Urinary stone composition in Germany: results from 45,783 stone analyses.

PURPOSE: Stone composition can provide valuable information for the diagnosis, treatment and recurrence prevention of urolithiasis. The aim of this study was to evaluate the distribution of urinary stone components and the impact of different crystal forms according to gender and age of patients in Germany. METHODS: A total of 45,783 urinary stones submitted from 32,512 men and 13,271 women between January 2007 and December 2020 were analyzed by infrared spectroscopy. Only the first calculus obtained per patient was included in the analysis. RESULTS: The most common main stone component was calcium oxalate (CaOx) (71.4%), followed by carbonate apatite (CA) (10.2%) and uric acid (UA) (8.3%). Struvite (2.1%), brushite (1.3%), protein (0.5%) and cystine (0.4%) stones were only rarely diagnosed. CaOx (75%) and UA stones (81%) were more frequently obtained from men than women (p < 0.001). Weddellite (COD) and uric acid dihydrate (UAD) were more common in younger ages than whewellite (COM) and anhydrous uric acid (UAA), respectively, in both men and women. The ratios of COM-to-COD and UAA-to-UAD calculi were approximately 4:1 and 8:1, respectively. The peak of stone occurrence was between the ages of 40 and 59 years. CONCLUSION: Stone composition is strongly associated with gender and age. The peak incidence of calculi in both women and men was in the most active phase of their working life. The distinction between different crystal forms could provide clues to the activity and mechanisms of lithogenesis. Further research is needed in understanding the causative factors and the process of stone formation.

[Intraoperative stress in orthopaedic spine surgery : Attending surgeon versus resident]. / Intraoperativer Stress bei Wirbelsäuleneingriffen : Operateur vs. Assistent.

INTRODUCTION: Requirements for orthopaedic spine surgeons include occupational skills, concentration, physical fitness and psychological stress resistance, depending on the attending surgeon's or the resident's position. MATERIAL AND METHODS: This study measured and evaluated stress-relevant cardiovascular parameters during 101 spinal surgical procedures of a 40-year old fellowship-trained spine surgeon with 12 years of practice. A training computer, personal scales and a thermometer were used to record the duration of surgery, heart rate, weight loss and calorie burning. RESULTS: The average maximum heart rate as an attending surgeon (124 bpm) was significantly higher than the resident's heart rate (99 bmp). A higher stress level resulted in an increasingly higher average maximum heart rate according to the duration of surgery. The mean loss of body fluids at an average room temperature of 20.4 C after surgery was 0.82 kg (0 to 2.3 kg). The mean loss of body weight was calculated as 1.12% of the attending surgeon versus 0.59% of the resident. DISCUSSION: Increasing complexity, longer duration and a higher potential of intraoperative complications arouse a strong response from the attending surgeon. The observed cardiovascular parameters are similar to those of a moderate to intense workout such as cycling. Long lasting surgeries result in a weight loss equivalent to a mild dehydration ranging from 2 to 5% of body fluids. Increasing dehydration will eventually worsen cognitive, visual and motor skills. Results of this study suggest early rehydration and utilization of mental relaxation techniques to minimize risks during prolonged, complex spine surgeries.

Mixed stones: urinary stone composition, frequency and distribution by gender and age.

Proper analysis of urinary stone composition is a cornerstone for diagnosis, targeted treatment and recurrence prevention of urolithiasis. The aim of this study was to determine the composition, frequency and distribution of mixed stones according to gender and age of patients. A total of 42,519 urinary stones from 30,311 men and 12,208 women submitted between January 2007 and December 2020 were studied. Most urinary calculi consisted of two components (50.9%), followed by stones of a single constituent (27.1%) and three-component stones (21.9%), while four-component stones were only rarely identified (0.1%). Among all stones, 49.8% consisted of whewellite (COM), weddellite (COD), and mixtures of COM and COD, 33.8% were pure carbonate apatite (CA) and mixtures of CA with COM and/or COD, while 7.6% were composed of uric acid anhydrous (UAA), uric acid dihydrate (UAD), and mixed UAA and UAD. The remaining 8.8% of calculi were rare single-component stones and rare mixtures of various constituents. The number of stone components was inversely associated with age (p < 0.001). The proportion of men decreased significantly with the number of stone constituents, from 3.01:1 for single-component stones to 1.0:1 for four-component urinary calculi (p < 0.001). The vast majority of urinary calculi consisted of two or more components in varying proportions. While age was inversely associated with the number of stone constituents, the proportion of women increased significantly from single-component to four-component urinary calculi. A significant proportion of mixed stones could present a challenge for diagnosis and targeted recurrence prevention.

An increase in serum tryptase even below 11.4 ng/mL may indicate a mast cell-mediated hypersensitivity reaction: a prospective study in Hymenoptera venom allergic patients.

