A German-Wide Systematic Study on Mobilization and Collection of Hematopoietic Stem Cells in Poor Mobilizer Patients with Multiple Myeloma prior to Autologous Stem Cell Transplantation.

Introduction: In patients with a clinical indication for autologous hematopoietic stem cell transplantation (ASCT), sufficient mobilization of CD34+ precursor cells into peripheral blood is essential to ensure adequate hematopoietic stem cell (HSC) collection prior to intensive therapy. However, with standard granulocyte-colony stimulating factor (G-CSF)-based mobilization schemes, an important minority of patients fail to mobilize sufficient (e.g., >10/µL) CD34+ cell counts into the peripheral blood and are considered as poor mobilizers (PM). Because failure to achieve sufficient CD34+ cell mobilization can negatively affect important clinical treatment endpoints, the use of plerixafor (PLX) was approved to increase CD34+ mobilization in PM patients. Methods: The German non-interventional, multicenter, open-label, prospective OPTIMOB study evaluated HSC mobilization strategies prior to planned ASCT in adult patients with hematologic malignancies (lymphomas or multiple myeloma [MM]) focusing on PM patients. PM patients were defined as follows: (1) never achieving ≥20 CD34+ cells/µL before 1st apheresis, (2) receiving PLX at any timepoint of mobilization, (3) their initially planned stem cell yield had to be reduced, or (4) they had not received apheresis due to low CD34+ count in peripheral blood. Results: 168 of 475 MM patients (35%) participating in the OPTIMOB study were classified as PM, and 155 of them (92%) received PLX (PM+PLX) during the study. PM patients were 40-78 years old, slightly more often male (n = 97, 58%), mostly newly diagnosed (n = 146, 87%) and received highly individualized previous treatments. Ninety-four of the PMs underwent chemotherapy mobilization (65%), and 51 patients (35%) received steady-state mobilization with G-CSF only during 1st mobilization attempt. 92% of the total PM population (n = 155) underwent apheresis, 78% of them (n = 117) achieved >2.0 × 106 CD34+ cells/kg body weight on the 1st day of apheresis. PM+PLX had a higher median total collection result than those PM patients without PLX support (7.2 vs. 5.7 × 106 CD34+ cells/kg body weight). In total, ASCT was performed in 136 PM+PLX (88%) versus 8 PM-PLX patients (62%). Conclusion: The OPTIMOB study showed that a considerable proportion of adult MM patients in Germany are PMs. Even though most of PMs were supported with PLX in the OPTIMOB study, PM-PLX also successfully mobilized HSCs, allowing ASCT in majority of all PMs. However, further analyses are required for treatment optimization in PMs.

Mobilization and Hematopoietic Stem Cell Collection in Poor Mobilizing Patients with Lymphoma: Final Results of the German OPTIMOB Study.

Introduction: Successful mobilization and collection of peripheral hematopoietic stem cells (HSCs) are necessary for lymphoma patients eligible for myeloablative chemotherapy with subsequent autologous stem cell transplantation (ASCT). Albeit G-CSF alone or combined with chemotherapy is well-established methods for HSC mobilization, up to 40% of the patients fail to mobilize (poor mobilizer, PM). Plerixafor (PLX) is commonly used in PM patients resulting in increased migration of HSCs into peripheral blood and thus improves the collection outcome. Methods: The prospective, multicenter, open-label, non-interventional OPTIMOB study assessed mobilization and collection parameter of patients with lymphoma or multiple myeloma to get deep insights in the treatment of those patients in clinical routine focusing on PM patients. PM was defined as follows: (1) no achievement of ≥20 CD34+ progenitor cells/µL before first apheresis, (2) PLX administration at any time point during the observational period, (3) reduction of the initially planned CD34+ progenitor cell yield as necessity due to failed mobilization or HSC collection, and (4) no performance of apheresis due to low CD34+ progenitor level. Primary objective of the study was to assess mobilization success by the proportion of PM patients achieving >2 × 106 CD34+ progenitor cells/kg body weight on the first day of apheresis. Here, the data of the lymphoma cohort are presented. Results: Out of 238 patients with lymphoma documented in the study, 32% were classified as PM. 87% of them received PLX. Demographic data revealed no obvious differences between PM and good mobilizing (GM) patients. All patients were treated highly individualized prior to mobilization. Majority of all PM patients were able to undergo apheresis (95%) and reached their individual requested CD34+ progenitor cell target (72%). 57% of the PM patients achieved >2.0 × 106 CD34+ progenitor cells/kg body weight on day 1 of apheresis and nearby 70% of them underwent ASCT. Median time to engraftment was similar in PM and GM patients of the lymphoma cohort. Conclusions: Majority of PM patients with lymphoma were successfully mobilized and underwent ASCT. Most of them received PLX during the study.

