Association between fitness tracker use, physical activity, and general health of adolescents in Eastern Province of Saudi Arabia.

BACKGROUND: Physical inactivity is a major problem of adolescents worldwide. Fitness trackers are widely used technologies that assess physical activity and allow self-monitoring of daily activities. Thirty-five percent of the Saudi population is made up of adolescents, which makes them an important target population. Few studies have evaluated the association of fitness trackers with physical activity levels of adolescents. This study aimed to evaluate physical activity among adolescents and its relationship to their use of fitness trackers and overall health. MATERIALS AND METHODS: A cross-sectional study was carried out among adolescents in middle and high schools in the Eastern Province. Data was collected using a structured questionnaire and physical activity was assessed using International Physical Activity Questionnaire for Adolescents. Chi-square test and ANOVA were performed to test for statistical significance. Unadjusted and adjusted odds ratios (ORs) were obtained through ordered logistic regression models. Model diagnostics were run as post hoc analyses. RESULTS: Majority of participants (82.6%) had low physical activity levels, 12.2% had moderate and 5.2% had vigorous activity level. The model revealed that as participants' ages increased, the odds of having higher levels of physical activity decreased (OR = 0.92; 95% confidence interval [CI]: 0.85-0.99). Moreover, participants who did not go to a gym regularly or own a fitness tracker were less likely to have higher physical activity levels (OR = 0.43; 95% CI:0.30-0.61, and OR = 0.44; 95% CI: 0.33-0.59, respectively). Motivation for using fitness trackers was mostly "no specific reason" for females. However, "luxury and esthetics" were mostly reported by males. CONCLUSION: Physical activity tends to be higher in younger adolescents who use fitness trackers, or go to the gym regularly, with no significant difference between males and females. However, the motivation behind adolescents' use of fitness trackers varied by gender.

Investigation on the self-assembly of the NFL-TBS.40-63 peptide and its interaction with gold nanoparticles as a delivery agent for glioblastoma.

NFL-TBS.40-63 peptide is a recently discovered peptide derived from the light neurofilament chain (NFL). In this study, we demonstrated that the Biotinylated-NFL-peptide (BIOT-NFL) can spontaneously self-assemble into well-organized nanofibers (approximately 5 nm width and several micrometers in length) in several solutions, whereas the typical self-assembly was not systematically observed from other peptides with or without coupling. The critical aggregation concentration that allows the BIOT-NFL-peptide to aggregate and auto associate was determined at 10-4 mol/L by surface tension measurements. X-ray scattering of BIOT-NFL-peptide also demonstrated its beta-sheet structure that can facilitate the intermolecular interactions involved in the self-assembly process. The possible disassembly of self-assembled BIOT-NFL-peptide-nanofibers was examined via a dialysis membrane study. We further investigated the interaction between nanofibers formed by BIOT-NFL-peptide and gold nanoparticles. Interestingly, a strong interaction was demonstrated between these nanoparticles and BIOT-NFL-peptide resulted in the formation of BIOT-NFL-peptide-nanofibers grandly decorated by gold nanoparticles. Finally, we investigated the internalization of gold nanoparticles coupled with BIOT-NFL-nanofibers into F98 rat glioblastoma cells, which was increased compared to the non-coupled control gold nanoparticles. All these results indicate that this peptide could be a promising therapeutic agent for targeted delivery.

Characterization and quantification of the interaction between the NFL-TBS.40-63 peptide and lipid nanocapsules.

Several studies previously showed that the NFL-TBS.40-63 peptide (NFL-peptide) is capable to specifically penetrating several glioblastoma cell lines (rat, mouse, human) and inhibiting their cell division in vitro and their tumor development in vivo. When lipid nanocapsules (LNCs) are functionalized with the NFL-peptide, their absorption is targeted in glioblastoma cells both in vitro and in vivo. In the present study, we investigated the molecular architecture of these nanovectors (LNC-NFL) by using several microscopy techniques (transmission electron microscopy, cryo-electron microscopy, and cryo-electron tomography). We also used high-performance liquid chromatography (UPLC) technique to evaluate the interaction between LNCs and peptides. The work shows that the NFL-peptide forms stable long filaments along which the lipid nanocapsules interact strongly to form some sort of nanomolecular bracelets. This new construction composed of the NFL-peptide and lipid nanocapsules shows a better internalization in rat glioblastoma cells (F98 cells) than lipid nanocapsules alone.

