Search

Introduction: Primary focal segmental glomerular sclerosis (FSGS) is a rare, likely immune-mediated disease. Rituximab (RTX) may play a role in management, although data in adults are scanty. Methods: We collected cases of RTX-treated primary FSGS within the Italian Society of Nephrology Immunopathology Working Group and explored response rate (24-hour proteinuria

Chronic kidney disease (CKD) is a major healthcare issue worldwide. However, the prevalence of pediatric CKD has never been systematically assessed and consistent information is lacking in this population. The current definition of CKD is based on glomerular filtration rate (GFR) and the extent of albuminuria. Given the physiological age-related modification of GFR in the first years of life, the definition of CKD is challenging per se in the pediatric population, resulting in high risk of underdiagnosis in this population, treatment delays and untailored clinical management. The advent and spreading of massive-parallel sequencing technology has prompted a profound revision of the epidemiology and on the causes of CKD in children, supporting the hypothesis that CKD is much more frequent than currently reported in children and adolescents. This acquired knowledge will eventually converge in the identification of the molecular pathways and cellular response to damage, with new specific therapeutic targets to control disease progression and clinical features of children with CKD. In this review, we will focus on recent innovations in the field of pediatric CKD and in particular those where advances in knowledge have become available in the last years, to the aim of providing a new perspective on CKD in children and adolescents.

Podocytopathies are glomerular disorders in which podocyte injury drives proteinuria and progressive kidney disease. They encompass a broad spectrum of aetiologies, resulting in pathological pictures of minimal-changes, focal segmental glomerulosclerosis, diffuse mesangial sclerosis or collapsing glomerulopathy. Despite improvement in classifying podocytopathies as a distinct group of disorders, the histological definition fails to capture the relevant biological heterogeneity underlying each case, manifesting as extensive variability in disease progression and response to therapies. Increasing evidence suggests that podocytopathies can result from a single causative factor or a combination of multiple genetic and/or environmental risk factors with different relative contributions, identifying complex physiopathological mechanisms. Consequently, the diagnosis can still be challenging. In recent years, significant advances in genetic, microscopy and biological techniques revolutionized our understanding of the molecular mechanisms underlying podocytopathies, pushing nephrologists to integrate innovative information with more conventional data obtained from kidney biopsy in the diagnostic workflow. In this review, we will summarize current approaches in the diagnosis of podocytopathies, focusing on strategies aimed at elucidating the aetiology underlying the histological picture. We will provide several examples of an integrative view of traditional concepts and new data in patients with suspected podocytopathies, along with a perspective on how a reclassification could help to improve not only diagnostic pathways and therapeutic strategies, but also the management of disease recurrence after kidney transplantation. In the future, the advantages of precision medicine will probably allow diagnostic trajectories to be increasingly focused, maximizing therapeutic results and long-term prognosis.

Chronic kidney disease (CKD) is a global public healthcare concern in the pediatric population, where glomerulopathies represent the second most common cause. Although classification and diagnosis of glomerulopathies still rely mostly on histopathological patterns, patient stratification should complement information supplied by kidney biopsy with clinical data and etiological criteria. Genetic determinants of glomerular injury are particularly relevant in children, with important implications for prognosis and treatment. Targeted therapies addressing the primary cause of the disease are available for a limited number of glomerular diseases. Consequently, in the majority of cases, the treatment of glomerulopathies is actually the treatment of CKD. The efficacy of the currently available strategies is limited, but new prospects evolve. Although the exact mechanisms of action are still under investigation, accumulating data in adults demonstrate the efficacy of sodium-glucose transporter 2 inhibitors (SGLT2i) in slowing the progression of CKD due to diabetic and non-diabetic kidney disease. SGLT2i has proved effective on other comorbidities, such as obesity, glycemic control, and cardiovascular risk that frequently accompany CKD. The use of SGLT2i is not yet approved in children. However, no pathophysiological clues theoretically exclude their application. The hallmark of pediatric CKD is the inevitable imbalance between the metabolic needs of a growing child and the functional capacity of a failing kidney to handle those needs. In this view, developing better strategies to address any modifiable progressor in kidney disease is mandatory, especially considering the long lifespan typical of the pediatric population. By improving the hemodynamic adaptation of the kidney and providing additional beneficial effects on the overall complications of CKD, SGLT2i is a candidate as a potentially innovative drug for the treatment of CKD and glomerular diseases in children.

BackgroundThe periprocedural antithrombotic regimen might affect the risk-benefit profile of emergent carotid artery stenting (eCAS) in patients with acute ischemic stroke (AIS) due to tandem lesions, especially after intravenous thrombolysis. We conducted a systematic review and meta-analysis to evaluate the safety and efficacy of antithrombotics following eCAS.MethodsWe followed PRISMA guidelines and searched MEDLINE, Embase, and Scopus from January 1, 2004 to November 30, 2022 for studies evaluating eCAS in tandem occlusion. The primary endpoint was 90-day good functional outcome. Secondary outcomes were symptomatic intracerebral hemorrhage, in-stent thrombosis, delayed stent thrombosis, and successful recanalization. Meta-analysis of proportions and meta-analysis of odds ratios were implemented.Results34 studies with 1658 patients were included. We found that the use of no antiplatelets (noAPT), single antiplatelet (SAPT), dual antiplatelets (DAPT), or glycoprotein IIb/IIIa inhibitors (GPI) yielded similar rates of good functional outcomes, with a marginal benefit of GPI over SAPT (OR 1.88, 95% CI 1.05 to 3.35, Pheterogeneity=0.31). Sensitivity analysis and meta-regression excluded a significant impact of intravenous thrombolysis and Alberta Stroke Program Early CT Score (ASPECTS). We observed no increase in symptomatic intracerebral hemorrhage (sICH) with DAPT or GPI compared with noAPT or SAPT. We also found similar rates of delayed stent thrombosis across groups, with acute in-stent thrombosis showing marginal, non-significant benefits from GPI and DAPT over SAPT and noAPT.ConclusionsIn AIS due to tandem occlusion, the periprocedural antithrombotic regimen of eCAS seems to have a marginal effect on good functional outcome. Overall, high intensity antithrombotic therapy may provide a marginal benefit on good functional outcome and carotid stent patency without a significant increase in risk of sICH.

Background Hemorrhage is the most devastating complication of brain arteriovenous malformations (bAVMs), and to date, there is still concern about the needing for treatment in case of unruptured and asymptomatic bAVM. In fact, the morbidity and mortality of treatments may exceed that of the AVM’s natural history. None of the classifications and scores for bAVM allows to predict the risk of bleeding. In this study, we aimed to identify the angio-architectural characteristics of brain AVMs associated with bleeding. Methods We retrospectively evaluated all consecutive patients diagnosed with cerebral AVMs, between January 2010 and December 2019 from our prospective bAVM database. Univariate and multivariate logistic regression analysis were used to evaluate relationships between angio-architectural features of ruptured and unruptured bAVMs. Results Of the 143 retrieved bAVMs, 65 were unruptured and 78 were ruptured. The univariate logistic regression analysis demonstrated statistically significant differences into angio-architectural features of unruptured and ruptured bAVMs. The multivariate logistic regression analysis fitted well ( p =.113) with a good discrimination capacity (ROC = 0.83) of three independent angio-architectural features mainly related to bleeding in bAVMs: a smaller diameter of the nidus ( p < .001), the absence of venous drainage alterations ( p = .047), of the presence of prenidal aneurysms ( p = .005). Conclusions In our study, several features resulted related to an increased probability of rupture for bAVMs, among which the more relevant were a small diameter of the nidus, the absence of venous drainage alterations, and the presence of prenidal aneurysms.

