What is the role of the microenvironment in MDS?

Treating myelodysplastic syndromes (MDS) remains challenging. Hematopoiesis occurs within a heterogeneous, complex and dynamic microenvironment, and a multiplicity of mutations in hematopoietic stem and progenitor cells (HSPCs) lead to MDS. But is there a role for the microenvironment? Here we review experimental and conceptual arguments that support a role for the microenvironment, provide evidence for the disruption of the microenvironment in MDS, and explore microenvironmental signals that may provide a targetable and conserved vulnerability in MDS that transcend genetic heterogeneity.     

What is the role of falls?

There is now firm evidence to support interventions in the prevention of falls in older people, and emerging data support prevention of falls as a method of fracture prevention. This chapter discusses the epidemiology of falls, risk factors associated with an increased risk of falling, assessment of the older faller, and evidence-based approaches to the prevention of falls in the older person. Several randomized controlled trials have found that hip protectors, if worn, probably prevent hip fractures, but that poor compliance is a major issue limiting the effectiveness of this form of intervention. More data are needed to support the role of prevention of falls in preventing fractures, as well as comparative cost-effectiveness data with other evidence-based approaches to preventing fractures in an older population.     

What is the role of internal medicine in the collective of a general hospital?

General internal medicine tends to decrease in many Belgian hospitals. On the opposite, United States are now clearly engaged in a reform of their health system, with a drastic augmentation of the number of general internists. This reflection recognizes the specificities of general internal medicine: the first contact, the longitudinal follow-up, the comprehensive approach and the coordination with other medical participants. The need for subspecialists would be reduced and the need for primary comprehensive care physicians would be increased. The development of a performent sector of general internal medicine is able to respond to the demand of the patients and also of the general family practitioners. This model has positive impacts for the whole hospital community. We are all weary of discussions of state medicine, of the high cost of medical care, of the adequacy of medical care for the indigent, of the shortage of hospital beds for those who can pay, of the shortage of nurses, and so on. But these are, in part our problems; if their solution is to be to our liking, we must be active in them. The spector of state medicine is continually raised before us. Greater participation, by the federal, state and local governments in matters of health seems inevitable although most of us think it is important to retain in some manner or other the principle of private enterprise. Change of some sort will come; it is evident that unless we ourselves reorganize the practice of medicine, it will be reorganized for us.     

What is the role of giant cells in AL-amyloidosis?

AL-amyloidosis is one of the most common amyloidoses and can be found in a localized and a systemic form. The precursor protein is an immunoglobulin light chain which as AL-protein in both localized and systemic AL-amyloidosis shows the same pattern of fragmentation and changes of primary structure. In this work it is shown that that there is a difference between localized and systemic amyloidosis in respect to accompanying giant cells which constantly are found associated with amyloid deposits in localized AL-amyloidosis. In addition, giant cells were found together with amyloid deposits in lymph nodes of some cases of systemic AL-amyloidosis. Based on these findings and electron microscopic studies, it is discussed whether the giant cells actively participate in amyloid fibril formation by uptake and modification of the precursor protein or the giant cells are part of a foreign body reaction. Included in this work are two new cases of localized lung (lambda I) and ureteric (kappa I) AL-amyloidosis.     

What is the role of serological markers in the diagnosis of IBD?

Research and technological advancements have fostered a novel approach to understanding the intricate relationship between genetic and clinical expression of disease. Both genetic and serum antibody markers hold the most promise in helping researchers better comprehend disease heterogeneity and natural history. Although our current gold standard diagnostic tests do not possess this capability, exciting preliminary research suggests IBD-specific antibody markers may serve as predictors of an individual's disease course. Thus, the foundation has been laid upon which the discovery of novel IBD-specific and IBD-sensitive markers will enable researchers to identify at-risk individuals, as well as diagnose IBD and stratify patients into homogeneous subtypes with certainty. Clinicians can then create and implement individual treatment plans designed to improve the long-term prognosis of these chronic diseases.     

What is the role of the bone marrow microenvironment in AML?

