Syringomyelia and hydromyelia: Current understanding and neurosurgical management.

Syringomyelia is a rare disorder in which a fluid-filled cyst forms within the spinal cord, resulting in myelopathy. Meanwhile, the abnormal dilatation of the central canal is referred to as hydromyelia or slit-like syrinx. The most prevailing classification is based on anatomical features and pathogeny rather than pathophysiological mechanisms. It is usual to distinguish foraminal syringomyelia related mainly to abnormalities at the craniocervical junction, non-foraminal syringomyelia dealing with any cause of arachnoiditis (infection, inflammation, trauma…) and more rarely syringomyelia associated with intramedullary tumors. Although many pathophysiological theories have been argued over time, the prevailing one is that disturbances in cerebrospinal fluid (CSF) flow in the sub-arachnoid spaces disrupt flow velocity leading to the syrinx. Symptoms of paralysis, sensory loss and chronic pain commonly develop during the third/fourth decades of life. The natural history of syringomyelia is typically one of gradual, stepwise neurological deterioration extending over many years. Diagnosis is based on magnetic resonance imaging (MRI) including excellent morphological sequences (T1-, T2-, FLAIR-, T2*-, enhanced T1-) and dynamic MRI with careful study of CSF velocity (CISS, cine-MR sequences). Surgical management is at first dedicated to treat the cause of the syringomyelia, mainly to re-establish a physiological CSF pathway in the subarachnoid spaces. Mostly, the surgical goal is to enlarge the craniocervical junction with duraplasty. Other surgical strategies such as arachnoidolysis or shunt procedures are performed based on the pathogenic mechanisms or as second-line treatment. Medical treatments are also necessary as chronic pain is the main long-lasting symptom. As evolutive syringomyelia is a severe disease with a high impact on quality of life, it is recommended to treat without delay. There is no evidence for surgery for incidental asymptomatic syringomyelia or hydromyelia. Finally, syringomyelia associated with intramedullary tumors resolves spontaneously after tumor resection. Syringomyelia is a rare disease, which requires a dedicated multidisciplinary approach, emphasizing the need for a nationwide scientific organization so as to offer optimal care to the patient.

Impact of acute exposure to cigarette smoke on airway gene expression.

BACKGROUND: Understanding effects of acute smoke exposure (ASE) on airway epithelial gene expression and their relationship with the effects of chronic smoke exposure may provide biological insights into the development of smoking-related respiratory diseases. METHODS: Bronchial airway epithelial cell brushings were collected from 63 individuals without recent cigarette smoke exposure and before and 24 h after smoking three cigarettes. RNA from these samples was profiled on Affymetrix Human Gene 1.0 ST microarrays. RESULTS: We identified 91 genes differentially expressed 24 h after ASE (false discovery rate < 0.25). ASE induced genes involved in xenobiotic metabolism, oxidative stress, and inflammation and repressed genes related to cilium morphogenesis and cell cycle. While many genes altered by ASE are altered similarly in chronic smokers, metallothionein genes are induced by ASE and suppressed in chronic smokers. Metallothioneins are also suppressed in current and former smokers with lung cancer relative to those without lung cancer. CONCLUSIONS: Acute exposure to as little as three cigarettes and chronic smoking induce largely concordant changes in airway epithelial gene expression. Differences in short-term and long-term effects of smoking on metallothionein expression and their relationship to lung cancer requires further study given these enzymes' role in the oxidative stress response.

Socioeconomic disparities in gait speed and associated characteristics in early old age.