Major cerebral vessels have been proposed as a target of defective mitochondrial metabolism in patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome (MELAS). Cerebral angiographic techniques are not routinely performed in MELAS patients. A systematic literature review was performed to identify studies describing major vessel caliber alterations in MELAS. Twenty-three studies reporting on 46 MELAS patients were included. Alterations in major caliber vessels were present in 59% (27/46) of patients. Dilation occurred in 37% (17/46) of patients, and in 88% (15/17) of them during a stroke-like episode (SLE). Stenosis was reported in 24% (11/46) of patients: 36% (4/11) related to an SLE and 64% (7/11) to dissections or degenerative changes. During an SLE, identification of intracranial vessels dilation or stenosis could be a selection tool for new treatment protocols. Outside SLE, identification of major cerebral vessels dissections and degenerative changes may help to prevent subsequent complications. (c) 2021 Elsevier Masson SAS. All rights reserved.

Erection is the final event of a complex phenomenon which involves psychological, neuronal, hormonal, vascular, and muscular systems. Nitric oxide (NO) is the most important molecule involved in many aspects of your health in vasodilation pathway. Erectile dysfunction (ED) is defined as the persistent inability to attain and/or maintain penile erection sufficient to permit satisfactory sexual performance with an high incidence worldwide and important impact on the quality of life.

BackgroundThere is no consensus on the most effective endovascular technique to use in patients with acute ischemic stroke due to terminal internal carotid artery (ICA) occlusion. The aim of this study was to compare safety and efficacy of the aspiration technique (AT) and combined technique (CT) as first-line approach in terminal ICA occlusions.MethodsWe performed a retrospective analysis of prospectively collected databases from seven Italian stroke centers. Patients were divided into two subgroups according to the first-line approach: AT group or CT group. We followed the STROBE guidelines for cohort studies. We used Chi-square test, one-way and multivariate ANOVA analysis, together with contrast analysis and post hoc tests, logistic regression and Pearson’s bivariate correlation for the statistical analyses.ResultsBetween January 2018 and August 2020, 353 patients were treated for a terminal ICA occlusion, with either AT or CT. CT was associated with a higher Thrombolysis in Cerebral Infarction (TICI) 2B-3 after the first pass (51.0% vs 26.9%) and at the end of the procedure (84% vs 73.3%) and with an improved clinical outcome at discharge (modified Rankin Scale (mRs) 0–2 of 47.8% vs 34.0%) and at 3 months’ follow-up (mRs 0–2 of 56.5% vs 38.9%) compared with AT.ConclusionThrombectomy of terminal ICA occlusions obtained using CT as first-line approach demonstrated better technical and functional outcomes in comparison with AT.

Hypouricemia is defined as a level of serum uric acid below 2 mg/dl. Renal hypouricemia is related to genetic defects of the uric acid tubular transporters urate transporter 1 and glucose transporter 9. Patients with renal hypouricemia can be completely asymptomatic or can develop uric acid kidney stones or acute kidney injury, particularly after exercise. Renal hypouricemia is especially challenging to diagnose in patients with acute kidney injury, due to the nonspecific clinical, hematochemical and histological features. No common features are reported in the literature that could help clinicians identify renal hypouricemia-acute kidney injury. Currently available guidelines on diagnosis and management of renal hypouricemia provide limited support in defining clues for the differential diagnosis of renal hypouricemia, which is usually suspected when hypouricemia is found in asymptomatic patients. In this paper we report a case of renal hypouricemia-acute kidney injury developing after exercise. We carried out a review of the literature spanning from the first clinical description of renal hypouricemia in 1974 until 2022. We selected a series of clinical features suggesting a diagnosis of renal hypouricemia-acute kidney injury. This may help clinicians to suspect renal hypouricemia in patients with acute kidney injury and to avoid invasive, costly and inconclusive exams such as renal biopsy. Considering the excellent outcome of the patients reported in the literature, we suggest a “wait-and-see” approach with supportive therapy and confirmation of the disease via genetic testing.

Primary testicular lymphoma (PTL) accounts for 1-2% of all cases of non-Hodgkin's lymphoma, with a higher incidence in patients aged >60 years. The most common histological subtype is diffuse large-cell B lymphoma. By contrast, the bilateral synchronous and multimetastatic clinical presentation is a rare and unusual clinical presentation. In testicular masses, orchiectomy is essential for histopathological evaluation of the disease and definition of the immunophenotypic structure. The present study reported the case of a paucisymptomatic 54-year-old patient, who presented with erectile dysfunction and increasing testicular volume. Although clinical assessment and ultrasound examination showed an abnormal structure, highly suspicious for testicular cancer, the subsequent bilateral radical orchiectomy permitted the diagnosis of an unusual and rare PTL with multiple metastases reported at the PET/CT scan. In conclusion, the rare and aggressive disease represented by PTL requires a multidisciplinary approach and an aggressive treatment in order to provide the best care for patients affected.

OBJECTIVESurgical treatment of orbital lesions is challenging because complex approaches with a high risk of postoperative sequelae are required. Recently, minimally invasive endoscopic approaches through endonasal (EEA) and transpalpebral (ETP) routes have been proposed. The objective of this study was to assess outcomes of EEA and ETP in the authors’ series of patients with orbital lesions.METHODSData from all patients who underwent operations for an orbital tumor through an endoscopic approach at the authors’ institution from 2002 to 2018 were retrospectively collected. All patients underwent preoperative MRI and ophthalmological evaluation, which was repeated 3 months after surgery and then at regular follow-up intervals. A systematic review of the literature was also performed using Medline, Embase, and Web of Science databases.RESULTSThe series includes 23 patients (14 males); the mean patient age was 48 ± 23.9 years. Most of the lesions were intraconal (n = 19, 83%). The more frequent histotype was cavernous hemangioma (n = 5, 22%). Exophthalmos was the most common symptom (21 of 23 patients). EEA was performed in 16 cases (70%) and ETP in 7 (30%). The aim of the surgery was achieved in 94% of the cases after an EEA (successful biopsy in 5 of 6 cases and radical resection in all 10 remaining patients), and in 86% after an ETP (successful biopsy in 2 cases and radical tumor resection in 4 of 5 cases). Complications consisted of 3 cases (13%) of transitory diplopia. One recurrence (4%) was observed at follow-up (mean 59 ± 55 months).CONCLUSIONSThe EEA and ETP have demonstrated to be safe and effective for tumors located respectively in medial and lateral quadrants, permitting one to approach orbital lesions endoscopically at 360°. Innovative surgical tools, including intraoperative ultrasonography, may be useful to potentially reduce surgical morbidity. Larger series are needed to validate these preliminary suggestions.

BACKGROUND AND AIMS With the spread of whole-exome sequencing techniques (WES), genetic kidney diseases are increasingly recognized across all age groups. However, accessibility, interpretation of results and costs limit the widespread of genomics use in daily practice [1]. In the very last years, first experiences in the implementation of renal genetic services have been started [2]. In this work, we explored the feasibility and diagnostic performance of a service delivery model based on a territorial network for patients’ selection, followed by referral to the renal genetic clinic of a tertiary centre for WES, results interpretation and counseling. We hypothesized that higher diagnostic yield and cost-effectiveness could be achieved by implementing a workflow that could solve three problems: (1) Give clear indications to the nephrologist about which patients with kidney diseases should undergo genetic testing, (2) Increase the rate and accuracy of genetic testing and evaluate the clinical impact and (3) Identify the kidney diseases for which early genetic testing is not only clinically, but also economically convenient for the healthcare provider based on pre-specified clinical criteria for tertiary centre referral. METHOD We set up a multi-step diagnostic workflow. We established specific clinical criteria for evaluation of patients who should undergo genetic testing on the suspicion of a genetic disease by a network of nephrology centres. Patients selected were referred to a tertiary centre for genetic diagnosis by WES, reverse-phenotyping and multidisciplinary board analysis. This workflow has been applied to pediatric and adult patients with kidney diseases belonging to eight clinical categories (Podocytopathies, Collagenopathies, Tubulopathies, Unknown familial nephropathies, Ciliopathies, Congenital anomalies of the kidney and urinary tract, Syndromic chronic kidney disease and Metabolic kidney disorders). We recorded clinical-laboratory-radiological information of patients included. We also performed a cost-analysis of the diagnostic workflow modelling the possible economic saving using it. RESULTS We included 402 patients, of note, 188 patients were female (46.8%) and 132 patients (33%) were >16 years of age. We obtained a global diagnostic yield of 69.2% (278–402), with category-specific diagnostic rates ranging from 38.5% to 87%. By reverse phenotyping, we reclassified diagnoses in 74–278 (26.6%) patients, thus increasing diagnostic accuracy. Overall, reverse phenotyping increased the diagnostic rate in an average of 20% of cases, irrespective of the age at clinical onset of the disease. Diagnostic yield was independent of the age at the onset of kidney disease. Genetic testing was offered as cascade screening to 67 families, providing a genetic diagnosis in 62 family members with previously unsuspected or unspecified kidney disorders. The clinical work-up changed and was redirected on average in 50% of patients. In 11.5% of patients, the results of genetic testing helped in guiding kidney transplant decisions. Finally, cost-analysis showed that our workflow is cost-efficient allowing to potentially save a mean of 1360 euros per patient. CONCLUSION Ordering genetic testing, interpreting results, counselling patients and their families, and tailoring clinical management (i.e. personalized nephrology) is feasible and saves costs in a real-world setting.

