Search

ObjectiveTo clinically characterize patients with anti-metabotropic glutamate receptor (mGluR) 1 encephalitis, to identify prognostic factors, and to study the immunoglobulin G (IgG) subclasses and effects of antibodies on neuronal mGluR1 clusters.MethodsClinical information on new and previously reported patients was reviewed. Antibodies to mGluR1 and IgG subclasses were determined with brain immunohistochemistry and cell-based assays, and their effects on mGluR1 clusters were studied on rat hippocampal neurons.ResultsEleven new patients were identified (10 adults, 1 child);4 were female. In these and 19 previously reported cases (n = 30, median age 55 years), the main clinical manifestation was a subacute cerebellar syndrome that in 25 (86%) patients was associated with behavioral/cognitive changes or other neurologic symptoms. A tumor was found in 3 of 26 (11%). Brain MRI was abnormal in 7 of 19 (37%) at onset and showed cerebellar atrophy in 10 of 12 (83%) at follow-up. Twenty-five of 30 (83%) patients received immunotherapy. Follow-up was available for 25: 13 (52%) had clinical stabilization; 10 (40%) showed significant improvement; and 2 died. At the peak of the disease, patients with bad outcome at 2 years (modified Rankin Scale score > 2, n = 7) were more likely to have higher degree of initial disability, as reflected by a worse Scale for Assessment and Rating of Ataxia score, and more frequent need of assistance to walk. Antibodies to mGluR1 were mainly IgG1 and caused a significant decrease of mGluR1 clusters in cultured neurons.ConclusionsAnti-mGluR1 encephalitis manifests as a severe cerebellar syndrome, often resulting in long-term disability and cerebellar atrophy. The antibodies are pathogenic and cause significant decrease of mGluR1 clusters in cultured neurons.

Alagille syndrome (ALGS) is a multisystemic disease caused by mutations in genes of Notch pathway, which regulates embryonic cell differentiation and angiogenesis. Clinically, ALGS is characterized by cholestasis, cardiac defects, characteristic facial features, skeletal and ophthalmologic abnormalities. The aim of this review is to illustrate neuroradiological findings in ALGS, which are less well-known and prevalent, including cerebrovascular anomalies (such as aneurysms, dolichoectasia, Moyamoya syndrome and venous peculiarities), Chiari 1 malformation, craniosynostosis, intracranial hypertension, and vertebral anomalies (namely butterfly vertebra, hemivertebra, and craniocervical junction anomalies). Rarer cerebral midline malformations and temporal bone anomalies have also been described.

BACKGROUND AND PURPOSE This study was undertaken to assess the long-term outcome of patients with paraneoplastic and non paraneoplastic autoimmune cerebellar ataxia (ACA) using the Scale for the Assessment and Rating of Ataxia (SARA). METHODS Patients with subacute cerebellar ataxia admitted to our institution between September 2012 and April 2020 were prospectively recruited. Serum and/or cerebrospinal fluid was tested for neural autoantibodies by indirect immunofluorescence on mouse brain, cell-based assays, and radioimmunoassay. SARA and modified Rankin Scale (mRS) score were employed to assess patients' outcome. RESULTS Fifty-five patients were recruited, of whom 23 (42%) met the criteria for cerebellar ataxia of autoimmune etiology. Neural autoantibodies were detected in 22 of 23 patients (Yo-immunoglobulin G [IgG], n = 6; glutamic acid decarboxylase 65-IgG, n = 3; metabotropic glutamate receptor 1-IgG, n = 2; voltage-gated calcium channel P/Q type-IgG, n = 2; Hu-IgG, n = 1; glial fibrillary acidic protein-IgG, n = 1; IgG-binding unclassified antigens, n = 7). Thirteen patients were diagnosed with paraneoplastic cerebellar syndrome (PCS) and 10 with idiopathic ACA. All patients received immunotherapy. Median SARA score was higher in the PCS group at all time points (p = 0.0002), while it decreased significantly within the ACA group (p = 0.049) after immunotherapy. Patients with good outcome (mRS ≤ 2) had less neurological disability (SARA

Metallic cerclage cables are reliable and cost-effective internal fixation devices, which are largely used in surgical practice for the treatment of periprosthetic fractures. Nevertheless, complications connected with their use have been described in the literature, including the following: third-body generation, failure and consequent migration, fraying, allergies, and injury to the surgical team. The development of new materials offers alternatives to traditional metallic cables. This study compares the outcomes between two groups of patients affected by periprosthetic hip fractures, treated with titanium cables or with ultra-high-molecular-weight polyethylene (UHMWPe) iso-elastic cables. Our retrospective study aims to compare the clinical and radiological outcomes of titanium cables and UHMWPe iso-elastic cables, isolated or associated with dedicated plates, for the surgical treatment of periprosthetic fractures with stable implants. Two groups of 30 (group A—metallic cables) and 24 (group B—UHMWPe iso-elastic cables) patients have been surgically treated in our institution for hip periprosthetic fractures, between September 2017 and June 2020. The mean age of the patients was 81 years in group A and 80 years in group B. In our study, we included fractures classified as B1 or C, according to the Vancouver postoperative fractures classification; the patients were evaluated retrospectively at 1 year postoperatively, regarding the following: surgery time, blood loss, partial weight-bearing time, radiographical healing time, Harris hip score, and postoperative complications. Comparable outcomes were observed in patients from both groups. Group A showed a higher complication rate compared to group B, at 1 year postoperatively. Non-metallic nylon fiber and ultra-high-molecular-weight polyethylene (UHMWPe) cerclage cables could represent a reliable fixation device, ensuring comparable healing and complication rates with traditional titanium cerclage cables.