BACKGROUND: During a systemic hypersensitivity reaction (SR), an increase in serum tryptase compared to the baseline value is an indicator of mast cell activation, most often due to an IgE-mediated mechanism. OBJECTIVE: To study the relevance of an increase in serum tryptase below the upper normal value of 11.4 ng/mL. METHODS: Serum tryptase levels were measured in 35 patients with Hymenoptera venom hypersensitivity before and during venom exposure. Of these, 20 developed SR to stings or following venom injections during immunotherapy (reactors), while 15 tolerated reexposure to stings or venom injections during immunotherapy without SR (non-reactors). Serum tryptase was estimated at 2, 5 and 24 h after exposure and was compared to a baseline value obtained before or at least 72 h after exposure. RESULTS: Considering circadian variation of serum tryptase, a relative increase to ≥135% of the baseline value (relative delta bound) was defined to indicate mast cell activation. Such an increase was observed in 17 of 20 reactors (85%), but none of 15 non-reactors. A serum tryptase of ≥11.4 ng/mL following venom exposure was observed in eight of the 20 reactors (40%) and 2 (13.3%) of the 15 non-reactors. Both these non-reactors also had an elevated baseline serum tryptase. CONCLUSIONS AND CLINICAL RELEVANCE: Serum tryptase values obtained during a suspected hypersensitivity reaction must always be compared to a baseline value. A relative tryptase increase to ≥135% of the baseline value during a suspected hypersensitivity reaction indicates mast cell activation even below 11.4 ng/mL.

Costimulation of T cell activation by integrin-associated protein (CD47) is an adhesion-dependent, CD28-independent signaling pathway.

The integrin-associated protein (IAP, CD47) is a 50-kD plasma membrane protein with a single extracellular immunoglobulin variable (IgV)-like domain, a multiply membrane-spanning segment, and alternatively spliced short cytoplasmic tails. On neutrophils, IAP has been shown to function in a signaling complex with beta 3 integrins. However, the function of IAP on T cells, which express little or no beta 3 integrin, is not yet defined. Here, we show that mAbs recognizing IAP can enhance proliferation of primary human T cells in the presence of low levels of anti-CD3, but have no effect on T cell proliferation on their own. Together with suboptimal concentrations of anti-CD3, engagement of IAP also enhances IL-2 production in Jurkat cells, an apparently integrin-independent function of IAP. Nonetheless, costimulation by IAP ligation requires cell adhesion. IAP costimulation does not require CD28. Furthermore, anti-IAP, but not anti-CD28, synergizes with suboptimal anti-CD3 to enhance tyrosine phosphorylation of the CD3 zeta chain and the T cell-specific tyrosine kinase Zap70. Ligation of human IAP transfected into the hemoglobin-specific 3.L2 murine T cell hybridoma costimulates activation for IL-2 secretion both with anti-CD3 and with antigenic peptides on antigen-presenting cells (APCs). Moreover, ligation of IAP but not CD28 can convert antagonist peptides into agonists in 3.L2 cells. Using costimulation by IAP ligation as an assay to analyze the structure-function relationships in IAP signaling, we find that both the extracellular and multiply membrane-spanning domains of IAP are necessary for synergy with the antigen receptor, but the alternatively spliced cytoplasmic tails are not. These data demonstrate that IAP ligation initiates an adhesion-dependent costimulatory pathway distinct from CD28. We hypothesize that anti-IAP generates the costimulatory signal because it modulates interactions of the IgV domain with other plasma membrane molecules; this in turn activates effector functions of the multiply membrane-spanning domain of IAP. This model may have general significance for how IAP functions in cell activation.

Operative treatment of 733 patients with acute thoracolumbar spinal injuries: comprehensive results from the second, prospective, Internet-based multicenter study of the Spine Study Group of the German Association of Trauma Surgery.

