Lymphoid aggregates in the bone marrow biopsies of patients with myelodysplastic syndromes – A potential prognostic marker?

BackgroundLymphoid aggregates (LA) are occasionally seen in bone marrow biopsies (BMB) of myelodysplastic syndromes (MDS) patients. Our aim was to evaluate their incidence and association with prognosis.MethodsWe compared BMB reports of MDS patients treated at the Tel Aviv Sourasky Medical Center (2011-2018), and controls (2015-2017, normal BMB), and examined the charts of the MDS patients (LA+ and LA-). Categorical, normally and non-normally distributed continuous variables were compared using Fisher’s exact, independent t and Mann-Whitney tests respectively. Adjusted [age, gender, lymphocytes, white blood cells (WBC) and diabetes mellitus (DM)] Cox proportional hazard model examined survival at 12 and 24 months.ResultsMDS patients (N=140) were older than controls (N=38; 74.1 vs 69.2 years, p=0.005); 34 MDS (24.3%) and 5 controls (13.2%) had LA+ (P=0.141). CD20/CD3 staining suggested LA polyclonality. MDS/LA+ (vs MDS/LA-) patients were younger, with a trend (not statistically significant) towards poor prognostic parameters: lower Hb, WBC, and platelets, higher LDH, BM cellularity, and IPSS-R score. The incidence of cardiovascular disease was similar, but MDS/LA+ had twice the incidence of DM (38.2% vs 19.0%, p=0.022). Similar trend for cancer (26.5% vs 14.3%, p=0.102). Twelve-month survival: 24/34 (70.6%) MDS/LA+; 88/106 (83.0%) MDS/LA- (p=0.140). This trend, seen in Kaplan-Meier curves, disappeared at 24 months. The hazard ratio for LA was 2.283 (p=0.055) for 12 months.ConclusionThese preliminary data suggest LA are relatively common (24%) in MDS BMB, and might indicate poor prognosis. This may reflect involvement of the immune system in MDS. Future studies will examine larger groups, to clarify the incidence, significance and the pathophysiology

Complex PTSD symptoms mediate the association between childhood trauma and physical health problems

The ICD-11 reconceptualized Posttraumatic Stress Disorder (PTSD) as a narrowly defined fear-based disorder, and introduced Complex PTSD (CPTSD) as a new diagnosis comprised of PTSD symptoms and symptoms of ‘Disturbances in Self-Organization’ (DSO) that are more reflective of general dysphoria. Previous research suggests that PTSD symptoms mediate the association between childhood trauma and physical health problems, including cardiovascular disease. No study has yet assessed how posttraumatic stress symptoms, as outlined in the ICD-11, influence the association between childhood trauma and somatic problems in adulthood.ObjectiveThis cross-sectional descriptive study examined whether PTSD and DSO symptoms mediated the associations between childhood physical and sexual abuse and childhood emotional abuse and neglect and somatic problems and cardiovascular diseases (CVD) load in adulthood.MethodsGeneral adult population samples from Ireland (N = 1020) and the United Kingdom (N = 1051) completed self-report questionnaires online.ResultsStructural equation modelling results indicated that PTSD and DSO symptoms fully mediated the association between both forms of childhood trauma and somatic problems, and that PTSD symptoms but not DSO symptoms fully mediated the association between childhood trauma and CVD load.ConclusionPsychological interventions that effectively treat CPTSD symptoms may have the added benefit of reducing risk of physical health problems

Posttraumatic stress disorder (PTSD) and complex PTSD (CPTSD) as per ICD-11 proposals: A population study in Israel

Background: The current study sought to advance the existing literature by providing the first assessment of the factorial and discriminant validity of the ICD-11 proposals for PTSD and CPTSD in a nation-wide level.Methods: A nationally representative sample from Israel (n = 1003) using a disorder-specific measure (ITQ; International Trauma Questionnaire) in order to assess PTSD and Complex PTSD along with the Life Events Checklist and the World Health Organization Well-Being Index.Results: Estimated prevalence rates of PTSD and CPTSD were 9.0% and 2.6% respectively. The structural analyses indicated that PTSD and disturbances in self-organization symptom clusters were multidimensional, but not necessarily hierarchical, in nature and there were distinct classes that were consistent with PTSD and CPTSD. Conclusions: These results partially support the factorial validity and strongly support the discriminant validity of the ICD-11 proposals for PTSD and CPTSD in a nationally representative sample using a disorder-specific measure, findings also supported the international applicability of these diagnoses.Further research is required to determine the prevalence rates of PTSD and CPTSD in national representative samples across different countries and explore the predictive utility of different types of traumatic life events on PTSD and CPTSD

