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International audience; Background and objectives Kidney impairment of ANCA-associated vasculitides can lead to kidney failure. Patients with kidney failure may suffer from vasculitis relapses but are also at high risk of infections and cardiovascular events, which questions the maintenance of immunosuppressive therapy. Design, setting, participants, & measurements Patients with ANCA-associated vasculitides initiating long-term dialysis between 2008 and 2012 in France registered in the national Renal Epidemiology and Information Network registry and paired with the National Health System database were included. We analyzed the proportion of patients in remission off immunosuppression over time and overall and event-free survival on dialysis (considering transplantation as a competing risk). We compared the incidence of vasculitis relapses, serious infections, cardiovascular events, and cancers before and after dialysis initiation. Results In total, 229 patients were included: 142 with granulomatous polyangiitis and 87 with microscopic polyangiitis. Mean follow-up after dialysis initiation was 4.6±2.7 years; 82 patients received a kidney transplant. The proportion of patients in remission off immunosuppression increased from 23% at dialysis initiation to 62% after 5 years. Overall survival rates on dialysis were 86%, 69%, and 62% at 1, 3, and 5 years, respectively. Main causes of death were infections (35%) and cardiovascular events (26%) but not vasculitis flares (6%). The incidence of vasculitis relapses decreased from 57 to seven episodes per 100 person-years before and after dialysis initiation ( P =0.05). Overall, during follow-up, 45% of patients experienced a serious infection and 45% had a cardiovascular event, whereas 13% experienced a vasculitis relapse. Conclusions The proportion of patients with ANCA-associated vasculitis in remission off immunosuppression increases with time spent on dialysis. In this cohort, patients were far less likely to relapse from their vasculitis than to display serious infectious or cardiovascular events. Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_11_08_CJN03190321.mp3

Introduction Childhood IgA nephropathy (cIgAN) is a primary glomerulonephritis clinically characterized by microscopic hematuria and proteinuria, the presence of which may potentially overlap with Alport syndrome. Interestingly, earlier studies suggested that familial IgAN could be linked to the chromosome 2q36 region, also the coding region for collagen type 4 alpha 3/4 (COL4A3/A4). Methods To investigate a possible relationship or phenocopy between Alport syndrome and cIgAN, COL4A3, COL4A4, and COL4A5 exons were sequenced in 36 cIgAN patients. Clinical data and treatment were collected retrospectively. COL4A3/A4/A5 variants were classified according to American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) guidelines. Results Four of 36 cIgAN patients were affected by ACMG class 4/5 COL4A3 heterozygous variants (COL4A3-cIgAN). We found no COL4A4 or COL4A5 variant. Despite having rare and deleterious COL4A3 variants, 3 of 4 COL4A3-cIgAN children developed clinical and biologic features of active IgAN rather than Alport syndrome. Response to intensive immunosuppressive treatment was favorable, leading to a reduction of endocapillary and extracapillary proliferation lesions. High levels of immune immunoglobulin G and A (IgG/IgA) complexes, reduction of proteinuria, and gradual stabilization of estimated glomerular filtration rate (eGFR) argued against Alport syndrome. Nevertheless, COL4A3-cIgAN patients seemed predisposed to a more serious IgAN presentation compared with the non‒COL4A3-cIgAN group, with more glomerulosclerosis and a lower eGFR over time. One of the 4 patients underwent kidney transplant with subsequent IgAN recurrence. Conclusions Predisposition factors for developing serious cIgAN flare-up should be considered for cIgAN with COL4A3 pathologic heterozygous variants. COL4A3 variants, usually responsible for Alport syndrome in adults, should not automatically exclude an immunosuppressive regimen in cIgAN. Moreover, evidence of an ACMG class 4/5 COL4A3 variant in early-stage cIgAN could be a helpful tool for stratifying severity of cIgAN beyond the Oxford classification., Graphical abstract

BACKGROUND Tacrolimus pharmacokinetics in obese (Ob) patients has been poorly studied. In this article, the authors explored the impact of obesity on tacrolimus exposure in kidney transplant recipients (KTRs) and estimated a more suitable initial dosage in this population. METHODS A retrospective, observational, monocentric case-control study was performed in obese KTRs (BMI > 30 kg/m2) who received tacrolimus between 2013 and 2017 (initial dose: 0.15 mg/kg/d) (actual weight). Nonobese (Nob) controls (BMI