The second, internet-based multicenter study (MCSII) of the Spine Study Group of the German Association of Trauma Surgery (Deutsche Gesellschaft für Unfallchirurgie) is a representative patient collection of acute traumatic thoracolumbar (T1-L5) injuries. The MCSII results are an update of those obtained with the first multicenter study (MCSI) more than a decade ago. The aim of the study was to assess and bring into focus: the (1) epidemiologic data, (2) surgical and radiological outcome, and (3) 2-year follow-up (FU) results of these injuries. According to the Magerl/AO classification, there were 424 (57.8%) compression fractures (A type), 178 (24.3%) distractions injuries (B type), and 131 (17.9%) rotational injuries (C type). B and C type injuries carried a higher risk for neurological deficits, concomitant injuries, and multiple vertebral fractures. The level of injury was located at the thoracolumbar junction (T11-L2) in 67.0% of the case. 380 (51.8%) patients were operated on by posterior stabilization and instrumentation alone (POSTERIOR), 34 (4.6%) had an anterior procedure (ANTERIOR), and 319 (43.5%) patients were treated with combined posteroanterior surgery (COMBINED). 65% of patients with thoracic (T1-T10) and 57% with lumbar spinal (L3-L5) injuries were treated with a single posterior approach (POSTERIOR). 47% of the patients with thoracolumbar junction (T11-L2) injuries were either operated from posterior or with a combined posterior-anterior surgery (COMBINED) each. Short angular stable implant systems have replaced conventional non-angular stable instrumentation systems to a large extent. The posttraumatic deformity was restored best with COMBINED surgery. T-spine injuries were accompanied by a higher number and more severe neurologic deficits than TL junction or L-spine injuries. At the same time T-spine injuries showed less potential for neurologic recovery especially in paraplegic (Frankel/AISA A) patients. 5% of all patients required revision surgery for perioperative complications. Follow-up data of 558 (76.1%) patients were available and collected during a 30-month period from 1 January 2004 until 31 May 2006. On average, a posterior implant removal was carried out in a total of 382 COMBINED and POSTERIOR patients 12 months after the initial surgery. On average, the rehabilitation process required 3-4 weeks of inpatient treatment, followed by another 4 months of outpatient therapy and was significantly shorter when compared with MCSI in the mid-1990s. From the time of injury until FU, 80 (60.6%) of 132 patients with initial neurological deficits improved at least one grade on the Frankel/ASIA Scale; 8 (1.3%) patients deteriorated. A higher recovery rate was observed for incomplete neurological injuries (73%) than complete neurological injuries (44%). Different surgical approaches did not have a significant influence on the neurologic recovery until FU. Nevertheless, neurological deficits are the most important factors for the functional outcome and prognosis of TL spinal injuries. POSTERIOR patients had a better functional and subjective outcome at FU than COMBINED patients. However, the posttraumatic radiological deformity was best corrected in COMBINED patients and showed significantly less residual kyphotic deformity (biseg GDW -3.8° COMBINED vs. -6.1° POSTERIOR) at FU (p = 0.005). The sagittal spinal alignment was better maintained when using vertebral body replacement implants (cages) in comparison to iliac strut grafts. Additional anterior plate systems did not have a significant influence on the radiological FU results. In conclusion, comprehensive data of a large patient population with acute thoracolumbar spinal injuries has been obtained and analyzed with this prospective internet-based multicenter study. Thus, updated results and the clinical outcome of the current operative treatment strategies in participating German and Austrian trauma centers have been presented. Nevertheless, it was not possible to answer all remaining questions to contradictory findings of the subjective, clinical outcome and corresponding radiological findings between different surgical subgroups. Randomized-controlled long-term investigations seem mandatory and the next step in future clinical research of Spine Study Group of the German Trauma Society.

Integrin-associated protein immunoglobulin domain is necessary for efficient vitronectin bead binding.

Integrin-associated protein (IAP/CD47) is physically associated with the alpha v beta 3 vitronectin (Vn) receptor and a functionally and immunologically related integrin on neutrophils (PMN) and monocytes. Anti-IAP antibodies inhibit multiple phagocyte functions, including Arg-Gly-Asp (RGD)-initiated activation of phagocytosis, chemotaxis, and respiratory burst; PMN adhesion to entactin; and PMN transendothelial and transepithelial migration at a step subsequent to tight intercellular adhesion. Anti-IAP antibodies also inhibit binding of Vn-coated particles to many cells expressing alpha v beta 3. However, prior studies with anti-IAP did not directly address IAP function because they could not distinguish between IAP blockade and antibody-induced signaling effects on cells. To better determine the function of IAP, we have characterized and used an IAP-deficient human cell line. Despite expressing alpha v integrins, these cells do not bind Vn-coated particles unless transfected with IAP expression constructs. Increasing the level of alpha v beta 3 expression or increasing Vn density on the particle does not overcome the requirement for IAP. All known splice variants of IAP restore Vn particle binding equivalently. Indeed, the membrane-anchored IAP Ig variable domain suffices to mediate Vn particle binding in this system, while the multiply membrane-spanning and cytoplasmic domains are dispensable. In all cases, adhesion to a Vn-coated surface and fibronectin particle binding through alpha 5 beta 1 fibronectin receptors are independent of IAP expression. These data demonstrate that some alpha v integrin ligand-binding functions are IAP independent, whereas others require IAP, presumably through direct physical interaction between its Ig domain and the integrin.

Combined posterior-anterior stabilisation of thoracolumbar injuries utilising a vertebral body replacing implant.

