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Introduction: Pregnancy and postpartum are phases in the women's life where the thrombotic risk is increased both on the venous and on the arterial side., Methods: We are presenting the case of a young woman at the third pregnancy, carried out without complications until delivery, whose postpartum was characterized by the occurrence of headache. Neuroimaging studies were performed, firstly brain computed tomography (CT) with CT Angiography and after brain Magnetic Resonance Imaging (MRI) with MR Angiography. The main finding was the simultaneous presence of two cerebrovascular vascular diseases, i.e. cerebral venous thrombosis (CVT) and left carotid dissection, without stroke. The neuroimaging features of both the diseases were analyzed and both CVT and dissection had neuroimaging markers of acute timing. After starting heparin therapy at anticoagulant dose the clinical symptoms disappeared within a few days., Discussion: CVT is a rare event with a peak in the late pregnancy and puerperium, but other arterial cerebrovascular events, as spontaneous dissection, have not an increased incidence in the postpartum. Headache is one of the main symptoms for all these cerebrovascular diseases, but usually stroke is the accompanying event. This is not always true and the presented case illustrates this unexpected occurrence., Conclusions: Headache is a nonspecific and highly prevalent symptom and in the postpartum period it could raise the suspicion of CVT. Sometimes several different causes are found for the same symptom and concurrent acute cerebrovascular diseases might be considered. Neuroimaging investigations may help for diagnosis and timing concurrent thrombotic diseases, particularly DWI-MRI., Competing Interests: Declarations. Competing interests: The authors have no competing interests to declare that are relevant to the content of this article. Ethics statement: Not applicable. The authors have no relevant financial or non-financial interests to disclose., (© 2024. Fondazione Società Italiana di Neurologia.)

Arteriovenous fistulas (AVFs) are the preferred vascular access for chronic hemodialysis patients due to their lower rates of infectious and thrombotic complications, reduced morbidity and mortality, and increased durability compared to central venous catheters. However, the creation of AVFs has become increasingly challenging due to the rising prevalence of chronic diseases like diabetes, hypertension, and cardiovascular conditions, which are leading causes of end-stage renal disease (ESRD). These comorbidities, coupled with the aging dialysis population, have led to an increase in peripheral vascular diseases, complicating AVF management. This paper discusses two major complications of AVFs: Hemodialysis Access-Induced Distal Ischemia (HAIDI) and high-flow AVFs. HAIDI is characterized by ischemia in extremities due to reduced capillary perfusion, potentially leading to severe outcomes such as tissue necrosis and digital amputations. Approximately 5% of hemodialysis patients with AVFs develop HAIDI, necessitating corrective treatment. High-flow AVFs, defined by excessive blood flow that disrupts overall circulatory dynamics, pose another significant challenge, particularly in patients with cardiovascular compromise. The management of these complications is complex and often requires specialized techniques to preserve the AVF and avoid its closure. This review presents both surgical and endovascular techniques aimed at reducing AVF flow and improving distal perfusion. Techniques discussed include vein approach like ligation, plication, banding, prosthetic graft interposition, and various arterial interventions like distal radial artery ligation and embolization. Additionally, the review presents techniques for anastomosis remodeling, offering innovative approaches to managing AVF complications. The review concludes with a proposed decision-making algorithm to guide clinicians in selecting appropriate interventions based on the specific AVF-related complications, ensuring optimal outcomes for hemodialysis patients. This comprehensive overview highlights the importance of individualized treatment strategies in the management of AVF complications., (Copyright by Società Italiana di Nefrologia SIN, Rome,Italy.)

In 2016, Sifrim and colleagues described the first group of patients carrying heterozygous pathogenic variants in CDK13 and sharing major clinical features mainly consisting of congenital heart defects, intellectual disability and peculiar facial features (Congenital Heart Defects, Dysmorphic Facial Features, and Intellectual Developmental Disorder; CHDFIDD, OMIM # 617360). This condition is generally referred to as CDK13-related disorder, and since then other reports have provided further clinical and molecular information. Here we describe a group of 27 previously unreported patients to more accurately profile the clinical spectrum associated with CDK13 variants, disclosing novel associated findings, such as complex craniosynostosis and variable skeletal features (e.g., cranio-cervical anomalies). We also focused on the ocular phenotype that appears to include bilateral congenital glaucoma, posterior embriotoxon, buphthalmos and Duane anomaly. Finally, we observed two cases of mother-to-daughter transmission. Our work clarifies some novel features of CHDFIDD, defines the differential diagnosis of this disorder, and provides recommendations for its clinical management., (© 2025 The Author(s). Clinical Genetics published by John Wiley & Sons Ltd.)

Newborns are at high risk to develop sepsis. This is linked to innate immune responses at birth which are not completely adapted to postnatal life. Neutrophils are key players of innate immunity and exhibit a marked ontogenetic regulation of their functionality. Here, we studied the NLRP3 inflammasome in neonatal neutrophils and found lower baseline expression of NLRP3, pro-caspase-1, and the K+-channel KV1.3 compared with adult neutrophils. Following stimulation with lipopolysaccharide/nigericin, apoptosis-related speck-like protein containing a caspase recruitment domain oligomerization, caspase-1 activation, and interleukin-1β (IL-1β) release were significantly reduced in neonatal compared with adult neutrophils. Similarly, stimulation of neonatal neutrophils with E-selectin led to reduced NLRP3 inflammasome activation accompanied by diminished release of the alarmin S100A8/A9. Taken together, our results strongly indicate diminished NLRP3 inflammasome activation in neonatal neutrophils leading to a significant reduction of released IL-1β and S100A8/A9. These findings identify reduced neutrophil NLRP3 inflammasome activation as a critical component contributing to the inherent susceptibility to infections in neonates., Competing Interests: Conflict of interest All authors declare that no conflict of interest exists., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology.)

Stenosis represents the most relevant arteriovenous fistula (AVF) pathology and can affects the entire conduit forming the fistula, from afferent artery to central venous vessels. Correction of vascular access stenosis significantly affects the survival and quality of life for end stage renal disease patients (ESRD) dependent on hemodialysis. Guidelines consider the procedure of percutaneous transluminal angioplasty (PTA) relevant for the primary treatment of these lesions with excellent results in restoring AVF immediately at the end of the procedure. From first AVF angioplasty in 1981 to now, wide scientific innovation has led to development of new devices, composed by different materials and technologies, specific for the site and the type of stenosis to be treated, able to manage resistant stenotic lesion and to reduce stenosis recurrences. International guidelines do not clearly specify all treatment possibilities in the individual case. In this review the authors want to provide specific information on most used devices for stenosis treatment based on literature evidence, showing when and where to use the various tools available with flow-chart treatment proposal., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disorder presenting with cerebellar ataxia, sensory-motor axonal neuropathy, oculomotor apraxia, cerebellar atrophy and high alpha-fetoprotein (AFP) serum level. AOA2 is due to coding mutations of the SETX gene, mapped to chromosome 9q34. Seldom noncoding mutations affecting RNA processing have been reported too. To date psychiatric symptoms have never been reported in AOA2., Case Presentation: A 19 years-old man came to our attention for progressive gait ataxia debuted five years earlier. His past medical history was unremarkable, while his parents were consanguineous. On neurological examination, he had bilateral horizontal gaze-evoked nystagmus with hypometric saccades and saccadic horizontal smooth pursuit, appendicular ataxia, limbs and trunk myoclonic involuntary movements with hands' dystonic postures and dance of the tendons. Psychological evaluation described intrusive and obsessive thoughts experienced by the patient, then diagnosed as obsessive-compulsive disorder. Blood tests detected an elevated AFP level. Brain MRI showed cerebellar atrophy, while electroneuromyography revealed an axonal sensory-motor polyneuropathy. In the suspicion of a pathology belonging to the autosomal recessive cerebellar ataxias (ARCA) spectrum disorder, a direct search of point mutations by whole-exome sequencing was performed revealing a novel biallelic variant in SETX gene (c.6208+2dupT), which was classified as likely pathogenic., Conclusion: The present case expands the genotypic and phenotypic spectrum of AOA2, reporting a novel likely pathogenic SETX mutation (c.6208+2dupT) and highlighting an early psychiatric involvement in AOA2, suggesting the need for psychiatric assessment in these neurologic patients., Competing Interests: Declaration. Ethical statement: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Written informed consent has been obtained from the patient. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines, (© 2024. Fondazione Società Italiana di Neurologia.)