A randomized study of pomalidomide vs placebo in persons with myeloproliferative neoplasm-associated myelofibrosis and RBC-transfusion dependence.

RBC-transfusion dependence is common in persons with myeloproliferative neoplasm (MPN)-associated myelofibrosis. The objective of this study was to determine the rates of RBC-transfusion independence after therapy with pomalidomide vs placebo in persons with MPN-associated myelofibrosis and RBC-transfusion dependence. Two hundred and fifty-two subjects (intent-to-treat (ITT) population) including 229 subjects confirmed by central review (modified ITT population) were randomly assigned (2:1) to pomalidomide or placebo. Trialists and subjects were blinded to treatment allocation. Primary end point was proportion of subjects achieving RBC-transfusion independence within 6 months. One hundred and fifty-two subjects received pomalidomide and 77 placebo. Response rates were 16% (95% confidence interval (CI), 11, 23%) vs 16% (8, 26%; P=0.87). Response in the pomalidomide cohort was associated with ⩽4 U RBC/28 days (odds ratio (OR)=3.1; 0.9, 11.1), age ⩽65 (OR=2.3; 0.9, 5.5) and type of MPN-associated myelofibrosis (OR=2.6; 0.7, 9.5). Responses in the placebo cohort were associated with ⩽4 U RBC/28 days (OR=8.6; 0.9, 82.3), white blood cell at randomization >25 × 109/l (OR=4.9; 0.8, 28.9) and interval from diagnosis to randomization >2 years (OR=4.9; 1.1, 21.9). Pomalidomide was associated with increased rates of oedema and neutropenia but these adverse effects were manageable. Pomalidomide and placebo had similar RBC-transfusion-independence response rates in persons with MPN-associated RBC-transfusion dependence.

Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis.

Ruxolitinib is a Janus kinase (JAK) (JAK1/JAK2) inhibitor that has demonstrated superiority over placebo and best available therapy (BAT) in the Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment (COMFORT) studies. COMFORT-II was a randomized (2:1), open-label phase 3 study in patients with myelofibrosis; patients randomized to BAT could crossover to ruxolitinib upon protocol-defined disease progression or after the primary end point, confounding long-term comparisons. At week 48, 28% (41/146) of patients randomized to ruxolitinib achieved ⩾35% decrease in spleen volume (primary end point) compared with no patients on BAT (P<0.001). Among the 78 patients (53.4%) in the ruxolitinib arm who achieved ⩾35% reductions in spleen volume at any time, the probability of maintaining response was 0.48 (95% confidence interval (CI), 0.35-0.60) at 5 years (median, 3.2 years). Median overall survival was not reached in the ruxolitinib arm and was 4.1 years in the BAT arm. There was a 33% reduction in risk of death with ruxolitinib compared with BAT by intent-to-treat analysis (hazard ratio (HR)=0.67; 95% CI, 0.44-1.02; P=0.06); the crossover-corrected HR was 0.44 (95% CI, 0.18-1.04; P=0.06). There was no unexpected increased incidence of adverse events with longer exposure. This final analysis showed that spleen volume reductions with ruxolitinib were maintained with continued therapy and may be associated with survival benefits.

Efficacy and safety of deferasirox in non-thalassemic patients with elevated ferritin levels after allogeneic hematopoietic stem cell transplantation.