The authors report on a prospectively followed series of 35 patients with injuries of the thoracolumbar spine from T7 to L3. The radiological course after combined posterior-anterior surgery with anterior column reconstruction with a distractible vertebral body replacing implant demonstrated a stable reconstruction technique with almost no re-kyphosing. In 18/18 patients with CT follow-up intervertebral fusion was observed as bony bridging lateral to the VBR implant. The functional/clinical outcome of the patients was analysed with a set of eight validated outcome scales. After an average follow-up period of 2(1/2) years encouraging results were noticed. The neurological improvement rate (> or =1 Frankel/ASIA grade) was 8/12 patients (67%) with a complete recovery in 6 cases. 17/29 patients returned to former occupation; 20/29 patients returned to former leisure activities; 24/28 patients rated their general outcome as "unlimited and pain free" or "occasionally and/or mild complaints" with a VAS score of >80 (scale 0-100). The psychometric questionnaires revealed good results with strong correlation comparing the different scoring systems statistically: mean McGill Pain Questionnaire 12.5 (0-40); mean Oswestry Disability Index 20% (0-51). 13/29 patients scored <4 in the Roland and Morris Disability Questionnaire. The German back pain questionnaire (Funktionsfragebogen Hannover Rücken) showed a mean "functional capacity" of 75%, corresponding with moderate restriction. We concluded the presented method as highly effective to completely reduce and maintain an anatomic spinal alignment. The outcome tended to be better in comparison with non-operatively treated patients as well as with norm populations with low back pain.

A new distractable implant for vertebral body replacement: biomechanical testing of four implants for the thoracolumbar spine.

INTRODUCTION: Expandable titanium implants for vertebral body replacement in the thoracolumbar spine have been well established in the reconstruction of the anterior spinal column. Load transfer at the bone-implant interface remains a point of concern. The purpose of the study was to compare the performance in axial load transfer from the implant to the vertebral body in four different implants, all of them in clinical use to date. MATERIALS AND METHODS: We tested a second generation implant (Synex II) in comparison to three different expandable titanium cages: Synex I, Obelisc and X-Tenz. Twenty-four intact fresh frozen human lumbar vertebrae (L1-L4) were distributed into four identical groups according to bone mineral density (BMD). The BMD was determined by quantitative computed tomography (qCT). Specimens were loaded in craniocaudal direction with a material testing machine (Mini Bionix II) at a constant speed of 5 mm/min. Load displacement curves were continuously recorded for each specimen until failure (diminishment of compressive force (F) and/or obvious implant migration through the vertebral body end plate). One-way analysis of variance (ANOVA) and post-hoc tests (Bonferroni) were applied to detect differences at 1, 2, 3, and 4 mm displacement (F (1-4 mm)) between implant groups. RESULT: No significant differences were observed with regard to maximum compression force (F (max)) and displacement (d (max)) until failure: Synex II (1,782.3 N/4.67 mm); Synex I (1,645.3 N/4.72 mm); Obelisc (1,314.0 N/4.24 mm); X-Tenz (1470.3 N/6.92 mm). However, the mean compression force at 1-4 mm displacement (F (1-4 mm): 300-1,600 N) was highest for Synex II. The difference at 2 mm displacement was significant (p = 0.028) between Synex II (F (2 mm) = 879 N) and X-Tenz (F (2 mm) = 339 N). CONCLUSION: The modified end plate design of Synex II was found to perform comparably at least with regard to the compressive performance at the implant-bone interface. The risk of the new implant for collapse into the vertebral body might be reduced when compared to the competitors.

[Operative treatment of traumatic fractures of the thorax and lumbar spine. Part II: surgical treatment and radiological findings]. / Operative Behandlung traumatischer Frakturen der Brust- und Lendenwirbelsäule. Teil II: Operation und röntgenologische Befunde.

