Aspirin Resistance

The development of adverse cardiovascular events despite aspirin use has established an interest in a possible resistance to the drug. Several definitions have been set and various laboratory testing modalities are available. This has led to a wide range of prevalence reports in different clinical entities. The etiologic mechanism has been related to clinical, genetic, and other miscellaneous factors. The clinical implications of this phenomenon are significant and warrant concern. Management strategies are currently limited to dosing alteration and introduction of other anitplatelet agents. However, these measures have not met the expected efficacy or safety

Thalassemia and Venous Thromboembolism

Although the life expectancy of thalassemia patients has markedly improved over the last few decades, patients still suffer from many complications of this congenital disease. The presence of a high incidence of thromboembolic events, mainly in thalassemia intermedia, has led to the identification of a hypercoagulable state in these patients. In this review, the molecular and cellular mechanisms leading to hypercoagulability in thalassemia are highlighted, with a special focus on thalassemia intermedia being the group with the highest incidence of thrombotic events as compared to other types of thalassemia. Clinical experience and available clues on optimal management are also discussed

Burkitt's lymphoma of the colon and bronchi: three case reports

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Thalassaemia Intermedia: an Update

Our understanding of the molecular and pathophysiological mechanisms underlying the disease process in patients with thalassaemia intermedia (TI) has substantially increased over the past decade. TI encompasses a wide clinical spectrum of beta-thalassaemia phenotypes. Some TI patients are asymptomatic until adult life, whereas others are symptomatic from as young as 2 years of age. A number of clinical complications commonly associated with TI are rarely seen in thalassaemia major, including extramedullary hematopoiesis, leg ulcers, gallstones, thrombosis and pulmonary hypertension. There are a number of options currently available for managing patients with TI, including transfusion therapy, iron chelation therapy, modulation of foetal haemoglobin production and haematopoietic stem cell transplantation. However, at present, there are no clear guidelines for an orchestrated optimal treatment plan

Coagulopathy in Beta-Thalassemia: Current Understanding and Future Perspectives

As the life expectancy of β-thalassemia patients has markedly improved over the last decade, several new complications are being recognized. The presence of a high incidence of thromboembolic events, mainly in thalassemia intermedia patients, has led to the identification of a hypercoagulable state in thalassemia. In this review, the molecular and cellular mechanisms leading to hypercoagulability in thalassemia are highlighted, and the current clinical experience is summarized. Recommendations for thrombosis prophylaxis are also discussed

Antithrombotic Prophylaxis in the Middle East

Several factors have been proposed to explain the persistence of a high incidence of venous thromboembolism worldwide with its associated morbidity and mortality. Underutilization of anticoagulants and failure of adherence to thromboprophylaxis guidelines are emerging global health concerns. We herein review this alarming observation with special emphasis on the Middle East region. We also discuss strategies that could help control this increasingly reported problem

Preoperative Hematocrit Concentration and the Risk of Stroke in Patients Undergoing Isolated Coronary-Artery Bypass Grafting

Background. Identification and management of risk factors for stroke following isolated coronary artery bypass grafting (CABG) could potentially lower the risk of such serious morbidity. Methods. We retrieved data for 30-day stroke incidence and perioperative variables for patients undergoing isolated CABG and used multivariate logistic regression to assess the adjusted effect of preoperative hematocrit concentration on stroke incidence. Results. In 2,313 patients (mean age 65.9 years, 73.6% men), 43 (1.9%, 95% CI: 1.4-2.5) developed stroke within 30 days following CABG (74.4% within 6 days). After adjustment for a priori defined potential confounders, each 1% drop in preoperative hematocrit concentration was associated with 1.07 (95% CI: 1.01-1.13) increased odds for stroke (men, OR: 1.08, 95% CI: 1.01-1.16; women, OR: 1.02, 95% CI: 0.91-1.16). The predicted probability of stroke for descending preoperative hematocrit concentration exceeded 2% for values <37% (<37% for men (adjusted OR: 2.39, 95% CI: 1.08-5.26) and <38% for women (adjusted OR: 2.52, 95% CI: 0.53-11.98), with a steeper probability increase noted in men). The association between lower preoperative hematocrit concentration and stroke was evident irrespective of intraoperative transfusion use. Conclusion. Screening and management of patients with low preoperative hematocrit concentration may alter postoperative stroke risk in patients undergoing isolated CABG

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Iron overload in non-transfusion-dependent thalassemia

Iron overload due to increased intestinal iron absorption remains a concern in patients with non-transfusion-dependent thalassemia (NTDT). A dynamic regulation between ineffective erythropiesis and iron metabolism in these disorders has been recently elucidated. Although the rate of iron loading in NTDT is slower than that observed in regularly transfused patients, the process is cumulative and patients may reach considerably high liver iron concentration levels. The clinical consequences of iron overload in patients with NTDT are various and include hepatic disease, endocrinopathy, bone disease, and vascular outcomes; while cardiac siderosis is less frequently observed. Although serum ferritin levels correlate with LIC in NTDT, they underestimate iron load when compared with transfusion-dependent patients with equivalent LIC. Therefore, direct measurement of LIC is recommended to identify patients at risk and guide iron chelation decisions