Hereditary congenital facial palsy (HCFP) is a medical condition caused by dysfunction of the seventh cranial nerve. HCFP is characterized by feeding difficulties and dysmorphic features in the orofacial region. In some cases hearing loss, strabismus, limb malformations, and musculoskeletal defects may be associated. There are three types of HCFP: HCFP3 (OMIM 614744) results from autosomal recessive pathogenic variants in the HOXB1 gene, while HCFP1 and 2 (OMIM 601471, 604185) are autosomal dominant, genetically less defined conditions. We report on a case of congenital bilateral facial palsy due to two novel compound heterozygous variants in the HOXB1 gene, found by exome sequencing (ES), in a child with facial nerve axonal neuropathy without evidence of nerve hypoplasia on neuroimaging. The results of this report suggest that in individuals with congenital facial paralysis and preserved ocular motor skills, with or without facial nerve hypoplasia and with confirmed facial nerve axonal neuropathy, HOXB1 variants and therefore a diagnosis of HCFP3 should be primarily considered., (© 2024 Wiley Periodicals LLC.)

S100A8/A9 is an endogenous alarmin secreted by myeloid cells during many acute and chronic inflammatory disorders. Despite increasing evidence of the proinflammatory effects of extracellular S100A8/A9, little is known about its intracellular function. Here, we show that cytosolic S100A8/A9 is indispensable for neutrophil post-arrest modifications during outside-in signaling under flow conditions in vitro and neutrophil recruitment in vivo, independent of its extracellular functions. Mechanistically, genetic deletion of S100A9 in mice caused dysregulated Ca 2+ signatures in activated neutrophils resulting in reduced Ca 2+ availability at the formed LFA-1/F-actin clusters with defective β 2 integrin outside-in signaling during post-arrest modifications. Consequently, we observed impaired cytoskeletal rearrangement, cell polarization, and spreading, as well as cell protrusion formation in S100a9 -/- compared to wildtype (WT) neutrophils, making S100a9 -/- cells more susceptible to detach under flow, thereby preventing efficient neutrophil recruitment and extravasation into inflamed tissue., Competing Interests: MN, RI, IR, VL, JP, MG, AY, TV, JR, MS, SD, MS, CM, BW, MS, MP No competing interests declared, (© 2024, Napoli et al.)

Background: Whether statin use after spontaneous intracerebral haemorrhage (ICH) increases the risk of recurrent ICH is uncertain., Methods: In the setting of the Multicentric Study on Cerebral Haemorrhage in Italy we followed up a cohort of 30-day ICH survivors, consecutively admitted from January 2002 to July 2014, to assess whether the use of statins after the acute event is associated with recurrent cerebral bleeding., Results: 1623 patients (mean age, 73.9±10.3 years; males, 55.9%) qualified for the analysis. After a median follow-up of 40.5 months (25th to 75th percentile, 67.7) statin use was not associated with increased risk of recurrent ICH either in the whole study group (adjusted HR, 0.99; 95% CI 0.64 to 1.53) or in the subgroups defined by haematoma location (deep ICH, adjusted HR, 0.74; 95% CI 0.35 to 1.57; lobar ICH, adjusted HR, 1.09; 95% CI 0.62 to 1.90), intensity of statins (low-moderate intensity statins, adjusted HR, 0.93; 95% CI 0.58 to 1.49; high-intensity statins, adjusted HR, 1.48; 95% CI 0.66 to 3.31) and use of statins before the index event (adjusted HR, 0.66; 95% CI 0.38 to 1.17)., Conclusions: Statin use appears to be unrelated to the risk of ICH recurrence., Competing Interests: Competing interests: AC reports grants from Daiichi-Sankyo; grants from Italfarmaco; and grants from Alexion Pharmaceuticals. MP reports compensation from SANOFI-AVENTIS US LLC for other services; compensation from PFIZER CANADA for other services; compensation from iRhythm Technologies for other services; compensation from Daiichi Sankyo Europe GmbH for other services; and compensation from Bristol-Myers Squibb for other services. The other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Polymers play a critical role in the biomedical and sustainable materials fields, serving as key resources for both research and product development. While synthetic and natural polymers are both widely used, synthetic polymers have traditionally dominated due to their ability to meet the specific material requirements of most fiber fabrication methods. However, synthetic polymers are derived from non-renewable resources, and their production raises environmental and health concerns. Natural polymers, on the other hand, are derived from renewable biological sources and include a subset known as biopolymers, such as proteins and polysaccharides, which are produced by living organisms. These biopolymers are naturally abundant and offer benefits such as biodegradability and non-toxicity, making them especially suitable for biomedical and green applications. Recently, air jet spinning has emerged as a promising method for fabricating biopolymer fibers, valued for its simplicity, cost-effectiveness, and safety-advantages that stand out compared to the more conventional electrospinning process. This review examines the methods and mechanisms of air jet spinning, drawing on empirical studies and practical insights to highlight its advantages over traditional fiber production techniques. By assembling natural biopolymers into micro- and nanofibers, this novel fabrication method demonstrates strong potential for targeted applications, including tissue engineering, drug delivery, air filtration, food packaging, and biosensing, utilizing various protein and polysaccharide sources.

Background: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are recommended for reducing the renal and cardiovascular risk in patients with chronic kidney disease (CKD) based on the positive results reported by clinical trials. However, real-world data on the efficacy and the safety of these drugs in CKD population followed in nephrology setting are lacking., Methods: We report the effects of dapagliflozin in CKD patients by using data collected during a learning program in which 105 nephrologists added dapagliflozin (10 mg/day) to consecutive patients referred to their renal clinics. Efficacy endpoints were the albuminuria change and the determinants of an albuminuria decline ≥30%. Adverse events were also collected., Results: A total of 1724 patients with CKD (age 67.4 ± 13.2 years, 72.8% males, diabetes 59.9%, eGFR 43.5 ± 17.4 ml/min/1.73 m 2 , severe albuminuria 70.1%) received dapagliflozin for 4 ± 1 months. Dapagliflozin significantly reduced body weight (-1.3 kg), eGFR (-0.27 ml/min/month), and blood pressure (-3.6/-1.7 mmHg). Albuminuria declined by 25.1% (95%CI 23.0-27.2) from 500 mg/day [IQR 225-1425] to 320 mg/day [IQR 100-900]. Albuminuria reduction was ≥30% in 48.3% of patients, 0-29% in 37.6% while it increased in 14.1% of patients. At logistic regression analysis, older age, female sex, use of mineralocorticoid receptor antagonist, higher eGFR, and higher albuminuria were all significant predictors of albuminuria decline ≥30%. We collected 46 side effects leading to drug discontinuation in 36 patients (2%), with acute kidney injury and urinary tract infection being the most frequent adverse events., Conclusions: We provide evidence of the anti-proteinuric efficacy of short-term dapagliflozin in the presence of good safety profile in patients with CKD followed in nephrology., Competing Interests: R.M. has been member of Advisory Boards for Amgen, Astellas, Bayer, and GSK, and has received fees for lectures from Amgen, Astellas, Bayer, and Vifor Pharma. F.A. has been member of Advisory Boards for Vifor and Sanofi, and has received fees for lectures from AstraZeneca and Amgen. V.B. fees for lectures from Astra Zeneca. Y.B. has received fees for scientific consultation and/or lectures by AstraZeneca and Vifor Pharma. V.M. has received fees for lectures or scientific consultation from Takeda, CSL Behring, BioCryst, Pharming, GSK, Astellas, Astra Zeneca, Bayer, Alexion, CSL Vifor, and Kiowa Kyrin. D.M. has received fees for lectures by Fresenius Medical Care and AstraZeneca. L.D.N. has received fees for scientific consultation and/or lectures by Astellas, AstraZeneca, Mundibiopharma, and Vifor Pharma. A.A., L.A., S.B., L.B., V.C., G.C., P.C., P.F., C.G., E.I., S.L.R., M.M., M.N., F.N., C.P., D.S., R.S., F.S., and T.T. declare no financial interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