Radiation and Dose-densification of R-CHOP in Aggressive B-cell Lymphoma With Intermediate Prognosis: The UNFOLDER Study.

UNFOLDER (Unfavorable Young Low-Risk Densification of R-Chemo Regimens) is an international phase-3 trial in patients 18-60 years with aggressive B-cell lymphoma and intermediate prognosis defined by age-adjusted International Prognostic Index (aaIPI) of 0 and bulky disease (≥7.5 cm) or aaIPI of 1. In a 2 × 2 factorial design patients were randomized to 6× R-CHOP-14 or 6× R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prediso[lo]ne) and to consolidation radiotherapy to extralymphatic and bulky disease or observation. Response was assessed according to the standardized response criteria published in 1999, not including F-18 fluordesoxyglucose positron emission tomography/computed tomography (FDG-PET). Primary endpoint was event-free survival (EFS). A total of 695 of 700 patients were eligible for the intention-to-treat analysis. Totally 467 patients qualified for radiotherapy of whom 305 patients were randomized to receive radiotherapy (R-CHOP-21: 155; R-CHOP-14: 150) and 162 to observation (R-CHOP-21: 81, R-CHOP-14: 81). Two hundred twenty-eight patients not qualifying for radiotherapy were randomized for R-CHOP-14 versus R-CHOP-21. After a median observation of 66 months 3-year EFS was superior in the radiotherapy-arm versus observation-arm (84% versus 68%; P = 0.0012), due to a lower rate of partial responses (PR) (2% versus 11%). PR often triggered additional treatment, mostly radiotherapy. No significant difference was observed in progression-free survival (PFS) (89% versus 81%; P = 0.22) and overall survival (OS) (93% versus 93%; P = 0.51). Comparing R-CHOP-14 and R-CHOP-21 EFS, PFS and OS were not different. Patients randomized to radiotherapy had a superior EFS, largely due to a lower PR rate requiring less additional treatment (NCT00278408, EUDRACT 2005-005218-19).

Effectiveness, safety and quality of life of trifluridine/tipiracil in pretreated patients with metastatic colorectal cancer: Real-world data from the noninterventional TACTIC study in Germany.

The prospective, multicenter, noninterventional TACTIC study assessed effectiveness and safety of trifluridine/tipiracil (FTD/TPI) in patients with metastatic colorectal cancer (mCRC) in a real-world setting in Germany, thus evaluating the external validity of the findings from the pivotal RECOURSE trial. Primary endpoint was overall survival (OS). Secondary objectives included progression-free survival (PFS), safety, and quality of life (QoL). Subgroups comprised patients with good (<3 metastatic sites at inclusion, ≥18 months from diagnosis of first metastasis to inclusion) or poor (remaining patients) prognostic characteristics (GPC/PPC). GPC without liver metastases was considered best prognostic characteristics (BPC). In total, 307 eligible patients (pretreated or not suitable for other available therapies) were treated with FTD/TPI. Overall, median [95%-CI] OS was 7.4 months [6.4-8.6], median PFS was 2.9 months [2.8-3.3]. In BPC (n = 65) and GPC (n = 176) compared to PPC (n = 124) subgroup, median OS (13.3 [9.1-17.6] vs 8.9 [7.6-9.8] vs 5.1 [4.4-7.0] months) and median PFS (4.0 [3.3-5.3] vs 3.4 [3.0-3.7] vs 2.6 [2.4-2.8] months) were longer. Patient-reported QoL, assessed by validated questionnaires (EQ-5D-5L, PRO-CTCAE), was stable throughout FTD/TPI treatment. Predominant FTD/TPI-related adverse events of grades 3 or 4 were neutropenia (13.0%), leukopenia (7.5%), and anemia (5.2%). Altogether, palliative FTD/TPI therapy in patients with pretreated mCRC was associated with prolonged survival, delayed progression, maintained health-related QoL, and manageable toxicity. Low metastatic burden and indolent disease were favorable prognostic factors for survival. TACTIC confirms the effectiveness and safety of FTD/TPI, highlighting its value in routine clinical practice.