The Spine Study Group (AG WS) of the German Trauma Association (DGU) presents its second prospective Internet-based multicenter study (MCS II) for the treatment of thoracic and lumbar spinal injuries. This second part of the study report focuses on the surgical treatment, course of treatment, and radiological findings in a study population of 865 patients. A total of 158 (18,3%) thoracic, 595 (68,8%) thoracolumbar, and 112 (12,9%) lumbar spine injuries were treated. Of these, 733 patients received operative treatment (OP group). Fifty-two patients were treated non-operatively and 69 patients were treated with kyphoplasty/vertebroplasty without additional instrumentation (Plasty group). In the OP group, 380 (51.8%) patients were instrumented from a posterior (dorsal) position, 34 (4.6%) from an anterior (ventral) position, and 319 (43.5%) cases with a combined posteroanterior procedure. Angular stable internal spine fixator systems were used in 86-97% of the cases for posterior and/or combined posteroanterior procedures. For anterior procedures, angular stable plate systems were used in a majority of cases (51.1%) for the instrumentation of mainly one or two segment lesions (72.7%). In 188 cases (53,3%), vertebral body replacement implants (cages) were used and were mainly implanted via endoscopic approaches (67,4%) to the thoracic spine and/or the thoracolumbar junction. The average operating time was 152 min in posterior-, 208 min in anterior-, and 298 min in combined postero-anterior procedures (p<0,001). The average blood loss was highest in combined operations, measuring 959 ml vs. 650 ml in posterior vs. 534 ml in anterior operations (p<0,001).Computer-assisted intraoperative navigation systems were used in 95 cases. At the time of hospital admission, 58,7% of the patients had spinal canal narrowing of an average of 36% (5-95%) at the level of their injury. The average spinal canal narrowing in patients with a complete spinal cord injury (Frankel/ASIA A) was calculated to be 70%, vs. 50% in patients with incomplete neurologic deficits (Frankel/ASIA B-D), and 20% in patients without neurologic deficits (Frankel/ASIS E; p<0,001). The average procedure in the plasty treatment subgroup was 50 min (18-145 min) to address one (n=59) or two (n=10) injured vertebral bodies. In patients with nonoperative treatment mainly three-point-corsets (n=36) were administered for a duration of 6-12 weeks. During their hospital stay 93 of 195 (44,7%) patients with initial neurologic deficits improved at least one Frankel/ASIA grade until the day of discharge. Two patients (0,2%) showed a neurologic deterioration. The highest rate of complete spinal cord injury (n=36, 23%) was associated with thoracic spine injuries. Nine (1%) patients died during the initial course of treatment. A total of 105 (14,3%) cases with intraoperative (n=56) and/or postoperative complications (n=69) were registered. The most common intraoperative complication was bleeding (n=35, 4,8%). A higher relative frequency of intraoperative complications was noticed in combined (n=34, 10,7%) vs. isolated posterior (n=22, 5,9%; p=0,021) procedures. The most common postoperative complication was associated with wound healing problems in 14 (1,9%) patients. Except in the non-operative treatment subgroup, a correction of the posttraumatic measured radiological deformity was achieved to a different extent within every treatment subgroup. There were no statistically significant differences between the postoperative radiological results of the treatment subgroups (dorsal vs. combination), taking into consideration the influence of relevant parameters such as different fracture types, patient age, and the amount of posttraumatic deformity (p=0,34, ANOVA).

[Operative treatment of traumatic fractures of the thoracic and lumbar spinal column: Part III: Follow up data]. / Operative Behandlung traumatischer Frakturen der Brust- und Lendenwirbelsäule: Teil III: Nachuntersuchung.

In this third and final part, the Spine Study Group (AG WS) of the German Trauma Association (DGU) presents the follow-up (NU) data of its second, prospective, internet-based multicenter study (MCS II) for the treatment of thoracic and lumbar spinal injuries including 865 patients from 8 trauma centers. Part I described in detail the epidemiologic data of the patient collective and the subgroups, whereas part II analyzed the different methods of treatment and radiologic findings. The study period covered the years 2002 to 2006 including a 30-month follow-up period from 01.01.2004 until 31.05.2006. Follow-up data of 638 (74%) patients were collected with a new internet-based database system and analyzed. Results in part III will be presented on the basis of the same characteristic treatment subgroups (OP, KONS, PLASTIE) and surgical treatment subgroups (Dorsal, Ventral, Kombi) in consideration of the level of injury (thoracic spine, thoracolumbar junction, lumbar spine). After the initial treatment and discharge from hospital, the average duration of subsequent inpatient rehabilitation was 4 weeks, which lasted significantly longer in patients with persistent neurologic deficits (mean 10.9 weeks) or polytraumatized patients (mean 8.6 weeks). Following rehabilitation on an inpatient basis, subsequent outpatient rehabilitation lasted on average 4 months. Physical therapy was administered significantly longer to patients with neurologic deficits (mean 8.7 months) or type C injuries (mean 8.6 months). The level of injury had no influence of the duration of the inpatient or outpatient rehabilitation. A total of 382 (72.2%) patients who were either operated from posterior approach only or in a combined postero-anterior approach had an implant removal after an average 12 months. During the follow-up period 56 (8.8%) patients with complications were registered and of these 18 (2.8%) had to have surgical revision. The most common complications reported were infection, loss of correction, or implant-associated complications. Clinical data showed a 2.9 higher relative risk for smokers compared to non-smokers to suffer from wound healing problems. The neurologic status of 81 (60.4%) out of 134 patients with neurologic deficits at the time of injury improved until follow-up. Neurologic deterioration was documented in 8 (1.3%) cases. Complete neurologic deficits after injury to the thoracic spine improved in 9% of the cases, whereas 59% of the cases with complete neurologic deficit improved after injury to the thoracolumbar junction. The surgical approach (posterior or combined postero-anterior) had no significant influence on neurological results at follow-up. Patient age, sex and neurologic deficits showed a statistically significant influence (p<0.05) on the fingertip-floor distance (FBA) at follow-up. Patient back function improved during the follow-up period. More than 2 years after the time of injury 32.2% of the patients had no complaints with respect to back function. The relative frequency of patients with unrestrained back function was greater after posterior surgery (24.2%), than anterior surgery (13.8%), or combined surgery (17.3%) (p=0.005; chi(2)-test). At follow-up there were no statistically significant differences of unrestrained back function between different levels of injury (thoracic spine 17.4%, TL junction 22.5% and lumbar spine 13.6%). The relative frequency of patients with injury to the thoracolumbar junction who reported "no complaints from the anterior approach" at follow-up, was calculated to be 55.6% after open versus 63.8% after endoscopic approaches with no significant differences. Of the patients 56.3% reported no donor site morbidity following iliac crest bone harvesting. The VAS spine score at follow-up was calculated within different treatment subgroups: OP 58.4 points, KONS 59.8 points, and PLASTIE 59.7 points. Statistically significant differences of the VAS spine score between posterior (64.9 points) versus combined surgery (47.8 points) were only verified at the level of injury of the thoracic spine (p=0.004). The relative frequency of patients regaining at least 80% of the initial score level was OP (posterior 60.4%, anterior 61.1%, combined 51.4%), 52.9% KONS and 67.6% PLASTIE. After surgery the mean period of incapacity from work was 4 months. Patients with a sedentary occupation before the time of injury were fully reintegrated into work in 71.1% of the cases. Patients with a physical occupation were fully reintegrated in 38.9% of the cases at follow-up. At follow-up 87 (31.2%) patients after posterior and 50 (20.1%) after combined surgery had no restrictions to their recreational activities (p=0.001). Treatment subgroups PLASTIE and KONS show a similar radiological result at follow-up with a bisegmental kyphotic deformity (GDW) of -9 degrees and -8.5 degrees, respectively. With all operative methods it was possible to correct or partly correct the posttraumatic kyphotic deformity. Until follow-up there was a loss of correction depending on the surgical approach and level of injury. Combined postero-anterior stabilization gave statistically significant better radiological results with less kyphotic deformity (-3.8 degrees) than posterior stabilization alone (-6.1 degrees) (p=0.005; ANOVA). Thus combined surgery was superior in its capability to restore spinal alignment within the observational period. At follow-up the use of titanium vertebral body replacement implants (cages) to reconstruct and support the anterior column showed significantly better radiological results with less kyphotic deformity and loss of correction (GDW 0.3 degrees) than the use of iliac bone strut grafts (-3.7 degrees ) (p<0.001). Neither additional anterior plates nor the combination of anterior plates with a cage or bone graft had a statistically significant influence on the kyphotic deformity measured at follow-up. A matched-pair analysis of anterior surgery alone versus combined surgery for the treatment of compression fractures (type A) at the thoracolumbar junction showed a significantly greater intraoperative blood loss but better radiological results in terms of monosegmental and bisegmental kyphotic deformity after combined surgery (p<0.05). A matched-pair analysis of treatment results between non-operative and operative treatment for burst fractures (type A3.1-2) showed a period of inability to work (6 months) which was twice as long for the non-operative treatment group. At the same time significantly better radiological results at follow-up were achieved after operative treatment of these fractures (p<0.05).