PCPE-2 was discovered at the beginning of this century, and was soon identified as a close homolog of PCPE-1 (procollagen C-proteinase enhancer 1). After the demonstration that it could also stimulate the proteolytic maturation of fibrillar procollagens by BMP-1/tolloid-like proteinases (BTPs), PCPE-2 did not attract much attention as it was thought to fulfill the same functions as PCPE-1 which was already well-described. However, the tissue distribution of PCPE-2 shows both common points and significant differences with PCPE-1, suggesting that their activities are not fully overlapping. Also, the recently established connections between PCPE-2 (gene name PCOLCE2) and several important diseases such as atherosclerosis, inflammatory diseases and cancer have highlighted the need for a thorough reappraisal of the in vivo roles of this regulatory protein. In this context, the recent finding that, while retaining the ability to bind fibrillar procollagens and to activate their C-terminal maturation, PCPE-2 can also bind BTPs and inhibit their activity has substantially extended its potential functions. In this review, we describe the current knowledge about PCPE-2 with a focus on collagen fibrillogenesis, lipid metabolism and inflammation, and discuss how we could further advance our understanding of PCPE-2-dependent biological processes., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Glioblastoma (GBM) displays significant gender disparities, being 1.6 times more prevalent in men, with a median survival time of 15.0 months for males compared to 25.5 months for females. These differences may be linked to gonadal steroid hormones, particularly testosterone, which interacts with the androgen receptor (AR) to promote tumor proliferation. Conversely, estrogen (E2), progesterone (P4), and P4 metabolites exert more complex effects on GBM. Despite these insights, the identification of reliable hormonal tumor markers remains challenging, and studies investigating hormone therapies yield inconclusive results due to small sample sizes and heterogeneous tumor histology. Additionally, genetic, epigenetic, and immunological factors play critical roles in sex disparities, with female patients demonstrating increased O6-Methylguanine-DNA methyltransferase promoter methylation and greater genomic instability. These complexities highlight the need for personalized therapeutic strategies that integrate hormonal influences alongside other sex-specific biological characteristics in the management of GBM. In this review, we present the current understanding of the potential role of sex hormones in the natural history of GBM.

Purpose: Arterial supply of thalamus is complex and highly variable. In particular, the distribution pattern of thalamoperforating arteries received more attention some decades ago than in recent years., Methods: We are presenting the case of a 46-year-old patient with wake-up drowsiness, complex oculomotor disorder and dysarthria. He was investigated in the acute phase using non-contrast brain Computed Tomography (NCCT), CT Angiography (CTA), and in the following days Digital Subtraction Angiography (DSA) was performed Results. The NCCT showed a subacute ischemic stroke in the right anterior thalamus and rostral midbrain with normal findings on CTA. DSA imaged a variant of thalamic supply (Percheron type III), constituted by perforating branches arising from an artery bridging the P1 segments of both Posterior Cerebral Arteries (PCAs)., Results: The thalamus has a complex and variable arterial supply, mainly in the pattern of paramedian thalamic-mesencephalic perforating arteries. The most reported variant is Percheron type IIb and supplies the paramedian thalami and the rostral midbrain. Type IIb occlusion usually causes a bilateral paramedian thalamic stroke, but rostral midbrain and anterior thalamus are involved in 57% and 19% cases. The rarer Type III variant probably prevented the bilateral extension of infarction and involved the territory of tuberothalamic and paramedian perforating arteries., Conclusions: Currently, DSA allows directly imaging variants in thalamic vascularization and better understanding the stroke mechanisms. In particular, in the presented case, a medium-sized vessel occlusion rather than a small vessel occlusion mechanism might be raised, leading to a different diagnostic pathway., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

The chromosome-19 miRNA cluster (C19MC) restricts viruses depending on the multinucleated state of placental trophoblasts. However, the relationship of C19MC to multinucleation is unknown. Here we show that C19MC is coexpressed in multiple cancer type subsets with meiosis-related genes. We discovered a novel meiosis-III that exhibits simultaneous progression of meiotic nuclear division (MND) and cytokinesis. C19MC promotes meiotic bridged-chromosomes to block MND and cytokinesis to generate multinucleated cells. MND starts with the invagination of nuclear membrane to form nucle(ol)ar invasive cytoplasm (NiC), mitochondria and protein cargoes. Aurora-B regulates the efflux of cargos from NiC, whereas C19MC, CDK1, and autophagy promote cargo influx to inflate NiC size for MND progression. Using CRISPR human genetic engineering we demonstrate that the C19MC expression is required for NiC-driven MND and multinucleation. This discovery has impacts on cancer-pathogen interactions, immunotherapy, vertical transmission of viruses, antiviral research and SpCas9-CRISPR therapeutics., Competing Interests: The authors G.G.J. and A.S.B. have a provisional patent application pending for the RNA probe Cy5-CSi000A and CRISPR-CpG86-chopper guides-1 and 2. A.S.B. has advisory board relationships with Bayer and Deciphera.

Introduction: It is unclear which patients with non-traumatic (spontaneous) intracerebral haemorrhage (ICH) are at risk of developing acute symptomatic seizures (provoked seizures occurring within the first week after stroke onset; early seizures, ES) and whether ES predispose to the occurrence of remote symptomatic seizures (unprovoked seizures occurring more than 1 week after stroke; post-stroke epilepsy, PSE) and long-term mortality., Patients and Methods: In the setting of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy) we examined the risk of ES and whether they predict the occurrence of PSE and all-cause mortality in a cohort of patients with first-ever spontaneous ICH and no previous history of epilepsy, consecutively hospitalized in 12 Italian neurological centers from 2002 to 2014., Results: Among 2570 patients (mean age, 73.4 ± 12.5 years; males, 55.4%) 228 (8.9%) had acute ES (183 (7.1%) short seizures and 45 (1.8%) status epilepticus (SE)). Lobar location of the hematoma (OR, 1.49; 95% CI, 1.06-2.08) was independently associated with the occurrence of ES. Of the 2,037 patients who were followed-up (median follow-up time, 68.0 months (25th-75th percentile, 77.0)), 155 (7.6%) developed PSE. ES (aHR, 2.34; 95% CI, 1.42-3.85), especially when presenting as short seizures (aHR, 2.35; 95% CI, 1.38-4.00) were associated to PSE occurrence. Unlike short seizures, SE was an independent predictor of all-cause mortality (aHR, 1.50; 95% CI, 1.005-2.26)., Discussion and Conclusion: The long-term risk of PSE and death after an ICH vary according to ES subtype. This might have implications for the design of future clinical trials targeting post-ICH epileptic seizures., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Ciccone reports grants from Daiichi-Sankyo; grants from Italfarmaco; and grants from Alexion Pharmaceuticals.Dr Paciaroni reports compensation from SANOFI-AVENTIS U.S. LLC for other services; compensation from PFIZER CANADA INC for other services; compensation from iRhythm Technologies for other services; compensation from Daiichi Sankyo Europe GmbH for other services; and compensation from Bristol-Myers Squibb for other services.The other Authors have nothing to disclose.

