior cruciate ligament (ACL) surgery in children and adolescents. METHODS: We electronically searched Medline, the Cochrane Controlled Trial Database, Embase, and Medpilot for studies on surgical treatment for ACL ruptures in skeletally immature patients. We extracted baseline demographics, follow-up intervals, surgical details (i.e., ligament suture or reconstruction, physeal-sparing or transphyseal techniques, type of transplant, and methods of fixation). Endpoints comprised rates of growth disturbances and reruptures, as well as knee function (measured by the International Knee Documentation Committee's documentation system and the Lysholm score). Unweighted overall effect sizes (risks, risk ratios [RRs], and means of functional scores) were estimated by use of crude nominators and denominators, and random-effects meta-regression analysis was used for weighted data synthesis. RESULTS: A total of 55 articles reporting on 935 patients (median age, 13 years; range, 1.5 to 16 years) were suitable for the study. After a median follow-up of 40 months (range, 14 to 89 months), the weighted rate of leg-length differences or axis deviations was 1.8% (95% confidence interval [CI], 0% to 3.9%] and that of reruptures was 4.8% (95% CI, 2.9% to 6.7%). Excellent or good function (International Knee Documentation Committee grade A or B) was achieved in 84.2% (95% CI, 75.8% to 92.6%) of all knees, and Lysholm scores averaged 96.3 (95% CI, 95.5 to 97.2). Transphyseal reconstruction was associated with a significantly lower risk of leg-length differences or axis deviations compared with physeal-sparing techniques (1.9% v 5.8%; RR, 0.34; 95% CI, 0.14 to 0.81) but had a higher risk of rerupture (4.2% v 1.4%; RR, 2.91; 95% CI, 0.70 to 12.12). Sutures did not result in any growth disturbances, with a weighted rerupture rate of 4.6% (95% CI, 2.6 to 6.7). Fixation far from the joint line fared better than close fixation with regard to this endpoint (1.4% v 3.2%; RR, 0.42; 95% CI, 0.09 to 1.93). Bone-patellar tendon-bone grafts, which are also less likely to fail, were associated with higher risks of leg-length differences or axis deviations than were hamstrings (3.6% v 2.0%; RR, 1.82; 95% CI, 0.66 to 5.03). Meta-regression did not show a significant impact of the publication year on event rates. CONCLUSIONS: This meta-analysis showed low rates of leg-length differences or axis deviations and graft failures after ACL reconstruction in skeletally immature patients. Hamstring transplants may lower the risk of leg-length differences or axis deviations, and physeal-sparing techniques may increase the risk. Randomized controlled trials are needed to clarify important issues in managing ACL ruptures in children and adolescents. LEVEL OF EVIDENCE: Level IV, meta-analysis of case series.

Arthroscopic locking plate removal after proximal humeral fractures.

The incidence of proximal humeral fractures increases. The locking plate osteosynthesis is a standard procedure to treat displaced proximal humeral fractures. In the mostly affected elderly patients with an osteoporotic bone structure, complication rate is still high. An implant removal is commonly required. But also younger patients often request for hardware removal. The open implant removal with a subacromial and subdeltoideal arthrolysis is an extensive secondary surgery for the patients. We present a new technique to remove a locking plate from the proximal humerus arthroscopically with all advantages of the minimally invasive surgery, and the possibility to treat concomitant intraarticular pathologies parallelly.

Bone quality measured by the radiogrammetric parameter "cortical index" and reoperations after locking plate osteosynthesis in patients sustaining proximal humerus fractures.

AIM: To analyse the radiogrammetric parameter "cortical index" (CI) and its predictive value for proximal humerus fractures. Furthermore, to investigate the reoperations and the cause of reoperations after locking plate osteosynthesis of displaced proximal humerus fractures. PATIENTS AND METHODS: 113 consecutive patients (73 women and 40 men) with a median age of 66 years (range 18-100 years) were included in this study. The median follow-up time in our database was 4.7 years (range 45-72 months). For a comparative matched-group analysis of the CI, patients with a fall on the shoulder without fracture were selected. Demographic data and all reoperations were recorded after median 58 months postoperatively. The CI was measured at the proximal humeral diaphysis. RESULTS: The CI showed to be significant lower in the fracture group (mean 0.28) when compared to the matched group (mean 0.47, p < 0.01). 39% patients underwent a reoperation within 40 months postoperatively. 24% were reoperated within the first 12 months postoperatively, and 15% were reoperated after 12 months or later. The reoperation was independent of bone quality (p = 0.85). CONCLUSIONS: The risk for reoperation is independent of the CI even though the CI may be a predictor for proximal humerus fracture. Younger patients should be aware that surgical treatment of proximal humerus fractures might be a two-stage surgery. Regular follow-up visits for older patients during the first postoperative year must be assured.