BACKGROUND AND AIMS In the last decade, the use of whole-exome sequencing techniques (WES) has provided many insights into inherited kidney diseases that are thought to represent at least 10%–15% of cases of end-stage CKD [1]. However, among others, cost concerns limit the widespread of genomics use in daily practice [1, 2]. Publicly funded genomic testing is restricted in most health care systems [2]. Consequently, the evaluation of cost-effectiveness is urgently required in order to establish genomic sequencing as a standard diagnostic test for nephropathic patients. The aim of this study was to perform a cost-analysis of genetic testing use in a diagnostic workflow. METHOD We recently set up a diagnostic workflow for the selection of patients that should undergo genetic testing in the suspicion of a genetic disease. This algorithm is applied by a network of nephrology centres on the regional territory. Selected patients are referred to a tertiary centre, Meyer University Hospital of Florence (Italy), for genetic diagnosis by WES. We enrolled paediatric and adult patients referred to the outpatient service based on the pre-specified clinical criteria. All the patients underwent genetic testing from 2018 to June 2021. We conducted a cost-analysis in two parts: (1) assessment of the cost-effectiveness cut-off; and (2) exploratory modeled cost-analysis using WES in different phases of the diagnostic trajectory. As a surrogate of the cost-effectiveness analysis, we calculated the cost-effectiveness cut-off, indicating the amount of expenses for diagnostic examinations at which WES sequencing would be cost-effective. For the exploratory cost-analysis, we defined two diagnostic trajectories: Model I, considering an ideal complete diagnostic pathway and late use of WES; and Model II, considering an early use of WES allowing to save a certain number of examinations. Genomic and non-genomic investigations were obtained from local practice, available clinical evidence and guidelines. We then calculated the cost per diagnosis according to each Model for different clinical categories and for the whole study population using the diagnostic rates of this study. We considered only direct medical costs, based on the regional health reimbursement system, which is comprehensive of materials and human resources. The prices are expressed in euros. The analysis was conducted from a regional healthcare system perspective. RESULTS The analysis included 402 patients. WES performed after the standard non-conclusive diagnostic work-up (at a mean cost of €2992/patient) resulted in cost-effectiveness at a cost of Overall, the exploratory cost-analysis showed Model II as cost reducing in comparison to Model I. The mean cost per diagnosis in Model I with late use of WES was estimated at €7700. Early use of WES in Model II had an estimated cost per diagnosis of €6340, leading to a cost saving of €1360/patient tested. Regarding the single clinical categories, the highest cost saving per diagnosis was obtained in podocytopathies (Model I: €13.010 versus Model II: €7261). The early use of WES produced a slight increase in estimated costs per diagnosis for tubulopathies, as well as for ciliopathies, while for syndromic CKD and metabolic kidney disorders, the costs per diagnosis did not result in major changes. CONCLUSION Early use of WES in the diagnostic pathway of inherited diseases, guided by a framework of specific criteria, is feasible and has the potential to produce substantial cost savings in healthcare.

Bartter (BS) and Gitelman (GS) syndrome are autosomal recessive inherited tubulopathies, whose clinical diagnosis can be challenging, due to rarity and phenotypic overlap. Genotype–phenotype correlations have important implications in defining kidney and global outcomes. The aim of our study was to assess the diagnostic rate of whole-exome sequencing (WES) coupled with a bioinformatic analysis of copy number variations in a population of 63 patients with BS and GS from a single institution, and to explore genotype-phenotype correlations. We obtained a diagnostic yield of 86% (54/63 patients), allowing disease reclassification in about 14% of patients. Although some clinical and laboratory features were more commonly reported in patients with BS or GS, a significant overlap does exist, and age at onset, preterm birth, gestational age and nephro-calcinosis are frequently misleading. Finally, chronic kidney disease (CKD) occurs in about 30% of patients with BS or GS, suggesting that the long-term prognosis can be unfavorable. In our cohort the features associated with CKD were lower gestational age at birth and a molecular diagnosis of BS, especially BS type 1. The results of our study demonstrate that WES is useful in dealing with the phenotypic heterogeneity of these disorders, improving differential diagnosis and genotype-phenotype correlation.

Introduction A reduction of the hospitalization and reperfusion treatments was reported during COVID-19 pandemic. However, high variability in results emerged, potentially due to logistic paradigms adopted. Here, we analyze stroke code admissions, hospitalizations, and stroke belt performance for ischemic stroke patients in the metropolitan Bologna region, comparing temporal trends between 2019 and 2020 to define the impact of COVID-19 on the stroke network. Methods This retrospective observational study included all people admitted at the Bologna Metropolitan Stroke Center in timeframes 1 March 2019–30 April 2019 (cohort-2019) and 1 March 2020–30 April 2020 (cohort-2020). Diagnosis, treatment strategy, and timing were compared between the two cohorts to define temporal trends. Results Overall, 283 patients were admitted to the Stroke Center, with no differences in demographic factors between cohort-2019 and cohort-2020. In cohort-2020, transient ischemic attack (TIA) was significantly less prevalent than 2019 (6.9% vs 14.4%, p = .04). Among 216 ischemic stroke patients, moderate-to-severe stroke was more represented in cohort-2020 (17.8% vs 6.2%, p = .027). Similar proportions of patients underwent reperfusion (45.9% in 2019 vs 53.4% in 2020), although a slight increase in combined treatment was detected (14.4% vs 25.4%, p = .05). Door-to-scan timing was significantly prolonged in 2020 compared with 2019 (28.4 ± 12.6 vs 36.7 ± 14.6, p = .03), although overall timing from stroke to treatment was preserved. Conclusion During COVID-19 pandemic, TIA and minor stroke consistently reduced compared to the same timeframe in 2019. Longer stroke-to-call and door-to-scan times, attributable to change in citizen behavior and screening at hospital arrival, did not impact on stroke-to-treatment time. Mothership model might have minimized the effects of the pandemic on the stroke care organization.

We present the neuroimaging findings of three cases of non-ketotic hyperglycaemia (NKH) associated with focal seizures and a review of the previous cases and series reported in literature. NKH is a cause of seizures in both long-standing and newly diagnosed diabetic patients. They are usually focal motor seizures, rarely with a secondary generalisation. This condition does not fully respond to anticonvulsant therapy if glycaemic levels are not normalised. Of interest, magnetic resonance imaging (MRI) of NKH could be different from those observed during other kinds of seizures. Indeed, seizure-related MRI abnormalities mainly involve the cortical grey matter, while NKH-related seizures usually appear as reversible subcortical T2/fluid attenuation inversion recovery (FLAIR) hypointensity. This latter abnormality shows a good spatial correlation with the area of the ictal focus on electroencephalogram and could be associated with other more common post-ictal MRI changes (cortical grey matter T2/FLAIR hyperintensity, cortical or leptomeningeal enhancement). Although these abnormalities tend to be transient, a focal volume loss or gliosis can result on follow-up imaging. Our cases confirm T2/FLAIR subcortical hypointensity as a main neuroradiological hallmark of NKH-induced seizures.

Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains.

Objective: The purpose of this study was to investigate if vessel-wall magnetic resonance imaging (VW-MRI) could differentiate among primary headaches disorders, such as migraine and cluster headache (CH), and detect the presence of neurogenic inflammation. Background: The pathophysiology of primary headaches disorders is complex and not completely clarified. The activation of nociceptive trigeminal afferents through the release of vasoactive neuropeptides, termed "neurogenic inflammation," has been hypothesized. VW-MRI can identify vessel wall changes, reflecting the inflammatory remodeling of the vessel walls despite different etiologies. Methods: In this case series, we enrolled seven patients with migraine and eight patients with CH. They underwent a VW-MRI study before and after the intravenous administration of contrast medium, during and outside a migraine attack or cluster period. Two expert neuroradiologists analyzed the magnetic resonance imaging (MRI) studies to identify the presence of vessel wall enhancement or other vascular abnormalities. Results: Fourteen out of 15 patients had no enhancement. One out of 15, with migraine, showed a focal parietal enhancement in the intracranial portion of a vertebral artery, unmodified during and outside the attack, thus attributable to atherosclerosis. No contrast enhancement attributable to neurogenic inflammation was observed in VW-MRI, both during and outside the attack/cluster in all patients. Moreover, MRI angiography registered slight diffuse vasoconstriction in one of seven patients with migraine during the attack and in one of eight patients with cluster headache during the cluster period; both patients had taken triptans as symptomatic therapy for pain. Conclusions: These preliminary results suggest that VW-MRI studies are negative in patients with primary headache disorders even during migraine attacks or cluster periods. The VW-MRI studies did not detect signs of neurogenic inflammation in the intracranial intradural vessels of patients with migraine or CH.

Recently, endoscopic approaches for orbital lesions have been proposed. Their results seem promising; however, orbital surgery remains challenging with possible significant morbidity, mostly because of orbital structures manipulation. Ultrasonography is an innovative intraoperative imaging technique that can assist the surgeon in these approaches.To assess the role of intraoperative ultrasound (IOUS) in endoscopic orbital surgery.All consecutive patients with orbital tumors operated in our institution through an endoscopic approach with IOUS have been prospectively collected from 2019 to May 2021.Fifteen patients were included. Based on tumor location, evaluated on preoperative MRI, the endoscopic endonasal approach was preferred in 7 tumors in medial quadrants while the endoscopic transpalpebral in 8 lateral ones. During surgery, IOUS allowed us to identify the tumors and the most relevant anatomic structures in all cases. Time spent for IOUS preparation before the first scan was 8 ± 6 minutes on average, and each intraoperative scan took approximately 30 to 120 seconds. Gross tumor removal was achieved in 8 patients, subtotal in 3, while in 4 patients, surgery was limited to a biopsy. No surgical complications were observed.IOUS has allowed us to localize the lesion and to identify the straighter surgical corridor and assess the tumor resection, effectively helping the surgeon and potentially reducing operative complications. This tool provides a real-time image, not affected by the orbital structures shift, which can be dynamically assessed multiple times during surgery. However, it is hampered by the need of specific training and possible artifacts.

Spinal cord injury (SCI) is a relevant medical and social problem. According to the World Health Organization, the commonly estimated worldwide annual incidence of SCI is 40 to 80 cases per million population. After the SCI experience, most men present with sexual dysfunction (erectile dysfunction (ED) and ejaculatory dysfunction), fertility problems (such as impaired spermatogenesis, abnormalities in sperm viability, motility, and morphology), and systemic disorders such as genitourinary infection and endocrine imbalances. The best options available for managing the ejaculatory disorders in patients suffering from SCI are penile vibratory stimulation (PVS) and electroejaculation (EEJ). Furthermore, the treatment of ED in SCI patients consists of medical therapies including phosphodiesterase 5 inhibitors (PDE5i), intracavernosal injections (ICI), vacuum erection devices (VEDs), and surgical as penile prosthesis (PP). This review provides a snapshot of the current evidence for the mechanisms of sexual dysfunction and infertility in SCI patients, discusses the best management strategies for these conditions, and offers our perspective on the direction of future research.

Purpose: To assess utility of computed tomography perfusion (CTP) protocols for selection of patients with acute ischemic stroke (AIS) for reperfusive treatments and compare the diagnostic accuracy (ACC) in predicting follow-up infarction, using time-to-maximum (Tmax) maps. Methods: We retrospectively reviewed consecutive AIS patients evaluated for reperfusive treatments at comprehensive stroke center, employing a multimodal computed tomography. To assess prognostic accuracy of CTP summary maps in predicting final infarct area (FIA) in AIS patients, we assumed the best correlation between non-viable tissue (NVT) and FIA in early and fully recanalized patients and/or in patients with favorable clinical response (FCR). On the other hand, the tissue at risk (TAR) should better correlate with FIA in untreated patients and in treatment failure. Results: We enrolled 158 patients, for which CTP maps with Tmax thresholds of 9.5s and 16s, presented sensitivity of 82.5%, specificity of 74.6%, and ACC of 75.9%. In patients selected for perfusion deficit in anterior circulation territory, CTP-Tmax > 16s has proven relatively reliable to identify NVT in FCR patients, with a tendency to overestimate NVT. Similarly, CTP-Tmax > 9.5s was reliable for TAR, but it was overestimated comparing to FIA, in patients with unfavorable outcomes. Conclusions: In our experience, Tmax thresholds have proven sufficiently reliable to identify global hypoperfusion, with tendency to overestimate both NVT and TAR, not yielding satisfactory differentiation between true penumbra and benign oligoemia. In particular, the overestimation of NVT could have serious consequences in not selecting potential candidates for a reperfusion treatment.

Background Occlusion of the internal carotid artery (ICA), whether isolated or in the setting of a tandem lesion (TL) have a poor response to treatment with intravenous thrombolysis. Previous studies ​​have demonstrated the superiority of mechanical thrombectomy in the treatment of acute ischemic stroke (AIS) following large vessel occlusion, compared to standard intravenous fibrinolysis. The aim of our study was to describe endovascular treatment (EVT) in AIS due to isolated ICA occlusion or TL. Methods We assessed the association between 90-day outcome and clinical, demographic, imaging, and procedure data in 51 consecutive patients with acute isolated ICA occlusion or TL who underwent EVT. We evaluated baseline NIHSS and mRS, ASPECTS, type of occlusion, stent placement, use of stent retrievers and/or thromboaspiration, duration of the procedure, mTICI, postprocedural therapy and complications. Results A favorable 90-day outcome (mRS 0–2) was achieved in 34 patients (67 %) and was significantly associated with the use of dual antiplatelet therapy after the procedure (p = 0.008), shorter procedure duration (p = 0.031), TICI 2b-3 (p p = 0.001). Four patients did not survive, resulting in a mortality rate of 8 %. Conclusions Our study has shown that EVT in the treatment of AIS due to ICA occlusion is safe, and effective in determining a good functional outcome. ICA stenting led to good angiographic results and therapy with a glycoprotein IIb / IIIa inhibitor immediately after stent release did not result in a greater risk of hemorrhage. The use of post-procedural dual antiplatelet therapy was associated with favorable outcome, without a significant increase in hemorrhagic transformation.

Acute kidney injury (AKI) is frequent, often fatal and, for lack of specific therapies, can leave survivors with chronic kidney disease (CKD). We characterize the distribution of tubular cells (TC) undergoing polyploidy along AKI by DNA content analysis and single cell RNA-sequencing. Furthermore, we study the functional roles of polyploidization using transgenic models and drug interventions. We identify YAP1-driven TC polyploidization outside the site of injury as a rapid way to sustain residual kidney function early during AKI. This survival mechanism comes at the cost of senescence of polyploid TC promoting interstitial fibrosis and CKD in AKI survivors. However, targeting TC polyploidization after the early AKI phase can prevent AKI-CKD transition without influencing AKI lethality. Senolytic treatment prevents CKD by blocking repeated TC polyploidization cycles. These results revise the current pathophysiological concept of how the kidney responds to acute injury and identify a novel druggable target to improve prognosis in AKI survivors.