First-line Treatment With Bendamustine and Rituximab for Old and Frail Patients With Aggressive Lymphoma: Results of the B-R-ENDA Trial.

The incidence of aggressive B-cell lymphomas increases with age, but for elderly or frail patients not eligible for doxorubicin-containing treatment standard therapy remains to be defined. In this prospective, multicenter, phase-2 B-R-ENDA trial, we investigated the feasibility, toxicity, and efficacy of 8 cycles rituximab combined with 6 cycles bendamustine (BR) in elderly or frail aggressive B-cell lymphoma patients: 39 patients aged >80 years and 29 patients aged 61-80 years with elevated Cumulative Illness Rating Scalescore >6 were included. Progression-free survival (PFS) and overall survival (OS) at 2 years were 45% (95% confidence interval [CI], 28%-61%) and 46% (28%-63%) for the patients age >80, as well 32% (13%-51%) and 37% (17%-57%) for frail patients age 64-80, respectively. In a preplanned retrospective analysis, we found no significant differences in PFS and OS comparing the outcome of the 39 patients age >80 years with 40 patients aged 76-80 years treated with 6xR-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) and 2 x rituximab in the RICOVER-60 trial (DSHNHL 1999-1, NCT00052936, EU-20243), yet we detected lower rates of infections and treatment-related deaths in the BR-treated patients. We demonstrate that older and frail patients with aggressive B-cell lymphoma who are not able to receive standard CHOP-based therapy can benefit from anthracycline-free therapy as a feasible and effective therapeutic option.

From inoperable to back to life: a case report of successfully treated obstructive right ventricular primary cardiac lymphoma.

BACKGROUND: Cardiac masses include various tumourous and non-tumourous lesions. Primary cardiac tumours are very rare and most commonly benign. Primary cardiac lymphomas (PCL) account for 1-2% of malignant primary cardiac tumours. Only 197 cases of PCL have been reported between 1949 and 2009. CASE SUMMARY: We report a case of a 73-year-old patient who presented with atrial flutter. The diagnosis was a tumourous cardiac mass in the right atrium with signs of the infiltration of the tricuspid valve insertion and pericardium. There were no signs of extracardiac disease at the initial presentation. The patient was deemed to be inoperable by cardiac surgeons. Rapid tumour progression caused atrioventricular-block type Mobitz 2 with concomitant obstruction of the tricuspid valve and axillary lymph node metastasizing. Excision of the axillary lymph node revealed a diffuse large B-cell non-Hodgkin lymphoma. An epicardial right ventricle single lead pacemaker was sited, and chemotherapy was administered, resulting in complete remission. DISCUSSION: Cardiac masses are rare and challenging cases. Although current imaging procedures deliver extensive information, histological examination is still required in many cases. We encountered a tumourous mass with deep infiltration. After the patient was deemed inoperable, later lymph node invasion allowed histological examination, revealing PCL. Primary cardiac lymphomas are life-threatening tumours with rapid and aggressive growth. Treatment is based on chemotherapy consisting of anthracycline-containing regimens. This case report highlights the curative potential of chemotherapy, as we report a rapid regression of the tumour as well as the disappearance of arrhythmias and conduction disorders after treatment.

Causes of mortality in elderly UICC stage III colon cancer (CC) patients--Tumor-related death and competing risks from the German AIO colorectal study group Colopredict Plus (CPP) registry.

BACKGROUND: Colon cancer (CC) is a disease of elderly patients (pts.) with a median age of 73 years (yrs.). Lack of data about the effects of adjuvant chemotherapy (ACT) is caused by underrepresentation of this clinically relevant cohort in interventional trials. We analyzed real-world data from the German CPP registry with regard to a possible benefit of ACT in elderly (70+ yrs.) versus younger pts. (50 to <70 yrs.) taking cause-specific deaths into account. METHODS: We analyzed the effect of age and ACT on overall survival (OS) and cause-specific death of stage III pts. using Cox regression. RESULTS: In total, 1558 pts. were analyzed and follow-up was 24.6 months. 62.6% of the elderly received ACT whereas 91.1% of younger pts. (p < 0.001). Oxaliplatin combinations were significantly less often given to older than younger pts. (38.8% vs. 88.9%; p < 0.001). Mean Charlson comorbidity score was significantly lower in pts. that received ACT (0.61) than in those without ACT (1.16; p < 0.001). ACT was an independent positive prognostic factor for cancer-related death in elderly pts. even in pts. 75+ yrs. No significant difference in the effect of ACT could be observed between age groups (interaction: cancer-specific death HR = 1.7948, p = 0.1079; death of other cause HR = 0.7384, p = 0.6705). CONCLUSION: ACT was an independent positive prognostic factor for OS. There may be a cohort of elderly with less co-morbidities who benefit from ACT.