Sofosbuvir-velpatasvir-voxilaprevir is a pangenotypic regimen for chronic HCV infection. In the USA and Europe, sofosbuvir-velpatasvir-voxilaprevir once daily for 12 weeks is indicated for adults who previously received an HCV NS5A inhibitor. In Europe, sofosbuvir-velpatasvir-voxilaprevir is also indicated in the absence of prior HCV direct-acting antiviral (DAA) therapy as an 8-week or 12-week regimen. In an open-label study, we evaluated the safety, efficacy, and pharmacokinetics of sofosbuvir-velpatasvir-voxilaprevir in adolescents 12 to 17 years with chronic HCV of any genotype.In this Phase 2, multicenter study, sofosbuvir-velpatasvir-voxilaprevir 400/100/100 mg daily was administered to adolescents for 8 weeks if DAA-naïve or for 12 weeks for cirrhosis or prior DAA failure. The key efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Intensive pharmacokinetic sampling was done in 14 patients at week 2 or 4, and samples for population pharmacokinetics were collected in all patients.All patients (n = 21) were naïve to HCV DAAs, and none had cirrhosis. HCV genotype 3a infection was most common, occurring in 43% of patients. Overall, 100% of patients (21 of 21) reached SVR12. The most common adverse events were abdominal pain and headache (24% each) and nausea (19%); no adverse events led to discontinuation. The only serious adverse event, hypotension, was considered related to study drug and resolved the same day without interruption of treatment. Sofosbuvir-velpatasvir-voxilaprevir exposures were similar to those observed in adults.The pangenotypic regimen of sofosbuvir-velpatasvir-voxilaprevir is highly efficacious and well-tolerated in treating chronic HCV infection in adolescents.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory syndrome characterized by the predominant involvement of the pons, the cerebellum and the spinal cord with a distinct corticosteroid responsiveness. To date, several cases of neurological disorders with a CLIPPERS-like phenotype have been described, including patients with Immunoglobulin G (IgG) antibodies binding to myelin oligodendrocyte glycoprotein (MOG). We herein report the case of a man with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) fulfilling the diagnostic criteria for probable CLIPPERS and a literature review of CLIPPERS-mimicking patients with MOG-IgG.

Background and ObjectivesTo report a case of anti-NMDAR encephalitis presenting with isolated memory dysfunction.MethodsA 29-year-old woman was admitted to the Neurology Department referring memory impairment with a subacute onset. The initial assessment included EEG, neuropsychological tests, and brain MRI. Serum and CSF samples were collected for immunologic studies. The diagnostic evaluation was completed with a total body PET scan.ResultsPatient's neurologic examination was unremarkable apart from an episodic memory deficit, confirmed by neuropsychological examination. The EEG revealed epileptiform discharges in the temporal lobes, whereas brain MRI showed bilateral temporal lobes hyperintense lesions on fluid-attenuated inversion recovery images and T2-weighted images. NMDAR-IgG was detected in the patient's serum and CSF by cell-based assay confirming the diagnosis of definite anti-NMDAR encephalitis. The total body PET showed only a slight hypometabolism in the right temporal cortex and in the cerebellar hemispheres. After a course of IV immunoglobulin and corticosteroid therapy, a marked improvement of the memory deficit was observed.DiscussionThis case shows that anti-NMDAR encephalitis can present with isolated memory loss. Neural antibody testing in these patients could play a pivotal role in early diagnosis and prompt treatment.

Wilson's Disease (WD) is an autosomal recessive disorder caused by excessive copper deposition in liver, brain and other organs. The clinical picture is characterized by hepatic, psychiatric and neurological dysfunction. Movement disorders are the core neurological features, although non-motor symptoms (NMS), as cognitive/affective, autonomic and sleep disorders, may occur over time. We aimed to assess the frequency of NMS in WD patients compared with healthy subjects.Twenty-seven patients affected with genetically proven WD (12 F, 15 M) and 35 healthy controls (Ctrl; 17 F, 18 M), comparable for age and education, were enrolled. Eighteen patients presented with the neurological form of the disease (NV) and nine with the non-neurological variant (NNV). NMS were assessed in all subjects by the following clinical scales: Mini-Mental State Examination (MMSE), Non-Motor Symptoms Scale (NMSS), SCOPA-AUT Questionnaire, Apathy Evaluation Scale (AES), Beck Depression Inventory (BDI), Epworth Sleepiness Scale (ESS), Restless Legs Syndrome Rating Scale (RLSRS), REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ), Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease (QUIP-RS).We found that the patients showed more severe and frequent NMS and daytime sleepiness, and lower MMSE than Ctrl. In comparison to healthy subjects, NV subjects showed statistically significant higher ESS, NMSS, and RLSRS scores, and a lower MMSE score. Subtle and subclinical extrapyramidal/pyramidal signs and brain MRI signal abnormalities were detected in patients considered as asymptomatic for neurological disturbances.NMS are common among WD patient, in particular those with NV, likely due to the widespread pathological changes throughout the central nervous system.