BACKGROUND: A few studies have documented associations between socioeconomic position and gait speed, but the knowledge about factors from various domains (personal factors, lifestyle, occupation…) which contribute to these disparities is limited. Our objective was to assess socioeconomic disparities in usual gait speed in a general population in early old age in France, and to identify potential contributors to the observed disparities, including occupational factors. METHODS: The study population comprised 397 men and 339 women, aged 55 to 69, recruited throughout France for the field pilot of the CONSTANCES cohort. Gait speed was measured in meters/second. Socioeconomic position was based on self-reported occupational class. Information on personal characteristics, lifestyle, comorbidities and past or current occupational physical exposure came either from the health examination, from interview or from self-administered questionnaire. Four groups were considered according to sex-specific distributions of speed (the two slowest thirds versus the fastest third, for each gender). Logistic regression models adjusted for health screening center and age allowed to the study of cross-sectional associations between: 1- slower speed and occupational class; 2- slower speed and each potential contributor; 3- occupational class and selected potential contributors. The association between speed and occupational class was then further adjusted for the factors significantly associated both with speed and occupational class, in order to assess the potential contribution of these factors to disparities. RESULTS: With reference to managers/executives, gait speed was reduced in less skilled categories among men (OR 1.21 [0.72-2.05] for Intermediate/Tradesmen, 1.95 [0.80-4.76] for Clerks, Sale/service workers, 2.09 [1.14-3.82] for Blue collar/Craftsmen) and among women (OR 1.12 [0.55-2.28] for Intermediate/Tradesmen, 2.33 [1.09-4.97] for Clerks, 2.48 [1.18-5.24] for Sale/service workers/Blue collar/Craftsmen). Among men, occupational exposure to carrying heavy loads explained a large part of socioeconomic disparities. Among women, obesity and occupational exposure to repetitive work contributed independently to the disparities. CONCLUSIONS: This study suggests that some potentially modifiable occupational and personal factors explain at least part of the differences in gait speed between occupational classes, and that these factors differ between men and women. Longitudinal studies are needed to confirm and complement these findings.

Musculoskeletal pain at various anatomical sites and socioeconomic position: Results of a national survey.

BACKGROUND: Prevalence of musculoskeletal pain according to sites of pain and associated factors in the community has not been thoroughly documented. The association between pain and socioeconomic position has been studied by several authors, but without details in most studies regarding sites of pain, whereas the relations with social position could differ according to the site of pain. The objective of this study was to explore these differences in the community in France. METHODS: The national Health and Occupational History survey was conducted in France in 2006 in subjects aged 20-74 years. Self-assessment of pain at various sites in the previous year was recorded. Five sites were considered here: back, neck, shoulder, upper limb, and lower limb. After a description of prevalence according to gender and age, the associations with socioeconomic position at the beginning of the subjects' working life, in seven categories, were studied with logistic models adjusted for age. The analyses were limited to those aged 30-74 years and were conducted separately for men and women. RESULTS: Of the 5520 males and 6643 females studied, prevalence was the highest for back pain (35% for males, 37% for females). Pain was globally more frequent for women. For all sites of pain an increase with age was significant for women. This was not observed in men for back pain (highest prevalence in the 40- to 49-year-old age group) or neck pain. Overall, prevalence of pain was the lowest for professionals (reference category in the analyses). For males, the first occupation as a farmer or blue-collar worker was associated with an increased prevalence for most sites of pain, with odds ratios close to 2. For females, prevalence was increased for more socioeconomic categories, as compared to professionals. Among the five sites, neck pain was an exception: for both men and women, no association was observed between neck pain and socioeconomic position. CONCLUSION: Although exploratory, these results are consistent with the available knowledge on occupational and personal risk factors for pain, which differ according to the site of pain. Other studies are needed to better understand the causal mechanisms underlying the associations observed.

Mutations in the laminin alpha 2-chain gene (LAMA2) cause merosin-deficient congenital muscular dystrophy.