Elevated serum ferritin contributes to treatment-related morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The multicenter DE02 trial assessed the safety, efficacy and impact of deferasirox on iron homeostasis after allogeneic HSCT. Deferasirox was administered at a starting dose of 10 mg/kg per day to 76 recipients of allogeneic HSCT, with subsequent dose adjustments based on efficacy and safety. Deferasirox was initiated at a median of 168 days after HSCT, with 84% of patients still on immunosuppression. Baseline serum ferritin declined from 2045 to 957 ng/mL. Deferasirox induced a negative iron balance in 84% of patients. Hemoglobin increased in the first 3 months, and trough serum cyclosporine levels were stable. Median exposure was 330 days, with a median compliance rate of >80%. The most common investigator-reported drug-related adverse events (AEs) were increased blood creatinine (26.5%), nausea (9.0%) and abdominal discomfort (8.3%). Fifty-four (71.1%) patients experienced drug-related AEs, which occasionally resulted in discontinuation (gastrointestinal (n=6), skin (n=3), elevated transaminases (n=1) and creatinine (n=1)). The incidence of AEs appeared to be dose related, with 7.5 mg/kg per day being the best-tolerated dose. Low-dose deferasirox is an effective chelation therapy after allogeneic HSCT, with a manageable safety profile, even in patients receiving cyclosporine.

Long-term follow-up of the AML97 study for patients aged 60 years and above with acute myeloid leukaemia: a study of the East German Haematology and Oncology Study Group (OSHO).

INTRODUCTION: Treatment of patients (pts) with acute myelogenous leukaemia (AML) above 60 years remains a challenge. We report long-term follow-up of the AML97 study, where pts were registered at diagnosis and received treatment dependent on their comorbidities: dose-intense cytarabine (AraC) and anthracycline in the curative arm, and low-dose chemotherapy in the palliative arm or best supportive care. MATERIALS AND METHODS: A total of 618 pts were enrolled in this protocol (curative 471, palliative 115 and supportive 32). In the curative arm, complete remission (CR) was obtained in 66.8 % of pts and the estimated probability of being alive at 2 years was 0.30 (±0.02 SE). In multivariate analysis, gender (p = 0.005), performance status (p = 0.04) and cytogenetics (p = 0.002) were significant factors for CR. With a median follow-up of 10 (range 0.1-11.8) years, the estimated probability of being event-free after 2 and 5 years according to cytogenetics was 0.48 ± 0.11 and 0.48 ± 0.11 for favourable, 0.20 ± 0.03 and 0.09 ± 0.03 for normal, 0.18 ± 0.06 and 0.10 ± 0.05 for other standard risk and 0.10 ± 0.03 and 0.05 ± 0.02 for unfavourable karyotypes, respectively. The median survival time for pts treated with palliative chemotherapy was 54 and 11 days with best supportive care only. CONCLUSION: In conclusion, treatment of older AML pts with dose-intense AraC is feasible in the majority of pts and induces high rates of CR. Nevertheless, except for favourable karyotype, OS and event-free survival remain low. These results need to be viewed in relation to the new modalities including stem cell transplantation following non-myeloablative conditioning, epigenetic and molecular therapies.

Favorable outcome in children and adolescents with a high proportion of advanced phase disease using single/multiple autologous or matched/mismatched allogeneic stem cell transplantations.

We determined the indication, outcome, and risk factors of single and multiple hematopoietic stem cell transplantation(s) (HSCT) in children and adolescents mostly with advanced disease. Forty-one out of 483 patients (8.5 %; median age 9 years) diagnosed at the University of Leipzig with hematological and oncological diseases required HSCT from 1999 to 2011. Patients had overall survival (OS) of 63 ± 10 and 63 ± 16 %, event-free survival (EFS) of 57 ± 10 and 42 ± 16 %, relapse incidence (RI) of 39 ± 10 and 44 ± 18 % and nonrelapse mortality (NRM) of 4 ± 4 and 13 ± 9 % at 10 years after one or more allogeneic and autologous HSCT, respectively. One patient in CR1 and five with advanced disease received two HSCT. Four of the six patients maintained/achieved CR for a median of 13 months. Three died of progression and one of NRM. Two patients had a third HSCT and one survived in CR +231 days after HSCT. Risk factors for OS and EFS were disease stage at HSCT and EBMT risk score. Center (pediatric or JACIE accredited pediatric/adult) was not a determinant for survival. Pediatric single and multiple HSCT are important curative approaches for high-risk malignant diseases with low NRM. Efforts to reduce high RI remain the major aim.

Comparable outcome after single-antigen-mismatched versus matched unrelated donor haematopoietic cell transplantation.