Background: The impact of anterior cruciate ligament reconstruction (ACLR) on the performance and career of professional soccer players has not been extensively investigated. Purpose: To evaluate in professional European soccer players (1) the ACL injury incidence, (2) the return-to-play (RTP) rate and time after ACLR, (3) career survival and athlete performance in the first 3 postoperative seasons after RTP, (4) factors likely related to different outcomes after ACLR, and (5) any related differences between the top 8 European soccer leagues. Study Design: Descriptive epidemiology study. Methods: Included were professional soccer players in the top 8 European Soccer leagues (Serie A [Italy], Premier League [England], Ligue 1 [France], LaLiga [Spain], Bundesliga [Germany], Jupiler Pro League [Belgium], Liga NOS [Portugal], and Premier Liga [Russia]) who sustained an ACL injury during seasons 2014 to 2015, 2015 to 2016, and 2016 to 2017. Data were retrieved from publicly available online sources. Outcomes were evaluated based on player age (30 years), position (goalkeeper, defender, midfielder, and forward), affected side (dominant vs nondominant), and league. Results: Overall, 195 players sustained an ACL injury, for a mean annual ACL injury incidence of 1.42%. The RTP rate was 95%, with a mean RTP time of 248 ± 136 days. Within the third postoperative season, 66 players (36%) competed in a lower level national league, and 25 (13.6%) ended their careers; a significant reduction in the mean minutes played per season was found in all 3 postoperative seasons. Player age correlated significantly with reduction in performance or recovery from an ACL injury. No significant correlation was found between postoperative player performance and affected side, position, league, or time to RTP. Conclusion: A substantial ACL injury incidence was found in top European elite soccer players; however, a high RTP rate in a reasonable time was seen after ACLR. Nevertheless, professional soccer players experienced a short-term decline in their performance.

Autoantibodies against the extracellular domain of the N-methyl-d-aspartate receptor (NMDAR) NR1 subunit cause a severe and common form of encephalitis. To better understand their generation, we aimed to characterize and identify human germinal centres actively participating in NMDAR-specific autoimmunization by sampling patient blood, CSF, ovarian teratoma tissue and, directly from the putative site of human CNS lymphatic drainage, cervical lymph nodes. From serum, both NR1-IgA and NR1-IgM were detected more frequently in NMDAR-antibody encephalitis patients versus controls (both P

Neuromyelitis optica (NMO) is an autoimmune disorder of the central nervous system that preferentially affects the optic nerve and the spinal cord. In around 80% of NMO patients, autoantibodies binding to aquaporin-4 (AQP4) are detected. AQP4-IgG unifies a spectrum of disorders (NMOSD) that include not only optic neuritis, longitudinally extensive transverse myelitis but also syndromes caused by lesion of the diencephalic region and the circumventricular organs (CVOs). The distinctive immunopathological characteristics of NMOSD lesions, occurring in regions where AQP4 is highly expressed, supports a central role for AQP4-IgG in disease pathogenesis. AQP4 expression is concentrated in CVOs and in the hypothalamus, mainly in the dorsal hypothalamic area, dorsomedial hypothalamic nucleus and suprachiasmatic nucleus. Several neuroendocrine disorders caused by inflammatory lesions involving the diencephalic region have been described in patients with NMOSD, including syndrome of inappropriate antidiuresis, sleep disorders, and other endocrinopathies caused by hypothalamic injury. Focus of this chapter is the involvement of hypothalamus and CVOs in AQP4 autoimmunity.

Background and aim: Neurodegeneration with brain iron accumulation (NBIA) and Wilson’s disease (WD) is considered the prototype of neurodegenerative disorders characterised by the overloading of iron and copper in the central nervous system. Growing evidence has unveiled the involvement of these metals in brain cortical neurotransmission. Aim of this study was to assess cortical excitability profile due to copper and iron overload. Methods: Three patients affected by NBIA, namely two patients with a recessive hereditary parkinsonism (PARK9) and one patient with aceruloplasminemia and 7 patients with neurological WD underwent transcranial magnetic stimulation (TMS) protocols to assess cortical excitability. Specifically, we evaluated the motor thresholds that reflect membrane excitability related to the voltage-gated sodium channels in the neurons of the motor system and the ease of activation of motor cortex via glutamatergic networks, and ad hoc TMS protocols to probe inhibitory-GABAergic (short interval intracortical inhibition, SICI; short-latency afferent inhibition, SAI; cortical silent period, CSP) and excitatory intracortical circuitry (intracortical facilitation, ICF). Results: Patients with NBIA exhibited an abnormal prolongation of CSP respect to HC and WD patients. On the contrary, neurological WD displayed higher motor thresholds and reduced CSP and SICI. Conclusion: Hereditary conditions due to overload of copper and iron exhibited peculiar cortical excitability profiles that can help during differential diagnosis between these conditions. Moreover, such results can give us more clues about the role of metals in acquired neurodegenerative disorders, such as Parkinson disease, Alzheimer disease, and multiple sclerosis.

As the population ages, it is important to determine whether total knee arthroplasties (TKA)s are safe and beneficial in the octogenarian population. The aims of the present study were: (1) to assess the effect of comorbidities and age on the incidence of postoperative complications following TKA and (2) to evaluate the mid-term outcome of octogenarian patients. A retrospective matched-paired analysis by gender, BMI and duration of follow-up was conducted on 206 patients older than 80 years and younger than 75 years between 2009 and 2016, undergoing primary TKA. The mean follow-up was 5 years. Outcome measures including Oxford Knee Score (OKS), Knee Society Score (KSS), Knee Society Function Score (KSFS), postoperative complications, length of stay (LOS) and survivorship were analysed. The association between complications and comorbidities was assessed using multivariable logistic regression after adjusting for age, Deyo-Charlson Comorbidity Index (D-CCI) and the American Society of Anesthesiologist’s (ASA) physical status classification. In the multivariable models, D-CCI class is an independent predictor for postoperative cardiac complications, delirium and transfusion rate (OR ranging from 1.2 to 69.5 in respect to D-CCI reference class 0). Being ≥ 80 years old was associated with an increased risk of transfusion (OR 3.4; 95% CI 1.7–6.8) and 1.7-day increase in LOS (p