Cerebellar mutism syndrome (CMS) is a frequent complication of surgical intervention on posterior fossa in children. It has been only occasionally reported in adults and its features have not been fully characterized. In children and in young adults, medulloblastoma is the main reason for neurosurgery. A single case of postsurgical CMS is presented in an adult patient with a cerebellar hemorrhage and a systematic review of the published individual cases of CMS in adults was done. Literature review of individual cases found 30 patients, 18/30 (60%) males, from 20 to 71 years at diagnosis. All but one case was post-surgical, but in one of the post-surgical cases iatrogenic basilar artery occlusion was proposed as cause for CMS. The causes were: primary tumors of the posterior fossa in 16/22 (72.7%) metastasis in 3/30 (10%), ischemia in 3/30 (10%) cerebellar hemorrhage in 3/30 (10%), and benign lesions in 2/30 (6.7%) patients. 8/30 patients (26.7%) were reported as having persistent or incomplete resolution of CMS within 12 months. CMS is a rare occurrence in adults and spontaneous cerebellar hemorrhage has been reported in 3/30 (10%) adult patients. The generally accepted hypothesis is that CMS results from bilateral damage to the dentate nucleus or the dentate-rubro-thalamic tract, leading to cerebro-cerebellar diaschisis. Several causes might contribute in adults. The prognosis of CMS is slightly worse in adults than in children, but two thirds of cases show a complete resolution within 6 months., (© 2024. Fondazione Società Italiana di Neurologia.)

Introduction: Calcified arterial cerebral embolism is a rare occurrence among large and medium vessel occlusions causing ischemic stroke and its diagnosis and treatment is a challenge. The sources of calcified embolism might be a calcific atheroma from the aortic arch and carotid artery, but also heart valve disease has been reported in the literature. Calcified embolism is frequently simultaneous on multiple vascular territories. The prognosis of patients is usually poor, including patients treated by using endovascular thrombectomy (EVT) and this diagnosis could be easily missed in the acute phase. In addition, the optimal secondary prevention has not been yet fully stated., Methods: We are presenting two cases of acute stroke due to calcified embolism in the middle cerebral artery (MCA) coming from a complicated carotid atheroma, non-stenosing in the first case (a 49 years old man) and stenosing in the second case (a 71 years old man) without clinical indications to intravenous thrombolysis and/or EVT, extensively investigated in the acute phase and followed-up for over 12 months with a favorable clinical course and the persisting steno-occlusion in the involved MCA. In both cases, antiplatelet treatment and targeting of vascular risk factors were done without recurrences in the follow-up period., Discussion: Cerebral calcified embolism has been reported in 5.9% of cases of acute ischemic stroke in a single center series and only in 1.2% of a large retrospective cohort of EVT-treated patients. In both series the prognosis was poor and only one third of EVT-treated patients had functional independence at 3-months follow-up. The natural history of these subtype of ischemic stroke is relatively poorly understood and both etiological diagnosis and treatment have not yet defined. It is possible that some cases might be underdiagnosed and underreported., Conclusions: Calcified cerebral embolism is a rare cause of stroke, but it is largely underreported and both acute phase and secondary preventive treatment have to be defined., (© 2024. Fondazione Società Italiana di Neurologia.)

Innate immune responses are linked to key metabolic pathways, yet the proximal signaling events that connect these systems remain poorly understood. Here we show that phosphofructokinase 1, liver type (PFKL), a rate-limiting enzyme of glycolysis, is phosphorylated at Ser775 in macrophages following several innate stimuli. This phosphorylation increases the catalytic activity of PFKL, as shown by biochemical assays and glycolysis monitoring in cells expressing phosphorylation-defective PFKL variants. Using a genetic mouse model in which PFKL Ser775 phosphorylation cannot take place, we observe that upon activation, glycolysis in macrophages is lower than in the same cell population of wild-type animals. Consistent with their higher glycolytic activity, wild-type cells have higher levels of HIF1α and IL-1β than Pfkl S775A/S775A after LPS treatment. In an in vivo inflammation model, Pfkl S775A/S775A mice show reduced levels of MCP-1 and IL-1β. Our study thus identifies a molecular link between innate immune activation and early induction of glycolysis., (© 2024. The Author(s).)

Background: International guidelines issued recommendations for vascular access (VA) care for hemodialysis, but there are no registry data regarding this topic in Italy., Methods: A survey consisting of 17 items was sent to all Italian dialysis wards, via the Italian Society of Nephrology (SIN) website, from April to June 2021. The items were defined, discussed and approved by experts in vascular access management within the Italian Society of Nephrology. A total of 124 dialysis units answered, accounting for 14% of all dialysis units. The survey thus encompasses all regions within the country, with some regional variations in terms of adherence., Results: One hundred twenty-four facilities provided data, regarding 12,276 patients: 61% had an arteriovenous fistula (AVF), 34% had a central venous catheter (CVC), and 5% had an arteriovenous graft (AVG). Among them, two-thirds of the facilities reported having a vascular access care pathway, formally standardized in 79% of cases. Forty-six % of centers had a fully equipped vascular access care pathway, encompassing preoperative mapping (80%), vascular access setup (71%), arteriovenous fistula maturation monitoring (76%), first-level (80%) and second-level (78%) monitoring, and surgical and/or endovascular treatment of complications (66%). Vascular access monitoring was computerized in 39% of facilities. First-level monitoring (physical examination) was primarily done by nurses in two-thirds of facilities. Of note, 45% of centers had nurses who were skilled in ultrasound-guided cannulation. Quite surprisingly, facilities with less than 100 patients had a greater prevalence of arteriovenous fistulas than those with more than 100 patients (p = 0.0023). A protocolled vascular access care pathway was associated with a higher likelihood of having an arteriovenous fistula (70% AVF vs 42,1% CVC; p = 0.04). The presence in the facility of interventional nephrologists or nurses with ultrasound-guided cannulation skills significantly reduced the prevalence of central venous catheters., Conclusion: These survey data further strengthen the need for formal and shared vascular access monitoring protocols., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Spontaneous convexity subarachnoid hemorrhage (cSAH) is a vascular disease different from aneurysmal SAH in neuroimaging pattern, causes, and prognosis. Several causes might be considered in individual patients, with a limited value of the patient's age for discriminating among these causes. Cerebral amyloid angiopathy (CAA) is the most prevalent cause in people > 60 years, but reversible cerebral vasoconstriction syndrome (RCVS) has to be considered in young people. CAA gained attention in the last years, but the most known manifestation of cSAH in this context is constituted by transient focal neurological episodes (TFNEs). CAA might have an inflammatory side (CAA-related inflammation), whose diagnosis is relevant due to the efficacy of immunosuppression in resolving essudation. Other causes are hemodynamic stenosis or occlusion in extracranial and intracranial arteries, infective endocarditis (with or without intracranial infectious aneurysms), primary central nervous system angiitis, cerebral venous thrombosis, and rarer diseases. The diagnostic work-up is fundamental for an etiological diagnosis and includes neuroimaging techniques, nuclear medicine techniques, and lumbar puncture. The correct diagnosis is the first step for choosing the most effective and appropriate treatment.

Antiphospholipid syndrome (APS) is an autoimmune prothrombotic condition characterized by venous thromboembolism, arterial thrombosis, and pregnancy morbidity. Among neurological manifestations, arterial thrombosis is only one of the possible associated clinical and neuroradiological features. The aim of this review is to address from a neurovascular point of view the multifaceted range of the arterial side of APS. A modern neurovascular approach was proposed, dividing the CNS involvement on the basis of the size of affected arteries, from large to small arteries, and corresponding clinical and neuroradiological issues. Both large-vessel and small-vessel involvement in APS were detailed, highlighting the limitations of the available literature in the attempt to derive some pathomechanisms. APS is a complex disease, and its neurological involvement appears multifaceted and not yet fully characterized, within and outside the diagnostic criteria. The involvement of intracranial large and small vessels appears poorly characterized, and the overlapping with the previously proposed inflammatory manifestations is consistent.

