Automatic depletion with Spectra Optia allows a safe 16% reduction of red blood cell pack consumption in exchanged sickle cell anemia patients.

BACKGROUND: Chronic red blood cell exchanges (RBCXs) are frequently used to prevent complications in patients with sickle cell anemia, but the scarcity of matched red blood cell packs (RBCPs) is a serious concern. The main goal of this study was to compare the number of RBCPs used during RBCXs between the Spectra Optia (SO) device (with the automatic depletion step) and the former Cobe Spectra (CSP) device. STUDY DESIGN AND METHODS: The performances and safety of 300 SO sessions using the automatic depletion step (SO/DE) in 50 patients with sickle cell anemia under a chronic transfusion program over a 1-year period were prospectively analyzed. The numbers of RBCPs saved using this protocol compared to the SO device without depletion and to the CSP device were determined. RESULTS: The SO/DE protocol appeared to be safe, as only 5% and 17% of the sessions were characterized by a significant decrease in blood pressure and increase in heart rate (grade 2 adverse events), respectively. Postapheresis hematocrit and fraction of cells remaining reached expected values. The SO/DE protocol required 16% fewer RBCPs compared to SO without depletion, allowing a mean saving of 12 RBCPs per patient and per year and 13% fewer compared to CSP device. Interestingly, the saving was more important for patients with high total blood volume and/or high preapheresis hematocrit. CONCLUSION: The SO/DE protocol is an efficient, safe and cost-effective procedure for patients with sickle cell anemia under a chronic transfusion program.

Depression, telomeres and mitochondrial DNA: between- and within-person associations from a 10-year longitudinal study.

Alterations in cellular aging, indexed by leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn), might partly account for the increased health risks in persons with depression. Although some studies indeed found cross-sectional associations of depression with LTL and mtDNAcn, the longitudinal associations remain unclear. This 10-year longitudinal study examined between- and within-person associations of depressive symptoms with LTL and mtDNAcn in a large community sample. Data are from years 15, 20 and 25 follow-up evaluations in 977 subjects from the Coronary Artery Risk Development in Young Adults study. Depressive symptoms (years 15, 20, 25) were assessed with the Center for Epidemiologic Studies Depression (CES-D) scale; LTL (years 15, 20, 25) and mtDNAcn (years 15, 25) were measured in whole blood by quantitative PCR. With mixed-model analyses, we explored between- and within-person associations between CES-D scores and cellular aging markers. Results showed that high levels of depressive symptomatology throughout the 10-year time span was associated with shorter average LTL over 10 years (B=-4.2; P=0.014) after covarying for age, sex, race and education. However, no within-person association was found between depressive symptoms and LTL at each year (B=-0.8; P=0.548). Further, we found no between-person (B=-0.2; P=0.744) or within-person (B=0.4; P=0.497) associations between depressive symptomatology and mtDNAcn. Our results provide evidence for a long-term, between-person relationship of depressive symptoms with LTL, rather than a dynamic and direct within-person relationship. In this study, we found no evidence for an association between depressive symptoms and mtDNAcn.

Decision support systems for incurable non-small cell lung cancer: a systematic review.

BACKGROUND: Individually tailored cancer treatment is essential to ensure optimal treatment and resource use. Treatments for incurable metastatic non-small cell lung cancer (NSCLC) are evolving rapidly, and decision support systems (DSS) for this patient population have been developed to balance benefits and harms for decision-making. The aim of this systematic review was to inventory DSS for stage IIIB/IV NSCLC patients. METHODS: A systematic literature search was performed in Pubmed, Embase and the Cochrane Library. DSS were described extensively, including their predictors, model performances (i.e., discriminative ability and calibration), levels of validation and user friendliness. RESULTS: The systematic search yielded 3531 articles. In total, 67 articles were included after additional reference tracking. The 39 identified DSS aim to predict overall survival and/or progression-free survival, but give no information about toxicity or cost-effectiveness. Various predictors were incorporated, such as performance status, serum and inflammatory markers, and patient and tumor characteristics. Some DSS were developed for the entire incurable NSCLC population, whereas others were specifically for patients with brain or spinal metastases. Few DSS had been validated externally using recent clinical data, and the discrimination and calibration were often poor. CONCLUSIONS: Many DSS have been developed for incurable NSCLC patients, but DSS are still lacking that are up-to-date with a good model performance, while covering the entire treatment spectrum. Future DSS should incorporate genetic and biological markers based on state-of-the-art evidence, and compare multiple treatment options to estimate survival, toxicity and cost-effectiveness.

