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.

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.

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.

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.

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.

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.

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.

Systemic arterial hypertension secondary to chronic kidney disease in two captive-born large felids.

Systemic arterial hypertension (SHT) has been widely described in the domestic cat (Felis catus). In these feline patients, SHT is considered as the most common vascular disorder of middle-aged to older animals, and secondary SHT related to chronic kidney disease (CKD) represents the most common form of the disease. We describe here the first two cases of spontaneous SHT in large felids, i.e. one 18-year old, 34.4 kg, male North-Chinese leopard (Panthera pardus japonensis, case #1) and one 20-year old, 28.7 kg, female snow leopard (Panthera uncia, case #2), both captive-bred and previously diagnosed with CKD. Both animals underwent complete echocardiographic examination under general anesthesia due to abnormal cardiac auscultation (heart murmur and/or gallop sound), and recurrent lethargy in case #1. The combination of left ventricular remodeling with moderate aortic regurgitation of high velocity was highly suggestive of SHT, which was confirmed by indirect blood pressure measurement (systolic arterial blood pressure of 183 mmHg for case #1 and 180 mmHg for case #2). Amlodipine was prescribed (0.35-0.70 mg/kg/day orally) for 31 and 6 months respectively after the initial diagnosis. In case #1, concurrent amlodipine and benazepril treatment was associated with decreased heart murmur grade and reduced aortic insufficiency severity. These reports illustrate that, similarly to domestic cats, SHT should be suspected in old large felids with CKD and that amlodipine is a well-tolerated antihypertensive drug in these species.

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.

[Calcified bullet thrombus of the inferior vena cava and left renal vein in an adult]. / Une calcification de la veine cave inférieure et de la veine rénale gauche chez l'adulte.

Calcifications are rarely located within the inferior vena cava and the renal veins. The etiology is poorly understood and the prognosis is uncertain. We report a case in a 55-year-old man.

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.

Carpal tunnel syndrome and computer exposure at work in two large complementary cohorts.

OBJECTIVES: The boom in computer use and concurrent high rates in musculoskeletal complaints and carpal tunnel syndrome (CTS) among users have led to a controversy about a possible link. Most studies have used cross-sectional designs and shown no association. The present study used longitudinal data from two large complementary cohorts to evaluate a possible relationship between CTS and the performance of computer work. SETTINGS AND PARTICIPANTS: The Cosali cohort is a representative sample of a French working population that evaluated CTS using standardised clinical examinations and assessed self-reported computer use. The PrediCTS cohort study enrolled newly hired clerical, service and construction workers in several industries in the USA, evaluated CTS using symptoms and nerve conduction studies (NCS), and estimated exposures to computer work using a job exposure matrix. PRIMARY AND SECONDARY OUTCOME MEASURES: During a follow-up of 3-5 years, the association between new cases of CTS and computer work was calculated using logistic regression models adjusting for sex, age, obesity and relevant associated disorders. RESULTS: In the Cosali study, 1551 workers (41.8%) completed follow-up physical examinations; 36 (2.3%) participants were diagnosed with CTS. In the PrediCTS study, 711 workers (64.2%) completed follow-up evaluations, whereas 31 (4.3%) had new cases of CTS. The adjusted OR for the group with the highest exposure to computer use was 0.39 (0.17; 0.89) in the Cosali cohort and 0.16 (0.05; 0.59) in the PrediCTS cohort. CONCLUSIONS: Data from two large cohorts in two different countries showed no association between computer work and new cases of CTS among workers in diverse jobs with varying job exposures. CTS is far more common among workers in non-computer related jobs; prevention efforts and work-related compensation programmes should focus on workers performing forceful hand exertion.

[Pediatric seizures and end-stage renal disease]. / État de mal convulsif révélateur d'une ostéodystrophie rénale.

Neonates and infants with hypocalcemia usually present with seizures, whereas this is less common in older children and teenagers. We report on a case of hypocalcemic seizures in a 16-year-old girl with undiagnosed end-stage renal disease with progressive growth retardation and bone deformations. We highlight the value of checking serum calcium, phosphate, and creatinine in children with growth retardation, seizures, and/or unexplained bone deformations. We also discuss the clinical consequences of pediatric renal osteodystrophy.

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.

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.