The ring finger protein 213 gene (RNF213) is involved in several vascular diseases, both intracranial and systemic ones. Some variants are common in the Asian population and are reported as a risk factor for moyamoya disease, intracranial stenosis and intracranial aneurysms. Among intracranial vascular diseases, both moyamoya disease and intracranial artery dissection are more prevalent in the Asian population. We performed a systematic review of the literature, aiming to assess the rate of RNF213 variants in patients with spontaneous intracranial dissections. Four papers were identified, providing data on 53 patients with intracranial artery dissection. The rate of RNF213 variants is 10/53 (18.9%) and it increases to 10/29 (34.5%), excluding patients with vertebral artery dissection. All patients had the RNF213 p.Arg4810Lys variant. RNF213 variants seems to be involved in intracranial dissections in Asian cohorts. The small number of patients, the inclusion of only patients of Asian descent and the small but non-negligible coexistence with moyamoya disease familiarity might be limiting factors, requiring further studies to confirm these preliminary findings and the embryological interpretation.

Eosinophil recruitment is a pathological hallmark of many allergic and helminthic diseases. Here, we investigated chemokine receptor CCR3-induced eosinophil recruitment in sialyltransferase St3gal4 -/- mice. We found a marked decrease in eosinophil extravasation into CCL11-stimulated cremaster muscles and into the inflamed peritoneal cavity of St3gal4 -/- mice. Ex vivo flow chamber assays uncovered reduced adhesion of St3gal4 -/- compared to wild type eosinophils. Using flow cytometry, we show reduced binding of CCL11 to St3gal4 -/- eosinophils. Further, we noted reduced binding of CCL11 to its chemokine receptor CCR3 isolated from St3gal4 -/- eosinophils. This was accompanied by almost absent CCR3 internalization of CCL11-stimulated St3gal4 -/- eosinophils. Applying an ovalbumin-induced allergic airway disease model, we found a dramatic reduction in eosinophil numbers in bronchoalveolar lavage fluid following intratracheal challenge with ovalbumin in St3gal4 -deficient mice. Finally, we also investigated tissue-resident eosinophils under homeostatic conditions and found reduced resident eosinophil numbers in the thymus and adipose tissue in the absence of ST3Gal-IV. Taken together, our results demonstrate an important role of ST3Gal-IV in CCR3-induced eosinophil recruitment in vivo rendering this enzyme an attractive target in reducing unwanted eosinophil infiltration in various disorders including allergic diseases., Competing Interests: Competing interests statement:The authors declare no competing interest.

Secondary neurodegeneration refers to the final result of several simultaneous and sequential mechanisms leading to the loss of substance and function in brain regions connected to the site of a primary injury. Stroke is one of the most frequent primary injuries. Among the subtypes of post-stroke secondary neurodegeneration, axonal degeneration of the corticospinal tract, also known as Wallerian degeneration, is the most known, and it directly impacts motor functions, which is crucial for the motor outcome. The timing of its appearance in imaging studies is usually considered late (over 4 weeks), but some diffusion-based magnetic resonance imaging (MRI) techniques, as diffusion tensor imaging (DTI), might show alterations as early as within 7 days from the stroke. The different sequential pathological stages of secondary neurodegeneration provide an interpretation of the signal changes seen by MRI in accordance with the underlying mechanisms of axonal necrosis and repair. Depending on the employed MRI technique and on the timing of imaging, different rates and thresholds of Wallerian degeneration have been provided in the literature. In fact, three main pathological stages of Wallerian degeneration are recognizable-acute, subacute and chronic-and MRI might show different changes: respectively, hyperintensity on T2-weighted sequences with corresponding diffusion restriction (14-20 days after the injury), followed by transient hypointensity of the tract on T2-weighted sequences, and by hyperintensity and atrophy of the tract on T2-weighted sequences. This is the main reason why this review is focused on MRI signal changes underlying Wallerian degeneration. The identification of secondary neurodegeneration, and in particular Wallerian degeneration, has been proposed as a prognostic indicator for motor outcome after stroke. In this review, the main mechanisms and neuroimaging features of Wallerian degeneration in adults are addressed, focusing on the time and mechanisms of tissue damage underlying the signal changes in MRI.

(1) Background: Non-stenotic complicated plaques are a neglected cause of stroke, in particular in young patients. Atherosclerosis has some preferential sites in extracranial arteries and the prepetrous segment of the internal carotid artery has been rarely described as site of atheroma in general and of complicated atheroma in stroke patients. The aim of this study is to describe the rate of the prepetrous internal carotid artery's (ICA) involvement in a single-center case series of young stroke patients. (2) Methods: All patients < 50 years old with acute ischemic stroke admitted to a single-center Stroke Unit during two time periods (the first one from 1 January 2018 to 31 December 2019, and the second one from 1 January 2021 to 30 June 2022), were prospectively investigated as part of a screening protocol of the Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO) study [ClinicalTrials.gov ID NCT01934725], including extracranial vascular examination by using computed tomography (CT) or magnetic resonance imaging (MRI). (3) Results: Two out of ninety-three consecutive patients (2.15%) had a complicated atheroma in the prepetrous ICA as the cause of stroke and both CT angiography and high-resolution vessel wall MRI were applied to document the main features of positive remodeling, cap rupture, ulceration, intraplaque hemorrhage, and a transient thrombus superimposed on the atheroma. The two patients had a different evolution of healing in the first case and a persisting ulceration at 12 months in the second case. (4) Conclusions: The prepetrous ICA is a rarely described location of complicated atheroma in stroke patients at all ages and it represents roughly 2% of causes of acute stroke in this single-center case series in young people.

Primary Angiitis of the Central Nervous System (PACNS) is a rare disease and its diagnosis is a challenge for several reasons, including the lack of specificity of the main findings highlighted in the current diagnostic criteria. Among the neuroimaging pattern of PACNS, a tumefactive form (t-PACNS) is a rare subtype and its differential diagnosis mainly relies on neuroimaging. Tumor-like mass lesions in the brain are a heterogeneous category including tumors (in particular, primary brain tumors such as glial tumors and lymphoma), inflammatory (e.g., t-PACNS, tumefactive demyelinating lesions, and neurosarcoidosis), and infectious diseases (e.g., neurotoxoplasmosis). In this review, the main features of t-PACNS are addressed and the main differential diagnoses from a neuroimaging perspective (mainly Magnetic Resonance Imaging-MRI-techniques) are described, including conventional and advanced MRI.

Background: Thousand and one amino-acid kinase 1 (TAOK1) encodes the MAP3K protein kinase TAO1, which has recently been displayed to be essential for neuronal maturation and cortical differentiation during early brain development. Heterozygous variants in TAOK1 have been reported in children with neurodevelopmental disorders, with or without macrocephaly, hypotonia and mild dysmorphic traits. Literature reports lack evidence of neuronal migration disorders in TAOK1 patients, although studies in animal models suggest this possibility., Case Presentation: We provide a clinical description of a child with a neurodevelopmental disorder due to a novel TAOK1 truncating variant, whose brain magnetic resonance imaging displays periventricular nodular heterotopia., Conclusions: To our knowledge, this is the first report of a neuronal migration disorder in a patient with a TAOK1-related neurodevelopmental disorder, thus supporting the hypothesized pathogenic mechanisms of TAOK1 defects., (© 2024. The Author(s).)