Concomitant injuries in patients with thoracic vertebral body fractures-a systematic literature review.

PURPOSE: The aim of this study was to give a systematic overview over the rate and location of concomitant injuries, the probability of suffering from neurological deficits, and to give evidence of the timing of surgery in severely injured patients with unstable thoracic vertebral body fractures. METHODS: This review is based on articles retrieved by a systematic search in the PubMed and Web of Science database for publications up to November 2020 dealing with unstable fractures of the mid-thoracic spine. RESULTS: Altogether, 1109 articles were retrieved from the literature search. A total of 1095 articles were excluded. Thus, 16 remaining original articles were included in this systematic review depicting the topics timing of surgery in polytraumatized patients, outcome neurologic deficits, and impact of concomitant injuries. The overall level of evidence of the vast majority of studies is low. CONCLUSION: The evidence of the available literature is low. The cited studies reveal that thoracic spinal fractures are associated with a high number of neurological deficits and concomitant injuries, particularly of the thoracic cage and the lung. Thereby, diagnostic algorithm should include computer tomography of the whole thoracic cage if there is any clinical sign of concomitant injuries. Patients with incomplete neurologic deficits benefit from early surgery consisting of decompression and long-segmental stabilization.

Multicenter evaluation of therapeutic strategies of inpatients with osteoporotic vertebral fractures in Germany.

PURPOSE: The aim of this study was to assess therapeutic strategies of inpatients with osteoporotic thoracolumbar fractures (OTF) in Germany. METHODS: Prospective multi-center study including 16 German-speaking trauma centers over a period of 7 months. All inpatients with OTF were included. Radiological and clinical data on admission and treatment modalities were assessed. RESULTS: Seven hundred and seven (99.3%) out of 712 included patients (73.3% female) could be evaluated. Mean age was 75 years (30-103). 51.3% could not remember any traumatic incident. Fracture distribution was from T2 to L5 with L1 (19%) most commonly affected. According to the Magerl classification type A1 (52.1%) and A3 (42.7%) were most common. B and C type injuries (2.6%) and neurological deficits (3.1%) were rare. Previous progression of vertebral deformation was evident in 34.4% of patients and related to t score below - 3 (Odds ratio 1.9661). Patients presented with anticoagulation medication (15.4%), dementia (13%), and ASA score > 3 (12.4%) frequently. 82.3% of patients complained of pain > 4 on VAS, 37% could not be mobilized despite pain medication according to grade II WHO pain ladder. 81.6% received operative treatment. Kyphoplasty (63.8%) and hybrid stabilization including kyphoplasty with (14.4%) or without screw augmentation (7.6%) were the techniques most frequently used. Invasiveness of treatment increased with degree of instability. CONCLUSIONS: OTF are mostly type A compression fractures. Patients suffer from severe pain and immobilization frequently. Progression of deformity is correlated to t score below - 3. Treatment of inpatients is mainly surgical, with kyphoplasty followed by hybrid stabilization as commonly used techniques.

Preinfection laboratory parameters may predict COVID-19 severity in tumor patients.

BACKGROUND: Infection with SARS-CoV-2 leads to COVID-19, the course of which is highly variable and depends on numerous patient-specific risk factors. Patients with tumor diseases are considered to be more susceptible to severe COVID-19; however, they also represent a heterogeneous group of individuals with variable risk. Identifying specific risk factors for a severe course of COVID-19 in patients with cancer is of great importance. METHODS: Patients diagnosed with solid tumors or hematological malignancies and PCR-confirmed SARS-CoV-2 infection were included into the multicentric ADHOK (Arbeitsgemeinschaft der Hämatologen und Onkologen im Krankenhaus e.V.) coronavirus tumor registry. Detailed information about the patients' cancer disease, treatment, and laboratory parameters prior to infection, was collected retrospectively. The outcome of the SARS-CoV-2 infection was graded according to the WHO. RESULTS: A total of 195 patients (68% with solid neoplasms and 32% with hematological malignancies) were included in the registry. Overall, the course of the SARS-CoV-2 infection varied greatly, as 69% of all patients were either asymptomatic or encountered a mild to moderate course, while 23% of the cohort died from COVID-19. In multivariable analysis, preinfection laboratory parameters (determined at least 10 days and a median of 21 days before the first documentation of SARS-CoV-2 infection) significantly correlated with severe course of the disease. Out of these, the absolute neutrophil count prior to infection showed the strongest association with COVID-19-related death. CONCLUSION: The course of COVID-19 in patients with tumor diseases is highly variable. Preinfection laboratory parameters may aid to identify patients at risk for severe COVID-19 at an early stage prior to infection with the virus. German Clinical Trials Register identification: DRKS00023012.

