Chordoma with a massive spindle-cell sarcomatous transformation. A light- and electron-microscopic and immunohistological study

A 26-year-old woman was operated on for a bulky tumor in the sacral region; she died of massive local tumor recurrence and pulmonary metastases 3 months later. Most of the original tumor showed a highly cellular spindle-cell sarcoma compatible with a fibrosarcoma of a high grade of malignancy. In a few small areas of the tumor, a chordoma-like pattern surrounded by growth of spindle-cell sarcoma was found. The spindle-cell component exhibited vimentin positivity in all tumor cells, but many cells were also cytokeratin-positive. The chordoma-like areas showed cytokeratin in all tumor cells. The chordoma-like areas, but not the spindle-cell areas also were positive for epithelial membrane antigen and S-100 protein. This case indicates that the sarcomatous change associated with chordoma may contain keratins as a sign of epithelial differentiation, and may thus represent sarcomatous transformation of chordoma cells, rather than a coincidental soft-tissue sarcoma or collision tumor.     

Disc degeneration and lumbar instability: Magnetic resonance examination of 16 patients

Flexion and extension radiographs of 75 young males with low back pain disclosed abnormal segmental motion of the lumbar spine in 16 patients with translational movements in 20 intervertebral segments. These 16 patients were further investigated by magnetic resonance imaging to assess disc degeneration in the unstable segments. On T2-weighted images of the 20 segments, the disc was normal in 13 and degenerated in only 7 patients. Thus, the initial factor in lumbar instability in young patients with low back pain is not always degeneration of the disc.     

Treatment of major depressive disorder in the Finnish general population

Background : Few general population studies of the treatment of major depressive disorder (MDD) have included the whole spectrum of treatments. We estimated the rates of different treatments and the effect of individual and disorder characteristics plus provider type on treatment received. Methods : In the Health 2000 Study, a representative sample (n=6,005) from the adult Finnish population (≥30 years) were interviewed (CIDI) in 2000–2001 for the presence of DSM‐IV mental disorders during the past 12 months. Logistic regression models were used to examine factors influencing the type of treatment: either pharmacotherapies (antidepressants, anxiolytics, sedatives/hypnotics, antipsychotics) or psychological treatment. Results : Of the individuals with MDD (n=288), currently 24% used antidepressants, 11% anxiolytics, 16% sedatives/hypnotics, 5% antipsychotics, and 17% reported having received psychological treatment. Overall, 31% received antidepressants or psychological treatment or both; 18% received minimally adequate treatment. Of those 33% (n=94) using health care services for mental reasons, 76% received antidepressants or psychological treatment or both; 54% received minimal adequate treatment. In logistic regression models, the use of antidepressants was associated with female sex, being single, severe MDD, perceived disability, and comorbid dysthymic disorder; psychological treatment with being divorced, perceived disability, and comorbid anxiety disorder. Conclusions : Due to the low use of health services for mental reasons, only one‐third of subjects with MDD use antidepressants, and less than one‐fifth receives psychological treatment. The treatments provided are determined mostly by clinical factors such as severity and comorbidity, in part by sex and marital status, but not education or income. Depression and Anxiety 26:1049–1059, 2009. © 2009 Wiley‐Liss, Inc.     

Three-year evaluation of late breast reconstruction with a free transverse rectus abdominis musculocutaneous flap in a county hospital in Sweden: a retrospective study.

We present our three-year experience of late breast reconstruction with conventional free TRAM flaps in 16 consecutive patients in a Swedish county hospital. The breast reconstruction was done unilaterally in 14 and bilaterally in two, giving a total of 18 free TRAM flaps in 16 patients. Six patients developed anastomotic or systemic thromboembolic events during or after the operation' three developed during the operation, and one required reoperation for postoperative thrombosis. No flaps were lost. Three patients developed deep venous thrombosis (DVT) or pulmonary embolism (PE) postoperatively; the two patients with DVT were later found to be resistant to activated protein C. The patient with a PE had developed multiple metastases by one year postoperatively. We compared the six patients who developed anastomotic and systemic thromboembolic events with those whose operations were uncomplicated and no significant differences were found either in their characteristics or overall events during operation.     

Circadian rhythm of white blood cells during clozapine treatment

Rationale: The atypical antipsychotic clozapine is effective in the treatment of patients with refractory schizophrenia. It carries a well-known risk of neutropenia and agranulocytosis, which necessitates the immediate discontinuation of clozapine. Objective: We report a patient who developed neutropenia on clozapine, but behind the cell count decrease showed to be a diurnal variation of the white blood cells (WBC). Methods: Due to the lack of efficacy of subsequent treatment of conventional and other atypical neuroleptics, treatment with clozapine was restarted after discontinuation. When the morning count of WBC began to fall, WBC count was repeated in the afternoons. Results: Careful blood cell monitoring showed a pronounced diurnal variation of WBC (2.9–4.2×10⁹/l in the morning and 3.6–7.1×10⁹/l in the afternoon) and granulocytes (0.8–1.4×10⁹/l and 2.9–5.5×10⁹/l, respectively). Conclusions: Some patients may thus have a spuriously low cell count and may be unnecessarily denied effective treatment. Received: 10 February 1999 / Final version: 22 March 1999     

Modeled Health Economic Impact of a Hypothetical Certolizumab Pegol Risk-Sharing Scheme for Patients with Moderate-to-Severe Rheumatoid Arthritis in Finland

Purpose

To model the American College of Rheumatology (ACR) outcomes, cost-effectiveness, and budget impact of certolizumab pegol (CZP) (with and without a hypothetical risk-sharing scheme at treatment initiation for biologic-naïve patients) versus the current mix of reimbursed biologics for treatment of moderate-to-severe rheumatoid arthritis (RA) in Finland.