Objectives: Twig-like middle cerebral artery (MCA) is a rare anomaly where the M1 MCA is partially or completely replaced by a plexiform network. It has been described in angiographic series from Asian and South-American cohorts, but has not yet been reported in a European population., Methods: The digital subtraction angiograms (DSAs) of adult patients referred to a single neurovascular center for a diagnostic hypothesis of moyamoya arteriopathy (MMA) from 2018 to 2023 were prospectively and retrospectively checked by experienced neuroradiologists for identifying patients with twig-like MCA. The angioarchitecture of twig-like MCA was systematically evaluated and described., Results: Five of 30 (16.7%) male patients (mean age 55.8 + 14.7 years) of European ancestry were identified as having twig-like MCA. The clinical presentations were ischemic stroke (2 of 5), hemorrhagic stroke (1 of 5), and headache (2 of 5). All patients showed a unilateral involvement on DSA and in 1 of 5 (20%) an intracranial aneurysm was found. DSA was used to confirm the diagnosis of twig-like MCA and define the angioarchitecture and associated anomalies. An accessory MCA and recurrent artery of Heubner were found in 3 of 5 (60%) cases, feeding the network together with the anterior choroidal artery (4 of 5, 80%)., Conclusions: Twig-like MCA is a rare vascular anomaly, but it seems to be less rare than expected among adult European patients with suspected MMA on noninvasive neuroimaging studies. DSA is fundamental for a reliable differential diagnosis and should not be omitted in these patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Posterior reversible encephalopathy syndrome (PRES) is a rare and complex disorder with variable clinical presentation and a typical magnetic resonance imaging (MRI) pattern of vasogenic edema with typical and atypical locations. It is often triggered by other diseases and drugs and the most prototypical association is with persistently elevated arterial pressure values. Among the potential cerebrovascular complications, intracranial bleeding has been described, but ischemic stroke is uncommonly reported., Methods: We are presenting a case of a male patient with prolonged and sustained arterial hypertension acutely presenting with lacunar ischemic stroke involving the right corona radiata and composite MRI findings with the association of chronic small vessel disease (SVD) markers, acute symptomatic lacunar stroke, and atypical, central variant, posterior fossa dominant PRES. In the MRI follow-up, the white matter hyperintensities in T2-fluid attenuated inversion recovery (FLAIR sequences) due to PRES., Discussion: The pathophysiology of PRES is not yet fully known, but the association with markedly increased values of arterial pressure is typical. In this context, ischemic stroke has not been considered in the clinical and neuroradiological manifestations of PRES and it has been only occasionally reported in the literature. In this case, the main hypothesis is that sustained hypertension may have triggered both manifestations, PRES, and ischemic stroke and the last one allowed to diagnose the first one., Conclusions: Atypical variants of PRES are not so rare and it may also occur in typical triggering situations. The association with ischemic stroke is even rarer and it may add some clues to the pathomechanisms of PRES., (© 2023. Fondazione Società Italiana di Neurologia.)

Background: The identification of patients surviving an acute intracerebral hemorrhage who are at a long-term risk of arterial thrombosis is a poorly defined, crucial issue for clinicians., Methods: In the setting of the MUCH-Italy (Multicenter Study on Cerebral Haemorrhage in Italy) prospective observational cohort, we enrolled and followed up consecutive 30-day intracerebral hemorrhage survivors to assess the long-term incidence of arterial thrombotic events, to assess the impact of clinical and radiological variables on the risk of these events, and to develop a tool for estimating such a risk at the individual level. Primary end point was a composite of ischemic stroke, myocardial infarction, or other arterial thrombotic events. A point-scoring system was generated by the β-coefficients of the variables independently associated with the long-term risk of arterial thrombosis, and the predictive MUCH score was calculated as the sum of the weighted scores., Results: Overall, 1729 patients (median follow-up time, 43 months [25th to 75th percentile, 69.0]) qualified for inclusion. Arterial thrombotic events occurred in 169 (9.7%) patients. Male sex, diabetes, hypercholesterolemia, atrial fibrillation, and personal history of coronary artery disease were associated with increased long-term risk of arterial thrombosis, whereas the use of statins and antithrombotic medications after the acute intracerebral hemorrhage was associated with a reduced risk. The area under the receiver operating characteristic curve of the MUCH score predictive validity was 0.716 (95% CI, 0.56-0.81) for the 0- to 1-year score, 0.672 (95% CI, 0.58-0.73) for the 0- to 5-year score, and 0.744 (95% CI, 0.65-0.81) for the 0- to 10-year score. C statistic for the prediction of events that occur from 0 to 10 years was 0.69 (95% CI, 0.64-0.74)., Conclusions: Intracerebral hemorrhage survivors are at high long-term risk of arterial thrombosis. The MUCH score may serve as a simple tool for risk estimation., Competing Interests: Disclosures Dr Ciccone reports grants from Daiichi Sankyo, Italfarmaco, and Alexion Pharmaceuticals. Dr Paciaroni reports compensation from Sanofi-Aventis U.S. LLC, Pfizer Canada, Inc, iRhythm Technologies, Daiichi Sankyo Europe GmbH, and Bristol Myers Squibb for other services. The other authors report no conflicts.

Primary Angiitis of the Central Nervous System (PACNS) is a rare cerebrovascular disease involving the arteries of the leptomeninges, brain and spinal cord. Its diagnosis can be challenging, and the current diagnostic criteria show several limitations. Among the clinical and neuroimaging manifestations of PACNS, intracranial bleeding, particularly intracerebral hemorrhage (ICH), is poorly described in the available literature, and it is considered infrequent. This review aims to summarize the available data addressing this issue with a dedicated focus on the clinical, neuroradiological and neuropathological perspectives. Moreover, the limitations of the actual data and the unanswered questions about hemorrhagic PACNS are addressed from a double point of view (PACNS subtyping and ICH etiology). Fewer than 20% of patients diagnosed as PACNS had an ICH during the course of the disease, and in cases where ICH was reported, it usually did not occur at presentation. As trigger factors, both sympathomimetic drugs and illicit drugs have been proposed, under the hypothesis of an inflammatory response due to vasoconstriction in the distal cerebral arteries. Most neuroradiological descriptions documented a lobar location, and both the large-vessel PACNS (LV-PACNS) and small-vessel PACNS (SV-PACNS) subtypes might be the underlying associated phenotypes. Surprisingly, amyloid beta deposition was not associated with ICH when histopathology was available. Moreover, PACNS is not explicitly included in the etiological classification of spontaneous ICH. This issue has received little attention in the past, and it could be addressed in future prospective studies.

Objectives: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset ataxia characterized by cerebellar dysfunction, spasticity, and sensory-motor polyneuropathy due to variations in the SACS gene (13q11). To date, no studies have instrumentally assessed vestibular function in this condition., Methods: We report a 36-year-old woman with diagnosis of ARSACS syndrome due to homozygous mutation (c.12232 C>T, p.Arg4078Ter) in the SACS gene. Neurologic examination showed spastic-ataxic gait, dysarthric speech, 4-limb ataxia, and spastic hypertonia with lower limb hyperreflexia., Results: A vestibular instrumental evaluation including bedside oculomotor testing found gaze-evoked and rebound nystagmus on horizontal and vertical gaze, saccadic movements within normality ranges, saccadic pursuit, and slightly impaired visually enhanced vestibulo-ocular reflex (VVOR). A near-normal VOR suppression (VORS) was recorded. Neither head shakings, skull vibrations, nor supine positionings could evoke nystagmus. Finally, the video-head impulse test detected a symmetrical VOR impairment for all the semicircular canals (SCs), mostly involving the horizontal SCs, with corrective saccades in all planes., Discussion: Vestibular hypofunction may be found in ARSACS syndrome and may represent a possible pitfall in the differential diagnosis of recessive cerebellar and afferent ataxias. In this setting, ARSACS syndrome should be considered in the differential diagnosis of CANVAS., Competing Interests: The authors report no relevant disclosures. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (© 2023 American Academy of Neurology.)