Vessel Wall MRI (VW-MRI) is an emerging MR sequence used for diagnosis, characterization, and treatment planning of cerebrovascular diseases. Although VW-MRI is not yet routinely used, most papers have emphasized its role in several aspects of the management of cerebrovascular diseases. Nowadays, no VW-MRI sequence optimized for the intracranial imaging is commercially available, thus the Spin Echo sequences are the more effective sequences for this purpose. Moreover, as one of the principal technical requirements for intracranial VW-MR imaging is to achieve both the suppression of blood in vessel lumen and of the outer cerebrospinal fluid, different suppression techniques have been developed. This short report provides the technical parameters of our VW-MR sequence developed over 3-years’ experience.

Background and Purpose: Acute ischemic stroke and large vessel occlusion can be concurrent with the coronavirus disease 2019 (COVID-19) infection. Outcomes after mechanical thrombectomy (MT) for large vessel occlusion in patients with COVID-19 are substantially unknown. Our aim was to study early outcomes after MT in patients with COVID-19. Methods: Multicenter, European, cohort study involving 34 stroke centers in France, Italy, Spain, and Belgium. Data were collected between March 1, 2020 and May 5, 2020. Consecutive laboratory-confirmed COVID-19 cases with large vessel occlusion, who were treated with MT, were included. Primary investigated outcome: 30-day mortality. Secondary outcomes: early neurological improvement (National Institutes of Health Stroke Scale improvement ≥8 points or 24 hours National Institutes of Health Stroke Scale 0–1), successful reperfusion (modified Thrombolysis in Cerebral Infarction grade ≥2b), and symptomatic intracranial hemorrhage. Results: We evaluated 93 patients with COVID-19 with large vessel occlusion who underwent MT (median age, 71 years [interquartile range, 59–79]; 63 men [67.7%]). Median pretreatment National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score were 17 (interquartile range, 11–21) and 8 (interquartile range, 7–9), respectively. Anterior circulation acute ischemic stroke represented 93.5% of cases. The rate modified Thrombolysis in Cerebral Infarction 2b to 3 was 79.6% (74 patients [95% CI, 71.3–87.8]). Thirty-day mortality was 29% (27 patients [95% CI, 20–39.4]). Early neurological improvement was 19.5% (17 patients [95% CI, 11.8–29.5]), and symptomatic intracranial hemorrhage was 5.4% (5 patients [95% CI, 1.7–12.1]). Patients who died at 30 days exhibited significantly lower lymphocyte count, higher levels of aspartate, and LDH (lactate dehydrogenase). After adjustment for age, initial National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and successful reperfusion, these biological markers remained associated with increased odds of 30-day mortality (adjusted odds ratio of 2.70 [95% CI, 1.21–5.98] per SD-log decrease in lymphocyte count, 2.66 [95% CI, 1.22–5.77] per SD-log increase in aspartate, and 4.30 [95% CI, 1.43–12.91] per SD-log increase in LDH). Conclusions: The 29% rate of 30-day mortality after MT among patients with COVID-19 is not negligible. Abnormalities of lymphocyte count, LDH and aspartate may depict a patient’s profiles with poorer outcomes after MT. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT04406090.

Spontaneous intracranial hypotension (SIH) results from low cerebrospinal fluid (CSF) volume, typically secondary to a spinal CSF leak. CSF hypovolemia leads to brain sagging, particularly in orthostatic position, and expansion of the intracranial venous compartment. These pathophysiological mechanisms are responsible for the clinical presentation that usually consists of postural headache variably associated with other neurological symptoms. The wide range of clinical manifestations, including the absence of typical headache, may delay diagnosis. Magnetic resonance imaging (MRI) supports diagnosis showing typical findings including subdural fluid collections, pachymeningeal enhancement and brain sagging.

Background and Aims C.septicum is an anaerobic bacterium that resides in the gastrointestinal tract of herbivores. Its presence in human fecal flora is still debated, being found in only 2.8% of healthy adults. Transmitted by oral-fecal route, it reaches the systemic circulation, causing bacteremia, myonecrosis, bowel necrosis, intracranial abscesses/encephalitis. Shiga-toxin producing E. Coli related hemolytic uremic syndrome (STEC-HUS) is a thrombotic microangiopathy characterized by hemolytic anemia, thrombocytopenia and kidney damage, related to STEC infection. Severe presentation includes gastrointestinal and neurologic involvement. Microangiopathic lesions in the colonic mucosa can facilitate the colonization of systemic circulation by C.septicum, spreading the superinfection. Since the first report in 1988, very few cases of STEC-HUS complicated by C.septicum superinfection have been described in literature and thus the factors predicting clinical outcome are not clear. Method We describe the case of a 5-years-old girl admitted for anemia, AKI, thrombocytopenia and diarrhea. Previous history was unremarkable. STEC-HUS diagnosis was made. Despite prompt conservative treatment, 12h later her clinical condition worsened, showing ESKD needing dialysis, abdominal pain, progressive hyporesponsiveness. The brain CT scan showed pneumocephalus and encephalitis; blood cultures were drawn and broad-spectrum antibiotic therapy was set (Tab.1). Cardiovascular instability prevented surgical treatment of pneumocephalus to be done. The patient died shortly after because of septic shock. Post-mortem stool and blood cultures confirmed STEC infection complicated by C.Septicum. Previous literature on this specific clinical picture has been reviewed and summarized. Results Eleven additional cases (7 males) have been previously described. Mean age of presentation was 2.9 years. A; abdominal symptoms (commonly distention and pain) were reported in all cases, while ESRD was present in 10 cases. Six patients presented fever. Central nervous system presentation as pneumocephalus was associated with poor prognosis, while surgical treatment availability of brain lesions to survival. In one case the infection caused myonecrosis (Tab. 1). The mortality rate was about 60%. In 7 cases, clinical conditions worsened in less than 24h and this was in all cases related to poor outcome. Conclusion C.septicum superinfection complicating STEC-HUS is a rare but fearsome complication to be aware of. Rapid diagnosis and surgical treatment are essential for the successful management of this particular condition.