Depressive and anxiety disorders and short leukocyte telomere length: mediating effects of metabolic stress and lifestyle factors.

BACKGROUND: Depressive and anxiety disorders are associated with shorter leukocyte telomere length (LTL), an indicator of cellular aging. It is, however, unknown which pathways underlie this association. This study examined the extent to which lifestyle factors and physiological changes such as inflammatory or metabolic alterations mediate the relationship. METHOD: We applied mediation analysis techniques to data from 2750 participants of the Netherlands Study of Depression and Anxiety. LTL was assessed using quantitative polymerase chain reaction. Independent variables were current depressive (30-item Inventory of Depressive Symptoms - Self Report) and anxiety (21-item Beck's Anxiety Inventory) symptoms and presence of a depressive or anxiety disorder diagnosis based on DSM-IV; mediator variables included physiological stress systems, metabolic syndrome components and lifestyle factors. RESULTS: Short LTL was associated with higher symptom severity (B = -2.4, p = 0.002) and current psychiatric diagnosis (B = -63.3, p = 0.024). C-reactive protein, interleukin-6, waist circumference, triglycerides, high-density lipoprotein cholesterol and cigarette smoking were significant mediators in the relationship between psychopathology and LTL. When all significant mediators were included in one model, the effect sizes of the relationships between LTL and symptom severity and current diagnosis were reduced by 36.7 and 32.7%, respectively, and the remaining direct effects were no longer significant. CONCLUSIONS: Pro-inflammatory cytokines, metabolic alterations and cigarette smoking are important mediators of the association between depressive and anxiety disorders and LTL. This calls for future research on intervention programs that take into account lifestyle changes in mental health care settings.

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability.

Vagus nerve stimulation (VNS) is effective in refractory epilepsy and depression and is being investigated in heart failure, headache, gastric motility disorders and asthma. The first VNS device required surgical implantation of electrodes and a stimulator. Adverse events (AEs) are generally associated with implantation or continuous on-off stimulation. Infection is the most serious implantation-associated AE. Bradycardia and asystole have also been described during implantation, as has vocal cord paresis, which can last up to 6 months and depends on surgical skill and experience. The most frequent stimulation-associated AEs include voice alteration, paresthesia, cough, headache, dyspnea, pharyngitis and pain, which may require a decrease in stimulation strength or intermittent or permanent device deactivation. Newer non-invasive VNS delivery systems do not require surgery and permit patient-administered stimulation on demand. These non-invasive VNS systems improve the safety and tolerability of VNS, making it more accessible and facilitating further investigations across a wider range of uses.

Development of model for analysing respective collections of intended hematopoietic stem cells and harvests of unintended mature cells in apheresis for autologous hematopoietic stem cell collection.