Biomechanics and clinical outcome after posterior stabilization of mid-thoracic vertebral body fractures: a systematic literature review.

PURPOSE: The aim of this review is to systematically screen the literature for clinical and biomechanical studies dealing with posterior stabilization of acute traumatic mid-thoracic vertebral fractures in patients with normal bone quality. METHODS: This review is based on articles retrieved by a systematic search in the PubMed and Web of Science database for publications up to December 2018 dealing with the posterior stabilization of fractures of the mid-thoracic spine. RESULTS: Altogether, 1012 articles were retrieved from the literature search. A total of 960 articles were excluded. A total of 16 articles were dealing with the timing of surgery in polytraumatized patients, patients suffering of neurologic deficits after midthoracic fractures, and the impact of concomitant thoracic injuries and were excluded. Thus, 36 remaining original articles were included in this systematic review depicting the topics biomechanics, screw insertion, and outcome after posterior stabilization. The overall level of evidence of the vast majority of studies is low. CONCLUSION: High quality studies are lacking. Long-segmental stabilization is indicated in unstable midthoracic fractures with concomitant sternal fractures. Generally, long-segmental constructs seem to be the safer treatment strategy considering the relative high penetration rate of pedicle screws in this region. Thereby, navigated insertion techniques and intraoperative 3D-imaging help to improve pedicle screw placement accuracy.

Prognostic model for newly diagnosed CLL patients in Binet stage A: results of the multicenter, prospective CLL1 trial of the German CLL study group.

The heterogeneity of early stage CLL challenges prognostication, and refinement of prognostic indices for risk-adapted management in this population is essential. The aim of the multicenter, prospective CLL1 trial was to explore a novel prognostic model (CLL1-PM) developed to identify risk groups, separating patients with favorable from others with dismal prognosis. A cohort of 539 clinically, biochemically, and genetically characterized Binet stage A patients were observed until progression, first-line treatment, or death. Multivariate analysis identified six independent factors associated with overall survival (OS) and time-to-first treatment (TTFT): del(17p), unmutated IGHV, del(11q), ß2-microglobulin >3.5 mg/dL, lymphocyte doubling time (LDT) <12 months, and age >60 years. These factors were integrated into the CLL1-PM, which stratified patients into four risk groups. The CLL1-PM was prognostic for OS and TTFT, e.g., the risk of treatment at 5 years was 85.9, 51.8, 27.6, and 11.3% for very low (0-1.5), low (2-4), high (4.5-6.5), and very high-risk (7-14) scores, respectively (P < 0.001). Notably, in addition to factors comprising CLL-IPI, we substantiated del(11q) and LDT as prognostic factors in early CLL. Altogether, our findings would be useful to effectively stratify Binet stage A patients, particularly within the scope of clinical trials evaluating novel agents.

Recommendations for Diagnosis and Treatment of Odontoid Fractures in Geriatric Patients. / Empfehlungen zu Diagnostik und Behandlung von Frakturen des Dens axis bei geriatrischen Patienten.

BACKGROUND: Odontoid fractures in geriatric patients represent an entity of increasing incidence with a high rate of morbidity and mortality. The optimal diagnostic and therapeutic management is being controversially discussed in the literature. METHODS: In a consensus process and based on the current literature, the members of the working groups "Osteoporotic Fractures" and "Upper Cervical Spine" of the German Society for Orthopaedics and Trauma Surgery (DGOU) defined recommendations for the diagnostics and treatment of odontoid fractures in geriatric patients. RESULTS: For the diagnosis of odontoid fractures in symptomatic patients, computed tomography represents the gold standard, along with conventional radiographs. Magnetic resonance and dynamic imaging can be used as ancillary imaging modalities. With regard to fracture classification, the systems described by Anderson/D'Alonzo and by Eysel/Roosen have proved to be of value. A treatment algorithm was developed based on these classifications. Anderson/D'Alonzo type 1, type 3, and non-displaced type 2 fractures usually can be treated non-operatively. However, a close clinical and radiological follow-up is essential. In Anderson/D'Alonzo type 2 fractures, operative treatment is associated with better fracture healing. Displaced type 2 and type 3 fractures should be stabilized operatively. Type 2 fractures with suitable fracture patterns (Eysel/Roosen 2A/B) can be stabilized anteriorly. Posterior C I/II-stabilization procedures are well established and suitable for all fracture patterns.

Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER): a randomised, phase 3, non-inferiority trial.

BACKGROUND: Six cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) are the standard treatment for aggressive B-cell non-Hodgkin lymphoma. In the FLYER trial, we assessed whether four cycles of CHOP plus six applications of rituximab are non-inferior to six cycles of R-CHOP in a population of patients with B-cell non-Hodgkin lymphoma with favourable prognosis. METHODS: This two-arm, open-label, international, multicentre, prospective, randomised phase 3 non-inferiority trial was done at 138 clinical sites in Denmark, Israel, Italy, Norway, and Germany. We enrolled patients aged 18-60 years, with stage I-II disease, normal serum lactate dehydrogenase concentration, ECOG performance status 0-1, and without bulky disease (maximal tumour diameter <7·5 cm). Randomisation was computer-based and done centrally in a 1:1 ratio using the Pocock minimisation algorithm after stratification for centres, stage (I vs II), and extralymphatic sites (no vs yes). Patients were assigned to receive either six cycles of R-CHOP or four cycles of R-CHOP plus two doses of rituximab. CHOP comprised cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), and vincristine (1·4 mg/m2, with a maximum total dose of 2 mg), all administered intravenously on day 1, plus oral prednisone or prednisolone at the discretion of the investigator (100 mg) administered on days 1-5. Rituximab was given at a dose of 375 mg/m2 of body surface area. Cycles were repeated every 21 days. No radiotherapy was planned except for testicular lymphoma treatment. The primary endpoint was progression-free survival after 3 years. The primary analysis was done in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of assigned treatment. A non-inferiority margin of -5·5% was chosen. The trial, which is completed, was prospectively registered at ClinicalTrials.gov, NCT00278421. FINDINGS: Between Dec 2, 2005, and Oct 7, 2016, 592 patients were enrolled, of whom 295 patients were randomly assigned to receive six cycles of R-CHOP and 297 were assigned to receive four cycles of R-CHOP plus two doses of rituximab. Four patients in the four-cycles group withdrew informed consent before the start of treatment, so 588 patients were included in the intention-to-treat analysis. After a median follow-up of 66 months (IQR 42-100), 3-year progression-free survival of patients who had four cycles of R-CHOP plus two doses of rituximab was 96% (95% CI 94-99), which was 3% better (lower limit of the one-sided 95% CI for the difference was 0%) than six cycles of R-CHOP, demonstrating the non-inferiority of the four-cycles regimen. 294 haematological and 1036 non-haematological adverse events were documented in the four-cycles group compared with 426 haematological and 1280 non-haematological adverse events in the six-cycles group. Two patients, both in the six-cycles group, died during study therapy. INTERPRETATION: In young patients with aggressive B-cell non-Hodgkin lymphoma and favourable prognosis, four cycles of R-CHOP is non-inferior to six cycles of R-CHOP, with relevant reduction of toxic effects. Thus, chemotherapy can be reduced without compromising outcomes in this population. FUNDING: Deutsche Krebshilfe.

Misdiagnosis of Thoracolumbar Posterior Ligamentous Complex Injuries and Use of Radiographic Parameter Correlations to Improve Detection Accuracy.

