Thomasencochrane1292

Atherosclerosis begins in youth and is directly linked with the presence and severity of cardiovascular risk factors, including dyslipidemia. Thus, the timely identification and management of dyslipidemia in childhood might slow atherosclerotic progression and decrease the risk of cardiovascular disease in adulthood. This is particularly true for children with genetic disorders resulting in marked dyslipidemia, including familial hypercholesterolemia, which remains frequently undiagnosed. Universal and cascade screening strategies can effectively identify cases of pediatric dyslipidemia. In the clinical evaluation of children with dyslipidemia, evaluating for secondary causes of dyslipidemia, including medications and systemic disorders is essential. The first line therapy generally centres around lifestyle modifications, with dietary changes specific to the dyslipidemia phenotype. Indications for medication depend on the severity of dyslipidemia and an individualized assessment of cardiovascular risk. Despite an expanding evidence base supporting the detection and timely management of pediatric dyslipidemia, numerous knowledge gaps remain, including a sufficient evidence base to support more widespread screening, thresholds for initiation of pharmacotherapy, and treatment targets. Further studies on the most appropriate age for statin initiation and long-term safety studies of statin use in youth are also required. The most pressing matter, however, is the development of knowledge translation strategies to improve the screening and detection of lipid disorders in Canadian youth.This guideline synthesizes clinical trial data supporting the role of glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter 2 inhibitors (SGLT2i) for treatment of heart failure (HF), chronic kidney disease, and for optimizing prevention of cardiorenal morbidity and mortality in patients with type 2 diabetes. It is on the basis of a companion systematic review and meta-analysis guided by a focused set of population, intervention, control, and outcomes (PICO) questions that address priority cardiorenal end points. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system and a modified Delphi process were used. We encourage comprehensive assessment of cardiovascular (CV) patients with routine measurement of estimated glomerular filtration rate, urinary albumin-creatinine ratio, glycosylated hemoglobin (A1c), and documentation of left ventricular ejection fraction (LVEF) when evaluating symptoms of HF. For patients with HF, we recommend integration of SGLT2i with other guideline-directed pharmacotherapy for the reduction of hospitalization for HF when LVEF is > 40% and for the reduction of all-cause and CV mortality, hospitalization for HF, and renal protection when LVEF is ≤ 40%. In patients with albuminuric chronic kidney disease, we recommend integration of SGLT2i with other guideline-directed pharmacotherapy to reduce all-cause and CV mortality, nonfatal myocardial infarction, and hospitalization for HF. We provide recommendations and algorithms for the selection of glucagon-like peptide-1 receptor agonists and SGLT2i for patients with type 2 diabetes and either established atherosclerotic CV disease or risk factors for atherosclerotic CV disease to reduce all-cause and CV mortality, nonfatal stroke, and for the prevention of hospitalization for HF and decline in renal function. We offer practical advice for safe use of these diabetes-associated agents with profound cardiorenal benefits.Death associated protein 5 (DAP5/eIF4G2/NAT1) is a member of the eIF4G translation initiation factors that has been shown to mediate noncanonical and/or cap-independent translation. It is essential for embryonic development and for differentiation of embryonic stem cells (ESCs), specifically its ability to drive translation of specific target mRNAs. In order to expand the repertoire of DAP5 target mRNAs, we compared ribosome profiles in control and DAP5 knockdown (KD) human ESCs (hESCs) to identify mRNAs with decreased ribosomal occupancy upon DAP5 silencing. A cohort of 68 genes showed decreased translation efficiency in DAP5 KD cells. Mass spectrometry confirmed decreased protein abundance of a significant portion of these targets. Among these was KMT2D, a histone methylase previously shown to be essential for ESC differentiation and embryonic development. We found that nearly half of the cohort of DAP5 target mRNAs displaying reduced translation efficiency of their main coding sequences upon DAP5 KD contained upstream open reading frames (uORFs) that are actively translated independently of DAP5. This is consistent with previously suggested mechanisms by which DAP5 mediates leaky scanning through uORFs and/or reinitiation at the main coding sequence. Crosslinking protein-RNA immunoprecipitation experiments indicated that a significant subset of DAP5 mRNA targets bound DAP5, indicating that direct binding between DAP5 protein and its target mRNAs is a frequent but not absolute requirement for DAP5-dependent translation of the main coding sequence. Thus, we have extended DAP5's function in translation of specific mRNAs in hESCs by a mechanism allowing translation of the main coding sequence following upstream translation of short ORFs.The burden of respiratory and upper-gastrointestinal diseases especially affects low- and middle-income countries. Five billion people lack access to safe, timely, and affordable surgical care, including thoracic surgical care. Minimally invasive thoracic surgery (MITS) has been shown to reduce complications, shorten