PURPOSE: Allogeneic haematopoietic stem cell transplantation (HSCT) is a proven treatment for patients with haematological malignancies. In this retrospective analysis, the impact of donor matching on outcome of unrelated HSCT was analysed in patients transplanted at the University of Leipzig. METHODS: From 2000 to 2009, 206 patients were transplanted from unrelated donors, of which 51 were mismatched (39 in 1 and 12 in ≥ 2 HLA-antigens), using peripheral blood or bone marrow grafts after total body irradiation and cyclophosphamide or busulfan and cyclophosphamide preparative regimens in combination with ATG. For graft-versus-host disease (GvHD) prophylaxis cyclosporine and MTX were administered. RESULTS: After a median follow-up of 49 months, outcome at 5 years in recipients of HLA-identical grafts was comparable to that of patients transplanted from HLA-incompatible donors with an overall survival (OS) of 52 % (95 % CI 43-61) versus 48 % (95 % CI 34-63), respectively (p = 0.48). Results were also comparable for event-free survival at 5 years [47 % (95 % CI 38-56) vs. 39 % (95 % CI 25-54); p = 0.44], relapse incidence (RI) [29 % (95 % CI 20-38) vs. 41 (95 % CI 25-57); p = 0.22] and non-relapse mortality [24 % (95 % CI 16-33) vs. 20 % (95 % CI 8-33); p = 0.84] in the matched versus mismatched groups. Incidence of acute and chronic GvHD was similar in both groups. Advanced disease (p = 0.02) and low-resolution typing (p = 0.04) are risk factors for OS and RI in univariate and multivariate analysis. CONCLUSIONS: Donors with one antigen mismatch are an acceptable option for patients with malignant disease for whom no fully matched donor is available.

Bone mineral density in midlife women: the Study of Women's Health in Qatar.

OBJECTIVES: The aim of this study is to investigate bone mineral density (BMD) for a large cross-section of midlife Arab women living in Qatar and to evaluate the association of body mass index (BMI), menopause status, and nationality, on BMD of the spine and femur. STUDY DESIGN: A cross-sectional study was conducted among women aged 40-60 years recruited from nine primary-care health centers in Qatar. BMD (g/m(2)) was assessed at the lumbar spine and the femur. RESULTS: The combined prevalence of osteopenia and osteoporosis was 4% at the femur and 16.2% at the spine. BMI and menstrual status were both independently associated with BMD at the spine and at the femur (all p values < 0.001). As BMI increased, BMD increased at both the spine and femur. Women who menstruated in the past 12 months had 0.82 g/cm(2) and 0.61 g/cm(2) greater BMD at the spine and femur, respectively, compared with women who had not menstruated in 12 months. Nationality was not associated with mean BMD of the spine or the femur. CONCLUSIONS: No significant differences were observed between Qatari and non-Qatari women in terms of mean BMD values at the spine and the femur except for the femur in the age group 55-60, where values were lower among non-Qataris (p = 0.04). Multivariable analyses showed that BMI and menstrual status were found to be strongly associated with BMD levels at the spine and femur. The high prevalence of obesity observed in this sample may explain the low levels of osteopenia and osteoporosis observed.

Allogeneic hematopoietic cell transplantation for myelofibrosis in patients pretreated with the JAK1 and JAK2 inhibitor ruxolitinib.

The Janus-activated kinase 1 (JAK1) and JAK2 inhibitor ruxolitinib is effective in decreasing symptomatic splenomegaly and myelofibrosis (MF)-related symptoms. However, allogeneic hematopoietic cell transplantation (HCT) remains the only curative option. We evaluated the impact of ruxolitinib on the outcome after HCT. A cohort of 14 patients (median age 58 years) received a subsequent graft from related (n=3) and unrelated (n=11) donors after a median exposure of 6.5 months to ruxolitinib. At HCT, MF risk for survival according to the International Prognostic Scoring System was intermediate-2 or high risk in 86% of patients. Under ruxolitinib, MF-related symptoms were ameliorated in 10 (71.4%) patients and the palpable spleen reduced by a median of 41% in 7 (64%) of 11 patients with splenomegaly. Engraftment occurred in 13 (93%) patients. Acute GvHD grade-III occurred in 2 (14%) patients. Median follow-up was 9 months. Survival, EFS and treatment-related mortality were 78.6, 64 and 7%, respectively. Through the anti-JAK-mediated reduction in both cytokines and splenomegaly as well as improvement in performance status, ruxolitinib might improve outcome after allogeneic HCT in patients with MF. The downregulation of inflammatory cytokines might have a beneficial impact on graft failure and acute GvHD.

