Bone Disease in Thalassemia: A Frequent and Still Unresolved Problem

Adults with β thalassemia major frequently have low BMD, fractures, and bone pain. The purpose of this study was to determine the prevalence of low BMD, fractures, and bone pain in all thalassemia syndromes in childhood, adolescence, and adulthood, associations of BMD with fractures and bone pain, and etiology of bone disease in thalassemia. Patients of all thalassemia syndromes in the Thalassemia Clinical Research Network, ≥6 yr of age, with no preexisting medical condition affecting bone mass or requiring steroids, participated. We measured spine and femur BMD and whole body BMC by DXA and assessed vertebral abnormalities by morphometric X‐ray absorptiometry (MXA). Medical history by interview and review of medical records, physical examinations, and blood and urine collections were performed. Three hundred sixty‐one subjects, 49% male, with a mean age of 23.2 yr (range, 6.1–75 yr), were studied. Spine and femur BMD Z‐scores < ?2 occurred in 46% and 25% of participants, respectively. Greater age, lower weight, hypogonadism, and increased bone turnover were strong independent predictors of low bone mass regardless of thalassemia syndrome. Peak bone mass was suboptimal. Thirty‐six percent of patients had a history of fractures, and 34% reported bone pain. BMD was negatively associated with fractures but not with bone pain. Nine percent of participants had uniformly decreased height of several vertebrae by MXA, which was associated with the use of iron chelator deferoxamine before 6 yr of age. In patients with thalassemia, low BMD and fractures occur frequently and independently of the particular syndrome. Peak bone mass is suboptimal. Low BMD is associated with hypogonadism, increased bone turnover, and an increased risk for fractures.     

Open‐MRI measures of cam intrusion for hips in an anterior impingement position relate to acetabular contact force

Open MRI in functional positions has potential to directly and non‐invasively assess cam femoroacetabular impingement (FAI). Our objective was to investigate whether open MRI can depict intrusion of the cam deformity into the intra‐articular joint space, and whether intrusion is associated with elevated acetabular contact force. Cadaver hips (9 cam; 3 controls) were positioned in an anterior impingement posture and imaged using open MRI with multi‐planar reformatting. The β‐angle (describing clearance between the femoral neck and acetabulum) was measured around the entire circumference of the femoral neck. We defined a binary “MRI cam‐intrusion sign” (positive if β < 0°). We then instrumented each hip with a piezoresistive sensor and conducted six repeated positioning trials, measuring acetabular contact force (F). We defined a binary “contact‐force sign” (positive if F > 20N). Cam hips were more likely than controls to have both a positive MRI cam‐intrusion sign (p = 0.0182, Fisher's exact test) and positive contact‐force sign (p = 0.0083), which represents direct experimental evidence for cam intrusion. There was also a relationship between the MRI cam‐intrusion sign and contact‐force sign (p = 0.033), representing a link between imaging and mechanics. Our findings indicate that open MRI has significant potential for in vivo investigation of the cam FAI mechanism. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:205–216, 2016.     

Expression of adhesion molecules and RANTES in kidney transplant from nonheart-beating donors

The main difference between cadaveric kidneys from donors with a heartbeat (HBD) and kidneys from nonheart-beating donors (NHBD) is related to warm ischemia/reperfusion time which constitutes an acute inflammatory process. On the contrary, brain death induces in HBD expression of pro-inflammatory adhesion molecules, making it important to evaluate this kind of molecules in both types of donors. Human renal biopsies from NHBD, HBD and normal kidneys (ischemia time = 0) were taken and frozen just before transplant. A semi-quantitative RT-PCR method was used to determine intracellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), lymphocyte function associated antigen (LFA-1), LFA-3, CD40, CD40 ligand (CD40L) and RANTES (regulated upon activation, normal T-cell expressed and secreted) gene expression. We have detected an elevated relative gene expression of ICAM-1, VCAM-1 and RANTES in NHBD biopsies compared with normal kidneys. In the case of RANTES, the gene expression from NHBD biopsies was higher than observed in HBD biopsies. The rest of genes were not augmented in any group. Preliminary data about early outcome of transplants indicates a correlation between pretransplant RANTES high gene expression levels and early post-transplant acute rejection. The gene expression of pro-inflammatory molecules like adhesion molecules and RANTES is augmented in kidneys from cadaveric NBD just before transplant. The expression is higher probably because of the prolonged warm ischemia period. A larger clinical study is necessary to clarify the effects of these variable expressions on the transplant outcome.     

Differences in CMV-Specific T-Cell Levels and Long-Term Susceptibility to CMV Infection after Kidney, Heart and Lung Transplantation

Patients after kidney, heart and lung transplantation differ in their immunosuppressive drug regimens and in susceptibility to infectious complications with cytomegalovirus (CMV). In this study, CMV-specific T-cell responses were characterized in long-term transplant recipients and associated with the frequency of infectious complications. CMV-reactive CD4 T cells from 50 healthy controls, 68 renal, 14 heart and 24 lung transplant recipients were flow cytometrically quantified by the induction of cytokines after specific stimulation. Moreover, the immunosuppressive effect of calcineurin inhibitors on specific T-cell reactivity was quantified in vitro and compared with responses in vivo. Median CMV-specific T-cell frequencies in long-term renal (1.48%; range 0.06-17.26%) and heart transplant recipients (0.90%; 0.13-12.49%) did not differ from controls (1.82%; 0.26-21.00%). In contrast, CMV-specific T-cell levels were significantly lower in lung transplant recipients (0.50%; <0.05-4.98%) and showed a significant correlation with the frequency of infectious episodes (r =-0.57, p = 0.005). The differences within the groups were associated with increasing dosages of immunosuppressive drugs, as exemplified for calcineurin inhibitors that dose dependently reduced specific T-cell reactivity in vitro. In conclusion, monitoring CMV-specific CD4 T cells may serve as a measure for long-term disease susceptibility and may contribute to an improved management of CMV complications after lung transplantation.     