Autoimmune encephalitis associated with antibodies against neuronal surface targets (NSAE) are rare but still underrecognized conditions that affect adult and pediatric patients. Clinical guidelines have recently been published with the aim of providing diagnostic clues regardless of antibody status. These syndromes are potentially treatable but the choice of treatment and its timing, as well as differential diagnoses, long-term management, and clinical and paraclinical follow-up, remain major challenges. In the absence of evidence-based guidelines, management of these conditions is commonly based on single-center expertise. Taking into account different published expert recommendations in addition to the multicenter experience of the Italian Working Group on Autoimmune Encephalitis, both widely accepted and critical aspects of diagnosis, management and particularly of immunotherapy for NSAE have been reviewed and are discussed. Finally, we provide consensus-based practical advice for managing hospitalization and follow-up of patients with NSAE.

Ultrasound scan is a painless and radiation-free imaging modality and, therefore, it is widely considered the first-choice diagnostic tool in the setting of hepatopathies in paediatric patients. This article focuses on the normal ultrasound anatomy of the liver in neonatal and paediatric age and reviews the ultrasound appearance of the most common diffuse and focal liver affections.

Objective The purpose of this study was to determine from which side of the spine the popping sound (PS) emanates during side-lying, rotatory high-velocity low-amplitude (HVLA) thrust manipulation directed to the L5-S1 articulation using a time-frequency analysis. Secondary aims were to calculate the average number of PSs, the duration of lumbar thrust manipulation, and the duration of a single PS. Methods Thirty-four asymptomatic participants received 2 lumbar HVLA thrust manipulations targeting the right and left L5-S1 articulations. Two high sampling rate accelerometers were secured bilaterally 25 mm lateral to the midline of the L5-S1 interspace. For each manipulation, 2 audio signals were extracted and singularly processed via spectrogram calculation to obtain the release of energy over time on each side of the lumbosacral junction. Results During 60 HVLA thrust manipulations, it was measured a total of 320 PSs. Of those PSs, 176 occurred ipsilateral and 144 occurred contralateral to the targeted L5-S1 articulation; that is, the PS was no more likely to occur on the upside than the downside facet after right or left rotatory L5-S1 HVLA thrust manipulation. Moreover, PSs occurring on both sides at the same time were detected very rarely (ie, 2% of cases) with the lumbar HVLA thrust manipulations. The mean number of audible PSs per lumbosacral HVLA thrust manipulation was 5.27 (range 2-9). The mean duration of a single manipulation was 139.13 milliseconds (95% confidence interval: 5.61-493.79), and the mean duration of a single PS was 2.69 milliseconds (95% confidence interval: 0.95-4.59). Conclusion Based on our findings, spinal manipulative therapy practitioners should expect multiple PSs that most often occur on the upside or the downside facet articulations when performing HVLA thrust manipulation to the lumbosacral junction (ie, L5-S1). However, whether the multiple PSs found in this study emanated from the same joint or adjacent ipsilateral or contralateral facet joints remains unknown. A single model may not necessarily be able to explain all of the audible sounds during HVLA thrust manipulation.

In this retrospective multicenter study, we evaluated the safety of SARS-CoV-2 vaccination in patients harboring autoantibodies targeting neuronal surface and/or synaptic antigens.From eight Italian Neurology Units, we included patients with: a) serum and/or CSF positivity for specific neuronal autoantibodies; b) a compatible neurological syndrome; and c) available follow-up ≥6 weeks after vaccination with any of the approved SARS-CoV-2 vaccines. Demographics, clinical data, and information regarding previous SARS-CoV-2 infection and vaccination were collected. Disease relapses were considered "post-infectious" or "post-vaccination" when occurring within 6 weeks from infection/vaccination.We included 66 patients; 7/66 (11%) had a previous history of SARS-CoV-2 infection and 1/7 (14%) had post-infection relapses. BNT162b2-Pfizer-BioNTec was administered in 55 cases (83.3%) and mRNA-1273-Moderna in 11 (16.7%). The median number of doses administered per patient was 2 (1-3) and50% of patients did not experience side effects. Five patients (8%) had post-vaccination relapses (seizure 3/5); 4/5 improved after immunotherapy, while one did not receive immunotherapy and worsened. Patients with post-vaccination relapses had higher disability scores at vaccination (p = 0.025), a trend favoring Leucine-rich glioma-inactivated protein 1 LGI1 glutamic acid decarboxylase 65 (GAD65) antibodies (p = 0.054) and shorter time from last relapse (p = 0.057).Our data support the safety of SARS-CoV-2 vaccines in patients with neurological disorders associated with antibodies to neuronal and synaptic antigens.