To provide data about surgical workflow, accuracy, complications, radiation exposure, and learning curve effect in patients who underwent minimally invasive (MIS) transforaminal lumbar interbody fusion with navigation coupled with mobile intraoperative computed tomography.A retrospective analysis was performed of data from consecutive patients who underwent single- or double-level MIS transforaminal lumbar interbody fusion at a single institution; mobile intraoperative computed tomography combined with a navigation system was used as the sole intraoperative imaging method to place pedicular screws; decompression and interbody fusion were performed through a 22-mm tubular retractor. Clinical data, perioperative complications, accuracy of pedicular screw placement, and radiation exposure were analyzed. A learning curve effect on surgical time and accuracy was assessed.A total of 408 screws in 100 patients were analyzed. In all cases, spinal navigation allowed for identification of pedicular trajectories and greatly facilitated nerve root decompression through the MIS approach. Overall accuracy according to Heary classification was 95.3%. Nineteen screws (4.7%) presented a minor lateral breach (2 mm), not clinically significant. Surgical time, blood loss, and patient radiation exposure compared favorably with reported values from other series using three-dimensional navigation. A learning curve effect on surgical time, but not on screw accuracy, was identified.MIS transforaminal lumbar interbody fusion can now be performed without any radiation exposure to the surgeon and operating room staff, with almost absolute accuracy during screw positioning and tubular decompression. A learning curve effect on surgical time, but not on overall screw accuracy, may be expected.

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International audience; Introduction. - There is no feasible benchmark in daily routine to estimate the hydration status of haemodialysis patients, which is essential to their management. Objective. - We performed a study in haemodialysis patients to assess the diagnostic performance of pulmonary ultrasound and clinical examination for the evaluation of fluid overload using transthoracic echocardiography as a gold standard.Methods. - Thirty-one patients receiving chronic haemodialysis patients were included. Evaluation of hydration status was assessed weekly before haemodialysis sessions using clinical and Echo Comet Score from pulmonary ultrasound and transthoracic echocardiography (reference method).Results. - Five patients had a transthoracic echocardiography overload. Compared with transthoracic echocardiography, the diagnostic performance of the clinical overload score has a sensitivity of 100%, a specificity of 77%, a positive predictive value of 50% and a negative predictive value of 100% with a k of 0.79. Only orthopnoea (P = 0.008), jugular turgor (P = 0.005) and hepatic-jugular reflux (P = 0.008) were significantly associated with transthoracic echocardiography overload diagnosis. The diagnostic performance of Echo Comet Score by pulmonary ultrasound has a sensitivity of 80%, a specificity of 58%, a positive predictive value of 26% and a negative predictive value of 94%. Ten patients (32.3%) had an increase of extravascular pulmonary water without evidence of transthoracic echocardiography or clinical overload.Conclusions. - Our clinical score has a convincing diagnostic performance compared to transthoracic echocardiography and could be easily used in daily clinical routine to adjust dry weight. The evaluation of the overload using pulmonary ultrasound seems poorly correlated with the overload evaluated by transthoracic echocardiography. Extravascular pulmonary water undetected by clinical examination and transthoracic echocardiography remains a parameter that requires further investigation. (C) 2020 Societe francophone de nephrologie, dialyse et transplantation.

Objective This study aimed to determine the relationship between early postoperative nonsteroidal anti-inflammatory drug (NSAID) administration and postoperative acute kidney injury (AKI) and anastomotic leak. Summary background data NSAIDs have analgesic, opioid-sparing, and anti-inflammatory effects. However, their postoperative use is limited by concerns around increased risk of AKI and anastomotic leak. Methods A secondary analysis of a multicenter, prospective cohort study including patients undergoing elective or emergency major gastrointestinal surgery from September to December 2015 across 173 hospitals in the United Kingdom and Ireland. Exposure to early postoperative NSAIDs was defined as NSAID administration on postoperative days 0 to 3. The primary outcome was the 7-day postoperative AKI rate. Propensity score matching was used to balance treatment groups and estimate treatment effects that are presented as odds ratios, alongside the corresponding 95% confidence interval (CI). Results Overall 19.8% (1039/5240) of patients received early NSAIDs. AKI rates were 10.6% in the early NSAID group and 14.9% in the no NSAID group. The anastomotic leak rate in patients who received an anastomosis was 4.8% in the NSAIDs group and 6.0% in the no NSAIDs group. Following propensity score matching, early use of NSAIDs was not significantly associated with AKI (adjusted odds ratio 0.80, 95% CI 0.63-1.00, P = 0.057). This finding was consistent in subgroup analyses by NSAID dosage and timing. In patients who had a gastrointestinal anastomosis, NSAIDs were not associated with anastomotic leak (adjusted odds ratio 0.85, 95% CI 0.58-1.21, P = 0.382). Conclusions Administration of NSAIDs in the early postoperative period is safe in selected patients following major gastrointestinal surgery.