Use of the burn intervention score to calculate the charges of the care of burns

Background

To our knowledge this is the first published estimate of the charges of the care of burns in Sweden. The Linköping Burn Interventional Score has been used to calculate the charges for each burned patient since 1993. The treatment of burns is versatile, and depends on the depth and extension of the burn. This requires a flexible system to detect the actual differences in the care provided. We aimed to describe the model of burn care that we used to calculate the charges incurred during the acute phase until discharge, so it could be reproduced and applied in other burn centres, which would facilitate a future objective comparison of the expenses in burn care.

POLLAR: Impact of air POLLution on Asthma and Rhinitis; a European Institute of Innovation and Technology Health (EIT Health) project

Allergic rhinitis (AR) is impacted by allergens and air pollution but interactions between air pollution, sleep and allergic diseases are insufficiently understood. POLLAR (Impact of air POLLution on sleep, Asthma and Rhinitis) is a project of the European Institute of Innovation and Technology (EIT Health). It will use a freely-existing application for AR monitoring that has been tested in 23 countries (the Allergy Diary, iOS and Android, 17,000 users, TLR8). The Allergy Diary will be combined with a new tool allowing queries on allergen, pollen (TLR2), sleep quality and disorders (TRL2) as well as existing longitudinal and geolocalized pollution data. Machine learning will be used to assess the relationship between air pollution, sleep and AR comparing polluted and non-polluted areas in 6 EU countries. Data generated in 2018 will be confirmed in 2019 and extended by the individual prospective assessment of pollution (portable sensor, TLR7) in AR. Sleep apnea patients will be used as a demonstrator of sleep disorder that can be modulated in terms of symptoms and severity by air pollution and AR. The geographic information system GIS will map the results. Consequences on quality of life (EQ-5D), asthma, school, work and sleep will be monitored and disseminated towards the population. The impacts of POLLAR will be (1) to propose novel care pathways integrating pollution, sleep and patients’ literacy, (2) to study sleep consequences of pollution and its impact on frequent chronic diseases, (3) to improve work productivity, (4) to propose the basis for a sentinel network at the EU level for pollution and allergy, (5) to assess the societal implications of the interaction. MASK paper N°32.     

A Systematic Review of Randomized Controlled Trials of Interventions to Improve the Health of Persons During Imprisonment and in the Year After Release

We systematically reviewed randomized controlled trials of interventions to improve the health of people during imprisonment or in the year after release. We searched 14 biomedical and social science databases in 2014, and identified 95 studies.Most studies involved only men or a majority of men (70/83 studies in which gender was specified); only 16 studies focused on adolescents. Most studies were conducted in the United States (n = 57). The risk of bias for outcomes in almost all studies was unclear or high (n = 91). In 59 studies, interventions led to improved mental health, substance use, infectious diseases, or health service utilization outcomes; in 42 of these studies, outcomes were measured in the community after release.Improving the health of people who experience imprisonment requires knowledge generation and knowledge translation, including implementation of effective interventions.Worldwide, more than 11 million people are imprisoned at any given time, and the prison population continues to grow at a rate faster than that of the general population.1 Substantial evidence reveals that people who have experienced imprisonment have poor health compared with the general population, as indicated by the prevalence of mental illness, infectious diseases, chronic diseases, and mortality.2There are several reasons to focus on improving the health of people who experience imprisonment.3 The burden of disease in this population affects the general population directly through increased health care costs and through the transmission of communicable diseases (e.g., HIV, HCV, and tuberculosis) after people are released from detention. Imprisonment has also been associated with worse health in family members of those who are detained, compared with the general population, including chronic diseases4 and poor mental health5,6 in adult relatives and mortality in male children.7 At the community level, higher rates of incarceration have been associated with adverse health outcomes, such as sexually transmitted infections and teen pregnancies.8 There is also evidence that poor health in persons who are released from detention, particularly those with inadequately treated mental illness and substance use disorders,3 may affect public safety and reincarceration rates,3 and that better access to health care is associated with less recidivism.9,10 Finally, the right to health and health care is enshrined in international human rights documents,11,12 and is a legislated responsibility of governments in many countries.Intervening during imprisonment and at the time of release could improve the health of people who experience imprisonment and public health overall.13 Knowledge translation efforts, such as syntheses of effective interventions, could lead to the implementation and further evaluation of interventions,14 and identify areas where further research is needed. To date, only syntheses with a limited focus have been conducted in this population, for example, reviews of interventions related to HIV15 or for persons with serious mental illness.16 Decision makers, practitioners, and researchers in this field would benefit from a broader understanding of the state of evidence regarding interventions to improve health in people who experience imprisonment.To address this gap, we systematically reviewed randomized controlled trials of interventions to improve health in persons during imprisonment and in the year after release. We chose this population because we view imprisonment as a unique opportunity to deliver and to link with interventions for this population, and to highlight interventions that could be implemented by those responsible for the administration of correctional facilities. We limited this study to randomized controlled trials, recognizing that randomized controlled trials provide the highest quality of evidence compared with other study designs.17