Congenital muscular dystrophies (CMDs), are heterogeneous autosomal recessive disorders. Their severe manifestations consist of early hypotonia and weakness, markedly delayed motor milestones and contractures, often associated with joint deformities. Histological changes seen in muscle biopsies consist of large variations in muscle fibre size, a few necrotic and regenerating fibres and a marked increase in endomysial collagen tissue. Diagnosis is based on clinical features and on morphological changes. In several CMD cases, we have demonstrated an absence of one of the components of the extracellular matrix around muscle fibres, the merosin M chain, now referred to as the alpha 2 chain of laminin-2 (ref.3). We localized this CMD locus to chromosome 6q2 by homozygosity mapping and linkage analysis. The laminin alpha 2 chain gene (LAMA2) maps to the same region on chromosome 6q22-23 (ref. 5). We therefore investigated LAMA2 for the presence of disease-causing mutations in laminin alpha 2 chain-deficient CMD families and now report splice site and nonsense mutations in two families leading presumably to a truncated laminin alpha 2 protein.

Impact of Covid-19 pandemic on neuro-oncology multidisciplinary tumor board in the pre-vaccine era: the Normandy experience.

INTRODUCTION: The COVID19 pandemic had a strong impact on the healthcare system, particularly in oncology. Brain tumor are usually revealed by acute and life threatening symptoms. We wanted to evaluate the possible consequences of the COVID19 pandemic in 2020 on the activity of neuro-oncology multidisciplinary tumor board in a Normandy region (France). METHODS: A descriptive, retrospective, multicenter study was conducted in the four referent centers (two universitary hospitals and two cancer centers). The main objective was to compare the average number of neuro-oncology patients presented per multidisciplinary tumor board per week between a pre-COVID19 reference period (period 1 from December 2018 to December 2019) and the pre-vaccination period (period 2 from December 2019 to November 2020). RESULTS: Across Normandy, 1540 cases were presented in neuro-oncology multidisciplinary tumor board in 2019 and 2020. No difference was observed between period 1 and 2: respectively 9.8 per week versus 10.7, P=0.36. The number of cases per week also did not significantly differ during the lockdown periods: 9.1/week versus 10.4 during the non-lockdown periods, P=0.26. The only difference observed was a higher proportion of tumor resection during the lockdown periods: 81.4% (n=79/174) versus 64.5% (n=408/1366), P=0.001. CONCLUSION: The pre-vaccination era of the COVID19 pandemic did not impact the activity of neuro-oncology multidisciplinary tumor board in the Normandy region. The possible consequences in terms of public health (excess mortality) due to this tumor location should now be investigated.

IVIg therapy in the management of BK virus infections in pediatric kidney transplant patients.

BK virus-associated nephropathy (BKPyVAN) induces kidney allograft dysfunction. Although decreasing immunosuppression is the standard for managing BK virus (BKPyV) infection, this strategy is not always effective. The use of polyvalent immunoglobulins (IVIg) may be of interest in this setting. We performed a retrospective single-center evaluation of the management of BKPyV infection in pediatric kidney transplant patients. Among the 171 patients who underwent transplantation between January 2010 and December 2019, 54 patients were excluded (combined transplant n = 15, follow-up in another center n = 35, early postoperative graft loss n= 4). Thus, 117 patients (120 transplants) were included. Overall, 34 (28%) and 15 (13%) transplant recipients displayed positive BKPyV viruria and viremia, respectively. Three had biopsy-confirmed BKPyVAN. The pre-transplant prevalence of CAKUT and HLA antibodies was higher among BKPyV-positive patients compared to non-infected patients. After the detection of BKPyV replication and/or BKPyVAN, the immunosuppressive regimen was modified in 13 (87%) patients: either by decreasing or changing the calcineurin inhibitors (n = 13) and/or switching from mycophenolate mofetil to mTor inhibitors (n = 10). Starting IVIg therapy was based on graft dysfunction or an increase in the viral load despite reduced immunosuppressive regimen. Seven of 15(46%) patients received IVIg. These patients had a higher viral load (5.4 [5.0-6.8]log vs. 3.5 [3.3-3.8]log). In total, 13 of 15 (86%) achieved viral load reduction, five of seven after IVIg therapy. As long as specific antivirals are not available for the management of BKPyV infections in pediatric kidney transplant patients, polyvalent IVIg may be discussed for the management of severe BKPyV viremia, in combination with decreased immunosuppression.