Hematopoietic stem cells (HSCs) required to perform peripheral hematopoietic autologous stem cell transplantation (APBSCT) can be collected by processing several blood volumes (BVs) in leukapheresis sessions. However, this may cause granulocyte harvest in graft and decrease in patient's platelet blood level. Both consequences may induce disturbances in patient. One apheresis team's current purpose is to improve HSC collection by increasing HSC collection and prevent increase in granulocyte and platelet harvests. Before improving HSC collection it seemed important to know more about the way to harvest these types of cells. The purpose of our study was to develop a simple model for analysing respective collections of intended CD34+ cells among HSC (designated here as HSC) and harvests of unintended platelets or granulocytes among mature cells (designated here as mature cells) considering the number of BVs processed and factors likely to influence cell collection or harvest. For this, we processed 1, 2 and 3 BVs in 59 leukapheresis sessions and analysed corresponding collections and harvests with a referent device (COBE Spectra). First we analysed the amounts of HSC collected and mature cells harvested and second the evolution of the respective shares of HSC and mature cells collected or harvested throughout the BV processes. HSC collections and mature cell harvests increased globally (p<0.0001) and their respective shares remained stable throughout the BV processes (p non-significant). We analysed the role of intrinsic (patient's features) and extrinsic (features before starting leukapheresis sessions) factors in collections and harvests, which showed that only pre-leukapheresis blood levels (CD34+cells and platelets) influenced both cell collections and harvests (CD34+cells and platelets) (p<0.001) and shares of HSC collections and mature unintended cells harvests (p<0.001) throughout the BV processes. Altogether, our results suggested that the main factors likely to influence intended HSC collections or unintended mature cell harvests were pre-leukapheresis blood cell levels. Our model was meant to assist apheresis teams in analysing shares of HSC collected and mature cells harvested with new devices or with new types of HSC mobilization.

Major depressive disorder and accelerated cellular aging: results from a large psychiatric cohort study.

Patients with major depressive disorder (MDD) have an increased onset risk of aging-related somatic diseases such as heart disease, diabetes, obesity and cancer. This suggests mechanisms of accelerated biological aging among the depressed, which can be indicated by a shorter length of telomeres. We examine whether MDD is associated with accelerated biological aging, and whether depression characteristics such as severity, duration, and psychoactive medication do further impact on biological aging. Data are from the Netherlands Study of Depression and Anxiety, including 1095 current MDD patients, 802 remitted MDD patients and 510 control subjects. Telomere length (TL) was assessed as the telomere sequence copy number (T) compared to a single-copy gene copy number (S) using quantitative polymerase chain reaction. This resulted in a T/S ratio and was converted to base pairs (bp). MDD diagnosis and MDD characteristics were determined by self-report questionnaires and structured psychiatric interviews. Compared with control subjects (mean bp=5541), sociodemographic-adjusted TL was shorter among remitted MDD patients (mean bp=5459; P=0.014) and current MDD patients (mean bp=5461; P=0.012). Adjustment for health and lifestyle variables did not reduce the associations. Within the current MDD patients, separate analyses showed that both higher depression severity (P<0.01) and longer symptom duration in the past 4 years (P=0.01) were associated with shorter TL. Our results demonstrate that depressed patients show accelerated cellular aging according to a 'dose-response' gradient: those with the most severe and chronic MDD showed the shortest TL. We also confirmed the imprint of past exposure to depression, as those with remitted MDD had shorter TL than controls.

Short-term effects of repetitive transcranial magnetic stimulation on speech and voice in individuals with Parkinson's disease.

The main characteristics of dysarthria in Parkinson's disease (PD) are monotony of pitch and loudness, reduced stress, variable speech rate, imprecise consonants, and breathy and harsh voice. Earlier treatment studies have shown that dysarthria is less responsive to both pharmacological and surgical treatments than other gross motor symptoms. Recent findings have suggested that repetitive transcranial magnetic stimulation (rTMS) may have a beneficial effect on vocal function in PD. In the present study, 10 individuals with mild PD and no or minimal dysarthria were treated with rTMS as well as placebo stimulation in a blinded experiment. Stimulation was delivered using a frequency of 10 Hz and a stimulation intensity of 90% of the motor threshold. The site of stimulation was the cortical area corresponding to the hand, on the hemisphere contralateral to the patient's most affected side. The participants were audio-recorded before and after both rTMS and sham stimulation. Acoustic analysis was performed on 3 sustained /a:/ for each of the 4 conditions, and analyzed both for the whole group as well as for men and women separately. Results showed that there were no significant differences between any of the conditions regarding duration of sustained fricative or sustained vowel phonation, diadochokinetic rates or intelligibility. Above all, the results of acoustic analyses showed an effect of placebo; there was a significant reduction in fundamental frequency (F(0)) variation, pitch period perturbation, amplitude period perturbation, noise-to-harmonics ratio and coefficient of variation in F(0) between the recordings performed before compared to after sham stimulation.