Background and Aims Bartter (BS) and Gitelman syndrome (GS) are autosomal recessive rare inherited disorders characterized by hypokalemic metabolic alkalosis and secondary hyperaldosteronism. The primary defect is a genetically determined impairment of sodium chloride reabsorption in the renal tubule, thus resulting in salt loss, dehydration and acid-base homeostasis perturbations. Although the diagnosis can be suspected based on presenting features, the clinical diagnosis of BS and GS can be challenging, as they are rare and phenotypically overlapping. As a consequence, the current clinical classification lacks of specificity and genetic testing represents the gold standard for the diagnosis. Driven by the rapidly decreasing costs and turn-around time, next-generation sequencing technologies are increasingly utilized in diagnostics and research of inherited tubulopathies, including BS and GS. Recently, sequencing of selected gene panels provided the advantage of achieving high coverage of genes of interest at lower costs, providing high diagnostic yield and new insights into the phenotypic spectrum of these rare disorders. However, whole-exome (WES) is not routinely performed for the molecular diagnosis of BS and GS. The aim of our study was to assess the diagnostic performance of WES in BS and GS and to establish genotype-phenotype correlations. Method We performed WES in all consecutive patients referred for genetic testing with a clinical suspect of BS or GS. Variant prioritization was carried out according to the American College of Medical Genetics and Genomics guidelines (ACMG). Parents and first-degree relatives were included, whenever available. Demographic, clinical and laboratory data were collected retrospectively, in order to establish genotype-phenotype correlations. Results We enrolled 50 patients (22 males, 46 Caucasians) with a clinical diagnosis of BS (19), GS (24) or BS/GS (7). All the patients showed hypokalemic metabolic alkalosis at onset (serum bicarbonate=29.5 mEq/l ± 4.4, potassium= 2.7 mEq/l ± 0.6). The median age at clinical diagnosis was 7 years (range 0-67 years). Three patients had familial history of tubulopathies. WES showed pathogenic variants in 42/50 patients (84%), thus establishing a conclusive diagnosis. Interestingly, a dedicated analytic pipeline allowed us to identify copy number variations (CNVs) in 7/42 patients with a confirmed genetic diagnosis. In detail, WES allowed us to confirm the clinical diagnosis in 33/50 patients, with an improvement in classification in at least 14 cases (i.e. subtype I-V of BS). In 9 additional patients, genetic testing changed the clinical diagnosis: 6 patients with a clinical of BS turned out to have pathogenic variants in SLC12A3, resulting in GS; in 3 patients, genetic testing revised the clinical diagnosis indicating inherited disorders outside the BS/GS spectrum (HELIX syndrome, Primary familial hypoparatiroidism, Type 2 renal hypomagnesemia). Only 38% of patients with a genetic diagnosis of BS showed nephrocalcinosis. Strikingly, this was present in 8% of patients with GS. On the other hand, hypomagnesemia, a distinctive feature of GS, was similarly distributed among BS and GS patients (45% vs. 68%, respectively). Finally, although patients with GS showed a median age at onset higher than patients with BS, some overlap did exist, making differential diagnosis challenging at single-patient level. Conclusion The results of our study demonstrate that WES ensures a high diagnostic yield (84%) in patients with a clinical diagnosis of BS or GS, especially if coupled with analysis of CNVs. This approach showed to be useful in dealing with the phenotypic heterogeneity typical of these rare disorders, improving differential diagnosis by detecting phenocopies also outside the BS/GS spectrum, enabling additional specific work-up, genetic counseling, and screening of at-risk relatives.

BACKGROUND: In many clinical trials endovascular procedures are suggested as the treatment of choice for aneurysmal Subarachnoid Hemorrhage (aSAH) whenever possible. However, in clinical practice this management is often controversial. The aim of this study is to analyze factors involved in this decision. METHODS: Our study included 317 consecutive cases of aSAH between 2010 and 2016, assessing clinical and neuroradiological features to evaluate their role in this choice. RESULTS: In our series coiling was preferred in 119 (37.6%) patients, while 198 (62.4%) were treated surgically. On univariate analysis location of aneurysms (p < 0.001), GCS score on admission (p: 0.105), degree of midline shift (p:0.015), Fisher' score (p: 0.002) and presence of vessels in the aneurysmal neck (p: 0.071) proved the most relevant factors in the choice. Also multivariate analysis confirmed the location and Fisher' grade as influential factors. Conversely, other radiological parameters, such as morphology, aspect and dome-neck ratio, presence of pre-operative vasospasm or hydrocephalus were not associated with this decision. CONCLUSIONS: The decision process in aSAH requires a multidisciplinary team, to singularly evaluate each patient. We found that the location of aneurysms in Vertebro-Basilar circulation, PCoM and ICA, greater GCS score, absence of vessels in the aneurysmal neck, lower midline shift and Fisher' score are factors influencing in choosing coiling. Conversely, morphology, Aspect and Dome-Neck ratio proved not relevant to this decision, due to technological improvement and increasing skills in the endovascular treatment.

Spontaneous intracranial hypotension results from a spinal CSF leak and usually presents with orthostatic headache, although acephalgic presentations have anecdotally been reported. The underlying low CSF volume, rarely, leads to serious complications such as cerebral venous thrombosis and coma. We report a patient presenting with cerebral venous thrombosis secondary to acephalgic spontaneous intracranial hypotension. An epidural blood patch was performed; nonetheless, the patient intracracal condition deteriorated to coma and neuroimages showed a deep brain swelling with midbrain distortion, subsequently complicated by intracranial pontine hemorrhage. © 2020, Fondazione Società Italiana di Neurologia.

Background Finding an intracranial aneurysm (IA) during a thunderclap headache (TCH) attack, represents a problem because it is necessary to distinguish whether the aneurysm is responsible for the headache as a warning leak or as an incidental finding. High-Resolution Vessel-Wall (HRVW) MRI sequences have been proposed to assess the stability of the wall, as it permits to detect the presence of aneurysmal wall enhancement (AWE). In fact, AWE has been confirmed due to inflammation, recognizable preceding rupture. Case 1: A 37-year-old woman with a migraine more intense than her usual. A CTA revealed a 10 mm AComA aneurysm without subarachnoid hemorrhage (SAH) and HRVW-MRI excluded AWE. The patient’s headache improved, and therefore, the aneurysm was considered an incidental finding, and the headache diagnosed as TCH attack. Subsequently, the aneurysm was surgically clipped, and typical migraine relapsed was reported at follow-up (FU). Case 2: A 67-year-old woman with no history of headaches underwent CTA for an abrupt onset of headache. A 7 mm right carotid-ophthalmic aneurysm with no sign of SAH was discovered. HRVW-MRI demonstrated AWE and thus, a TCH attack for a warning leak of an unstable wall was suspected. Endovascular coiling was immediately performed and at FU any further headache attack was reported. Conclusions HRVW-MRI is useful in case of finding aneurysm as the cause of headaches, particularly the TCH attack. In fact, HRVW-MRI could assess the stability of the aneurysms wall, allowing different patient management and eventually the aneurysmal treatment.

Simple Summary Patients with oligometastatic urothelial carcinoma represent a challenging subset of subjects to manage. Herein we summarized evidence about the role of metastasis-directed radiation therapy in this clinical setting. Available preliminary evidence supports the role of metastasis-directed radiation therapy as a safe and efficacious option as it has the potential to facilitate local disease control and overall survival. However, in the absence of data from high-quality trials, definitive recommendations cannot be provided, and patients should be counseled on an individual basis. The management of patients with oligometastatic urothelial carcinoma (UC) represents an evolving field in uro-oncology, and the role of metastasis-directed therapies, including metastasectomy and metastasis-directed radiation therapy (MDRT), is gaining increasing attention. Herein, we summarize available evidence about the role of MDRT with consolidative intent in oligometastatic UC patients. A systematic review was performed in December 2021. Six studies involving 158 patients were identified. Most patients (n = 120, 90.2%) had a history of bladder cancer and the most frequent sites of metastases were lymph nodes (n= 61, 52.1%) followed by the lungs (n = 34, 29%). Overall, 144 metastases were treated with MDRT. Median follow-up ranged from 17.2 to 25 months. Local control rates ranged from 57% to 100%. Median Overall Survival (OS) ranged from 14.9 to 51.0 months and median progression-free survival ranged from 2.9 to 10.1 months. Rates of OS at one and two years ranged from 78.9% to 96% and from 26% to 63%, respectively. Treatment-related toxicity was recorded in few patients and in most cases a low-grade toxicity was evident. MDRT with consolidative intent represents a potential treatment option for selected patients with oligometastatic UC.

Background Brain stroke is a rare, life-threatening condition associated with pituitary apoplexy (PA), resulting from direct arterial occlusion due to mechanical compression secondary to the sudden enlargement of the pituitary adenoma, or to vessel vasospasm, induced by tumor hemorrhage. Case report We report the case of a 64-year-old woman with PA complicated by bilateral anterior circulation stroke due to critical stenosis of both anterior cerebral arteries (ACA). Despite the quick surgical decompression and consequent blood flow restoration, the neurological conditions of the patient did not improve and she died 18 days later. Ten other cases of anterior circulation stroke due to PA were retrieved in a systematic review of literature. Clinical and neuroradiological features of these patients and treatment outcome were assessed to suggest the most proper management. Conclusion The onset of neurological symptoms suggestive for brain stroke in patients with PA requires performing an emergency Magnetic Resonance Imaging (MRI), including Diffusion-weighted and angiographic MR-sequences. The role of surgery in these cases is debated, however, transsphenoidal adenomectomy would permit us to decompress the ACA and restore blood flow in their territories. Although the prognosis of PA-induced anterior circulation stroke is generally poor, a timely diagnosis and treatment would be paramount for improving patient outcome.

