Thorsten Jentzsch

Cyr61 Expression in Osteosarcoma Indicates Poor Prognosis and Promotes Intratibial Growth and Lung Metastasis in Mice

Osteosarcoma is the most frequent primary malignant bone tumor in children and adolescents with a high propensity for lung metastasis, the major cause of disease‐related death. Reliable outcome‐predictive markers and targets for osteosarcoma metastasis‐suppressing drugs are urgently needed for more effective treatment of metastasizing osteosarcoma, which has a current mean 5‐year survival rate of approximately 20%. This study investigated the prognostic value and the biological relevance of the extracellular matrix‐associated growth factor Cyr61 of the CCN family of secreted proteins in osteosarcoma and metastasis. The prognostic value of Cyr61 was assessed with Kaplan‐Meier analyses based on Cyr61 immunostaining of a tissue microarray of osteosarcoma biopsies collected from 60 patients with local or metastatic disease. Effects of Cyr61 overexpression on intratibial tumor growth and lung metastasis of the low metastatic human SaOS‐2 osteosarcoma cell line were examined in severe combined immunodeficiency (SCID) mice. Cyr61‐provoked signaling was studied in vitro in nonmanipulated SaOS‐2 cells. Cyr61 immunostaining of osteosarcoma tissue cores correlated significantly (p = 0.02) with poor patient survival. Mice intratibially injected with Cyr61‐overexpressing SaOS‐2 cells showed faster tumor growth and an increase in number and outgrowth of lung metastases and consequently significantly (p = 0.0018) shorter survival than mice injected with control SaOS‐2 cells. Cyr61‐evoked PI‐3K/Akt/GSK3β signaling in SaOS‐2 cells resulted in a subcellular redistribution of the cell cycle inhibitor p21Cip1/WAF1. Cyr61 has considerable potential as a novel marker for poor prognosis in osteosarcoma and is an attractive target for primary tumor‐ and metastases‐suppressing drugs.

Immunomodulatory effects of 25-hydroxyvitamin D3 on monocytic cell differentiation and influence of vitamin D3 polymorphisms in type 1 diabetes.

BACKGROUND Preventive measures and a causal therapy for type 1 diabetes (T1D) remain elusive. An imbalance between different dendritic cells (DC) with increased immunogenic DC and decreased tolerogenic DC (tDC) may lead to T1D. Furthermore, 25(OH)D3 is associated with less adverse effects than 1,25(OH)2D3. PURPOSE The present study was performed to clarify the remaining issues about the cellular effects of 25(OH)D3 in patients with T1D and the role of genetic polymorphisms of the vitamin D3 (VD3) metabolism on a functional cellular level. MATERIALS AND METHODS Twelve patients with T1D were case-matched to twelve healthy controls (HC). Monocytes (MC) were either not supplemented or supplemented with 25(OH)D3 in vitro and phenotyped with fluorescence-activated cell sorting. In vitro synthesis and plasma levels of 25(OH)D3 and 1,25(OH)2D3 were analyzed as well as twelve gene polymorphisms of the VD3 metabolism. RESULTS 25(OH)D3 significantly inhibited differentiation of MC into DC and led to an increase of intermediate cells (IC), which show a similar phenotype as tDC. The patient with a recent onset of T1D showed a higher increase in MC and IC compared to patients with long-standing T1D. There were significant differences for the increase of IC with supplementation of 25(OH)D3 between different genotypes within the polymorphisms of VDR-BsmI-rs1544410, VDR-TaqI-rs731236 and CYP24A1-rs927650. CONCLUSION This study suggests that 25(OH)D3 shows immunomodulatory effects on a cellular level in patients with T1D and HC by inhibiting the differentiation of MC into DC and promoting the formation of IC, which are similar to tDC, thereby shifting immunity to self-tolerance. The potency of 25(OH)D3 did not differ between patients with T1D and HC. Increased plasma levels of 25(OH)D3 may inhibit a proinflammatory cell milieu. Despite of the limited patient number, this study generates the hypothesis that the immunmodulatory effects may be influenced by genotypes of the VDR and CYP24A1 illustrating their functional role in T1D susceptibility, which is worth further investigation.

Lumbar Facet Joint Arthritis Is Associated with More Coronal Orientation of the Facet Joints at the Upper Lumbar Spine

We retrospectively analyzed CT scans of 620 individuals, who presented to our traumatology department between 2008 and 2010. Facet joint (FJ) arthritis was present in 308 (49.7%) individuals with a mean grade of 1. It was seen in 27% of individuals ≤40 years and in 75% of individuals ≥41 years (P < 0.0001) as well as in 52% of females and 49% of males (P = 0.61). Mean FJ orientation was 30.4° at L2/3, 38.7° at L3/4, 47° at L4/5, and 47.3° at L5/S1. FJ arthritis was significantly associated with more coronal (increased degree) FJ orientation at L2/3 (P = 0.03) with a cutoff point at ≥32°. FJs were more coronally oriented (48.8°) in individuals ≤40 years and more sagittally oriented (45.6°) in individuals ≥41 years at L5/S1 (P = 0.01). Mean FJ asymmetry was 4.89° at L2/3, 6.01° at L3/4, 6.67° at L4/5, and 7.27° at L5/S1, without a significant difference for FJ arthritis. FJ arthritis is common, increases with age, and affects both genders equally. More coronally oriented FJs (≥32°) in the upper lumbar spine may be an individual risk factor for development of FJ arthritis.