The p53 family member TP63 encodes two sets of N-terminal isoforms, TAp63 and ΔNp63 isoforms. They each regulate diverse biological functions in epidermal morphogenesis and in cancer. In the skin, where their activities have been extensively characterized, TAp63 prevents premature aging by regulating the quiescence and genomic stability of stem cells required for wound healing and hair regeneration, while ΔNp63 controls maintenance and terminal differentiation of epidermal basal cells. This functional diversity is surprising given that these isoforms share a high degree of similarity, including an identical sequence for a DNA-binding domain. To understand the mechanisms of the transcriptional programs regulated by each p63 isoform and leading to diverse biological functions, we performed genome-wide analyses using p63 isoform-specific chromatin immunoprecipitation, RNA sequencing, and metabolomics of TAp63-/- and ΔNp63-/- mouse epidermal cells. Our data indicate that TAp63 and ΔNp63 physically and functionally interact with distinct transcription factors for the downstream regulation of their target genes, thus ultimately leading to the regulation of unique transcriptional programs and biological processes. Our findings unveil novel transcriptomes regulated by the p63 isoforms to control diverse biological functions, including the cooperation between TAp63 and NRF2 in the modulation of metabolic pathways and response to oxidative stress providing a mechanistic explanation for the TAp63 knock out phenotypes., Significance: The p63 isoforms, TAp63 and ΔNp63, control epithelial morphogenesis and tumorigenesis through the interaction with distinct transcription factors and the subsequent regulation of unique transcriptional programs., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Introduction: During the last year, the features of peritoneal dialysis patients have changed, and the cases in which there is a need to perform abdominal surgery are growing. Reports of abdominal surgery in patients who are able to continue peritoneal dialysis are increasing. The minimally invasive techniques represent the preferred and safest approach. Such techniques are associated with reduced hospitalization time, less invasiveness, peritoneal integrity preservation, and reduced intra-abdominal inflammation due to regenerative processes., Case Presentation: In this case report, we present a case of major abdominal surgery, in the form of hepatic metastasectomy, performed with the robotic-assisted technique, which allowed catheter and intracorporeal dialysis preservation. The patient showed a strong determination to continue with peritoneal dialysis as long as possible. During the switch to hemodialysis, he performed prophylactic antibiotic therapy to preserve the peritoneal catheter, and the patient was instructed to have a reduced water intake, avoiding excessive ultrafiltration potentially deteriorating the residual renal function. Special care was also taken to avoid any nephrotoxic drug. The peritoneal treatment was restarted after 3 weeks with low volume exchange for the first 10 days, and the pre-surgery dialysis volumes were then re-established. After surgery, the patient showed adequate clearance of solutes and ultrafiltration similar to the preoperative period. The patient did not encounter any wound complications., Conclusion: Robotic surgery represents a further aid in peritoneal dialysis preservation after abdominal surgery. A detailed communication with the patient before performing this kind of procedure and a strong will to preserve the peritoneal method are essential., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Since in Italy there are no official data on vascular access (VA) for hemodialysis the Vascular Access Project Group (VAPG) of the Italian Society of Nephrology (SIN) designed a national survey., Methods: A 35-question survey was designed and sent it to the Italian facilities through the SIN website. The basic questions were the prevalence, the location, and the surveillance of VA, the bedside use of ultrasound, the use of fluoroscopy for central venous catheter (CVC) placement, and of buttonhole technique, the role of nephrologist in the access creation., Result: The questionnaire was completed in June 2022 by 161 facilities. The survey registered 15,499 patients, approximately one-third of the Italian dialysis population. The prevalence of arteriovenous fistula (AVF), arteriovenous Graft (AVG), and CVC were 61.8%, 3.7%, and 34.5% respectively. The AVF location was 50% in distal forearm, 20% in meanproximal forearm, 30% in upper arm. For AVF creation, nephrologists were involved in 72% of facilities while for CVC placement in 62%. As regards VA monitoring, 21% of the facilities did not have a surveillance protocol; 60% did not register AVF thrombosis and 53% did not register CVC infections. Most of facilities use the fluoroscope during CVC placement, 37% when needed, and 22% never. Ultrasound-guided puncture of complex AVFs was used by 80% of facilities. Buttonhole puncture was used in 5% of patients., Conclusions: Some considerations emerge from the survey data: (1) The increasing CVC prevalence compared to DOPPS 5 study. (2) The low rate of AVG prevalence. (3) The nephrologist is the operator in many VA procedures. (4) The fluoroscopy for CVC placement and the US-guide puncture of the complex AVF are widely used in most facilities. (5) The practice of the buttonhole is not widespread. (6) When the operator is the nephrologist more distal fistulas are performed., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Tick-Borne Encephalitis virus (TBEV) is a positive-sense single-stranded RNA virus belonging to the Flaviviridae family. TBEV transmission typically occurs through infected Ixodes tick bite or by consumption of unpasteurised milk from infected cattle. Case report: We report the clinical, neuroimaging, electroencephalogram (EEG), and laboratory (microbiological tests and spinal tap) data of a 6- year-old boy with Tick-borne encephalitis. Our patient presented with a biphasic course, initially with a myositis-like picture on his first admission to the emergency department, and after a few days with an encephalitic picture, resulting in a second hospitalization. EEG showed focal slow activity, while his brain magnetic resonance imaging (MRI) showed a signal abnormality, which completely resolved on repeat MRI after 3 months. Conclusion: To our knowledge, this is the youngest patient presenting with myositis in the first phase of Tick-borne encephalitis (TBE). In the presence of a biphasic clinical course, with previous myositis, aspecific MRI changes in the thalamic and midbrain regions and an EEG documenting slowed bioelectrical activity should prompt suspicion of TBEV infection., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (© The Author(s) 2023.)

Background: Hypertension and chronic kidney disease (CKD) are closely interlinked pathophysiologic states, such that high blood pressure (BP) is an independent risk factor for disease progression in both adult and pediatric patients with kidney disorders and progressive decline in kidney function can conversely lead to worsening BP control., Summary: Hypertension in CKD is not only associated with GFR loss, but increases cardiovascular risk, which is the leading source of mortality and morbidity in this population. Given this complex relationship between hypertension, CKD, and CVD, an optimal management of BP in CKD is mandatory to break an established vicious pathophysiological cycle that leads to adverse outcomes., Key Messages: New promising molecules for the treatment of CKD, with interesting mechanisms, particularly regarding their pathophysiological interactions with arterial hypertension, are available or under development and in the very next future they may change the way we treat high BP in CKD patients., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Coronavirus disease 2019 (COVID-19) has been associated with a variety of neurological manifestations (i.e., anosmia, ageusia, myalgia, headache) and neurological syndromes (i.e., encephalopathy, ischemic and hemorrhagic stroke, myelitis, encephalitis) underlying different pathogenetic mechanisms. COVID-19 has also been associated with various movement disorders including acute or subacute parkinsonism. However, to date, only few cases of parkinsonism linked to COVID-19 have been reported, nevertheless raising the possibility of a post-viral parkinsonian syndrome. Furthermore, various studies in vitro and in animal models have highlighted a close relationship between SARS-CoV-2 virus and α-synuclein, leading to the hypothesis that COVID-19 could represent a factor favoring the long-term development of α-synucleopathies. In this chapter, we will discuss the pathophysiological mechanisms related to movement disorders' manifestations of COVID-19 focusing on the possible overlap between pathogenetic mechanisms of Parkinson's Disease and COVID-19., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Neurological manifestations are frequent in patients with SARS-CoV-2 infection and can be correlated with different pathogenic mechanisms which can be divided into two categories: direct invasion of the central nervous system by the virus and indirect effects deriving from the severity of the systemic infection and by the inflammatory response correlated with cytokine storm. Among the neurological manifestations, acute encephalopathy is very frequent and its nomenclature has recently been updated. The occurrence of a condition of altered mental status, reduced consciousness, delirium up to coma represents an element associated with a greater severity of the infection and mortality both in an Intensive Care Unit setting and in an Emergency Department setting. The tissue damage mechanisms found in COVID-19 patients' encephalopathy and neuroimaging patterns, as well as histopathology, are similar to those described in sepsis-associated encephalopathy, further confirming the role of indirect mechanisms, with no CNS invasion by the virus. The available data have some limitations, notably the underuse of diagnostic neuroimaging techniques in severely affected patients, particularly in the first wave of the pandemic., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Severe non-infectious or non-haemorrhagic brain edema surrounding the electrode represents a rare complication of subthalamic nucleus deep brain stimulation (STN-DBS) surgery. The aim of this study is to report three patients with advanced Parkinson's Disease (PD) who developed symptomatic brain edema after STN-DBS surgery treated with intravenous steroids with a specific profile of reversible cognitive alterations. Patients were both assessed with a comprehensive neuropsychological battery including attention, memory, visuo-spatial and executive tasks. They were also briefly assessed for emotional and behavioural alterations, and for possible limitations in the activities of daily living. Normative data for an Italian population were available for all neuropsychological tests. The patients were firstly assessed before the surgery (baseline) as soon as they became symptomatic for the post-surgery edema and a few more times in follow-up up to ten months. In all patients we observed the resolution of cognitive deficits within six months after surgery with the corresponding reabsorption of edema at brain CT scans. The appearance of post-DBS edema is a fairly frequent and clinically benign event. However, in some rare cases it can be very marked and lead to important clinical-albeit transient-disturbances. These events can compromise, at least from a psychological point of view, the delicate path of patients who undergo DBS and can prolong the post-operative hospital stay. In this setting it could be helpful to perform a brain CT scan in 2-3 days with the aim of detecting the early appearance of edema and treating it before it can constitute a relevant clinical problem.