Noninvasive tools for diagnosis or prediction of acute kidney allograft rejection have been extensively investigated in recent years. Biochemical and molecular analyses of blood and urine provide a liquid biopsy that could offer new possibilities for rejection prevention, monitoring, and therefore, treatment. Nevertheless, these tools are not yet available for routine use in clinical practice. In this systematic review, MEDLINE was searched for articles assessing urinary biomarkers for diagnosis or prediction of kidney allograft acute rejection published in the last five years (from 1 January 2015 to 31 May 2020). This review follows the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Articles providing targeted or unbiased urine sample analysis for the diagnosis or prediction of both acute cellular and antibody-mediated kidney allograft rejection were included, analyzed, and graded for methodological quality with a particular focus on study design and diagnostic test accuracy measures. Urinary C-X-C motif chemokine ligands were the most promising and frequently studied biomarkers. The combination of precise diagnostic reference in training sets with accurate validation in real-life cohorts provided the most relevant results and exciting groundwork for future studies.

Background and Aims Congenital anomalies of the kidney and urinary tract (CAKUT) are the major cause of chronic kidney disease and end-stage kidney disease in childhood. Solitary functioning kidney (SFK) is part of the spectrum of CAKUT. Congenital SFK is mainly due to unilateral renal agenesis (URA) and multi-cystic dysplastic kidney (MCDK). With the implementation of routine fetal ultrasound screening, SFK is increasingly recognized before birth, significantly raising the number of patients referred to paediatric nephrology units for clinical monitoring during childhood. Understanding the pathophysiology of SFK is pivotal for guiding the clinical management and informing long-term outcome. However, observational studies performed in children with SFK are controversial, especially about the need, methodology and timing of functional assessment. This may be at least in part due to the fact that different models of SFK, including congenital and acquired after unilateral nephrectomy, are often grouped together. The aim of this study was to assess the clinical, laboratory and functional features of congenital SFK caused by URA and MCDK in children, with a particular focus on the role of renal scintigraphy in estimating kidney function during childhood and adolescence. Method We retrospectively collected clinical, laboratory and instrumental records of all consecutive pediatric patients (aged 0-18 years) affected by congenital SFK caused by URA or MCDK referred to the Nephrology and Dialysis Unit of Meyer Children’s Hospital of Florence (Italy) from 1992 to 2019. Patients with unilateral kidney hypodysplasia were excluded. In particular, we reviewed data from ultrasound scanning and sequential renal scintigraphy over time. URA and MCDK were compared for clinical features, long-term course and outcome. Results A total of 155 patients with congenital SFK were included in the study and divided in two groups according to the cause of SFK (URA, n=100; MCDK, n=55). The median length of follow-up was 47 and 45 months, respectively. Male sex and ethnicity were equally distributed in the two groups. Prenatal diagnosis was more frequent in MCDK group. We did not observe either preterm birth or low birth weight in patients enrolled. Overall, the clinical features were not statistically different between the two groups. In particular, SFK associated CAKUT, including vesicoureteral reflux, occurred at a comparable frequency. Also, measurement of kidney length by ultrasound scanning, which is often considered suggestive of compensatory hypertrophy, did not differ between groups. Although renal clearance from sequential renal scintigraphy appeared not statistically different between URA and MCDK, the latter seems to reach complete functional adaptation more rapidly and earlier in the first two years of life. Conclusion The clinical course and long-term outcome of SFK has been a topic of extensive debate. Due to poor-quality of data (unclear inclusion/exclusion criteria, lack of uniformity in data collection and outcome definition), generalization of findings from observational studies to all patients with SFK could be inappropriate. Congenital SFK could represent the most unbiased group to analyze and this study provides a thorough clinical characterization of a large and strictly selected cohort. Insights from sequential renal scintigraphy suggest a different trend in reaching single kidney complete functional adaptation in URA and MCDK. These results could potentially reveal significant differences in the pathophysiologic mechanisms of reaching compensatory hypertrophy and functional adaptation by the solitary kidney in the two models. Whether confirmed in larger cohorts, these findings could provide important implications for follow-up planning, informing the need, methodology and timing for function assessment, tailoring the clinical management and understanding long-term prognosis.

Background and Aims Secondary hemolytic-uremic syndrome (HUS) is currently defined in the absence of genetic defects in complement genes (primary or atypical HUS, aHUS) or Shiga-toxin producing E. Coli infection (STEC-HUS). However, the role of complement genes abnormalities in secondary HUS is still a matter of debate as results coming from studies performed in adults are controversial. Moreover, genetic defects of complement regulation have been recently described in children with STEC-HUS, thus challenging the current HUS classification. The identification of a role of complement genes abnormalities in these patients could have important clinical implications for diagnosis and treatment. In this study, we assessed the presence of complement genes abnormalities in children with secondary HUS. Method We describe a case series of pediatric patients diagnosed with secondary HUS. All patients were screened for the presence of ADAMTS13 auto-antibody and ADAMTS13 deficiency. We performed next-generation sequencing for a panel of complement genes reported in association with aHUS (CFH, CFI, MCP, C3, FB, and THBD). Copy number variations and hybrid genes assessment were included in the analysis. Results Four patients aged 1-4 years with a diagnosis of sporadic secondary HUS were included in the study. HUS was secondary to glomerulopathy, cobalamin deficiency, bone marrow transplantation, and pneumococcal pneumoniae. Two out of four patients showed hypocomplementaemia (both C3 and C4). Diarrhea was a common clinical feature in all patients at onset, and none of these patients showed neurologic involvement. Renal replacement therapy was required in two patients at onset. Only one patient did not recover kidney function, and subsequently underwent kidney transplantation. Next-generation sequencing showed genetic abnormalities in all the patients (Table 1). All but one genetic variants have already been described in association with atypical HUS. Interestingly, haplotypes in CHF and MCP were present in three patients, all of Caucasian ethnicity. Conclusion According to the current HUS classification, complement abnormalities are diagnostic of aHUS. However, results coming from pediatric cohorts of STEC-HUS patients already claimed a role for genetic background also outside the aHUS spectrum, suggesting that the current terminology lacks both specificity and suggestion of cause. In this case series, complement genes abnormalities were present in all patients. Whether confirmed in larger cohorts, these findings would support the role of genetic background even in secondary HUS, suggesting the need for a revision of the current HUS classification, in agreement with the pathogenic mechanisms, in order to tailor the optimal treatment.

Introduction: CKD is associated with a reduction of patients’ health-related quality of life. Considering the time spent in dialysis, satisfaction with care is essential for patients QOL. Objective: Since the possible association between satisfaction with the dialysis care and QOL has never been studied, in this study, we explore this plausible link. Methods: One hundred three patients on hemodialysis (HD) and peritoneal dialysis (PD) filled-in patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs). QOL was assessed by Kidney Disease Quality of Life-36 and satisfaction by Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) questionnaire. The analysis was conducted on patient-level, considering for single patient sociodemographic characteristics and presence of depression/anxiety. One-way ANOVA was used to compare QOL mean scores for patients who answered “excellent” and for those who answered “other ratings” in CHOICE questionnaire and the Pearson χ2 test to compare the patients’ characteristics between these 2 groups of patients. Results: The analysis showed a significant positive association between PREM and PROM scores for 8 out of 23 CHOICE items. Six of them were related to the figure of nephrologist, 1 to dialysis access site, and 1 to the social worker support. Significant association (p < 0.05) were between frequency of seeing nephrologist and physical component plus mental component, accuracy of information from nephrologist and burden of disease, accuracy of instructions from nephrologist and burden of disease, coordination between nephrologist and other physicians plus mental component, attention to cleanliness of access site and mental component, amount of dialysis information from staff and burden of disease, information from staff when choosing between HD or PD and physical component plus burden of disease, and ease of seeing social worker and burden of disease. Conclusions: The study provides support for the relationship between the care satisfaction and QOL, highlighting the central role of the nephrologist-patient communication in the QOL of dialysis patients.