Hyperlordosis Is Associated With Facet Joint Pathology At The Lower Lumbar Spine.

Study Design: A retrospective study. Objective: Our study opted to clarify the remaining issues of lumbar lordosis (LL) with regard to (1) its physiological values, (2) age, (3) sex, and (4) facet joint (FJ) arthritis and orientation using computed tomography (CT) scans. Summary of Background Data: Recent studies have questioned whether LL really decreases with age, but study sample sizes have been rather small and mostly been based on x-rays. As hyperlordosis increases the load transferred through the FJs, it seems plausible that hyperlordosis may lead to FJ arthritis at the lower lumbar spine. Methods: We retrospectively analyzed the CT scans of 620 individuals, with a mean age of 42.5 (range, 14–94) years, who presented to our traumatology department and underwent a whole-body CT scan, between 2008 and 2010. LL was evaluated between the superior endplates of L1 and S1. FJs of the lumbar spine were evaluated for arthritis and orientation between L2 and S1. Results: (1) The mean LL was 49.0 degrees (SD 11.1 degrees; range, 11.4–80.1 degrees). (2) LL increased with age and there was a significant difference in LL in our age groups (30 y and below, 31–50, 51–70, and ≥71 y and above) (P=0.02). (3) There was no significant difference in LL between females and males (50 and 49 degrees) (P=0.17). (4) LL showed a significant linear association with FJ arthritis [P=0.0026, OR=1.022 (1.008–1.036)] and sagittal FJ orientation at L5/S1 (P=0.001). In a logistic regression analysis, the cutoff point for LL was 49.4 degrees. Conclusions: This is the largest CT-based study on LL and FJs. LL significantly increases with age. As a novelty finding, hyperlordosis is significantly associated with FJ arthritis and sagittal FJ orientation at the lower lumbar spine. Thus, hyperlordosis may present with back pain and patients may benefit from surgical correction, for example, in the setting of trauma.

Obesity measured by outer abdominal fat may cause facet joint arthritis at the lumbar spine

BACKGROUND AND OBJECTIVES There is a lack of studies on obesity measured by outer abdominal fat (OAF), which describes abdominal subcutaneous adipose tissue thickness with regard to spino-pelvic parameters. We investigated OAF and its physiologic values on computed tomography (CT) scans with regard to age, gender, facet joint (FJ) arthritis, FJ orientation, lumbar lordosis (LL) and pelvic incidence (PI). MATERIAL AND METHOD OAF, lumbar FJs, LL and PI were evaluated on CT scans. RESULTS CT scans of 620 individuals with a mean age of 42.5 years were reviewed. OAF showed a mean value of 19.7 millimeters (mm). It significantly increased with age until 70 years and decreased thereafter (p 0.0001). There was no significant gender difference. OAF was significantly increased with FJ arthritis (p = 0.01), but not with FJ orientation, LL or PI. CONCLUSION OAF on CT scans seems to have a mean value of 19.7 mm. It is higher in the older age groups until 70 years and declines again afterward. As a novelty finding, OAF significantly increases with higher degrees of FJ arthritis, but is not related to gender or other spino-pelvic parameters such as FJ orientation, LL or PI. Differences in fat distribution may be found at other anatomic sites, such as visceral fat. Obese patients may benefit from weight loss by decreasing their FJ arthritis, which may potentially decrease associated back pain, which may be worth further investigations.

Why We Need Postmortem Analysis of Cardiac Implantable Electronic Devices.

The prevalence of cardiac implantable electronic devices (CIEDs), pacemakers and implantable cardioverter defibrillators (ICDs) is increasing. However, postmortem analysis of CIEDs is not performed routinely. Fourteen consecutive CIEDs were analyzed. The indication for and date of implantation, technical data, CIED reprogramming, heart rhythm disturbances, patient demographics and medical consultations were investigated. Death during the first year after implantation was seen in 54%, whereof 71% consulted a physician within 10 days before death. The time of death was attributed to a particular day in 29%. There was a relationship between CIEDs and cause/manner of death in 50%. Although limited by a small sample size, this study advocates the routine postmortem CIED analysis for forensic and clinical purposes in selected cases. Patients with CIEDs seem to show an increased risk of death during the first year after implantation. The analysis of CIEDs can be helpful in evaluating the time/cause/manner of death.