STUDY DESIGN: Retrospective study. PURPOSE: To evaluate radiological parameters as indicators for posterior ligamentous complex (PLC) injuries in the case of limited availability of magnetic resonance imaging. OVERVIEW OF LITERATURE: Traumatic thoracolumbar spinal fractures with PLC injuries can be misdiagnosed on X-rays or computed tomography scans. This study aimed to retrospectively assess unrecognized PLC injuries and evaluate radiographic parameters as indicators of PLC injuries requiring surgery. METHODS: In total, 314 patients with type A and type B2 fractures who underwent surgical treatment between 2001 and 2010 were included. The frequency of misdiagnosis was reassessed, and radiographic parameters were evaluated and correlated. RESULTS: The average age of the patients was 51.8 years. There were 225 type A3/A4 and 89 type B2 fractures; 39 of the type B2 fractures (43.8%) had been misdiagnosed as type A fractures. Type B fractures presented with a significantly higher kyphotic wedge angle and Cobb angle and a lower sagittal index (SI) than type A fractures. In addition, the normalized interspinous distance was higher in type B2 fractures. The significant mathematical indicators for PLC injuries were as follows: Cobb angle+kyphotic wedge angle >29°; Cobb angle2 >170°; and vertebral angle/SI >25. CONCLUSIONS: The results demonstrated that PLC injuries are frequently misdiagnosed. Correlations between certain radiological parameters associated with PLC injuries can be useful indicators of the presence of such injuries requiring surgery.

Two-year results of vertebral body stenting for the treatment of traumatic incomplete burst fractures.

PURPOSE: Vertebral body stenting (VBS) was developed to prevent loss of reduction after balloon deflation during kyphoplasty. The aim of this study is the radiological and clinical mid-term evaluation of traumatic incomplete burst fractures treated by vertebral body stenting. MATERIAL AND METHODS: This retrospective study included patients with traumatic thoracolumbar incomplete burst fractures treated with VBS between 2009 and 2010. The outcome was evaluated with the visual analogue pain scale (VAS), the Oswestry Disability Score (ODI), the SF-36 Health Survey and radiologically assessed. RESULTS: Eighteen patients with an average age of 74.8 years were treated with VBS. Twelve were female and six were male. Two years after the operation the ODI and SF-36 showed a moderate limitation of daily activities and quality of life without neurological deficits. VBS restored the vertebral kyphosis by 3.2° and segmental kyphosis by 5°. A minor sintering was observed at follow-up losing 0.8° vertebral kyphosis and 2.1° segmental kyphosis correction. Two asymptomatic cement leakages were detected. CONCLUSION: VBS provides clinical outcomes comparable with BKP. The stent allows a reconstruction of the anterior column with reduced subsequent loss of correction.

A new angle stable nailing concept for the treatment of distal tibia fractures.

PURPOSE: Surgical treatment of distal tibial fractures demands a stable fracture fixation while minimizing the irritation to the soft tissues by approach and implant. Biomechanical studies have demonstrated superior performance for angular-stable locked nails over standard locked nails in distal tibial fractures. The experimental Retrograde Tibial Nail (RTN) is a minimally invasive local intramedullary osteosynthesis, which has been under design by our group. We conducted a biomechanical comparison in composite tibiae of the Retrograde Tibial Nail against the Expert Tibial Nail (Synthes®). Our hypothesis was that the RTN would provide equivalent biomechanical stability with respect to extra-axial compression, torsion and load to failure testing, in an extra-articular distal tibia fracture model. METHODS: Biomechanical composite bone testing was conducted in 14 biomechanical composite tibiae in an AO 43 A3 fracture model. In both groups, triple angle stable interlocking was performed in the distal fragment. RESULTS: Results show a statistically non-significant higher stability of the ETN during the axial loading tests. Torsional stability testing resulted in a statistically superior performance for the RTN (p = 0.018). Destructive extra-axial compression resulted in failure of six ETN constructs, while all RTN specimens survived the maximal load. CONCLUSIONS: The experimental Retrograde Tibial Nail provides the key features for the treatment of distal tibial fractures. It combines a minimally invasive local intramedullary osteosynthesis with the ability to securely fix the fracture by multiple angle stable locking options.

Long-term outcome after operative treatment of traumatic patellar dislocation in adolescents.

