Donor cell chimerism evaluation in cerebrospinal fluid by short tandem repeat analysis following allogeneic hematopoietic stem cell transplantation

Cerebrospinal fluid (CSF) cell count, morphology and flow cytometric evaluations are used to investigate central nervous system (CNS) involvement in leukemia/lymphoma. We performed CSF short tandem repeat (STR) analysis to monitor CSF chimerism status and evaluate for disease involvement in 11 asymptomatic pediatric allogeneic hematopoietic stem cell transplantation (HSCT) recipients with hemato-lymphoid neoplasms and high risk for or history of CNS involvement. Eighteen (64%) of the samples with median CSF cell count of 1/mm³ with 90% lymphocytes gave conclusive STR results, suggesting that this DNA-based method can be used in monitoring CSF chimerism status after HSCT with an acceptable yield.     

Non-surgical treatment for adult spinal deformity: results of an intensive combined physical and psychological programme for patients with adult spinal deformity and chronic low back pain—a treatment-based cohort study

Objectives

No evidence-based treatment exists for adult spinal deformity (ASD) patients with chronic low back pain (CLBP). Aim of this study: evaluate a combined physical and psychological programme (CPPP) for ASD patients with CLBP and to compare this with a non-ASD-cohort with CLBP.

Methods

Data were extracted from the database of CLBP-patients for whom surgery is not an option and completed CPPP. Two cohorts were selected: an ASD-cohort (n = 80) based on a Cobb angle of > 10° and a consecutive age- and gender-matched non-ASD-cohort (n = 240). Primary outcome: functional status (Oswestry Disability Index; ODI). Secondary outcomes: pain intensity, self-efficacy and quality of life. Assessments: pre and post treatment, one-month and one-year follow-up (FU). Clinical relevance: minimal important clinical change (MCIC; ODI 10 points), patient acceptable symptom state (PASS; ODI ≤ 22).

Results

Demographics ASD-cohort: 79% female, mean age 50.9 (± 14.1) years, mean CLBP duration 15.5 (± 12.5) years, mean Cobb angle 21.4 (± 9.4)°. Non-ASD-cohort: not significantly different. Both cohorts improved in functional status (F[1,318] = 142.982, p < .001; r = 0.31). The ASD-cohort improved from mean ODI 39.5(± 12.0) at baseline to mean ODI 31.8(± 16.5) at one-year FU. Clinical relevance: 51% of the ASD patients reached MCIC and 33% reached a PASS. An interaction effect is shown between time and both cohorts (F[1,318] = 8.2, p = .004; r = 0.03); however, not clinically relevant. All secondary outcomes: improvement at one-year FU.

Conclusion

This is the first study showing beneficial outcomes of a non-surgical treatment in selected ASD patients with longstanding CLBP. Improvement is shown in functional status, and appeared equivalent to the non-ASD cohort.

Level of Evidence 1

Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.

     

No effect of additional screw fixation of a cementless,all-polyethylene press-fit socket on migration,wear, and clinical outcome

Background and purpose — Additional screw fixation of the all-polyethylene press-fit RM cup (Mathys) has no additional value for migration, in the first 2 years after surgery. However, the medium-term and long-term effects of screw fixation remain unclear. We therefore evaluated the influence of screw fixation on migration, wear, and clinical outcome at 6.5 years using radiostereometric analysis (RSA).

Patients and methods — This study involved prolonged follow-up from a previous randomized controlled trial (RCT). We analyzed RSA radiographs taken at baseline and at 1-, 2-, and 6.5-year follow-up. Cup migration and wear were assessed using model-based RSA software. Wear was calculated as translation of the femoral head model in relation to the cup model. Total translation, rotation, and wear were calculated mathematically from results of the orthogonal components.

Results — 27 patients (15 with screw fixation and 12 without) were available for follow-up at 6.5 (5.6–7.2) years. Total translation (0.50?mm vs. 0.56?mm) and rotation (1.01 degrees vs. 1.33 degrees) of the cup was low, and was not significantly different between the 2 groups. Wear increased over time, and was similar between the 2 groups (0.58?mm vs. 0.53?mm). Wear rate (0.08?mm/year vs. 0.09?mm/year) and clinical outcomes were also similar.

Interpretation — Our results indicate that additional screw fixation of all-polyethylene press-fit RM cups has no additional value regarding medium-term migration and clinical outcome. The wear rate was low in both groups.     

Risk factors for osteoporosis in Caucasian patients with moderate chronic obstructive pulmonary disease: a case control study

The prevalence of osteoporosis is high in chronic obstructive pulmonary disease (COPD) patients. The gold standard for the diagnosis of osteoporosis is bone mineral density (BMD) measurements as assessed by dual energy absorptiometry (DXA) scanning as well as vertebral fractures as assessed by instant vertebral assessment (IVA). The aim of this study was to compare COPD GOLD II patients (that is, patients with moderate COPD, stage II, according to the GOLD classification) with osteoporosis (cases) to COPD GOLD II patients without osteoporosis (controls) to identify risk factors for osteoporosis. The diagnosis of osteoporosis was based on BMD and vertebral fractures. Cases (n=49) were matched for gender, age and forced expiratory volume in the first second to controls (n=49). We assessed pulmonary function, body composition, vitamin D, emphysema score (by high-resolution computer tomography), medical history and medication use in all patients. Variables that were significantly different between the cases and controls were included in a logistic regression analysis. COPD patients with osteoporosis had a significantly lower body mass index (BMI) and higher residual volume as the percentage of total lung capacity (RV%TLC) compared to COPD patients without osteoporosis. Decreasing BMI and increasing RV%TLC increased the odds ratio for osteoporosis. Overweight and obese BMI values were protective for osteoporosis. Screening for osteoporosis should be performed even in moderate COPD patients, especially in those with a low BMI and/or a high RV%TLC.     