Introduction: Up to 30% of patients with spinal cord injury and to 20% of patients with traumatic brain injury develop neurogenic heterotopic ossification (NHO). Patients develop restriction in joint range of motion (ROM) and impairment in activities of daily life. When neurological recovery occurs, joints dysfunction represents the cause for patients’ autonomy loss. Case Report: We present the case of a 39-year-old Caucasian male involved in a car accident and experienced 14 days of post-traumatic coma. After rehabilitation, no residual motor or sensory neurological deficit was present, but bilateral NHOs surrounding hip joints developed. Seventeen months after trauma, the patient was admitted to our institute. He was confined to bed, absolutely unable to walk, stand or sit. Radiological evaluation consisted in Antero-Posterior X-ray view only, due to the inability to open up his hips for lateral views, and 3D computed tomography scan. “Functional resection” of the ossifications was performed and rehabilitation started from day 1 after surgery. At the final follow-up 24 months from the second operation high grade of clinical satisfaction was reported. The patients were able to walk independently, to put on his socks, and to drive a car and bike. Painless right and left hip ROM was, respectively, 100° and 90° for flexion, 10° for extension, 35° and 30° for abduction, and near normal internal and external rotation. The patient referred that further improvement in mobility and fluency was still present day by day. Conclusion: The rarity of the condition frequently bring to a delay in treatment and the absence of specific guidelines made treatment still dependent on surgeon experiences. A multidisciplinary approach is essential for success. Surgeons should be aware that it is important to refer patients to specialized center, because early resection could provide excellent results, preserving hip, and restoring function and patient independency. Keywords: hip, ossifica

Background and Aims: Disease progression in children with primary sclerosing cholangitis (PSC) is variable. Prognostic and risk-stratification tools exist for adult-onset PSC, but not for children. We aimed to create a tool that accounts for the biochemical and phenotypic features and early disease stage of pediatric PSC. Approach and Results: We used retrospective data from the Pediatric PSC Consortium. The training cohort contained 1,012 patients from 40 centers. We generated a multivariate risk index (Sclerosing Cholangitis Outcomes in Pediatrics [SCOPE] index) that contained total bilirubin, albumin, platelet count, gamma glutamyltransferase, and cholangiography to predict a primary outcome of liver transplantation or death (TD) and a broader secondary outcome that included portal hypertensive, biliary, and cancer complications termed hepatobiliary complications (HBCs). The model stratified patients as low, medium, or high risk based on progression to TD at rates of

Tissue-based assay (TBA) is a widely-used method to detect neural autoantibodies, but the diagnostic accuracy for autoimmune encephalitis (AE) has not yet been adequately measured. We retrospectively evaluated the sensitivity and specificity of an indirect immunofluorescence TBA (IIF-TBA) in 159 patients with suspected AE. Serum and cerebrospinal fluid (CSF) specimens were collected and tested from December 2012 to September 2020. In the paired sample analysis, serum testing showed higher sensitivity than CSF, while the latter had higher specificity. Based on these results, we clarify the advantages of using a TBA as the principal screening method for patients with suspected AE.

Kasai portoenterostomy (KP) represents the first-line treatment for biliary atresia (BA). The purpose was to compare the accuracy of quantitative parameters extracted from laboratory tests, US imaging, and MR imaging studies using machine learning (ML) algorithms to predict the long-term medical outcome in native liver survivor BA patients after KP. Twenty-four patients were evaluated according to clinical and laboratory data at initial evaluation (median follow-up = 9.7 years) after KP as having ideal (n = 15) or non-ideal (n = 9) medical outcomes. Patients were re-evaluated after an additional 4 years and classified in group 1 (n = 12) as stable and group 2 (n = 12) as non-stable in the disease course. Laboratory and quantitative imaging parameters were merged to test ML algorithms. Total and direct bilirubin (TB and DB), as laboratory parameters, and US stiffness, as an imaging parameter, were the only statistically significant parameters between the groups. The best algorithm in terms of accuracy, sensitivity, specificity, and AUCROC was naive Bayes algorithm, selecting only laboratory parameters (TB and DB). This preliminary ML analysis confirms the fundamental role of TB and DB values in predicting the long-term medical outcome for BA patients after KP, even though their values may be within the normal range. Physicians should be alert when TB and DB values change slightly.

Background and aims The COVID‐19 pandemic represents a source of stress and potential burnout for many physicians. This single‐site survey aimed at assessing perceived stress and risk to develop burnout syndrome among physicians operating in COVID wards. Methods This longitudinal survey evaluated stress and burnout in 51 physicians operating in the COVID team of Gemelli Hospital, Italy. Participants were asked to complete the Maslach Burnout Inventory (MBI) and the Perceived Stress Questionnaire on a short run (PSQs) (referring to the past 7 days) at baseline (T0) and then for four weeks (T1‐T4). Perceived Stress Questionnaire on a long run (PSQl) (referring to the past 2 years) was completed only at T0. Results Compared with physicians board‐certified in internal medicine, those board‐certified in other disciplines showed higher scores for the Emotional Exhaustion (EE) score of the MBI scale (P

Neuromyelitis optica (NMO) is an autoimmune disorder of the central nervous system that preferentially affects the optic nerve and the spinal cord. In around 80% of NMO patients, autoantibodies binding to aquaporin-4 (AQP4) are detected. AQP4-IgG unifies a spectrum of disorders (NMOSD) that include not only optic neuritis, longitudinally extensive transverse myelitis but also syndromes caused by lesion of the diencephalic region and the circumventricular organs (CVOs). The distinctive immunopathological characteristics of NMOSD lesions, occurring in regions where AQP4 is highly expressed, supports a central role for AQP4-IgG in disease pathogenesis. AQP4 expression is concentrated in CVOs and in the hypothalamus, mainly in the dorsal hypothalamic area, dorsomedial hypothalamic nucleus and suprachiasmatic nucleus. Several neuroendocrine disorders caused by inflammatory lesions involving the diencephalic region have been described in patients with NMOSD, including syndrome of inappropriate antidiuresis, sleep disorders, and other endocrinopathies caused by hypothalamic injury. Focus of this chapter is the involvement of hypothalamus and CVOs in AQP4 autoimmunity.