The middle meningeal artery is the major human dural artery. Its origin and course can vary a great deal in relation, not only with the embryologic development of the hyostapedial system, but also because of the relationship of this system with the ICA, ophthalmic artery, trigeminal artery, and inferolateral trunk. After summarizing these systems in the first part our review, our purpose is to describe, in this second part, the anatomy, the possible origins, and courses of the middle meningeal artery. This review is enriched by the correlation of each variant to the related embryologic explanation as well as by some clinical cases shown in the figures. We discuss, in conclusion, some clinical conditions that require detailed knowledge of possible variants of the middle meningeal artery.

Previous reports suggest initial presentation of IgA nephropathy (IgAN) in children is different from adults. No systematic comparison of clinical, biological, and histological childhood- and adult-onset IgAN is currently available. We compared pediatric and adult clinical and histological characteristics at IgAN diagnosis. Data on 211 consecutive patients from two different centers in Paris (82 children, 129 adults) were reviewed. Kidney biopsies were scored for Oxford classification and podocytopathic (P1) features. We report higher eGFR at diagnosis in children compared to adults (89.5 vs. 64 ml/min/1.73 m2; p = 0.0001) but no difference in proteinuria. Histological analysis of kidney biopsy found higher proportions of mesangial (M1) and endocapillary (E1) hypercellularity in children compared with adults (M1 [80.7% vs. 27.9%, p = 0.0001]; E1 [71.3% vs. 30%, p = 0.0001]). Focal glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis ≥ 25% (T1), and P1 were more frequent in adults (S1 [81.5% vs. 61.3%, p = 0.0012], T1 [49.5% vs. 1.35%, p = 0.0001], P1 [33.8% vs. 16.4%, p = 0.008). Proteinuria associated with M1, E1, and C1 in children (M1, p = 0.0001; E1, p = 0.0005; C1, p = 0.0014) but S1, P1, and T1 in adults (S1, p = 0.0001; P1, p = 0.0001; T1, p = 0.001). After steroid treatment (41 children and 28 adults), proteinuria decreased in children (p < 0.001, follow-up 38 months) and adults (p < 0.001, follow-up 76.9 months), whereas eGFR remained stable in adults but increased significantly in children (90.6 to 110 ml/min/1.73m2). Proteinuria in children with IgAN is a marker of glomerular proliferative lesions whereas its presence in adults often reflects the presence of chronic lesions. This suggests the need for histological assessment.

We describe a case of a patient suffering with cervical radiculopathy due to vertebral artery loop with nerve root compression, treated with an epidural steroid injection. A 37-year-old man presented with a 2-year history of right-sided radicular pain along the C7 dermatome. Imaging showed a right-sided loop of the vertebral artery at the V1-V2 transition with contact on the C7 nerve root. The pain was resistant to conservative treatment, and the decision was made to perform a focused fluoroscopy-guided translaminar epidural steroid injection near the C7 nerve root. The procedure was uneventful, and the symptoms resolved completely after the procedure. Targeted epidural steroid injection might be a useful and safe diagnostic and therapeutic approach in patients affected by cervical radiculopathy due to a VA loop. To our knowledge, this is the first case of a VA loop associated with cervical radiculopathy treated with this technique.

IgA nephropathy (IgAN) is observed in subjects of any age, however perspective and management of this disease are different between adult and pediatrician Nephrologists. Most children with IgAN present with gross hematuria rapidly vanishing or persistent mild microscopic hematuria, which rarely progresses to end stage renal disease (ESRD) over the pediatric observation. The perspective of IgAN in adults is of a slowly progressive glomerular disease with 30-40% probabilities to reach ESRD. However, mild cases of IgAN in children might be missed with manifestation of irreversible damage only decades after the true onset, as 50% of subjects with IgAN enter renal replacement treatment before the age of 50 years. In both adults and children the assessment of risk profile is crucial to avoid overtreatment in benign cases or institute a prompt and valid therapy in potentially progressive cases. In case of common risk factors, new therapeutic opportunities tested in adults might be applied to children with the expectation of similar results. If IgAN is the same disease in spite of different clinical profiles in children and adults, an early intervention may be the correct way to prevent progression decades later. On the contrary, if we are dealing with different clinical entities, the treatment in pediatric and in adult settings must be kept apart. This review addresses to report similarities and differences of IgAN across the life periods in order to reason on the application of newly offered treatments over the entire spectrum of this disease or in focused age indications.

The ophthalmic artery (OA) has one of the most complex anatomy and the most fascinating embryological development. The complexity of the embryologic development of the OA resides in the implication of three different embryological systems: the carotid system, the stapedial system, and the ventral pharyngeal system. This explains very well the numerous variations in origin of the OA and the importance of vascular anastomoses developed with branches of the external carotid artery and with the middle meningeal artery. In this review, authors propose a comprehensive description of different hypotheses on the embryologic development of the OA and, in a second part, explain all anatomical variations and clinical implications of this artery.