Constrained adiabatic trajectory method: a global integrator for explicitly time-dependent Hamiltonians.

The constrained adiabatic trajectory method (CATM) is reexamined as an integrator for the Schrödinger equation. An initial discussion places the CATM in the context of the different integrators used in the literature for time-independent or explicitly time-dependent Hamiltonians. The emphasis is put on adiabatic processes and within this adiabatic framework the interdependence between the CATM, the wave operator, the Floquet, and the (t, t') theories is presented in detail. Two points are then more particularly analyzed and illustrated by a numerical calculation describing the H(2)(+) ion submitted to a laser pulse. The first point is the ability of the CATM to dilate the Hamiltonian spectrum and thus to make the perturbative treatment of the equations defining the wave function possible, possibly by using a Krylov subspace approach as a complement. The second point is the ability of the CATM to handle extremely complex time-dependencies, such as those which appear when interaction representations are used to integrate the system.

Massive non-aneurysmal subarachnoid hemorrhage after cervical carotid angioplasty and stenting: A case report and review of the literature.

INTRODUCTION: Carotid angioplasty and stenting (CAS) of the cervical segment is a safe and effective procedure for the treatment of carotid artery disease. In rare cases, this procedure causes intracranial hemorrhage (ICH), which is described most often as an ipsilateral intra-parenchymal hematoma. This ICH is the result of a cerebral hyperperfusion syndrome (CHS). Isolated subarachnoid hemorrhage may occur exceptionally, with only 9 cases that have been reported in the literature. OBSERVATION: We reported a case of a 71-year-old man who presented a massive non-aneurysmal subarachnoid hemorrhage one hour after angioplasty and stenting of the cervical segment of the left internal carotid artery. Medical and surgical management included external ventricular drain placement. Rebleeding occurred two days later, worsening the patient's clinical condition. Finally, the patient died 2 weeks later. COMMENTS: This rare presentation of ICH following CAS allows us to discuss the risk factors, complications and management of CHS.

Ganglioglioma revealed by spontaneous intracerebral hematoma: A cohort study.

BACKGROUND: Gangliogliomas are rare tumors of the central nervous system. Intracerebral hemorrhage (ICH) is a frequent pathological event, rarely related to intracranial tumor. Here we report a cohort of 14 gangliogliomas, 3 of which were revealed by ICH. We also performed a systematic review of the literature on gangliogliomas revealed by ICH. PATIENTS AND METHODS: We retrospectively collected data for all gangliogliomas operated on in our department between January 2015 and December 2019: clinical history, radiological data and outcome, with a special focus on gangliogliomas revealed by spontaneous ICH. All cases had pathological validation. For the systematic review, relevant studies were identified by systematic search of the scientific literature in PubMed. RESULTS: Fifteen patients underwent surgery for ganglioglioma during the study period. Six cases were revealed by seizures, 3 by headache, 1 by hydrocephaly and 1 by developmental disorder. Three patients (21%) had hemorrhagic presentation. All patients were male, aged 30 to 48 years, diagnosed with atypical ICH without vascular abnormality on cerebral angiogram. Conservative management was first decided. Diagnosis of ganglioglioma was made within 3 months for 2 patients and 9 years later for 1, after surgical removal and histological analysis. All hemorrhagic gangliogliomas were BRAF wild type. The systematic review of the literature identified 8 other cases of ganglioglioma revealed by ICH. CONCLUSION: ICH may be a mode of revelation of ganglioglioma, and ganglioglioma is a possible etiology of atypical ICH in young patients. Long-term imaging follow-up is mandatory in patients with unexplained ICH.

Mutational analysis reveals the FUS homolog TAF15 as a candidate gene for familial amyotrophic lateral sclerosis.

