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 Comparison of Liver Disease Mortality With HIV and Overdose Mortality Among Georgia Prisoners and Releasees: A 2-Decade Cohort Study of Prisoners Incarcerated in 1991

Objectives. We investigated whether eventual causes of death among a cohort of inmates imprisoned in the southeastern United States differed from those in previous prisoner studies.Methods. We matched 23 510 prisoners in Georgia, a state with historically low levels of heroin consumption but moderate amounts of injection drug use, who were incarcerated on June 30, 1991, to death registries through 2010. Main exposure was 4-year time intervals over 2 decades of observation; main outcome was mortality from liver disease, HIV, and overdose.Results. Although the HIV-related mortality rate exceeded that from liver-related conditions before 2003, liver disease subsequently surpassed HIV as a cause of death. Among 3863 deaths, 22 (0.6%) occurred within 2 weeks after release from prison. Of these, only 2 were caused by accidental poisoning (likely drug overdose). Cardiovascular disease and cancer were the most frequent causes of death in this aging cohort.Conclusions. Our study design deemphasized immediate deaths but highlighted long-term sequelae of exposure to viral hepatitis and alcohol. Treating hepatitis C and implementing interventions to manage alcohol use disorders may improve survival among prisoners in the Southeast.Drug use, incarceration, and mortality are intertwined: the use of illicit drugs can result in both incarceration and premature death. A 2010 international meta-analysis of prisoners'' survival after their release into the community emphasized mortality from overdose in the 2 weeks following discharge, possibly attributable to loss of opiate tolerance after forced sobriety in prison,1 but a more recent publication illustrates how this pattern may vary among subpopulations.2Long-term consequences of injection drug use include hepatitis C and HIV infection. In the United States, sexual exposure is the most common mode of HIV transmission, but the hepatitis C epidemic is mainly driven by the injection of drugs, even if the drug use is not sustained.3 HIV prevalence is 3 times as common among prisoners as among the general population,4 but hepatitis C prevalence is 13 times as high.5,6 Sequelae that could lead to death from hepatitis C typically occur 2 to 4 decades after injection drug use was initiated. Little is known about the long-term survival of inmates, particularly in the southeastern United States, where historical and recent patterns of drug use may differ from those in other regions.In contrast with other studies that have examined cohorts of released inmates, we sought to assess long-term prisoner survival by retrospectively following a cohort composed of a cross section of all imprisoned persons in the state of Georgia on a single day in 1991. In a previous study, we did not observe significantly higher mortality among members of this cohort immediately after release from prison than in the subsequent postrelease period.7 Multiple sources suggest that heroin use is less common in Georgia than in other states. Between 2002 and 2012, consistently fewer than 6.5% of men jailed in Atlanta, the capital of and largest city in Georgia, had evidence of heroin in their urine samples.8,9 The prevalence of opiate use in Atlanta was among the lowest for any city studied in the past decade by the Office of the National Drug Control Policy.8–10 In particular, heroin use was lower than in Washington State, site of a previous study of former inmate mortality.11 According to the Treatment Episode Data Set–Admissions for 1992 to 2010 from the Substance Abuse and Mental Health Services Administration, heroin addiction accounted for only 1.6% of admissions for drug rehabilitation in Georgia, but 9.7% in Washington State and 14.2% nationally.12In assessment of risk for hepatitis C, needle use—whether for heroin, cocaine, or another drug—is more important than what is injected. Needle use in Georgia is not uncommon. According to population-wide National Survey on Drug Use and Health data for 2002 to 2009, 1.1% of Georgians have ever used a needle to inject drugs, including cocaine—a moderate rate compared with the frequency in Washington State, where lifetime prevalence is 2.7%, and nationally, where prevalence is 1.6%.13 State-level data on needle use prior to 2002 are not publically available from the Substance Abuse and Mental Health Services Administration.The prevalence of hepatitis C in the Georgia general population is moderately high, especially in Atlanta. At Grady Memorial Hospital, the safety net charity hospital for Atlanta, the prevalence of hepatitis C among ambulatory primary care patients is 7%. A liver clinic established at this hospital saw 807 unique patients in its first 5 years of existence and was still receiving 60 new patient referrals each month through 2010.14 Three quarters of the patients were African American, and most patients were born between 1945 and 1965; 64% were former drug users, and only 4% were currently using.14 High prevalence of hepatitis C in this baby boomer birth cohort probably reflects time-limited parenteral drug use decades ago, perhaps as early as the Vietnam war era.15 Despite relatively low levels of heroin use in the state, we hypothesized that the prevalence of hepatitis C would be high among inmates in the Georgia prison system who were born between 1945 and 1965.We sought to describe the leading causes of death over 2 decades in a large cohort of all Georgians who were in state prisons on June 30, 1991, and to evaluate whether the immediate mortality following prison discharge was low, because Georgia is a state with low heroin use. In light of the moderate background rates of injection drug use in Georgia, we hypothesized that mortality from liver-related causes would rise over time as the cohort aged. Our first aim was to rank the causes of death and categorize which deaths occurred in prison, immediately after release, and subsequently. Second, we compared deaths from liver disease to those from HIV in 4-year intervals between 1991 and 2010.