[Operative treatment of traumatic fractures of the thoracic and lumbar spinal column. Part I: epidemiology]. / Operative Behandlung traumatischer Frakturen der Brust- und Lendenwirbelsäule: Teil I: Epidemiologie.

The Spine Study Group (AG WS) of the German Trauma Association (DGU) has now been in existence for more than a decade. Its main objective is the evaluation and optimization of the operative treatment for traumatic spinal injuries. The authors present the results of the second prospective internet-based multicenter study (MCS II) of the AG WS in three consecutive parts: epidemiology, surgical treatment and radiologic findings and follow-up results. The aim of the study was to update and review the state-of-the art for treatment of spinal fractures for thoracic and lumbar spine (T1-L5) injuries in German-speaking countries: which lesions will be treated with which procedure and what differences can be found in the course of treatment and the clinical and radiological outcome? This present first part of the study outlines the new study design and concept of an internet-based data collection system. The epidemiologic findings and characteristics of the three major treatment subgroups of the study collective will be presented: operative treatment (OP), non-operative treatment (KONS), and patients receiving a kyphoplasty and/or vertebroplasty without additional instrumentation (PLASTIE). A total of 865 patients (OP n=733, KONS n=52, PLASTIE n=69, other n=7) from 8 German and Austrian trauma centers were included. The main causes of accidents in the OP subgroup were motor vehicle accidents 27.1% and trivial falls 15.8% (KONS 55.8%, PLASTIE 66.7%). The Magerl/AO classification scheme was used and 548 (63.3%) compression fractures (type A), 181 (20.9%) distraction injuries (type B), and 136 (15.7%) rotational injuries (type C) were diagnosed. Of the fractures 68.8% were located at the thoracolumbar junction (T11-L2). Type B and type C injuries carried a higher risk for concomitant injuries, neurological deficits and additional vertebral fractures. The average initial VAS spine score, representing the status before the trauma, varied between treatment subgroups (OP 80, KONS 75, PLASTIE 72) and declined with increasing patient age (p<0.01).

Comparison of two novel fluoroscopy-based stereotactic methods for cervical pedicle screw placement and review of the literature.