INTRODUCTION: A direct aspiration first pass technique (ADAPT) is an alternative technique as first-line thrombectomy for large vessel occlusion in acute ischemic stroke, still debated when compared to first-line stent retriever. To retrospectively evaluate technical and clinical outcomes of the ADAPT as first-line treatment for anterior circulation acute ischemic stroke with large-bore reperfusion catheters. METHODS: A multicentric data collection from 14 medical centers was retrospectively analyzed. Large-bore catheters had a distal diameter between 0.64 and 0.71 in; stent retriever was added when aspiration alone failed. Baseline characteristics, technical and clinical variables were collected, including NIHSS, thrombolysis in cerebral infarction (TICI), peri-procedural complications, 90-day mRS and 90-day mortality. RESULTS: Overall, 501 patients were treated. No statistically significant difference in terms of baseline features or tPA administration was recorded between patients treated with ADAPT and with additional stent retriever. ADAPT alone was successful in achieving TICI ≥ 2b in 71.8% with a median of 1.55 aspiration attempts. In terms of TICI ≥ 2b, ADAPT alone was better than additional stent retriever (p

Purpose: Intracranial carotid artery occlusion represents an underinvestigated cause of acute ischemic stroke as well as an indication for mechanical thrombectomy. We investigated baseline and procedural characteristics, outcomes and predictors of outcome in patients with acute ischemic stroke secondary to intracranial carotid artery occlusion. Methods: A retrospective analysis of the Italian Registry of Endovascular Treatment in Acute Stroke was performed. Patients with intracranial carotid artery occlusion (infraclinoid and supraclinoid) with or without cervical artery occlusion but with patent intracranial arteries were included. The 3‑month functional independence, mortality, successful reperfusion and symptomatic intracranial hemorrhage were evaluated. Results: Intracranial carotid artery occlusion with patent intracranial arteries was diagnosed in 387 out of 4940 (7.8%) patients. The median age was 74 years and median baseline National Institute of Health Stroke Scale (NIHSS) was 18. Functional independence was achieved in 130 (34%) patients, successful reperfusion in 289 (75%) and symptomatic intracranial hemorrhage in 33 (9%), whereas mortality occurred in 111 (29%) patients. In univariate analysis functional independence was associated with lower age, lower NIHSS at presentation, higher rate of successful reperfusion and lower rate of symptomatic intracranial hemorrhage. Multivariable regression analysis found age (odds ratio, OR:1.03; P = 0.006), NIHSS at presentation (OR: 1.07; P < 0.001), diabetes (OR: 2.60; P = 0.002), successful reperfusion (OR:0.20; P < 0.001) and symptomatic intracranial hemorrhage (OR: 4.17; P < 0.001) as the best independent predictors of outcome. Conclusion: Our study showed a not negligible rate of intracranial carotid artery occlusion with patent intracranial arteries, presenting mostly as severe stroke, with an acceptable rate of 3‑month functional independence. Age, NIHSS at presentation and successful reperfusion were the best independent predictors of outcome. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

Patient with surgically treated right temporo-occipito-parietal glioblastoma multiforme. Postoperative follow-up performed early (24 hours and 2 weeks) with MR morphologic sequences.

Giant intracranial aneurysms still represent a serious threat because of high mortality and morbidity and an absence of a widely accepted treatment. Herein, we illustrate the case of a 54-yr-old woman with progressive neurological decline who was found to have an unruptured, giant, partially thrombosed aneurysm of the left supraclinoid portion of internal carotid artery (ICA) with brainstem compression. In this video, we demonstrate the successful stepwise treatment of this lesion with endovascular embolization of the patent portion of the aneurysm, followed by microsurgical debulking and clipping. At 3-yr follow-up, the patient experienced a neurological improvement and performed all normal activity. For patients in which single-modality therapy does not assure a safe treatment option, multimodal management with endovascular and open techniques should be considered as a therapeutic option for complex giant intracranial aneurysms. Consent was given by the patient prior to the surgical procedure. Consent and approval for this operative video, in light of the retrospective nature and use of anonymized material, were waived.

// Alba A. Brandes 1 , Gaetano Finocchiaro 2 , Vittorina Zagonel 3 , Michele Reni 4 , Alessandra Fabi 5 , Claudia Caserta 6 , Alicia Tosoni 1 , Marica Eoli 2 , Giuseppe Lombardi 3 , Matteo Clavarezza 7 , Alexandro Paccapelo 1 , Stefania Bartolini 1 , Luigi Cirillo 8 , Raffaele Agati 8 and Enrico Franceschi 1 1 Department of Medical Oncology, Bellaria-Maggiore Hospitals, Azienda USL, IRCCS Institute of Neurological Sciences, Bologna, Italy 2 Molecular Neuro-Oncology Unit, IRCCS Foundation Carlo Besta, Milan, Italy 3 Department of Clinical and Experimental Oncology, Medical Oncology 1, Veneto Institute of Oncology, IRCCS, Padua, Italy 4 Department of Medical Oncology, IRCCS San Raffaele, Milan, Italy 5 Medical Oncology 1, Regina Elena National Cancer Institute, Rome, Italy 6 Oncology Department, Santa Maria Hospital, Terni, Italy 7 Medical Oncology Unit, Ente Ospedaliero Ospedali Galliera, Genova, Italy 8 Department of Neuroradiology, Bellaria Hospital, IRCCS Institute of Neurological Sciences, Bologna, Italy Correspondence to: Alba A. Brandes, email: // Keywords : glioblastoma, RANO, bevacizumab, fotemustine, ETS Received : January 21, 2017 Accepted : February 08, 2017 Published : February 25, 2017 Abstract BACKGROUND: Disease assessment for recurrent glioblastoma (GBM) represents a challenge, especially with the use of antiangiogenic agents. Moreover, validated neuroradiological predictors of outcome are lacking. Recently, the concept of early tumor shrinkage (ETS) has been developed to better assess the ability of treatments in determining a rapid and remarkable tumor response. The aim of the study was to evaluate the role of ETS in predicting survival of GBM patients treated with BEV METHODS: We examined the radiological data of patients with recurrent GBM treated with bevacizumab (BEV) or fotemustine (FTM) in the randomized phase II AVAREG trial (EudraCT: 2011-001363-46). Radiologic assessments at first disease assessment (day 46) were used to calculate the relative change in the sum of the products of perpendicular diameters of all measurable lesions determined by either T1 contrast and T2/FLAIR. RESULTS: In patients treated with BEV, the best ETS cut-off was reduction of 15% with T1 contrast and of 40% with T2/FLAIR. Adopting this cut-off for T1 contrast radiological changes, ETS was a significant predictor of OS for patients treated with BEV (HR = 0.511, 95%CI:0.269-0.971, p = 0.040). The cut-off obtained for T2/FLAIR was not significantly correlated with OS ( p = 0.102), but we found a trend for correlation with survival when considering the variable as continuous ( p = 0.058). CONCLUSIONS: ETS evaluating T1 contrast reduction is a helpful predictor of survival in patients with recurrent GBM treated with BEV, and if validated in a larger prospective trial could be a helpful surrogate endpoint.

Increasing evidence has demonstrated the bidirectional link between acute kidney injury (AKI) and chronic kidney disease (CKD) such that, in the clinical setting, the new concept of a unified syndrome has been proposed. The pathophysiological reasons, along with the cellular and molecular mechanisms, behind the ability of a single, acute, apparently self-limiting event to drive chronic kidney disease progression are yet to be explained. This acute injury could promote progression to chronic disease through different pathways involving the endothelium, the inflammatory response and the development of fibrosis. The interplay among endothelial cells, macrophages and other immune cells, pericytes and fibroblasts often converge in the tubular epithelial cells that play a central role. Recent evidence has strengthened this concept by demonstrating that injured tubules respond to acute tubular necrosis through two main mechanisms: The polyploidization of tubular cells and the proliferation of a small population of self-renewing renal progenitors. This alternative pathophysiological interpretation could better characterize functional recovery after AKI.