FUS, EWS, and TAF15 belong to the TET family of structurally similar DNA/RNA-binding proteins. Mutations in the FUS gene have recently been discovered as a cause of familial amyotrophic lateral sclerosis (FALS). Given the structural and functional similarities between the three genes, we screened TAF15 and EWS in 263 and 94 index FALS cases, respectively. No coding variants were found in EWS, while we identified six novel changes in TAF15. Of these, two 24 bp deletions and a R388H missense variant were also found in healthy controls. A D386N substitution was shown not to segregate with the disease in the affected pedigree. A single A31T and two R395Q changes were identified in FALS cases but not in over 1,100 controls. Interestingly, one of the R395Q FALS cases also harbors a TARDBP mutation (G384R). Altogether, these results suggest that additional studies are needed to determine whether mutations in the TAF15 gene represent a cause of FALS.

[Personal and occupational factors associated with low-back pain in a general working population in France]. / Facteurs personnels et professionnels associés aux lombalgies en population générale au travail en France.

BACKGROUND: Low-back pain is a major public health concern because of its socioeconomic burden, especially for chronic forms. The purpose of this study was to analyse the associations between low-back pain and occupational and personal factors, with a special focus on interactions between age and occupational exposures. METHODS: The study population comprised a sample of 3958 and 4526 working women and men aged 30 to 59 derived from a national health survey (2002-2003 EDS). Low-back pain was assessed using the French version of the Nordic questionnaire. Weight, height and smoking status were obtained through interview at home. Occupational exposures were self-assessed. The associations between low-back pain for more than 30 days in the previous year and occupational and personal factors were assessed using logistic models. An interaction between age and each occupational exposure was studied. RESULTS: In the multivariate models, age was the only personal factor significantly associated with low-back pain for both genders. The other personal factors studied were significantly associated with low-back pain for women only. Handling heavy loads and awkward postures at work were strongly associated with low-back pain for both genders (respectively OR=1.80 [1.46-2.23] and OR=1.65 [1.34-2.03] for men, and OR=1.65 [1.32-2.06] and OR=1.28 [1.04-1.59] for women). A high level of psychological demands at work and a low level of decision latitude were also associated with low-back pain for both genders (respectively OR=1.22 [1.03-1.46] and OR=1.32 [1.11-1.57] for men, and OR=1.31 [1.10-1.56] and OR=1.27 [1.06-1.51] for women). Only the interaction between age and awkward postures for men was borderline significant. CONCLUSION: This study showed strong associations between occupational exposures and persistent/recurrent low-back pain in a general working population in France. Targeting these exposures in prevention programs could be useful.

Sub-lethal effects of calcium dinonylnaphthalenesulfonate on Western clawed frog embryos.

Naphthalene sulfonic acids (NSAs) are used as additives in lubricants, dyes, and greases and commonly act as surfactants in many industrial processes. The calcium salt of dinonyl NSA (calcium dinonylnaphthalenesulfonate; CaDNS) is listed among thousands of chemicals identified as priorities for assessment by the Government of Canada's Chemical Management Plan due to the limited toxicity data. The purpose of this study was two-fold: 1) to establish the toxicity of CaDNS to Western clawed frog (Silurana tropicalis) embryos and 2) to assess the sub-lethal effects and mechanisms of toxicity of CaDNS in amphibians through targeted gene expression and metabolite analyses. Frog embryos were exposed to water overlying sand spiked with a range of concentrations of CaDNS (17-1393 µg/g) over a 72-h period. Results indicated significantly higher mortality and presence of malformations in frog larvae exposed to over 672 µg/g CaDNS in the sand (14 ng/mL CaDNS in the water) compared to control treatments. An overall decrease in the glutathione redox cycle was observed, including decreases in relative mRNA levels of enzymes (glutathione S-transferase (gst), glutathione reductase (gsr), glutathione peroxidase (gpx)) and decreases in the glutathione (GSH) and glutathione disulfide (GSSG) metabolite concentrations. In addition, transcript levels of genes involved in antioxidant capacity and essential amino acid metabolites decreased significantly in embryos exposed to low levels of CaDNS. This is the first study to assess the toxicity of NSAs in amphibians, contributing important data to aid in the assessment of NSAs.