This experimental study was designed to compare two different fluoroscopy-based stereotactic surgical techniques for transcutaneous cervical pedicle screw (CPS) placement in the subaxial human cervical spine: (1) a custom-made aiming frame (AF) in combination with conventional fluoroscopy versus (2) a targeting device in combination with a computer-assisted image guidance system [i.e. virtual fluoroscopy (VF)]. Surgery was carried out on six preserved human total body specimens in a laboratory setting. Sixty pedicles (levels C3-C7) were measured in a multislice computed tomography (CT) image data set prior to surgery. Two groups consisting of three specimens and 30 pedicles each were defined according to the surgical technique. The AF consisted of radiolucent components with a fully adjustable arm for carrying the instruments necessary for placing the screws. The arm was angled according to the cervical pedicle axis, as determined by the preoperative CT scans and intraoperative lateral fluoroscopy. For VF, a targeting device was combined with a computer-assisted image-guided surgery unit. For both stereotactic techniques, 3.5 mm screws made of carbon fibre polyetheretherketone (ECF-PEEK) were inserted transcutaneously through stab incisions. Screw placement was assessed using a four-point grading system ranging from ideal (I) to unacceptable (III) where I = screw centred in pedicle, IIa = perforation of pedicle wall is less than one-fourth of the screw diameter, IIb = perforation of the pedicle wall is more than one-fourth of the screw diameter without contact to neurovascular structures, and III = CPS in contact with neurovascular structures. Fifty-eight pedicle screws could be evaluated without interfering metal artefacts according to the same CT protocol that was used preoperatively. The AF technique achieved a significantly smaller number of screws in contact with neurovascular structures compared with the VF technique (P = 0.021; Fisher's exact test) (Grade I n = 15; 64.3% AF vs. n = 13; 43.3% VF and Grade III n = 2; 7.1% AF vs. n = 10; 33.3% VF). Although neither of the two techniques was capable of completely preventing CPS perforations, transcutaneous CPS placement with a conventional fluoroscopy-based stereotactic AF can be considered a less expensive alternative to VF. This AF technique is able to reduce the number and severity of lateral pedicle wall violations compared to screw placement via the wide standard posterior open midline approach to the subaxial cervical spine. The results of this study are discussed in context with those obtained from different published modifications, since the first technical description of this surgical technique in 1994 by Abumi and co-workers.

Increased binding of beta-2-microglobulin to blood cells in dialysis patients treated with high-flux dialyzers compared with low-flux membranes contributed to reduced beta-2-microglobulin concentrations. Results of a cross-over study.

BACKGROUND: Patients on long-term dialysis eventually develop amyloid deposits with beta2-microglobulin as a predominant component. Although several studies have suggested that high-flux membranes reduce beta2-microglobulin in plasma compared with low-flux dialyzers, the mechanisms underlying this observation are still discussed. METHODS: We revisited this important subject and measured beta2-microglobulin in the plasma of healthy individuals (n = 8), and patients undergoing hemodialysis (n = 20) who for assigned periods of time were either treated with a low-flux membrane (cuprophan) or high-flux (polyamide) dialyzer with an ELISA. The number of blood cells was determined by FACS. Beta2-microglobulin was also measured on the surface of granulocytes, lymphocytes, and monocytes before, directly after, and 4 h after hemodialysis. Expression of beta2-microglobulin, c-fos, tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 mRNA was determined in whole blood samples with quantitative RT-PCR using an internal standard in parallel. In the second part of the study, patients were assigned in a two-group cross-over design either to low- or high-flux dialyzers (n = 9 in each group), and dialyzer membranes were changed every 4 weeks for two consecutive periods. Serum beta2-microglobulin concentrations were measured at the end of each period. RESULTS: Healthy controls had a low plasma beta2-microglobulin level of 1.2 +/- 0.3 mg/l. Before hemodialysis, patients on low-flux dialyzers had a plasma beta2-microglobulin level of 42.0 +/- 14.0 mg/l, patients treated with high-flux dialyzers 21.5 +/- 10.8 mg/l (p < 0.05 vs. low-flux dialyzers). In contrast, there was no significant difference in plasma concentrations of active transforming growth factor-beta1 with the two different membrane types. The difference in serum beta2-microglobulin between low- and high-flux membranes was more prominent directly after hemodialysis as well as 4 h after hemodialysis compared with the values directly before the start of treatment. At all studied time-points, leukocytes and platelets were significantly higher in patients on low-flux membranes. Healthy control persons exhibited a significantly higher amount of beta2-microglobulin bound to granulocytes, lymphocytes, and monocytes compared with dialysis patients. Interestingly, beta2-microglobulin bound to granulocytes, lymphocytes, and monocytes was significantly increased in patients treated with high-flux membranes compared with low-flux filters. Quantitative RT-PCR revealed no significant difference in beta2-microglobulin expression in whole blood before hemodialysis, directly after hemodialysis, and 4 h after hemodialysis. However, TNF-alpha and c-fos transcripts were significantly higher in whole blood obtained from patients treated with low-flux membranes compared to high-flux dialyzers. The two-group cross-over study over three periods of 4 weeks revealed that switching from low-flux to high-flux dialyzers significantly reduced serum beta2-microglobulin levels. CONCLUSION: Patients treated with a polyamide high-flux membrane had lower beta2-microglobulin concentrations compared with those patients on low-flux dialyzers. This difference might not be mediated by an increase in beta2-microglobulin mRNA, but may be caused by less beta2-microglobulin released from the blood cells in patients treated with high-flux dialyzers, in addition to a better beta2-microglobulin clearance.