Methods

A probabilistic model with 12-week cycles and a societal approach was developed for the years 2015–2019, accounting for differences in ACR responses (meta-analysis), mortality, and persistence. The risk-sharing scheme included a treatment switch and refund of the costs associated with CZP acquisition if patients failed to achieve ACR20 response at week 12. For the current treatment mix, ACR20 at week 24 determined treatment continuation. Quality-adjusted life years were derived on the basis of the Health Utilities Index.

Results

In the Finnish target population, CZP treatment with a risk-sharing scheme led to a estimated annual net expenditure decrease ranging from 1.7% in 2015 to 5.6% in 2019 compared with the current treatment mix. Per patient over the 5 years, CZP risk sharing was estimated to decrease the time without ACR response by 5%-units, decrease work absenteeism by 24 days, and increase the time with ACR20, ACR50, and ACR70 responses by 5%-, 6%-, and 1%-units, respectively, with a gain of 0.03 quality-adjusted life years. The modeled risk-sharing scheme showed reduced costs of €7866 per patient, with a more than 95% probability of cost-effectiveness when compared with the current treatment mix.

Conclusion

The present analysis estimated that CZP, with or without the risk-sharing scheme, is a cost-effective alternative treatment for RA patients in Finland. The surplus provided by the CZP risk-sharing scheme could fund treatment for 6% more Finnish RA patients.

Funding

UCB Pharma.

     

Volumetric capnography as a bedside monitoring of thrombolysis in major pulmonary embolism

Objective To describe the use of volumetric capnography, a plot of expired CO₂ concentration against expired volume, in monitoring fibrinolytic treatment of major pulmonary embolism.Design and setting Two case reports in the emergency department of a teaching hospital.Patients Two conscious and spontaneously breathing patients (69- and 31-year-old women) with major pulmonary embolism requiring thrombolysis. Decision for thrombolysis was based on the association of right ventricular afterload on echocardiography, with respiratory failure and hypotension in the first patient, and dyspnea and hemodynamically stable parameters in the second one.Interventions Successive capnographic measurements were performed before, during, and after thrombolysis. Curves of volumetric capnography were obtained from a sidestream gas monitor with flow sensor and an arterial blood gas analysis for CO₂ partial pressure.Measurements and results We calculated late deadspace fraction, previously suggested as the most effective capnographic parameter in the diagnosis of pulmonary embolism. Late deadspace fraction decreased in the two patients, respectively, from 64.4% to 1.1% and from 25.6% to 5.7% after thrombolysis, with a concomitant disappearance of right heart dysfunction signs on echocardiography.Conclusions Volumetric capnography can monitor thrombolysis in major pulmonary embolism. Differences between volumetric capnography technology and the more traditional arterial to end-tidal CO₂ gradient are important to take into account for clinical application.     

Reliability and validity of the Finnish version of the Lower Extremity Functional Scale (LEFS)

Purpose: The present study aimed to assess the psychometric properties of the Finnish version of the Lower Extremity Functional Scale (LEFS) among foot and ankle patients.

Methods: The LEFS was translated and cross-culturally adapted to Finnish. We assessed the test–retest reliability, internal consistency, floor-ceiling effect, construct validity and criterion validity in patients who underwent surgery due to musculoskeletal pathology of the foot and ankle (N?=?166).

Results: The test–retest reliability was high (ICC = 0.93, 95% CI: 0.91–0.95). The standard error of measurement was 4.1 points. The Finnish LEFS showed high internal consistency (Cronbach’s α?=?0.96). A slight ceiling effect occurred as 17% achieved the maximum score. The LEFS correlation was strong with the 15D Mobility dimension (r?=?0.74) and overall HRQoL (r?=?0.66), pain during foot and ankle activity (r=??0.69) and stiffness (r=??0.62). LEFS correlated moderately with foot and ankle pain at rest (r=??0.50) and with physical activity (r?=?0.46).

Conclusions: The Finnish version of the LEFS showed reliability and validity comparable to those of the original version. This study indicates that the Finnish version of the LEFS serves both clinical and scientific purposes in assessing lower-limb function.

• Implications for Rehabilitation

• The Finnish version of the Lower Extremity Functional Scale (LEFS) is a reliable and valid tool for assessing lower-extremity musculoskeletal disability in Finnish-speaking population.

• Investigation of the psychometric properties of the Finnish version of the LEFS showed validity and reliability comparable to those of the original English version.

• The Finnish LEFS is easy to complete and suitable for clinical, rehabilitation and research purposes.

     

Role of angiogenic growth factors in transplant coronary artery disease

Transplant coronary artery disease (TxCAD) as a manifestation of chronic rejection is a major limitation to long-term survival of heart transplant recipients. Although the exact molecular and cellular mechanisms contributing to neointimal formation are unknown, it has been generally believed that smooth muscle cells (SMC) of donor origin migrate from the media into the subendothelial layer of the vascular wall, where SMC proliferate and synthesize extracellular matrix resulting in intimal thickening. However, recent observations indicate that hematopoietic and vascular progenitor cells derived from recipient bone marrow may contribute to the arteriosclerotic lesion formation in the coronary arteries of the transplant. On the other hand, studies on postnatal hematopoiesis indicate that angiogenic growth factors such as vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1) may regulate the recruitment of these cells into distant organs. Furthermore, embryonic VEGFR-2 /CD34+ stem cells may serve as vascular progenitor cells and their differentiation into endothelial cells and SMC may be regulated by VEGF and platelet-derived growth factor (PDGF), respectively. In this review, we discuss the role of angiogenic growth factors such as VEGF, Ang, and PDGF in the recruitment of hematopoietic and vascular progenitor cells in TxCAD and suggest novel therapies targeted at homing, differentiation and proliferation of these cells in the allograft.