Wilson's disease (WD) is a disorder of copper metabolism that can cause hormonal alterations. The impact of WD and its therapies on fertility is not well defined. The aim of this study was to evaluate ovarian reserve and sperm parameters in long-term treated WD patients with hepatic onset.WD patients with hepatic onset treated for at least 5 years were compared with healthy controls. Men underwent spermiogram and sperm DNA fragmentation (SDF) analysis. Women were tested for serum FSH, anti-Müllerian hormone (AMH) and sonographic antral follicle count (AFC) in the early follicular phase. Ovulation was monitored with ultrasound and progesterone serum concentrations in the luteal phase.The WD group included 26 patients (12 males), the control group 19 subjects (9 males). All patients apart from four (one male) were responders to WD treatment. Sperm count and morphology were comparable between cases and controls. Sperm motility (total and after 1 h) was significantly lower in cases (44.78 ± 21.65%; 47.85 ± 21.52%) than controls (61.88 ± 11.03; 69.44 ± 11.02%, P = 0.03 and 0.01, respectively). The only non-responder had severe oligo-astheno-teratozoospermia. SDF values were normal in cases and controls. AMH, AFC and FSH did not differ between cases and controls. LH was significantly lower in cases (3.36 ± 1.65 mIU/ml) than controls (6.25 ± 1.03 mIU/ml, P 0.0001). A non-responder woman who developed neurological signs had a 7-year history of infertility.WD patients with hepatic onset, diagnosed early and treated, have no impairment in fertility potential even if males show reduced sperm motility and females lower LH values. Only patients with poor disease control have some evidence of impaired fertility.

Background Two methods for detecting synovial fluids alpha defensins are available: the enzyme-linked immunosorbent assay and the lateral flow test. For both, the proper role and accuracy remain uncertain. The purpose of this study was to assess the accuracy of the matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) for alpha defensin detection in synovial fluids of patients with total knee arthroplasty/total hip arthroplasty failures. The hypothesis was that the alpha defensin measurement through MALDI-TOF MS assay could be a high sensitive and specific test for periprosthetic joint infections (PJI) diagnosis as compared with Musculoskeletal Infection Society (MSIS) criteria. Methods The study included 138 patients. The 2018 MSIS criteria were used to diagnose PJIs. Synovial fluids were assessed for routinely synovial fluid tests and alpha defensin measurement through MALDI-TOF MS. Sensitivity, specificity, overall diagnostic accuracy, positive and negative predictive values, receiver operator curves, and area under the curve were calculated. Results As per the 2018 MSIS criteria, 59 PJIs (43%) and 79 aseptic failures (57%) were diagnosed. The MALDI-TOF MS assay showed an overall accuracy of 94.9%. The sensitivity was 93%, the specificity was 96%, the positive predictive value was 95%, and the negative predictive value was 95%. Receiver operator curves analysis demonstrates an area under the curve of 0.95 (P Conclusion The MALDI-TOF MS assay showed high sensitivity and specificity for alpha defensin detection in case of total knee arthroplasty/total hip arthroplasty failures. The advantages of the technology, such as the few milliliters of sample needed, the rapidity of obtaining results, and the cost-effectiveness of the procedure could make the MALDI-TOF MS alpha defensin assay a useful and widespread test in clinical practice.

In biliary atresia, infants left untreated, and in those with unsuccessful porto-enterostomy, hepatic condition and function worsen rapidly towards cirrhosis, malnutrition, portal hypertension with ascites, and variceal haemorrhage; many die within the first 3 years of life unless they benefit from liver replacement. We describe a girl with biliary atresia splenic malformation syndrome, who had portal vein cavernoma and microsplenia; she did not undergo porto-enterostomy. She survived with her native liver over the age of 3 years. Remarkably, she remained in satisfactory condition in absence of ascites or severe hepatic dysfunction, when 4 other similar patients-managed during the same period of time-all had the usual clinical deterioration and ascites, with the need for liver replacement. To our knowledge, there is no similar report in literature. Possible pathogenetic mechanisms and the role of portal hypertension as important factors are discussed.

Anti-acetylcholine receptor antibodies (AChR Abs) are detected in 85% of myasthenia gravis (MG) patients, at higher rates in patients with late-onset disease. AChR Ab frequency is generally thought to be much lower in ocular MG (OMG), although recent studies reported positivity rates higher than 70%. We hypothesized that the improved AChR Ab diagnostic yield in OMG could be related to an increased frequency of late-onset disease, as observed in generalized MG. We compared OMG patients, with disease onset before or after 1998, for the age of onset, sex, presence of thymoma, immunosuppressive therapy rate, AChR Ab positivity, and follow-up duration. All patients had a follow-up ≥ 2 years. AChR Abs were tested by radioimmunoassay. The study included 133 patients. Disease onset occurred before 1998 in 54/133 cases (41%). Age of onset, the proportion of late-onset patients, and AChR Ab positivity rate were significantly increased in the more recent population. Thymoma frequency was similar in the two series. On multivariate analysis, the only variable predicting AChR Ab positivity was the age at onset ≥ 50 years (OR = 6.50, 95% CI = 2.70–15.63, p

Binding proteins (G-proteins) mediate signalling pathways involved in diverse cellular functions and comprise Gα and Gβγ units. Human diseases have been reported for all five Gβ proteins. AWe discovered aWe identified 12 unrelated individuals with fiveMissense variants in

Gentamicin-impregnated cement beads and spacers are frequently used in case of infective complications after Total Knee Arthroplasty (TKA). A great number of studies in the literature demonstrated that the local administration of gentamicin produces high local antibiotic levels but low serum and urine gentamicin concentrations. Gentamicin-impregnated cement spacer can induce nephrotoxicity in patients presenting major renal impairment susceptibility. We report a case of acute renal failure using a gentamicin-impregnated block spacer. An 83-year-old woman underwent a gentamicinimpregnated bone–cement spacer implant because of an infected TKA removal. Three days later patient clinical status got worse reporting a decreased urine output and increasing C-reactive protein (CRP), Serum Creatinine (SCr) and Blood Urea Nitrogen (BUN). Because the symptoms could be related to the knee spacer lead us to the decision of gentamicin-impregnated cement spacer removal. The day following the removal procedure showed progressive improvement of general condition with evidence of SCr and BUN normalization. Gentamicin-impregnated cement spacer can induce nephrotoxicity in patients presenting major renal impairment susceptibility.