OBJECTIVES: Retrospective evaluation of the long-term outcomes after surgical treatment of traumatic patellar dislocations in adolescents and identification of possible predictive factors of poor outcomes. DESIGN: Retrospective clinical study. SETTING: University Clinic, Level I Trauma Center. PATIENTS: All 33 adolescents, with a mean age of 14.8 years, who were treated surgically after traumatic patellar dislocation between 1994 and 2006, were involved in this study. INTERVENTION: Mini-open medial reefing and arthroscopic lateral release. MAIN OUTCOME MEASUREMENTS: The clinical outcome was evaluated with the visual analogue scale, the Lysholm score, the Kujala score, and the Tegner activity level scale. On preoperative radiographs and magnetic resonance imaging scans, trochlear dysplasia and patella alta were assessed. The variables analyzed were sex, associated osteochondral injuries, the number of redislocations before surgery, and the number of redislocations after surgery. RESULTS: At the mean follow-up of 9.8 years, the mean Lysholm score was 82.6, the mean Kujala score was 84.4, the mean Tegner activity level was 4.8, and the mean visual analogue scale was 0.2. We found no significant differences in the subgroups regarding functional outcomes. Fifteen patients with patella alta and 4 patients with trochlear dysplasia were assessed radiologically. Redislocations after surgery were observed in 4 patients, 2 of them were female patients who exhibited quadriceps angles requiring tibial tubercle osteotomy to be performed after maturation. CONCLUSIONS: The techniques of mini-open medial reefing and lateral release demonstrate a good functional long-term outcome and effectively prevent recurrent instability. The major predictive factor for poor outcomes and redislocations is an inadequately addressed pathology. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Combining magnetic resonance imaging within six-hours of symptom onset with clinical follow-up at 24 h improves prediction of 'malignant' middle cerebral artery infarction.

BACKGROUND: A large diffusion-weighted imaging lesion ≤six-hours of symptom onset was found to predict the development of 'malignant' middle cerebral artery infarction with high specificity, positive predictive value, and negative predictive value, but sensitivity was low. HYPOTHESIS: We tested the hypothesis that sensitivity can be improved by adding information from clinical follow-up examination after 24 h. METHODS: We analyzed data from a prospective, multicenter, observational cohort study of patients with acute ischemic stroke and middle cerebral artery occlusion studied by stroke magnetic resonance imaging ≤six-hours of symptom onset. We used the National Institutes of Health Stroke Scale to assess severity of symptoms after 24 h. We used the Classification and Regression Trees analysis to define the optimal thresholds of diffusion-weighted imaging lesion volume and the National Institutes of Health Stroke Scale after 24 h in patients developing 'malignant' middle cerebral artery infarction. We calculated sensitivity, specificity, positive predictive value, and negative predictive value for two simple predictive models based on acute diffusion-weighted imaging lesion volume alone and acute diffusion-weighted imaging lesion volume together with the National Institutes of Health Stroke Scale after 24 h. RESULTS: Of 135 patients, 27 (20%) developed a 'malignant' middle cerebral artery infarction. The Classification and Regression Trees analysis identified acute diffusion-weighted imaging lesion ≥78 ml and the National Institutes of Health Stroke Scale score after 24 h ≥22 as optimal cut-offs. Inclusion of the National Institutes of Health Stroke Scale score after 24 h in a simple two-step decision tree increased sensitivity from 0·59 to 0·79, while specificity, positive predictive value, and negative predictive value remained largely unchanged. CONCLUSION: Clinical follow-up examination after 24 h helps identify patients at risk of 'malignant' middle cerebral artery infarction that are missed by predictive algorithms based on early diffusion-weighted imaging lesion volume alone.

Mutated Ras-transfected, EBV-transformed lymphoblastoid cell lines as a model tumor vaccine for boosting T-cell responses against pancreatic cancer: a pilot trial.

Genetically modified lymphoblastoid cell lines (LCL) have been shown to be an attractive alternative source of antigen-presenting cells for cancer vaccination in vitro. We tested their application in patients with pancreatic cancer in a phase I clinical trial. As a model tumor antigen, we selected the point-mutated (codon 12) Ki-Ras p21 oncogene (muRas) frequently (∼85%) present in pancreatic adenocarcinoma. Autologous LCLs were established in vitro by spontaneous outgrowth from peripheral blood lymphocytes of seven pancreatic carcinoma patients and were genetically modified with an episomal Epstein-Barr virus (EBV)-based expression vector to express muRas (muRas-LCL). Weekly vaccinations with subcutaneous injection of 5×10(6) muRas-LCL were done. In six of seven patients, therapeutic vaccination elicited a T-cell response with an increase in the frequency of muRas-specific precursor cytotoxic T lymphocytes in the peripheral blood and positive delayed-type hypersensitivity reactions at the injection site. Besides local reactions and flu-like symptoms, there were no signs of toxicity and no acute EBV infection, onset of EBV-associated lymphoma, or other severe complications. A clinical response (stable disease) was observed for a short time period (2-4 months) in four of seven patients (57%), mostly in earlier tumor stages. Our results indicate that LCL presenting genetically modified antigen represent a valuable and easily available tool for in vivo autologous tumor vaccination. LCL can be transfected with any known tumor antigen and therefore should be further clinically investigated.