BMP-1/tolloid-like proteinases (BTPs) are major players in tissue morphogenesis, growth and repair. They act by promoting the deposition of structural extracellular matrix proteins and by controlling the activity of matricellular proteins and TGF-β superfamily growth factors. They have also been implicated in several pathological conditions such as fibrosis, cancer, metabolic disorders and bone diseases. Despite this broad range of pathophysiological functions, the putative existence of a specific endogenous inhibitor capable of controlling their activities could never be confirmed. Here, we show that procollagen C-proteinase enhancer-2 (PCPE-2), a protein previously reported to bind fibrillar collagens and to promote their BTP-dependent maturation, is primarily a potent and specific inhibitor of BTPs which can counteract their proteolytic activities through direct binding. PCPE-2 therefore differs from the cognate PCPE-1 protein and extends the possibilities to fine-tune BTP activities, both in physiological conditions and in therapeutic settings., (© 2023. The Author(s).)

Background: Disposable N95 respirator shortages during the COVID-19 and 2009 H1N1 influenza pandemics highlighted the need for reusable alternatives, such as elastomeric half-mask respirators (EHMRs). Two US medical organizations deployed reusable EHMRs during the COVID-19 response. In addition to wipe-based disinfection following patient care episodes expected per local policies at both organizations, postshift centralized cleaning and disinfection (C&D) was expected at one site (A), permitting shared-pool EHMR use, and optional at the other (Site B), where EHMRs were issued to individuals. Using a survey, we evaluated disinfection practices reported by EHMR users and predictors of disinfection behaviors and perceptions., Methods: Surveys assessed EHMR disinfection practices, occupational characteristics, EHMR use frequency, training, and individual-issue versus shared-pool EHMR use., Results: Of 1080 EHMR users completing the survey, 76% reported that they disinfect the EHMR after each patient encounter, which was the expected practice at both sites. Increasing EHMR use, recall of disinfection training, and work in intensive care or emergency settings significantly influenced higher reporting of this practice. 36% of respondents reported using centralized C&D, although reporting was higher at the site (A) where this was expected (53%). Confidence in cleanliness of the EHMR following centralized C&D was not influenced by individual versus shared-pool EHMR issue., Conclusions: Most EHMR users reported adherence with expected post-care individual-based disinfection of EHMRs but did not necessarily use standardized, centralized C&D. Future efforts to limit reliance on behavior related to respirator disinfection may improve EHMR implementation in healthcare to avert dependence on single-use, disposable N95 respirators., (© 2023 Wiley Periodicals LLC.)

S100A8/S100A9 is a proinflammatory mediator released by myeloid cells during many acute and chronic inflammatory disorders. However, the precise mechanism of its release from the cytosolic compartment of neutrophils is unclear. Here, we show that E-selectin-induced rapid S100A8/S100A9 release during inflammation occurs in an NLRP3 inflammasome-dependent fashion. Mechanistically, E-selectin engagement triggers Bruton's tyrosine kinase-dependent tyrosine phosphorylation of NLRP3. Concomitant potassium efflux via the voltage-gated potassium channel K V 1.3 mediates ASC oligomerization. This is followed by caspase 1 cleavage and downstream activation of pore-forming gasdermin D, enabling cytosolic release of S100A8/S100A9. Strikingly, E-selectin-mediated gasdermin D pore formation does not result in cell death but is a transient process involving activation of the ESCRT III membrane repair machinery. These data clarify molecular mechanisms of controlled S100A8/S100A9 release from neutrophils and identify the NLRP3/gasdermin D axis as a rapid and reversible activation system in neutrophils during inflammation., (© 2023. The Author(s).)

Background: KBG syndrome is caused by haploinsufficiency of ANKRD11 and is characterised by macrodontia of upper central incisors, distinctive facial features, short stature, skeletal anomalies, developmental delay, brain malformations and seizures. The central nervous system (CNS) and skeletal features remain poorly defined., Methods: CNS and/or skeletal imaging were collected from molecularly confirmed individuals with KBG syndrome through an international network. We evaluated the original imaging and compared our results with data in the literature., Results: We identified 53 individuals, 44 with CNS and 40 with skeletal imaging. Common CNS findings included incomplete hippocampal inversion and posterior fossa malformations; these were significantly more common than previously reported (63.4% and 65.9% vs 1.1% and 24.7%, respectively). Additional features included patulous internal auditory canal, never described before in KBG syndrome, and the recurrence of ventriculomegaly, encephalic cysts, empty sella and low-lying conus medullaris. We found no correlation between these structural anomalies and epilepsy or intellectual disability. Prevalent skeletal findings comprised abnormalities of the spine including scoliosis, coccygeal anomalies and cervical ribs. Hand X-rays revealed frequent abnormalities of carpal bone morphology and maturation, including a greater delay in ossification compared with metacarpal/phalanx bones., Conclusion: This cohort enabled us to describe the prevalence of very heterogeneous neuroradiological and skeletal anomalies in KBG syndrome. Knowledge of the spectrum of such anomalies will aid diagnostic accuracy, improve patient care and provide a reference for future research on the effects of ANKRD11 variants in skeletal and brain development., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Secondary neurodegeneration after stroke is a complex phenomenon affecting remote and synaptically linked cerebral areas. The involvement of the substantia nigra in this process has been rarely described in infarcts involving the striatum., Methods: We are presenting a case of ischemic stroke involving the right striatum due to atrial fibrillation and associated in a few days with the neuroimaging finding of hyperintensity of the ipsilateral substantia nigra and striatonigral tract on T2-fluid attenuated inversion recovery and diffusion-weighted imaging sequences of brain magnetic resonance imaging. This finding was not related to clinical manifestations and substantially disappeared within 3 months from stroke onset., Discussion: The pathophysiology of secondary degeneration of the substantia nigra is poorly understood and it relies on animal models and autoptic studies. The main putative mechanism is not ischemic but excitotoxic with a different role of the internal and external globus pallidus and a different effect on the pars compacta and pars reticularis of the substantia nigra. In animal models, inflammatory mechanisms seem play a role only in the late phase. The main studies on humans were presented in detail., Conclusions: A better understanding of the secondary degeneration of the substantia nigra has the potentiality to offer a chance for neuroprotection in acute stroke, but further studies are needed., (© 2023. Fondazione Società Italiana di Neurologia.)