Advantages of minimally invasive approaches for total hip arthroplasty are still matter of debate. Serum markers have been assessed as objective method to quantify muscle damage after surgery but in literature ambiguous results have been reported. The aim of this prospective randomized study was to: 1) compare serum markers elevation between a minimally invasive direct anterior approach (DAA) and a direct lateral approach (DLA); 2) to establish a correlation between serum markers increase and other perioperative variables.A lesser elevation of markers could be found in patients who underwent a minimally invasive DAA.Seventy patients were enrolled and randomly divided in two groups according to the type of the approach. All patients were treated with the same implant by the same surgeon and received the same rehabilitation protocol. Demographic data, preoperative Harris Hip Score (HHS) and operative time were recorded. Myoglobin, creatine kinase MB (CK-MB), troponin I, C-reactive protein (CRP), haemoglobin (HB) and pain levels were measured pre- and postoperatively.Mean postoperative rise were 524.9±134.6 and 667.8±409.5 for myoglobin, 4.8±2.5 and 6.6±3.7 for CK-MB, and 16.9±5.3 and 15.4±6.4 for PCR, in DAA and DLA groups, respectively. In both groups, postoperatively values were significantly higher than preoperatively (p0.05). Comparing the two groups, no significant differences in serum markers elevations were found. A significantly lower postoperative pain was found in DAA group than in DLA group (2.9 vs. 4.2 and 2.7 vs. 3.6 in second and third day, respectively (p0.05)). No significant correlation was present between the serum marker elevations and age, BMI, HHS, operative time, HB or pain levels (p0.05).Serum markers of muscle damage and inflammation increased in the postoperative period without significant differences between DAA and DLA, even though overall trend was higher in DLA group. The DAA group had significantly lower levels of postoperative pain. No significant correlation between pain and serum markers levels was found.I; randomized study.

H1069Q substitution represents the most frequent mutation of the copper transporter ATP7B causing Wilson disease in Caucasian population. ATP7B localizes to the Golgi complex in hepatocytes but moves in response to copper overload to the endo-lysosomal compartment to support copper excretion via bile canaliculi. In heterologous or hepatoma-derived cell lines, overexpressed ATP7B-H1069Q is strongly retained in the ER and fails to move to the post-Golgi sites, resulting in toxic copper accumulation. However, this pathogenic mechanism has never been tested in patients' hepatocytes, while animal models recapitulating this form of WD are still lacking. To reach this goal, we have reprogrammed skin fibroblasts of homozygous ATP7B-H1069Q patients into induced pluripotent stem cells and differentiated them into hepatocyte-like cells. Surprisingly, in HLCs we found one third of ATP7B-H1069Q localized in the Golgi complex and able to move to the endo-lysosomal compartment upon copper stimulation. However, despite normal mRNA levels, the expression of the mutant protein was only 20% compared to the control because of endoplasmic reticulum-associated degradation. These results pinpoint rapid degradation as the major cause for loss of ATP7B function in H1069Q patients, and thus as the primary target for designing therapeutic strategies to rescue ATP7B-H1069Q function.

Purpose To investigate the relationship between the Segond fracture and the anterolateral complex of the knee. Methods Between January 2014 and March 2020, patients who presented with an anterior cruciate ligament (ACL) tear requiring acute surgical reconstruction (within 10 days from trauma) were evaluated for inclusion in this study. Patients were included if they had an acute ACL tear with an associated Segond fracture (or “Segond lesion”) as detected by radiograph or magnetic resonance imaging. The lateral compartment was exposed in all cases using a 5-cm lateral hockey-stick incision, which was carried down to the iliotibial band. The fascia lata was first inspected and then longitudinally divided along its fibers to expose lateral compartment. The posterolateral corner to Gerdy’s tubercle anteriorly was exposed and examined. Once the Segond fracture was identified, it was recorded and photographed. Results Seventeen patients were enrolled in the study. Dissection of the Segond fracture demonstrated attachment to the anterolateral capsule only. No other discernible attachment to the Segond fracture was noted. Surgical exploration of the anterolateral knee did not reveal injury to the iliotibial band. Conclusions Careful dissection of Segond fractures during repair revealed that there is a discernible attachment with the anterolateral capsule to the bone injury in all patients with acute ACL tears undergoing surgical reconstruction and no connections to the iliotibial band. Clinical Relevance The precise pathogenesis of Segond fractures has been the subject of debate, partially due to the complexity of the anatomy of the anterolateral aspect of the knee. Proper understanding of the anatomy of type IV ALL injures with Segond fractures is important to improve treatment of these injuries.

Suprascapular neuropathy is more frequent in volleyball as compared to other overhead sports. This study aims to report the actual prevalence of suprascapular neuropathy among elite volleyball play...