Background Muscle strength decreases as kidney failure progresses. Low muscle strength affects more than 50% of hemodialysis patients and leads to daily life activities impairment. In the general population, numerous studies have linked low 25OH-vitamin D (25OHD) concentrations to the loss of the muscle strength and low physical performances. Data on native vitamin D and muscle function are scarce in the chronic kidney disease (CKD) population, but low 25OHD levels have been associated with poor muscle strength. We present in this article the protocol of an ongoing study named VITADIAL testing if cholecalciferol supplementation in hemodialysis patients with low 25OHD improves their muscle strength. Methods/design VITADIAL is a prospective open randomized French multicenter study. All patients will have 25OHD levels ≤50nmol/L at randomization. One group will receive 100,000 UI cholecalciferol once a month during 6 months; the other group will receive no treatment during 6 months. In order to randomize patients with 25OHD ≤50nmol/L, supplemented patients will undergo a 3 months wash-out period renewable 3 times (maximum of 12 months wash-out) until 25OHD reaches a level ≤50nmol/L. The main objective of this study is to analyze if a 6-month period of oral cholecalciferol (i.e., native vitamin D) supplementation improves muscle strength of hemodialysis patients with low 25OHD vitamin D levels. Muscle strength will be assessed at 0, 3, and 6 months, by handgrip strength measured with a quantitative dynamometer. Secondary objectives are (1) to analyze 25OHD plasma levels after vitamin D wash-out and/or supplementation, as well as factors associated with 25OHD lowering speed during wash-out, and (2) to analyze if this supplementation improves patient’s autonomy, reduces frailty risk, and improves quality of life. Fifty-four patients are needed in each group to meet our main objective. Discussion In the general population, around 30 randomized studies analyzed the effects of vitamin D supplementation on muscle strength. These studies had very different designs, sizes, and studied population. Globally, these studies and the meta-analysis of studies favor a beneficial effect of vitamin D supplementation on muscle strength, but this effect is mainly found in the subgroup of aged patients and those with the lowest 25OHD concentrations at inclusion. We reported a positive independent association between 25OHD and handgrip strength in a population of 130 hemodialysis patients in a dose-dependent manner. In our cohort, a plateau effect was observed above 75 nmol/L. Only two randomized studies analyzed the effect of native vitamin D supplementation on muscle strength in hemodialysis patients, but unfortunately, these two studies were underpowered. VITADIAL is a trial specifically designed to assess whether cholecalciferol might benefit to hemodialysis patient’s muscle strength. Trial registration ClinicalTrials.govNCT04262934. Registered on 10 February 2020 - Retrospectively registered.

The purpose of this work is to investigate the protein kinase inhibitory activity of constituents from ethyl acetate soluble fraction of Acacia auriculiformis stem bark. Column chromatography, gel filtration and NMR spectroscopy were used to purified and characterized betulin from the extract. Betulin which is a known inducer of apoptosis was screened against a panel of 16 disease-related protein kinases. Betulin was shown to inhibit Abelson murine leukemia viral oncogene homolog 1 (ABL1) kinase, casein kinase 1epsilon (CK1epsilon), glycogen synthase kinase 3alpha/β (GSK-3alpha/β), Janus kinase 3 (JAK3), NIMA Related Kinase 6 (NEK6) and vascular endothelial growth factor receptor 2 kinase (VEGFR2) and with activity in µM range. The effect of betulin on the cell viability of doxorubicin-resistant K562R chronic myelogenous leukemia cells was then verified to underline its putative use as anti-cancer compound. Betulin was shown to modulate the mitogen-activated protein (MAP) kinase pathway similarly to imatinib mesylate, a well-known inhibitor of ABL1 kinase. The interaction of betulin and ABL1 was studied by molecular docking showing an interaction of the inhibitor with the ATP binding pocket. Altogether, these data demonstrate that betulin is a multi-target inhibitor of protein kinases, an activity that can contribute to the anticancer properties of the natural compound and notably for treatment of leukemia.

SB'20, 45ème Congrès de la Société de Biomécanique, Metz, France, 26-/10/2020 - 28/10/2020; The present study was thus designed to test the hypothesis that different types of footwear could induce a change in mediolateral stability.