The French Musculoskeletal Disorders Surveillance Program: Pays de la Loire network.

OBJECTIVES: An epidemiological surveillance system for work-related musculoskeletal disorders (MSDs) was implemented in 2002 in France's Pays de la Loire region to assess the incidence and prevalence of MSDs in the general and working populations, identify levels of exposure to occupational risk factors and investigate the proportion of cases attributable to work exposure. METHODS: The program combines (1) surveillance of sentinel health events in the general population (carpal tunnel syndrome (CTS) was the sentinel event for upper limb MSDs), (2) assessment of the prevalence of the main upper limb MSDs and their risk factors in the workplace based on a network of occupational physicians and (3) registration of the notification of work-related diseases (WRDs). RESULTS: 1168 incident cases of CTS were included over a 3 year period. The estimated incidence of CTS was 1.00 per 1000 person-years in those aged 20-59 years (0.60 in men and 1.40 in women). The incidence rate was higher in employed than unemployed persons in the year of diagnosis (0.6 per 1000 vs 0.3 in men and 1.7 vs 0.8 in women). The occupational physician network noted high prevalence rates: 11% of men and 15% of women had at least one of the six main upper limb clinically-diagnosed MSDs. The WRD survey showed that MSDs represented 65% of notified WRDs. CONCLUSION: The Pays de la Loire program plays a significant role in informing the authorities and the public about the state of current MSDs. It is planned to extend it to a routine national surveillance program.

Biomechanical strains and low back disorders: quantifying the effects of the number of years of exposure on various types of pain.

OBJECTIVE: To assess the effects of duration of exposure to biomechanical strains on various types of low back pain (LBP). METHODS: The population study was a random sample from the GAZEL cohort. Durations of exposure to selected biomechanical strains during subjects' working lifetime and potential confounders were assessed in 1996 by self-administered questionnaires. Data on LBP in the previous 12 months were collected in 2001. Relations between various dimensions of LBP and durations of exposure to the biomechanical strains were analysed with multivariate regression models. Polytomous models were built to determine whether some biomechanical strains were specifically associated with some types of LBP. RESULTS: Analyses were performed separately for men (n = 2218) and women (n = 383). Significant associations were observed (ORs reported are those for 20 years of exposure) between LBP and durations of driving and bending/twisting for men (OR 1.24 and 1.37 respectively); LBP for more than 30 days and duration of exposure to bending/twisting for men and women (OR 2.20 and 2.00 respectively) and duration of driving for women (OR 3.15); LBP radiating to the leg and duration of driving for men (OR 1.43) and bending/twisting for women (OR 1.95); LBP radiating below the knee and duration of exposure to pulling/pushing/carrying for men (OR 1.88). Bending/twisting in both men and women, and driving for women appeared to be stronger risk factors for LBP for more than 30 days. Pulling/pushing/carrying heavy loads appeared to be a risk factor specific for LBP radiating below the knee for men. CONCLUSION: This study suggests that exposure to biomechanical strains has long-term effects and a dose-response relation with duration of exposure and specific effects for some types of LBP.

Do workers with self-reported symptoms have an elevated risk of developing upper extremity musculoskeletal disorders three years later?