Long-term follow-up of high-dose chemotherapy with autologous stem-cell transplantation and response-adapted whole-brain radiotherapy for newly diagnosed primary CNS lymphoma: results of the multicenter Ostdeutsche Studiengruppe Hamatologie und Onkologie OSHO-53 phase II study.

BACKGROUND: We previously reported the results of a phase II study for patients with newly diagnosed primary central nervous system lymphoma treated with autologous peripheral blood stem-cell transplantation (aPBSCT) and response-adapted whole-brain radiotherapy (WBRT). Now, we update the initial results. PATIENTS AND METHODS: From 1999 to 2004, 23 patients received high-dose methotrexate. In case of at least partial remission, high-dose busulfan/thiotepa (HD-BuTT) followed by aPBSCT was carried out. Patients refractory to induction or without complete remission after HD-BuTT received WBRT. Eight patients still alive in 2011 were contacted and Mini-Mental State Examination (MMSE) and the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire (QLQ)-C30 were carried out. RESULTS: Of eight patients still alive, median follow-up is 116.9 months. Only one of nine irradiated patients is still alive with a severe neurologic deficit. In seven of eight patients treated with HD-BuTT, health condition and quality of life are excellent. MMSE and QLQ-C30 showed remarkably good results in patients who did not receive WBRT. All of them have a Karnofsky score of 90%-100%. CONCLUSIONS: Follow-up shows an overall survival of 35%. In six of seven patients where WBRT could be avoided, no long-term neurotoxicity has been observed and all patients have an excellent quality of life.

Kidney transplant from the same donor without maintenance immunosuppression after previous hematopoietic stem cell transplant.

In January 2005, an 18-year-old male patient with acute myeloid leukemia (AML) received a haploidentical hematopoietic stem cell transplantation (HSCT) from his father. He developed hemolytic uremic syndrome and end-stage renal disease (ESRD) requiring hemodialysis on day 357 after HSCT. On day 1020 after HSCT, a living kidney donation from the stem cell donor was carried out. The creatinine before kidney transplantation (KT) was ≈450 µmol/L, 268 µmol/L on day 2 after KT, 88 µM on day 38 and 89 µmol/L on day 960 (day 1980 after HSCT). Immunosuppression was gradually discontinued: cortisone on day 28, tacrolimus on day 32 and MMF on day 100 after KT (day 1120 after HSCT). As of June 2010, 66 months after HSCT and 32 months after KT, the patient has had neither rejection episodes nor clinical manifestations of transplantation-related complications. The patient reached 100% hematopoietic donor chimerism prekidney transplant and retained this state postkidney transplant. This unique case is the first report of a successful kidney transplant without immunosuppression after HSCT from the same haploidentical donor.

The impact of the age of HLA-identical siblings on mobilization and collection of PBSCs for allogeneic hematopoietic cell transplantation.

With the increasing age of patients undergoing allogeneic hematopoietic cell transplantation (HCT), the age of matched related sibling donors (MRDs) is expected to increase. Donor safety and the impact of donors' age on mobilization, collection of peripheral hematopoietic progenitor cells (HPCs), subsequent engraftment and the incidence of GVHD were retrospectively analyzed. A total of 167 patients received HCT from an MRD. Median donors' age was 48 years (67 (40%) donors were ≥50 years including 34 donors ≥60 years). Side effects under mobilization and apheresis were age independent. Grafts from donors <50 years contained more CD34+ cells (median 9 × 10(6)/kg recipient's body weight (RBW)) compared with older donors (median 5.9 × 10(6)/kg RBW) (P<0.0005), whereas harvests from donors ≥60 years contained more natural killer (NK) cells (P=0.003). Engraftment occurred at a median of 12 days after HCT irrespective of donors' age. Increasing age of MRD did not preclude successful mobilization, collection of HPC and engraftment. In the context of more NK cells in grafts from elderly donors, the impact of donors' age on outcome after HCT warrants further studies. Although short-term toxicities of apheresis were not increased with increasing age, long-term donor safety remains an important issue.