OBJECTIVETreatment of posterior fossa arteriovenous malformations (PFAVMs) remains controversial as it is always challenging and may lead to major complications. Nonetheless, these lesions are more likely to bleed and generate poorer outcomes than other brain AVMs. The aim of this study was to evaluate the effect of endovascular treatment on long-term outcomes and identify the patient subgroups that might benefit from endovascular treatment.METHODSThe authors performed a retrospective analysis of all consecutive cases of PFAVM managed at the Fondation Rothschild Hospital between 1995 and 2018. Clinical, imaging, and treatment data were prospectively gathered; these data were analyzed with respect to long-term outcomes.RESULTSAmong the 1311 patients with brain AVMs, 114 (8.7%) had a PFAVM, and 88 (77.2%) of these patients had a history of bleeding. Of the 114 PFAVMs, 101 (88.6%) were treated (83 ruptured and 18 unruptured). The mean duration of follow-up was 47.6 months (range 0–240 months). Good neurological outcome at last follow-up was achieved in 79 cases (78.2%). Follow-up angiography showed obliteration of the PFAVM in 68.3% of treated cases. The presence of direct vertebrobasilar perforator feeders was associated with neurological deterioration (OR 5.63, 95% CI 11.15–30.76) and a lower obliteration rate (OR 15.69, 95% CI 2.52–304.03) after endovascular treatment. Other predictors of neurological deterioration and obliteration rate were consistent with the Spetzler-Martin grading system.CONCLUSIONSAdvances in endovascular techniques have enabled higher obliteration rates in the treatment of PFAVMs, but complication rates are still high. Subgroups of patients who might benefit from treatment must be carefully selected and the presence of direct vertebrobasilar perforator feeders must call into question the indication for endovascular treatment.

BACKGROUND AND PURPOSE Aneurysms of the posterior inferior cerebellar artery (PICA) are relatively uncommon and evidence is sparse about patients presenting with ruptured PICA aneurysms. We performed an analysis of the Swiss SOS national registry to describe clinical presentation, treatment pattern, and neurological outcome of patients with ruptured PICA aneurysms compared with other ruptured posterior circulation (PC) aneurysms. METHODS This was a retrospective analysis of anonymized data from the Swiss SOS registry (Swiss Study on Aneurysmal Subarachnoid Hemorrhage; 2009-2014). Patients with ruptured PC aneurysms were subdivided into a PICA and non-PICA group. Clinical, radiological, and treatment-related variables were identified, and their impact on the neurological outcome was determined in terms of modified Rankin score at discharge and at 1 year of follow-up for the two groups. RESULTS Data from 1864 aneurysmal subarachnoid hemorrhage patients were reviewed. There were 264 patients with a ruptured PC aneurysm. Seventy-four PICA aneurysms represented 28% of the series; clinical and radiological characteristics at admission were comparable between the PICA and non-PICA group. Surgical treatment was accomplished in 28% of patients in the PICA group and in the 4.8% of patients in the non-PICA group. No statistically significant difference was found between the two groups in terms of complications after treatment. Hydrocephalus requiring definitive shunt was needed in 21.6% of PICA patients (p = 0.6); cranial nerve deficit was present in average a quarter of the patients in both PICA and non-PICA group with no statistical difference (p = 0.3). A more favorable outcome (66.2%) was reported in the PICA group at discharge (p

International audience; Hemophilia A is an X-linked genetic hemorrhagic disorder characterized by a factor VIII deficiency. The availability of secured substitution products has led to a dramatic improvement of life expectancy in hemophiliac patients. Nowadays, adult hemophiliac patients may develop Chronic Kidney Disease (CKD) resulting from age-related comorbidities (hypertension, obesity, diabetes). In addition, the high prevalence of viral infections in this population exposes patients to an increased risk of CKD. The risk of hemorrhage in hemophiliac patients is a challenge for their clinical management, both for diagnostic procedures (kidney biopsy in particular) and for renal replacement therapy (dialysis or renal transplantation) when it is needed. This work provides an update of the literature data concerning the management of hemophiliac patients in nephrology, illustrated by the cases of two patients.

IgA nephropathy (IgAN) is one the most common primary glomerulonephritis in children and adolescents worldwide, with 20% of children developing end-stage kidney disease (ESKD) within 20 years of diagnosis. There is a need for treatment guidelines, especially for steroids in children with primary IgAN, since the STOP-IgA trial casts doubts on the use of steroids in adults with intermediate risk. Pediatricians are prone to prescribe steroids in addition to renin–angiotensin system blockade (RASB) when proteinuria is > 0.5 g/l, eGFR deteriorates

International audience; Objective: Severe preeclampsia may require the delivery of the placenta to avoid life-threatening complications for the mother. Before 26 weeks of gestation, this often results in perinatal death. A decrease in soluble fms-like tyrosine kinase 1 (sFlt1), an anti-angiogenic factor central to the pathophysiology of the maternal syndrome, has been reported after LDL- apheresis. The present study tested whether LDL-apheresis could be used to allow women with early and severe preeclampsia to reach a gestational age where the baby had a viable chance of survival.Study Design: A phase II prospective study. Adult women were included if they had very early (