Etoposide, mitoxantrone and prednisone: a salvage regimen with low toxicity for refractory or relapsed non-Hodgkin's lymphoma

BACKGROUND AND OBJECTIVES: Relapsed non-Hodgkin's lymphoma (NHL) is preferably treated with high-dose therapy and stem cell support. However, not all patients qualify for intensive chemotherapy. We evaluated the efficacy and toxicity of a new salvage chemotherapy regimen designed for patients with relapsed or refractory NHL who are not appropriate candidates for high-dose therapy (HDT). DESIGN AND METHODS: Seventy-nine patients received a regimen consisting of etoposide (350 mg/m(2) i.v. day 1), mitoxantrone (14 mg/m(2) i.v. day 1) and prednisone (80 mg/m(2) p.o. days 1-5) (EMP). The majority had aggressive NHL. Twenty-one patients were elderly, i.e. >60 years of age; RESULTS. The overall response rate in the 79 patients was 38% as compared to 67% in the elderly. The progression-free survival was 54% and 30% at 12 months and 24 months, respectively. The toxicity of the regimen was relatively low. No toxic deaths have occurred. In 28 of 231 cycles (12%) a CTC-grade 2-4 infection was encountered. Twenty-one hospital admissions were necessary because of infection or fever. Other toxicity was rare. Toxicity was not greater in the elderly patients. WHO performance status 2-4 and elevated serum lactate dehydrogenase (LDH) concentrationv were adverse prognostic factors for response as well as for overall survival. Another adverse prognostic factor for response was age <60 years. INTERPRETATION AND CONCLUSIONS: EMP is a new salvage regimen with a relatively low toxicity. It should be considered for patients with relapsed or refractory NHL who are not candidates for standard reinduction therapy and stem cell transplantation.     

Hypogonadism in male outpatients with sarcoidosis

Hypogonadism is assumed to be present in sarcoidosis. Nevertheless, a comparison of circulating sex hormone concentrations of male sarcoidosis patients with those of healthy men has never been done. Moreover, it remains unknown if hypogonadism may contribute to a reduced muscle function, exercise intolerance, diminished vitality and depressed mood in male sarcoidosis patients. Pulmonary function, muscle function, exercise tolerance, vitality, mood, circulating sex hormone concentrations and C-reactive protein were assessed in 30 male sarcoidosis patients and 26 age-matched men with a normal pulmonary function. On average, patients had a restrictive pulmonary function, worse inspiratory and quadriceps muscle function, functional exercise intolerance, diminished vitality, depressed mood and increased systemic inflammation. Moreover, patients had significantly lower circulating (free) testosterone concentrations, while circulating sex hormone-binding globulin tended to be lower (p=0.0515). Circulating gonadotrophin concentrations were comparable. Non-significant relationships were found between sex hormones, clinical outcomes and C-reactive protein in patients with sarcoidosis. A significant number of male outpatients with sarcoidosis (46.7%) had low circulating testosterone concentrations, which was most probably caused by hypogonadotrophism. The clinical relevance of hypogonadism in male outpatients with sarcoidosis, however, remains currently unknown. Indeed, poor inspiratory and quadriceps muscle function, exercise intolerance, diminished vitality and depressed mood were not related to hypogonadism in these patients.     

Hypogonadism, quadriceps weakness, and exercise intolerance in chronic obstructive pulmonary disease

RATIONALE: Circulating levels of testosterone and gonadotrophins of patients with chronic obstructive pulmonary disease (COPD) have never been compared with those of elderly men with normal pulmonary function. Moreover, the relationship of hypogonadism with quadriceps muscle weakness and exercise intolerance has been studied scarcely in men with COPD. OBJECTIVES: To compare circulating levels of hormones of the pituitary-gonadotrophic axis of men with COPD with those of age-matched control subjects. Moreover, to study the relationship of hypogonadism with quadriceps muscle force, 6-min walking distance, and systemic markers of inflammation in the patients. METHODS AND MEASUREMENTS: Circulating levels of follicle-stimulating hormone, luteinizing hormone, testosterone, and sex hormone-binding globulin were determined, and free testosterone was calculated in 78 patients (FEV1: 44 +/- 17% of the predicted values) and 21 control subjects. Moreover, quadriceps muscle force, 6-min walking distance, number of pack-yr, and systemic inflammation were determined. MAIN RESULTS: Follicle-stimulating hormone and luteinizing hormone were higher in the patients, whereas testosterone was lower (p < or = 0.05). The latter finding was also present in 48 non-steroid-using patients with normal blood gases. Low androgen status was significantly related to quadriceps muscle weakness (r = 0.48) and C-reactive protein (r = -0.39) in the patients, but not to exercise intolerance, the number of pack-yr, or increased circulating levels of interleukin 8 or soluble receptors of tumor necrosis factor alpha. CONCLUSIONS: In contrast to exercise intolerance, quadriceps muscle weakness is related to low circulating levels of testosterone in men with COPD.