Background Biliary atresia (BA) is a rare obliterative cholangiopathy and Kasai portoenterostomy (KP) represents its first-line treatment; clinical and laboratory parameters together with abdominal ultrasound (US) are usually performed during the follow-up. Shear-wave elastography (SWE) is able to evaluate liver parenchyma stiffness; magnetic resonance imaging (MRI) has also been proposed to study these patients. Purpose To correlate US, SWE, and MRI imaging findings with medical outcome in patients with BA who are native liver survivors after KP. Material and Methods We retrospectively enrolled 24 patients. They were divided in two groups based on “ideal” (n = 15) or “non-ideal” (n = 9) medical outcome. US, SWE, and MRI exams were analyzed qualitatively and quantitatively for imaging signs suggestive of chronic liver disease (CLD). Results Significant differences were found in terms of liver surface ( P = 0.007) and morphology ( P = 0.013), portal vein diameter ( P = 0.012) and spleen size ( P = 0.002) by US, liver signal intensity ( P = 0.013), portal vein diameter ( P = 0.010), presence of portosystemic collaterals ( P = 0.042), and spleen size ( P = 0.001) by MRI. The evaluation of portal vein diameter (moderate, κ = 0.44), of portosystemic collaterals (good, κ = 0.78), and spleen size (very good, κ = 0.92) showed the best agreement between US and MRI. A significant ( P = 0.01) difference in liver parenchyma stiffness by SWE was also found between the two groups (cut-off = 9.6 kPa, sensitivity = 55.6%, specificity = 100%, area under the ROC curve = 0.82). Conclusion US, SWE, and MRI findings correlate with the medical outcome in native liver survivor patients with BA treated with KP.

Rationale Detection of α-defensins in synovial fluid is gaining more and more interest in the field of correct diagnosis of periprosthetic joint infections (PJIs). At present, they can be assessed by a quantitative enzyme-linked immunosorbent assay which is expensive and time-consuming and by a qualitative lateral flow immunoassay which is rapid but quite expensive and whose clinical sensitivity is debated. Thus, developing an alternative rapid, accurate, and low-cost assay for α-defensins is important to make α-defensins actionable as novel key clinical markers. Methods Synovial fluid (SF) samples were obtained from 18 patients undergoing revision of primary joint arthroplasty. Of these, eight met the 2013 Musculoskeletal Infection Society (MSIS) criteria for PJIs, the remaining were classified as aseptic failure. Microbiological analysis and Synovasure assays were carried out on all samples. Sample preparation and the matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) settings were adjusted to detect human neutrophil peptide (HNP)-1, -2 and -3 and to obtain optimal results in term of sensitivity and stability. Results MALDI-TOF MS was able to detect HNPs in SF from septic patients. No signals for HNPs were detected in SF from aseptic failure. The limits of detection (LOD) were 2.5 and 1.25 μg/mL for HNP-2 and HNP-1, respectively. The turnaround time of the analysis is 20 min, and SF samples are stable at -20°C for up to 3 days. Assay sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were 100% for all parameters. On the same SF samples, the Synovasure assay showed lower sensitivity specificity, and PPV and NPV of 87.5%, 90%, 87.5% and 90%, respectively. Microbiological analysis of SF confirmed the presence of bacteria only in SF MSIS-positive patients. Conclusions The reported MALDI-TOF MS assay was able to detect and differentiate HNPs in SF samples and showed a slightly better diagnostic accuracy than the Synovasure assay.

Most reports of post-transplant erythrocytosis have involved kidney recipients and, so far, there have been no large studies of onset of erythrocytosis after orthotopic liver transplantation (OLT) in children. We present a long-term survey of pediatric liver recipients, evaluating prevalence, outcome and the main potential causes of erythrocytosis, including a comprehensive mutational analysis of commonly related genes (mutations of HBB and HBA, JAK2, EPOR, VHL, EPAS1 and EGLN1). Between 2000 and 2015, 90 pediatric OLT recipients were observed for a median period of 8.7 years (range 1–20.4 [IQR 4.9–13.6] years). Five percent of the study population (4 males and 1 female) developed erythrocytosis at 8.5 years post OLT (range 4.1–14.9 [IQR 4.7–14.7]) at a median age of 16.6 years (range 8.2–18.8 [IQR 11.7–17.7]). Erythrocytosis-free survival after OLT was 98.6% at 5 years, 95% at 10 years, and 85% at 15 years, with an incidence rate of 6/1000 person-years. No cardiovascular events or thrombosis were reported. No germinal mutation could be clearly related to the development of erythrocytosis. One patient, with high erythropoietin levels and acquired multiple bilateral renal cysts, developed clinical hyper-viscosity symptoms, and was treated with serial phlebotomies. In conclusion, this prospective longitudinal study showed that erythrocytosis is a rare complication occurring several years after OLT, typically during adolescence. Erythrocytosis was non-progressive and manageable. Its pathogenesis is still not completely understood, although male gender, pubertal age, and renal cysts probably play a role.

The aim of this prospective study was to perform a clinical and radiologic evaluation of patients undergoing total hip arthroplasty (THA). The hypothesis is that there is a correlation between the pre-operative degeneration state of the gluteal muscle-tendinous unit and the clinical outcome in terms of functional recovery. Fifty-five patients have met inclusion criteria. All patients included in the sample were subjected to clinical evaluation. The ultrasound examination of the patients of the study was conducted and the following parameters were assessed: Thickness in mm of the gluteus medius tendon; Quality of the gluteus medius tendon; and Trophy and muscular composition. The degree of degeneration of the pre-operative tendon shows a negative statistical correlation with all the pre- and post-operative clinical scales, but presents statistical significance (p