Background Humoral response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines needs to be evaluated in the fragile population of patients on maintenance haemodialysis (HD). Methods We analysed the antibody response to the spike (S) antigen of SARS-CoV-2 before and after each dose of the messenger RNA (mRNA) Comirnaty vaccine (BNT162b2; BioNTech & Pfizer) in patients from a single dialysis centre and detected the presence of neutralizing antibodies (Nabs). Results Among the 90 vaccinated HD patients (mean age 69 years, 61% male), 19 (21%) had a history of SARS-CoV-2 infection. A seroconversion with anti-S immunoglobulin G antibodies (Sabs) was documented in 20% of patients after the first dose (early responders) and in 77% after the second dose, while 23% were non-responders. Cardiac disease, cirrhosis and gamma globulin levels were independently predictive of the absence of seroconversion. Nabs were detected in 15.4% of early responders after the first dose and in 84.6% of early responders and 57.9% of late responders after the second dose. Sab titres after the second dose were higher in patients with Nab than without Nab {598 [interquartile range (IQR) 246–882]) versus 134 [IQR 61–390]; P Conclusions Most HD patients develop a substantial humoral response against SARS-CoV2, with Nabs, following the mRNA vaccine. Whether this immunity persists over time and is able to efficiently protect patients from coronavirus disease 2019 remains to be determined.

A 64-year-old man was referred to A&E by his general practitioner with worsening back and acute bilateral leg pain and weakness with urinary retention. His MRI scan demonstrated spinal canal stenosis at the level of L1–L2 and a diagnosis of cauda equina syndrome (CES) was made. CES is a rare neurological condition caused by compression of the central spinal nerves at the termination of the cord. CES is a surgical emergency requiring urgent assessment and treatment. The patient underwent urgent surgical decompression; however, he required a second surgery for further decompression as repeat MRI showed persistent stenosis with further extension. Intraoperative Doppler ultrasonography revealed an intradural lesion, which was surgically excised and found to be a sequestrated lumbar disc in the intrathecal space. The patient showed significant neurological improvement post revision decompression.

The embryological development of the cerebral vasculature is very complex. Historical and also more recent studies based on human embryos, comparative anatomy and cerebral angiographies allowed us to better understand this vasculature development. The knowledge and understanding of such embryological development are important for physicians interested in neurovascular pathologies. Indeed, all vascular variants and almost all vascular pathologies, such as aneurysms, dolichoectasia, atherosclerosis, and neurovascular conflicts could be explained by an alteration during the embryological life. There are also many variants of these vascular structures present in normal developed adults, which are variably associated with pathological entities. Understanding the process which leads to the development of the normal cerebral arterial system in humans is, therefore, very important to have a better knowledge of the possible clinical and surgical implications of these anomalies. In this paper, we review the embryological development of the cranio-facial arterial vasculature from its beginning at approximately days 21–50 of intrauterine life, with pictures illustrating each developmental phase.

Intracerebral hemorrhage (ICH) can be considered one of the major neurologic and neurosurgical emergencies that need a time-dependent diagnosis and treatment. On rare occasions, an aneurysmal rupture may also present with isolated ICH without subarachnoid hemorrhage. We present the case of a 48-year-old woman presenting in our neurosurgical department with ICH and a right middle cerebral artery (MCA) occlusion that, 6 weeks after the initial surgical management, unveiled a large MCA aneurysm treated with a clipping. In this study, we discuss our hypothesis about the etiology and the pathophysiology of this rare phenomenon in the light of the literature in the field.

BACKGROUND Current prognostic tools in aneurysmal subarachnoid hemorrhage (aSAH) are constrained by being primarily based on patient and disease characteristics on admission. OBJECTIVE To develop and validate a complication- and treatment-aware outcome prediction tool in aSAH. METHODS This cohort study included data from an ongoing prospective nationwide multicenter registry on all aSAH patients in Switzerland (Swiss SOS [Swiss Study on aSAH]; 2009-2015). We trained supervised machine learning algorithms to predict a binary outcome at discharge (modified Rankin scale [mRS] ≤ 3: favorable; mRS 4-6: unfavorable). Clinical and radiological variables on admission ("Early" Model) as well as additional variables regarding secondary complications and disease management ("Late" Model) were used. Performance of both models was assessed by classification performance metrics on an out-of-sample test dataset. RESULTS Favorable functional outcome at discharge was observed in 1156 (62.0%) of 1866 patients. Both models scored a high accuracy of 75% to 76% on the test set. The "Late" outcome model outperformed the "Early" model with an area under the receiver operator characteristics curve (AUC) of 0.85 vs 0.79, corresponding to a specificity of 0.81 vs 0.70 and a sensitivity of 0.71 vs 0.79, respectively. CONCLUSION Both machine learning models show good discrimination and calibration confirmed on application to an internal test dataset of patients with a wide range of disease severity treated in different institutions within a nationwide registry. Our study indicates that the inclusion of variables reflecting the clinical course of the patient may lead to outcome predictions with superior predictive power compared to a model based on admission data only.