OBJECTIVES: Few prospective studies have evaluated outcomes of workers with self-reported symptoms of upper extremity musculoskeletal disorders (UEMSD). The objective was to study the three-year outcomes of workers with self-reported symptoms, with or without a positive physical examination. METHODS: In 1993-4, 598 subjects highly exposed to repetitive work filled out a Nordic-style questionnaire. They underwent a standardised physical examination at that time and again in 1996-7 by the same occupational physician. The three-year outcomes (based on physical examination) of workers with a self-administered questionnaire positive at baseline for UEMSD, with or without a positive physical examination, were studied. RESULTS: The three-year incidence rate was 44.1%; one third of these incident cases had self-reported symptoms in 1993-4. Workers with a positive questionnaire had a significantly higher risk of UEMSD at physical examination three years later (80.1% UEMSD cases with positive questionnaires n = 354, vs 44.2% cases without positive questionnaires n = 69, p<0.001). Moreover, workers with positive questionnaires but without UEMSD diagnosed in 1993-4 (n = 177) also had a significantly higher risk of UEMSD at physical examination three years later (60.5% cases with positive questionnaires n = 26, vs 38.8% cases without positive questionnaires n = 52, p = 0.01). Results were similar when gender and age were taken into account. CONCLUSION: Workers highly exposed to repetitive movements have a high risk of developing UEMSD and should be followed closely in surveillance programmes. Workers with self-reported symptoms without UEMSD diagnosed in physical examination represented only one third of new cases three years later. However, their risk of developing UEMSD was significantly increased, compared with those without symptoms.

Sickness absence as a prognostic marker for common chronic conditions: analysis of mortality in the GAZEL study.

OBJECTIVES: To determine whether sickness absence is a prognostic marker in terms of mortality among people with common chronic conditions. METHODS: Prospective occupational cohort study of 13,077 men and 4871 women aged 37-51 from the National Gas and Electricity Company, France. Records of physician-certified sickness absences over a 3-year period were obtained from employers' registers. Chronic conditions were assessed in annual surveys over the same period. The main outcome measure was all-cause mortality (803 deaths, mean follow-up after assessment of sickness absence: 13.9 years). RESULTS: In Cox proportional hazard models adjusted for age, sex, socioeconomic position and co-morbidity, >28 annual sickness-absence days versus no absence days was associated with an excess mortality risk among those with cancer (hazard ratio 5.4, 95% CI 2.2 to 13.1), depression (1.7, 1.1 to 2.8), chronic bronchitis or asthma (2.7, 1.6 to 4.6) and hypertension (1.6, 1.0 to 2.6). The corresponding hazard ratios for more than five long (>14 days) sickness-absence episodes per 10 person-years versus no such episodes were 5.4 (2.2 to 13.1), 1.8 (1.3 to 2.7), 2.0 (1.3 to 3.2) and 1.8 (1.2 to 2.7), respectively. Areas under receiver operating characteristics curves for these absence measures varied between 0.56 and 0.73, indicating the potential of these measures to distinguish groups at high risk of mortality. The findings were consistent across sex, age and socioeconomic groups and in those with and without co-morbid conditions. CONCLUSION: Data on sickness absence may provide useful prognostic information for common chronic conditions at the population level.

Eculizumab and thrombotic microangiopathy after hematopoietic stem cell transplantation: A report on its efficacy and safety in two pediatric patients.

BACKGROUND: Thrombotic microangiopathy (TMA) is a severe complication after hematopoietic stem cell transplantation (HSCT), with the reported mortality rate in such cases usually reaching 90%. CASES: We report on two pediatric cases of patients successfully treated by eculizumab for severe HSCT-TMA, occurring in two girls (8.4 and 3.6 years). The first patient developed TMA with hematologic abnormalities and renal/pulmonary lesions after allogeneic HSCT for Philadelphia-positive acute lymphoblastic leukemia; she received eculizumab 7 months after HSCT, with a dramatic improvement of renal function. The second patient developed severe TMA (cardiac tamponade, renal failure requiring dialysis, gastritis) after autologous HSCT for metastatic neuroblastoma. She received eculizumab for 7 months, with a dramatic improvement of renal function. No side effects were observed. CONCLUSION: The use of eculizumab as first-line therapy in pediatric patients with severe HSCT-TMA with multisystemic lesions appears promising. Larger international studies are required to confirm its benefit and safety for this specific indication.