Psychological interventions for ICD-11 complex PTSD symptoms: systematic review and meta-analysis

Background The 11th revision to the WHO International Classification of Diseases (ICD-11) identified complex post-traumatic stress disorder (CPTSD) as a new condition. There is a pressing need to identify effective CPTSD interventions. Methods We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) of psychological interventions for post-traumatic stress disorder (PTSD), where participants were likely to have clinically significant baseline levels of one or more CPTSD symptom clusters (affect dysregulation, negative self-concept and/or disturbed relationships). We searched MEDLINE, PsycINFO, EMBASE and PILOTS databases (January 2018), and examined study and outcome quality. Results Fifty-one RCTs met inclusion criteria. Cognitive behavioural therapy (CBT), exposure alone (EA) and eye movement desensitisation and reprocessing (EMDR) were superior to usual care for PTSD symptoms, with effects ranging from g = −0.90 (CBT; k = 27, 95% CI −1.11 to −0.68; moderate quality) to g = −1.26 (EMDR; k = 4, 95% CI −2.01 to −0.51; low quality). CBT and EA each had moderate–large or large effects on negative self-concept, but only one trial of EMDR provided useable data. CBT, EA and EMDR each had moderate or moderate–large effects on disturbed relationships. Few RCTs reported affect dysregulation data. The benefits of all interventions were smaller when compared with non-specific interventions (e.g. befriending). Multivariate meta-regression suggested childhood-onset trauma was associated with a poorer outcome. Conclusions The development of effective interventions for CPTSD can build upon the success of PTSD interventions. Further research should assess the benefits of flexibility in intervention selection, sequencing and delivery, based on clinical need and patient preferences

A predictive algorithm using clinical and laboratory parameters may assist in ruling out and in diagnosing MDS

We present a noninvasive Web-based app to help exclude or diagnose myelodysplastic syndrome (MDS), a bone marrow (BM) disorder with cytopenias and leukemic risk, diagnosed by BM examination. A sample of 502 MDS patients from the European MDS (EUMDS) registry (n \gt; 2600) was combined with 502 controls (all BM proven). Gradient-boosted models (GBMs) were used to predict/exclude MDS using demographic, clinical, and laboratory variables. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were used to evaluate the models, and performance was validated using 100 times fivefold cross-validation. Model stability was assessed by repeating its fit using different randomly chosen groups of 502 EUMDS cases. AUC was 0.96 (95\ 0.95-0.97). MDS is predicted/excluded accurately in 86\range, 0-1) of less than 0.68 (GBM \lt; 0.68) resulted in a negative predictive value of 0.94, that is, MDS was excluded. GBM ≥ 0.82 provided a positive predictive value of 0.88, that is, MDS. The diagnosis of the remaining patients (0.68 ≤ GBM \lt; 0.82) is indeterminate. The discriminating variables: age, sex, hemoglobin, white blood cells, platelets, mean corpuscular volume, neutrophils, monocytes, glucose, and creatinine. A Web-based app was developed; physicians could use it to exclude or predict MDS noninvasively in most patients without a BM examination. Future work will add peripheral blood cytogenetics/genetics, EUMDS-based prospective validation, and prognostication

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions

Proceedings of the Thirteenth International Society of Sports Nutrition (ISSN) Conference and Expo

Meeting Abstracts: Proceedings of the Thirteenth International Society of Sports Nutrition (ISSN) Conference and Expo Clearwater Beach, FL, USA. 9-11 June 201

Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. METHODS: The causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries-Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODEm), to generate cause fractions and cause-specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised

4Q249 Midrash Moshe: A New Reading and Some Implications

International audienceThis article proves that the title “Midrash Sepher Moshe,” written in Jewish square characters on the verso of the cryptic scroll 4Q249, is the product of a correction. Initially it had been “Sepher Moshe” which was subsequently corrected to “Midrash Moshe.” This is therefore a rare attestation of canonical awareness on the part of Qumran librarians. The terms “midrash” and “sepher” are discussed accordingly

A New Join of Two Fragments of 4QcryptA Serekh haEdah and Its Implications

International audienc