hospital lengths of stay, and minimize health care costs, thereby enabling patients to pay less out-of-pocket and/or limit time away from work and families. Experiences with MITS exist but are limited in low- and middle-income countries; professional societies, academic institutions, policymakers, and industry can facilitate scale-up of MITS by increasing financing, expanding surgical training, and optimizing surgical supply chains.Due to the luminal nature of the disease, esophageal cancer diagnosis and treatment is challenging. Majority of the patients usually present with dysphagia, at which point the disease is often locally advanced. Diagnosis and treatment need a multidisciplinary approach which often involves endoscopy, imaging services, oncology services, surgical services, and critical care services. Surgery is associated with significant morbidity and mortality and care should be domiciled in high-volume centers. see more Training and mentorship are key to building capacity for esophageal cancer care.Lung cancer is an increasing problem in the developing world due to rising trends in smoking, high incidence of air pollution, lack of awareness and screening, delayed presentation, and diagnosis at the advanced stage. Even after diagnosis, there are disparities in access to health care facilities and inequitable distribution of resources and treatment options. In addition, the shortage of trained personnel and infrastructure adds to the challenges faced by patients with lung cancer in these regions. A multi-pronged effort targeting tobacco cessation, health promotion and awareness, capacity building, and value-based care are the need of the hour.Tracheobronchial surgery is widely performed in emerging countries mainly as a consequence of the high number of airway-related complications and poor management in intensive care units. This has led to great expertise in the surgical management of postintubation tracheal stenosis, and opportunity for advancing scientific knowledge. Nonetheless, tracheal stenosis has a severe impact on a patient's quality of life, is a major burden to the health system, and should be prevented. Incorporation of innovative techniques, technologies, and prospective databases should prompt earlier diagnosis and lead to fewer complications.Most cases of empyema thoracis are sequelae of severe pneumonia, but chest trauma and complications of chest tube insertion as cause are not uncommon in low-resource settings. Diagnosis is usually delayed due to delayed presentation to health care facilities, low index of suspicion among health care professionals, and inability to properly stage the disease with the available diagnostic tools. Early use of antibiotics and appropriate-sized and well-placed chest tube drainage is associated with good outcomes at a decreased cost. Surgical management of empyema thoracis is indicated when chest tube drainage and antibiotic treatment fail to achieve complete resolution.In the modern era, infections of the lung are typically managed medically. However, all pulmonary hydatid cysts require surgery with rare exceptions, and bacterial abscesses require surgery if they are complicated, resistant to treatment, and/or large. Surgical treatment of these pulmonary conditions requires clinical knowledge of tests for causative organisms, perioperative antimicrobial therapies, options for surgical management, and postoperative care.Owing to the advent of effective drugs for tuberculosis in the mid-twentieth century, few cases require surgery for active tuberculosis in the present day in areas where effective drugs are available. However, surgical techniques developed to combat tuberculosis in the predrug era are still useful to manage the challenging chest pathology of our time surgically, such as destroyed lung or postresectional empyema. Thoracoplasty and open window thoracostomy are representative procedures and discussed in detail in this review.Trauma is a leading cause of death and disability worldwide and disproportionately affects those in low- and middle-income countries (LMICs). Globally, two-thirds of injured patients sustain trauma to the thoracic cavity. Further research, capacity building, and increased awareness are needed to limit the high thoracic trauma-associated morbidity and mortality in LMICs.Gastrointestinal and pulmonary disease is prevalent in many developing countries. Establishing an endoscopy training partnership can transfer skills that can influence policy and stakeholder support to address disease morbidity and mortality. Any new program needs to consider the environmental services that will be delivered and give consideration to the sustainability of the program over time. This article outlines what we have learned from our training partnership in the Pacific Islands Region.Anesthesia in low-to-middle income countries (LMICs) is often provided by nonphysician anesthetists. The training and resources for anesthesia in LMICs are limited, and this must be evaluated when starting or expanding a thoracic surgery program in LMICs. The ability to access a patient's baseline pulmonary and cardiovascular status is often based on rudimentary studies and a thorough history and physical. Advance studies, such as echocardiograms, cardiovascular stress test, cardiac catherizations, pulmonary function tests, and MRIs, are often not available. Careful assessment of both preoperative patient selection, intraoperative ability to provide one-lung ventilation, and postoperative critical care management must be considered when surgical planning is occurring.