International audience; Proviral integration site for Moloney murine leukemia virus (Pim)-1/2 kinase overexpression has been identified in a variety of hematologic (e.g., multiple myeloma or acute myeloid leukemia (AML)) and solid (e.g., colorectal carcinoma) tumors, playing a key role in cancer progression, metastasis, and drug resistance, and is linked to poor prognosis. These kinases are thus considered interesting targets in oncology. We report herein the design, synthesis, structure–activity relationships (SAR) and in vitro evaluations of new quinoxaline derivatives, acting as dual Pim1/2 inhibitors. Two lead compounds (5c and 5e) were then identified, as potent submicromolar Pim-1 and Pim-2 inhibitors. These molecules were also able to inhibit the growth of the two human cell lines, MV4-11 (AML) and HCT-116 (colorectal carcinoma), expressing high endogenous levels of Pim-1/2 kinases.

Background and Purpose: The purpose of this study was to assess nationwide incidence and outcomes of aneurysmal subarachnoid hemorrhage (aSAH). The Swiss SOS (Swiss Study on Subarachnoid Hemorrhage) was established in 2008 and offers the unique opportunity to provide this data from the point of care on a nationwide level. Methods: All patients with confirmed aneurysmal subarachnoid hemorrhage admitted between January 1, 2009 and December 31, 2014, within Switzerland were recorded in a prospective registry. Incidence rates were calculated based on time-matched population data. Admission parameters and outcomes at discharge and at 1 year were recorded. Results: We recorded data of 1787 consecutive patients. The incidence of aneurysmal subarachnoid hemorrhage in Switzerland was 3.7 per 100 000 persons/y. The number of female patients was 1170 (65.5%). With a follow-up rate of 91.3% at 1 year, 1042 patients (58.8%) led an independent life according to the modified Rankin Scale (0–2). About 1 in 10 patients survived in a dependent state (modified Rankin Scale, 3–5; n=185; 10.4%). Case fatality was 20.1% (n=356) at discharge and 22.1% (n=391) after 1 year. Conclusions: The current incidence of aneurysmal subarachnoid hemorrhage in Switzerland is lower than expected and an indication of a global trend toward decreasing admissions for ruptured intracranial aneurysms. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03245866.

Background Although end-stage renal disease (ESRD) is frequently used as an outcome marker for primary immunoglobulin A nephropathy (IgAN), the clinical course after reaching ESRD is not well documented. This study examined patients’ characteristics and survival in ESRD-related biopsy-proven IgAN in France. Methods French Renal Epidemiology and Information Network Registry data from 2010 to 2014 were used to analyse patients’ survival and outcome in incident ESRD patients >16 years of age with biopsy-proven primary IgAN, in comparison with other primary and secondary glomerulonephritis (GN), adult polycystic kidney disease (ADPKD) or diabetes. Multivariable survival analysis was adjusted for age, sex, time on dialysis and comorbidities. Results Among 17 138 incident dialysis patients with ESRD, IgAN (242.8/10 000 dialysis initiation) represents the most common GN related to ESRD during 2010. IgAN patients were the youngest, and had the fewest comorbidities and the highest use of peritoneal dialysis (PD) (17%). In comparison with the haemodialysis group, hazard ratios for death were not different in the preemptive transplantation group [0.46, 95% confidence interval (CI) 0.17–1.28] and in the PD group (0.77, 95% CI 0.44–1.33). Mortality rates in IgAN patients with preemptive transplantation and in those receiving dialysis waiting for transplantation were 2.9% (95% CI 0.0–5.6) and 6.7% (95% CI 0.9–12.3). Mortality rates of ADPKD patients receiving dialysis waiting for transplantation were higher (18%, 95% CI 3.1–30.6). Conclusion IgAN has the best prognosis among primary and secondary GN. IgAN patients receiving dialysis waiting transplantation seem to have a more favourable prognosis than ADPKD patients, who usually comprise the reference population. The underlying reasons for the difference in access treatment modalities should be investigated to improve survival with respect to renal disease.

Beside the commonly described pulmonary expression of the coronavirus disease 2019 (COVID-19), major vascular events have been reported. The objective of this study was to investigate whether increased levels of circulating endothelial cells (CECs) might be associated with severe forms of COVID-19. Ninety-nine patients with COVID-19 were enrolled in this retrospective study. Patients in the intensive care units (ICU) had significantly higher CEC counts than non-ICU patients and the extent of endothelial injury was correlated with putative markers of disease severity and inflammatory cytokines. Together, these data provide in vivo evidence that endothelial injury is a key feature of COVID-19.