Salvage by timed sequential chemotherapy in primary resistant acute myeloid leukemia: analysis of prognostic factors.

Primary resistant acute myeloid leukemia (AML) has a very poor prognosis. Etoposide-mitoxantrone-cytarabine (EMA) timed sequential chemotherapy including a first sequence combining mitoxantrone (12 mg/m(2) per day over 3 days) with cytarabine (500 mg/m(2) per day over the same period), and a second sequence consisting in etoposide (200 mg/m(2) per day for 3 days) and cytarabine as in the first sequence, has been proposed as a salvage regimen. Over a 10-year period, 66 primary resistant AML patients have been treated by EMA salvage chemotherapy. All patients displayed intermediate- or high-risk karyotypic abnormalities. Of the 66 patients, 24 [36%, 95% confidence interval (CI): 25-49%] achieved complete remission (CR). Thirty-eight patients were resistant to EMA chemotherapy and four patients died from toxicity during aplasia. After CR achievement, 18 patients received consolidation therapy. Five patients with an HLA-identical sibling donor underwent allogeneic stem cell transplantation (SCT), one patient received autologous SCT, two patients received a second course of EMA chemotherapy, and ten were scheduled for 6-monthly maintenance courses (mini-EMA). Median follow-up was 7.3 years. At the time of analysis, 21 of the 24 patients (87%) who achieved CR have relapsed. Median disease-free survival (DFS) was 5 months (95% CI: 4.3-7.7 months). Median overall survival (OS) was 5 months (95% CI: 3.8-6.7 months). There were only two long-term remitters (3%). In the univariate analysis, CR achievement was mainly related to white blood cell (WBC) count at the time of starting salvage therapy with poorer outcome for patients with more aggressive leukemia (WBC count > or =10 x 10(9)/l) (CR rates: 50% vs 10%, p<0.001). Overall survival was also influence by WBC count (median OS: 7.2 months vs 2.8 months, respectively, for WBC or =10 x 10(9)/l, p<0.0001). Initial karyotype was not a significant prognostic factor either for CR achievement or for DFS or OS when comparing patients with normal karyotype and those with chromosomal abnormality. In multivariate analysis, WBC count less than 10 x 10(9)/l with the absence of circulating blasts at the time of starting salvage therapy appeared to be of favorable prognostic value for CR achievement ( p=0.002), while WBC count less than 10 x 10(9)/l appeared to be of favorable prognostic value for survival ( p<0.0001). Using these two objective parameters of proven significance, we devised a prognostic system of immediate clinical utility for prognostic stratification and risk-adapted therapeutic choices. Patients with both factors (WBC count <10 x 10(9)/l and no circulating blasts) or with at least one at the time of starting salvage therapy had a CR rate of 50% and were therefore candidates for intensified post-remission therapy. All other patients displayed a very poor outcome and must be oriented after failure of first-line therapy to alternate therapeutic programs based on investigational drugs.

Multifocal progressive leukoencephalopathy occurring after refractory anemia and multiple infectious disorders consecutive to severe lymphopenia.

Progressive multifocal leukoencephalopathy (PML) is related to central nervous system infection with JC virus (JCV). This leukoencephalopathy occurs in immunocompromised patients such as those with acquired immunodeficiency syndrome (AIDS) or lymphoid malignancies. We describe here a patient with myelodysplastic syndrome who developed several life-threatening infections including listeriosis, tuberculosis, and PML. Listeriosis and recurrence of tuberculosis preceded the occurrence of PML. Neurologic features associated with major ataxia, speech disorders, and PML were documented by cranial magnetic resonance imaging showing typical features in the cerebellum and proven by polymerase chain reaction (PCR) detection of JCV DNA in the cerebrospinal fluid. No specific treatment was decided because of progression toward acute myeloid leukemia. In this case, PML occurred with no susceptibility and without immunosuppressive treatment. Our case adds further support to the association between the impairment of T-cell immune responses and myelodysplastic disorders.