Anita Zahlten-Hinguranage

Prognostic significance of drug-regulated genes in high-grade osteosarcoma

About 25–45% of patients with high-grade osteosarcoma poorly respond to chemotherapy with an increased risk of relapse and the development of metastasis. Therefore, the aim of this study was the evaluation of the prognostic value of eight previously identified drug-regulated candidate genes on osteosarcoma therapy outcome. Gene expression of 8 candidate genes was analyzed in 35 formalin-fixed, paraffin-embedded, laser-microdissected osteosarcoma biopsies. The prognostic value of these genes was evaluated by the correlation of gene expression with therapy outcome, overall survival and event-free survival in univariate and multivariate analysis. Upon univariate analysis, the expression of MALAT-1, IMPDH2, FTL and RHOA significantly correlated with response to chemotherapy. Expression of all four genes was increased in the poor responder group. Upon multivariate analysis, IMPDH2 maintained its independent prognostic value (P=0.025). Concerning the overall survival of the patients, we observed a significant association with the expression of FTL, PHB, ATAD2, ACTN1 and RRM2 as well as lactate dehydrogenase serum levels. In the subgroups of patients with high expression of these genes and those with elevated lactate dehydrogenase levels, the mean overall survival was decreased 1.7-, 1.9-, 2.2-, 2.4-, 1.5- and 4.5-fold, respectively. Except RRM2, all genes and lactate dehydrogenase serum levels remained significant in the multivariate analysis. In addition, the event-free survival was significantly decreased in the subgroups of patients with high FTL, ATAD2 and IMPDH2 expression (1.8-, 6.3- and 2.4-fold, respectively). These data demonstrate that among the identified genes are valuable markers for the prediction of osteosarcoma therapy outcome. Especially IMPDH2 and FTL are promising candidates for the stratification of osteosarcoma patients into low- and high-risk groups. Owing to their involvement in drug action these genes may further be potential targets for the modulation of drug sensitivity.

Therapy outcome after multidisciplinary treatment for chronic neck and chronic low back pain: a prospective clinical study in 365 patients

Objectives: This prospective longitudinal clinical study analyses the therapy outcome of 365 patients with either chronic neck (n = 134) or low back (n = 231) pain treated with a multidisciplinary biopsychosocial therapy approach. Methods: Patients with chronic neck pain (NP) or low back pain (LBP) for 3 months or longer, corresponding sick leave for longer than 6 weeks, and clearly defined inclusion and exclusion criteria underwent a 3‐week standardized inpatient multidisciplinary biopsychosocial therapy. Baseline sociodemographic, occupational, functional, and psychological data at entry into the study (T0) were comparable in both groups. At the 6‐month follow‐up (T1), five different therapy outcomes were analysed in both groups: back‐to‐work status, generic health status (the 36‐item Short Form Health Survey, SF‐36), pain intensity (visual analogue scale), functional capacity (Hannover back capacity score), and satisfaction with the therapy. Results: Both treatment groups improved significantly in all outcome criteria between T0 and T1. In the total group, the back‐to‐work rate was 67.4%. At the final follow‐up there were no significant differences between the group with chronic NP and the group with chronic LBP in the outcome criteria back‐to‐work status, improvement of health status and functional capacity, satisfaction with therapy, and reduction of pain. Conclusion: Evaluation of the main results of this study suggests that patients with chronic NP also derive significant benefit from a multidisciplinary treatment strategy, demonstrated in the literature so far mainly for patients with chronic LBP.

The influence of the grade of chronicity on the outcome of multidisciplinary therapy for chronic low back pain.

Study Design. Prospective longitudinal clinical study. Objective. The objective of the study was to analyze the outcome of different stages of chronicity in patients with chronic low back pain treated with a multidisciplinary therapy. Summary of Background Data. Results of studies comparing different grades of chronicity in therapy for chronic low back pain have not been published so far. Methods. A total of 387 patients with chronic low back pain for 3 months or longer and a corresponding sick leave for longer than 6 weeks underwent a 3-week standardized multidisciplinary therapy. At baseline (T0), patients were assigned into 3 groups of chronicity grades according to the classification of von Korff et al (Group A, Grades I and II; Group B, Grade III; Group C, Grade IV) and were prospectively followed. At the the 6-month follow-up (T1), 5 different therapy outcomes were analyzed and compared in the 3 groups: back-to-work status, generic health status (SF-36), pain intensity (visual analogue scale), functional capacity (Hannover back capacity score), and satisfaction with the therapy. Results. At T0, patients in Group C had a higher pain level, a longer history of pain, and more general and more psychosomatic comorbidities than patients with lower levels of chronicity. All 3 treatment groups improved significantly in all outcome criteria between T0 and T1. In the total group, the back-to-work rate was 67.4%. At the final follow-up, there were significantly better results in terms of functional capacity and pain level in patients with lower grades of chronicity but mostly due also to worse initial baseline values. Back-to-work rate, satisfaction with therapy, and the Mental Component Summary of the SF-36 did not show a significant difference at T1 between the groups analyzed. Conclusion. According to the results of this study, patients with chronic low back pain also derive significant benefit from a multidisciplinary treatment strategy in higher stages of chronicity. Therefore, therapy should not be limited to the patients in lower stages of chronicity.