Acute myeloid leukemia (AML) continues to be associated with relapse and resistance to chemotherapy. The bone marrow microenvironment in AML has been shown to regulate responsiveness to chemotherapy and to support disease progression. This review summarizes some recent experimental insights into the crucial role of the bone marrow microenvironment in AML and persistence after chemotherapy.     

What is the role of the occupational therapist?

Occupational therapy (OT) is widely provided for people with chronic musculoskeletal conditions. The aims are to improve their ability to perform daily occupations (i.e. activities and valued life roles at work, in the home, at leisure and socially), facilitate successful adaptations to disruptions in lifestyle, prevent losses of function and improve or maintain psychological status. This chapter reviews the evidence for the effectiveness of OT interventions, suggests who is relevant for referral and indicates the appropriate timing for referral. The main emphasis is on OT for people with rheumatoid arthritis-primarily because most evidence to date is for this condition. Comprehensive OT is effective in improving function in people with moderate-severe arthritis. Some interventions (e.g. joint protection and hand exercises) are effective. People are increasingly being referred sooner after diagnosis for interventions to help prevent progression of functional, physical and psychological problems. Little is known of the effectiveness of therapy at this early stage.     

What is the role of circulating IGF-I?

Postnatal growth and development are coordinated by genetic and environmental influences and numerous growth factors. The growth hormone-insulin-like growth factor-I (GH-IGF-I) axis plays an essential role in these processes. Although the GH-IGF-I axis is a closely coordinated system, both GH and IGF-I have independent actions, many of which have become apparent more recently following the characterization of clinical syndromes and the development of mouse models. Genetic manipulation of mice has enabled investigators to re-examine many of the established hypotheses regarding the GH-IGF-I axis. Results gleaned from a mouse model created by tissue-specific gene deletion of liver IGF-I has enabled investigators to re-evaluate the original 'somatomedin hypothesis'.     

What is the role of septal myectomy in aortic stenosis?

Asymmetric basal septal hypertrophy is present in 10% of patients with hemodynamic significant aortic valve stenosis. From the surgeon's standpoint, it represents a dilemma as it may be implicated in suboptimal short and long-term results after aortic valve replacement (AVR), but also heighten unwarranted complications at the time of surgical correction. To provide insight about the usefulness and safety of concomitant septal myectomy in this setting, we performed a literature review searching Medline from its inception to November 2020 using the Pubmed interface. Only five low evidence retrospective analyses, comprising a total of <200 patients undergoing AVR with concomitant septal myectomy, were found in the literature. In summary, routine myectomy, in the presence of suspected or directly visualized asymmetric septal hypertrophy on echocardiogram during AVR, seems to be a safe procedure, with all authors reporting a low rate or absence of complications. Overall, myectomy in this setting is associated with superior echocardiographic results concerning surrogates of LV remodelling (LVM; LVM index; LVM/height) and diastolic function (E/E’), suggesting some benefit for hemodynamic outcomes. However, to what extent hemodynamic improvement is exclusively attributable to myectomy is uncertain, as is, the clinical significance of such an improvement, with similar short and mid-term survival rates being reported.     

What is the role of beta-adrenergic signaling in heart failure?

This review addresses open questions about the role of beta-adrenergic receptors in cardiac function and failure. Cardiomyocytes express all three beta-adrenergic receptor subtypes-beta1, beta2, and, at least in some species, beta3. The beta1 subtype is the most prominent one and is mainly responsible for positive chronotropic and inotropic effects of catecholamines. The beta2 subtype also increases cardiac function, but its ability to activate nonclassical signaling pathways suggests a function distinct from the beta1 subtype. In heart failure, the sympathetic system is activated, cardiac beta-receptor number and function are decreased, and downstream mechanisms are altered. However, in spite of a wealth of data, we still do not know whether and to what extent these alterations are adaptive/protective or detrimental, or both. Clinically, beta-adrenergic antagonists represent the most important advance in heart failure therapy, but it is still debated whether they act by blocking or by resensitizing the beta-adrenergic receptor system. Newer experimental therapeutic strategies aim at the receptor desensitization machinery and at downstream signaling steps.