BackgroundRhabdomyolysis is a life-threatening disease that can lead to severe hyperkalemia, acute kidney injury (AKI) and hypovolemic shock. The predictive factors of AKI and acute to chronic kidney disease (CKD) transition remain poorly described.MethodsThis multicenter retrospective study enrolled 387 patients with severe rhabdomyolysis (CPK > 5000 U/L). Primary end-point was the development of severe AKI, defined as stage 2 or 3 of KDIGO classification. Secondary end-points included the incidence of AKI to CKD transition.ResultsAmong the 387 patients, 315 (81.4%) developed AKI, including 171 (44.1%) with stage 3 AKI and 103 (26.6%) requiring RRT. Stage 2–3 AKI was strongly correlated with serum phosphate, potassium and bicarbonate at admission, as well as myoglobin over 8000 U/L and the need for mechanical ventilation. 42 patients (10.8%) died before day 28. In the 80 patients with available eGFR values both before and 3 months after the rhabdomyolysis, the decrease in eGFR (greater than 20 mL/min/1.73 m2in 23 patients; 28.8%) was correlated to the severity of the AKI and serum myoglobin levels > 8000 U/L at admission.ConclusionsSevere rhabdomyolysis leads to AKI in most patients admitted to an ICU. Mechanical ventilation and severity of the rhabdomyolysis, including myoglobin level, are associated with the risk of stage 2–3 AKI. The long-term renal decline is correlated to serum myoglobin at admission.

Background The middle cerebral artery (MCA) bifurcation represents the most frequent location for intracranial aneurysms. Often, the aneurysmal dome can hide the origin of perforating arteries from the M1 segment during the surgical clipping causing ischemic lesions and worse clinical outcome. The aim of this paper is to analyze the association between the orientation of the aneurysm sac and the clinical and radiological outcomes after surgical clipping. Methods Data from 50 MCA bifurcation clipped aneurysms in 47 patients were collected retrospectively. Three different groups were identified according to the aneurysmal sac orientation: anterior-inferior, posterior and superior. A possible association between the aneurysmal sac projection and the outcome was searched through a univariable logistic regression analysis. Results Statistical analysis showed significant correlation between the radiologic evidence of post-operative ischemia in the posterior group (p = 0.046, RR = 1.65) and an increased risk in the superior orientation group (p = 0.145, RR = 1.38). The anterior-inferior group was, instead, significantly associated with no evidence of radiologic ischemia (p = 0.0019, RR = 0.58). Conclusion The orientation of the aneurysmal dome and sac represents a fundamental feature to be considered during the surgical clipping of the MCA aneurysms. Indeed, its posterior and superior projection is associated with a higher incidence of radiologic ischemic lesions due to the origin of perforating arteries from M1 segment behind the aneurysmal sac. The anterior-inferior orientation, on the contrary, is associated with a lower risk.

SB'20, 45eme Congrès de la Société de Biomécanique, Metz, France, 26-/10/2020 - 28/10/2020; Therefore, the aim of this work was to complement the CSRT with additional tasks to better assess in elderly people perception and response execution, attention and inhibition capacity. For this purpose, a test with different tasks is proposed. It was tested in two different samples, young and elderly, in order to determinate differences between them and anticipate relevant conclusions.

BackgroundCoronavirus disease 2019 (COVID-19) is an emerging infectious disease, related to severe acute respiratory syndrome coronavirus 2 infection. Few data are available in patients with end-stage renal disease (ESRD).MethodsWe conducted an observational cohort study of COVID-19 patients at 11 dialysis centres in two distinct districts of France to examine the epidemiological and clinical characteristics of COVID-19 in this population, and to determine risk factors of disease severity (defined as a composite outcome including intensive care unit admission or death) and mortality.ResultsAmong the 2336 patients enrolled, 5.5% had confirmed COVID-19 diagnosis. Of the 122 patients with a follow-up superior to 28 days, 37% reached the composite outcome and 28% died. Multivariate analysis showed that oxygen therapy on diagnosis and a decrease in lymphocyte count were independent risk factors associated with disease severity and with mortality. Chronic use of angiotensin II receptor blockers (ARBs) (18% of patients) was associated with a protective effect on mortality. Treatment with azithromycin and hydroxychloroquine (AZT/HCQ) (46% of patients) were not associated with the composite outcome and with death in univariate and multivariate analyses.ConclusionsCOVID-19 is a severe disease with poor prognosis in patients with ESRD. Usual treatment with ARBs seems to be protective of critical evolution and mortality. There is no evidence of clinical benefit with the combination of AZT/HCQ.