Efficacy of Multidisciplinary Treatment for Patients With Chronic Low Back Pain A Prospective Clinical Study in 395 Patients

BackgroundThe effectiveness of multidisciplinary treatment programs varies throughout the literature, and it remains controversial how therapy outcome is affected by patients’ individual parameters and which treatment settings work best. ObjectivesWe set out to examine the impact of patient variables on the effectiveness of a 3-week multidisciplinary treatment program in patients with chronic low back pain. By presenting effect sizes, we aimed to enable the comparison of our findings with other studies across disciplines. MethodsData on 395 patients were prospectively collected at study entry, at the end of the program (T1) and after 6 months’ follow-up (T2). Relevant therapy outcomes were analyzed by presenting effect sizes with Cohen’s d. Group comparisons were performed for sociodemographic and clinical features to determine the impact on therapy outcome. ResultsMedium effect sizes (d = −0.6 to −0.7) were shown for visual analog scale (VAS) after treatment and at T2, indicating clinically relevant pain relief. Significant changes in pain-related disability were observed immediately at T1 with a strong treatment effect (d = 0.8). Functional capacity was improved with low to medium effect sizes (0.4–0.5). Quality-of-life subscales (36-item Short Form Health Survey) improved significantly at T1 for physical function, vitality, and mental health (d = 0.5–0.8). Center for Epidemiological Studies – Depression Scale scores improved significantly with strong effect sizes of d = 0.7. Sociodemographic parameters displayed a significant impact on effect sizes for visual analog scale at T2, with females (d = −0.9), age group 30 to 39 years (d = −1), and patients with low physical job exposure (d = −0.9) benefiting most. An increase in number of pain locations (−0.7) and severity of accompanying pain (−0.7) in other body areas significantly impaired therapy outcome and effect sizes of VAS. ConclusionsThus, multidisciplinary treatment ameliorates pain, functional restoration, and quality of life with medium to high effect sizes even for patients with a long history of chronic back pain. Effect sizes are higher than for monodisciplinary treatments and treatment effects remained stable at 6-month follow-up in a longitudinal uncontrolled study design. Thus, we believe that multidisciplinary treatment is vital for the treatment of patients with chronic low back pain. The impact of sociodemographic and pain-related parameters needs to be taken into account when including patients in an appropriate treatment program. We emphasize the presentation of effect sizes as a vital treatment evaluation to enable cross-sectional comparison of therapy outcomes.

[Bone and soft-tissue tumors of the foot and ankle].

ZusammenfassungHintergrundDiese Studie berichtet über die Epidemiologie der Knochen- und Weichteiltumoren des Fußes und Sprunggelenkes, stellt eine differenzierte Therapieplanung vor und evaluiert mittelfristige klinisch-funktionelle Ergebnisse nach Operation der malignen Tumoren.Methode204 Patienten mit Tumoren des Fußes wurden analysiert (163 benigne und 41 maligne Tumoren). Epidemiologie und operative Versorgung werden dargestelltErgebnisseHäufigste benigne Tumoren waren Exostosen, Knochenzysten und Osteoidosteom, häufigste maligne Tumoren Metastasen, Chondrosarkom und Ewing-Sarkom. Bei benignen Tumoren konnte in über 90% eine lokale Resektion durchgeführt werden, während sich bei malignen Tumoren Amputation und Arthrodese einerseits und Extremitäten- oder Gelenkerhalt andererseits die Waage hielten. Klinisch ergaben sich nach operativer Versorgung der primär malignen Tumoren gute funktionelle Resultate und eine 5-Jahres-Überlebensrate von 84%.SchlussfolgerungTumoren des Fußes erfordern eine differenzierte Versorgungsstrategie. Trotz eines hohen Anteils an extremitäten- und gelenkopfernden Operationen sind die mittelfristigen funktionellen Ergebnisse und die Überlebensrate gut.AbstractBackgroundThis study reports the epidemiology of bone and soft-tissue tumors of the foot and ankle, presents therapy strategies, and evaluates mid-term clinicofunctional outcome after surgery for malignant tumors.MethodsTwo hundred four patients with tumors of the foot and ankle were analyzed (163 benign and 41 malignant). Epidemiology and surgical therapy are reported.ResultsThe most frequent tumors were exostosis, bone cyst, and osteoid osteoma for benign tumors and metastases and chondrosarcoma and Ewing’s sarcoma for malignant tumors. In more than 90% of the benign tumors, local resection could be carried out, whereas in malignant tumors, ablative procedures and arthrodeses were almost as common as limb- and joint-sparing techniques. However, follow-up revealed good functional results and a 5-year survival rate of 84% for patients with primary malignant tumors.ConclusionTumors of the foot and ankle require a thorough therapeutic strategy. Mid-term functional results and survival rate after surgical treatment are good, although a high percentage of ablative procedures or fusions could not be avoided in our patients.

The impact of pain spread on the outcome of multidisciplinary therapy in patients with chronic musculoskeletal pain – A prospective clinical study in 389 patients

Background: Musculoskeletal pain represents a continuous process ranging from single‐site to multiple‐site pain, with an increase in pain sites accompanied by an increasing risk of chronification and the development of further comorbidities. Within this context, the impact of pain spread on therapy outcome is still unknown.