Monitoring of WT1 expression in PB and CD34(+) donor chimerism of BM predicts early relapse in AML and MDS patients after hematopoietic cell transplantation with reduced-intensity conditioning.

Relapse of malignant disease remains the major complication in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) after hematopoietic cell transplantation (HCT) with reduced-intensity conditioning (RIC). In this study, we investigated the predictive value of disease-specific markers (DSMs), donor chimerism (DC) analysis of unsorted (UDC) or CD34(+) sorted cells and Wilms' tumor gene 1 (WT1) expression. Eighty-eight patients with AML or MDS were monitored after allogenic HCT following 2 Gy total-body irradiation with (n=84) or without (n=4) fludarabine 3 × 30 mg/m(2), followed by cyclosporin A and mycophenolate mofetil. DSMs were determined by fluorescence in situ hybridization (FISH) and WT1 expression by real-time polymerase chain reaction. Chimerism analysis was performed on unsorted or CD34(+) sorted cells, by FISH or short tandem repeat polymerase chain reaction. Twenty-one (24%) patients relapsed within 4 months after HCT. UDC, CD34(+) DC and WT1 expression were each significant predictors of relapse with sensitivities ranging from 53 to 79% and specificities of 82-91%. Relapse within 28 days was excluded almost entirely on the basis of WT1 expression combined with CD34(+) DC kinetics. Monitoring of WT1 expression and CD34(+) DC predict relapse of AML and MDS after RIC-HCT.

Adult metachromatic leukodystrophy treated by allo-SCT and a review of the literature.

Five patients with adult-onset metachromatic leukodystrophy (MLD) underwent allo-SCT. Conditioning was reduced in intensity and grafts were obtained from voluntary unrelated donors. All but one graft were depleted of T-lymphocytes. Patient age at transplantation varied from 18 to 29 (median, 27) years. Two patients rejected their graft and MLD progressed. The recipient of the unmanipulated graft converted to complete donor chimerism with normalization of arylsulphatase A (ARSA) levels. Despite ARSA normalization, he deteriorated. Another patient was a mixed chimera. Following escalated doses of donor lymphocyte infusions he converted to complete donor chimerism. His levels of ARSA correlated positively with the percentage of donor cells and MLD was not progressive. The fifth patient died after 35 days from complications associated with GVHD. We conclude that results of allo-SCT in symptomatic MLD patients are poor. However, allo-SCT may stop progression of MLD in selected patients.

UVA (UVA-1) therapy for the treatment of acute GVHD of the skin.

Long-wavelength UVA (340-400 nm UVA-1) phototherapy has been reported to be effective in atopic dermatitis, localized scleroderma and T-cell-derived skin diseases. We retrospectively investigated 70 patients with acute cutaneous GVHD after allogeneic haematopoietic cell transplantation or donor lymphocyte infusion. Complete and partial responses with a median duration of 10 months were achieved in 49 (70%) and 17 (24.3%) patients, respectively. Overall, 47 (67.1%) patients were not treated with systemic steroids. Furthermore, immunosuppression could be tapered in 24 (34.3%) patients while they were receiving UVA-1 treatment. Responses were seen irrespective of age or type of conditioning. Treatment was very well tolerated. After a median follow-up of 18 (range 10-60) months, three patients developed epithelial skin neoplasia. We conclude that UVA-1 therapy is feasible, well tolerated and can be an effective treatment for acute GVHD of the skin, thereby avoiding the use of systemic steroids and/or allowing a more rapid tapering of systemic immunosuppression in a substantial number of patients. The results of this retrospective analysis warrant larger, prospective studies and the effectiveness of UVA-1 therapy should be compared with other established treatment modalities.