Correlation of pelvic incidence with radiographical parameters for acetabular retroversion: a retrospective radiological study

BackgroundPelvic incidence (PI) has been linked to several degenerative processes within the spinopelvic system. Acetabular retroversion is a recognised risk factor for osteoarthritis of the hip. We therefore hypothesised that these two factors might be part of a specific anatomical variant associated with degenerative changes. This study was performed to clarify this issue.MethodsThe pelvic incidence was measured on 589 computertomographical data sets acquired between 2008 and 2010. For 220 patients a 2D rendering in an antero-posterior view of the CT data set was performed to evaluate the parameters of acetabular retroversion. Those included the prominence of the ischial spine sign (PRISS), the cross-over sign (COS) and the posterior wall sign (PWS). Between 477 and 478 hips were evaluated depending on the parameter of retroversion.ResultsThe mean pelvic incidence was significantly lower in hips positive for the PRISS and the PWS. However, there were no significant differences between hips positive or negative for the COS.DiscussionAs hypothesised, the lower PI values in PWS and PRISS positive hips suggest a link between PI and retroversion of the acetabulum. Whether this is of any clinical relevance remains, however, unknown.ConclusionAcetabular retroversion is linked to PI. In hips where the prominence of the ischial spine sign and/or the posterior wall sign was present, the mean pelvic incidence value was lower.

Paradigm shifts in diagnostics and treatment of multiply injured patients – How does it affect visceral injuries?

EAC 0.62 TRISS 0.717 ISS 0.777 NISS 0.849 APACHE II 0880 TTS 0.917 RISC 0.939 RISC II 0.953 Abdominal injuries in polytraumatized patients [1] can be life threatening and require careful assessment. They may alter the way of management in the polytrauma patient and can dominate the clinical course. There have been several changes in the philosophy of management over the last 50 years [2]. These were associated with changes in the type of injury, caused by improved injury prevention and passive car safety. Changes in the management of nonsurgical bleeding, intensive care options and perioperative care were also relevant. All these initiated the development of multiple changes in treatment.

Is rivaroxaban associated with higher morbidity and mortality in patients with traumatic head injuries? A retrospective cohort study comparing rivaroxaban, no anticoagulation, and phenprocoumon

OBJECTIVES The use of new anticoagulants potentially carries the risk of increased intracranial bleeding, but there is a lack of evidence. The aim of this study was to investigate whether the morbidity and mortality differs in head trauma patients depending on the type of anticoagulation. PATIENTS AND METHODS A retrospective cohort study was conducted in 2009-2014. Based on sex, age, and Glasgow-Coma Scale (GCS), patients that received rivaroxaban were matched to two control groups, one that received no anticoagulant and another one that received phenprocoumon. The primary outcome was mortality. Among others, secondary outcome variables were the length of stay (LOS) at the hospital and presence of an intracranial injury. RESULTS Sixty-nine patients (23 patients per group) were analyzed. The characteristics of patients did not differ significantly across groups. There were no significant differences between groups for the primary and secondary outcomes. Two patients died in the rivaroxaban group (one of them likely due to head trauma), while one patient died in the phenprocoumon group (likely not due to head trauma), and no patient died in the no anticoagulatoin group (p = 0.36). The LOS at the hospital was similar (5.0, 4.0, and 5.0 days; p = 0.94). An intracranial injury was observed in a similar number of patients in all groups (n = 11, n = 10, and n = 8; p = 0.75). CONCLUSION Although limited in size, this study did not observe significant outcome differences in patients with traumatic head injuries, who received rivaroxaban, no anticoagulant or phenprocoumon. Although not significant, the only death likely due to head trauma in the study occurred in the rivaroxaban group. Larger studies are needed before clinical application of these findings.

Illustrated operative management of spontaneous bleeding and compartment syndrome of the lower extremity in a patient with acquired hemophilia A: a case report

IntroductionSpontaneous bleeding resulting in compartment syndrome at the lower adult leg due to acquired hemophilia A is rare. There are no reports on operative management of this entity.Case presentationWe present a case of atraumatic compartment syndrome of the lower leg due to acquired factor VIII deficiency, in an 83-year-old Caucasian man of European descent. He was treated surgically with a long and complicated postoperative course after presenting to a community hospital with a 2-day history of increasing pain and swelling in his left lower leg without a previous history of trauma.ConclusionsAwareness, prompt diagnosis and effective treatment of compartment syndrome caused by a rare bleeding disorder, which is usually acquired by the elderly, is essential and may spare a patient from surgery or even limb loss, if early administration of recombinant factor VIIa is effective. The course of disease in a patient with operative management of spontaneous bleeding, compartment syndrome and acquired hemophilia A may be prolonged. However, an interdisciplinary approach with meticulous surgical treatment and bleeding management with recombinant factor VIIa as well as inhibitor eradication by immunosuppressive treatment can be successful and expensive.