Improved anchorage in osteoporotic vertebrae with new implant designs.

The goal of our study was to evaluate two newly developed implant designs and their behavior in terms of subsidence in lumbar vertebral bodies under cyclic loading. The new implants were evaluated in two different configurations (two small prototypes vs. one large prototype with similar load-bearing area) in comparison to a conventional screw-based implant (MACS TL). A pool of 13 spines with a total of 65 vertebrae was used to establish five testing groups of similar bone mineral density (BMD) distribution with eight lumbar vertebrae each. In additional to BMD assessment via dual-energy X-ray absorptiometry, cancellous BMD and structural parameters were determined using a new generation in vivo 3D-pQCT. The specimens were loaded sinusoidally in force control at 1 Hz for 1000 cycles at three load levels (100, 200, and 400 N). A survival analysis using the number of cycles until failure (Cox regression with covariates) was applied to reveal differences between implant groups. All new prototype configurations except the large cylinder survived significantly longer than the control group. The number of cycles until failure was significantly correlated with the structural parameter Tb.Sp. and similarly with the cancellous BMD for three of five implants. In both large prototypes the cycle number until failure significantly correlated with the preoperative distance to the upper endplates. Although the direct relationship between bone structure or density and mechanical breakage behavior cannot be conclusively proven, all the prototypes adapted for poor bone structure performed better than the comparable conventional implant.

[The AOSpine Classification of Thoraco-Lumbar Spine Injuries]. / Die AOSpine-Klassifikation thorakolumbaler Wirbelsäulenverletzungen.

Optimal treatment of injuries to the thoracolumbar spine is based on a detailed analysis of instability, as indicated by injury morphology and neurological status, together with significant modifying factors. A classification system helps to structure this analysis and should also provide guidance for treatment. Existing classification systems, such as the Magerl classification, are complex and do not include the neurological status, while the TLICS system has been accused of over-simplifying the influence of fracture morphology and instability. The AOSpine classification group has developed a new classification system, based mainly upon the Magerl and TLICS classifications, and with the aim of overcoming these drawbacks. This differentiates three main types of injury: Type A lesions are compression lesions to the anterior column; Type B lesions are distraction lesions of either the anterior or the posterior column; Type C lesions are translationally unstable lesions. Type A and B lesions are split into subgroups. The neurological damage is graded in 5 steps, ranging from a transient neurological deficit to complete spinal cord injury. Additional modifiers describe disorders which affect treatment strategy, such as osteoporosis or ankylosing diseases. Evaluations of intra- and inter-observer reliability have been very promising and encourage the introduction of this AOSpine classification of thoracolumbar injuries to the German speaking community.

MEK1-RSK2 contributes to Hedgehog signaling by stabilizing GLI2 transcription factor and inhibiting ubiquitination.

The transcription factor GLI2 has an important role in the transduction of Hedgehog signaling and thereby regulates tumorigenesis in a wide variety of human tumors. However, the mechanisms controlling GLI2 protein expression and stabilization are incompletely understood. In this study, we show that the mitogen-activated protein kinase MEK1 modulates GLI2 both at the mRNA and protein level. Constitutively activated MEK1 prolonged the half-life of GLI2 and increased its nuclear translocation, accompanied by attenuated ubiquitination of GLI2 protein. RSK2, a protein kinase lying downstream of MEK-ERK cascade, mimicked the effect of MEK on GLI2 stabilization. MEK1 and RSK2 failed to augment the half-life of GLI2 lacking GSK-3ß phosphorylation sites, indicating that MEK-RSK stabilizes GLI2 by controlling targeting GSK-3ß-mediated phosphorylation and ubiquitination of GLI2. The significance of MEK-RSK stabilization was demonstrated in experiments showing that activation of MEK-RSK paralleled higher protein level of GLI2 in several multiple myelomas (MM) cells relative to normal B cells. Moreover, combined treatment with RSK and GLI inhibitors led to an enhanced apoptosis of MM cells. Thus, our results indicate that MEK-RSK cascade positively regulates GLI2 stabilization and represses its degradation via inhibiting GSK-3ß-dependent phosphorylation and ubiquitination of GLI2.