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Purpose SARS-CoV-2 is an RNA virus responsible for COVID-19 pandemic. Some authors described the set of persistent symptoms COVID-related as "Long-COVID Syndrome." Several cases of post-COVID-19 osteonecrosis (ON) are described. Our primary aim was to study the hypothetical correlation between SARS-CoV-2 infection and ON; our secondary aim was to understand if ON can be considered part of Long-COVID. Materials and methods We performed a systematic review following the Preferred Reporting Items for Systematic Reviewers and Meta-analysis (PRISMA) guidelines. Because COVID-19 is a recently described disease, we included all levels of evidence studies. We excluded studies lacking specification regarding the use of corticosteroids (CCS) and studies not related to COVID-19. The variables extracted were age, sex, risk factors, affected joints, signs and symptoms, magnetic resonance imaging (MRI) and X-ray features, histology, treatment of COVID-19, dose and duration of treatment with CCS, treatment of ON, follow-up, and treatment outcome. Results A total of 13 studies were included, involving 95 patients and 159 joints. Time between the diagnosis of COVID-19 and the onset of symptoms related to ON was 16 weeks on average. Time between the onset of symptoms and the MRI was 6 weeks. An average of 926.4 mg of prednisolone equivalent per patient were administered. On average, CCS were administered for 20.6 days. Conclusions Patients with a history of COVID-19 infection developed osteonecrosis prematurely and with a lower dose of CCS than usually reported in the literature. Symptoms of osteonecrosis occur within the interval of the period described as Long-COVID. Surgeons should not underestimate the persistence of arthralgia when a history of SARS-CoV-2 infection and use of CCS is reported., (© 2024. The Author(s), under exclusive licence to Istituto Ortopedico Rizzoli.)

Chronic kidney disease (CKD) represents a significant global health challenge, characterized by kidney damage and decreased function. Its prevalence has steadily increased, necessitating a comprehensive understanding of its epidemiology, risk factors, and management strategies. While traditional prognostic markers such as estimated glomerular filtration rate (eGFR) and albuminuria provide valuable insights, they may not fully capture the complexity of CKD progression and associated cardiovascular (CV) risks.This paper reviews the current state of renal and CV risk prediction in CKD, highlighting the limitations of traditional models and the potential for integrating artificial intelligence (AI) techniques. AI, particularly machine learning (ML) and deep learning (DL), offers a promising avenue for enhancing risk prediction by analyzing vast and diverse patient data, including genetic markers, biomarkers, and imaging. By identifying intricate patterns and relationships within datasets, AI algorithms can generate more comprehensive risk profiles, enabling personalized and nuanced risk assessments.Despite its potential, the integration of AI into clinical practice faces challenges such as the opacity of some algorithms and concerns regarding data quality, privacy, and bias. Efforts towards explainable AI (XAI) and rigorous data governance are essential to ensure transparency, interpretability, and trustworthiness in AI-driven predictions., (© 2024. The Author(s).)

Purpose: Interest in bilateral total hip arthroplasty (THA) has been increasing over the past decade. This study aims to compare postoperative local and systemic complications, hospital readmissions, and satisfaction assessment in patients undergoing simultaneous versus staged bilateral THA., Methods: A retrospective observational study was conducted among patients who underwent simultaneous or staged bilateral THA between 2017 and 2020. Data on perioperative parameters, local and systemic complications, and 30-day hospital readmissions were collected. Patient satisfaction was assessed using Forgotten Joint Score (FJS). The comparison of continuous variables with normal distribution of variance was performed by ANOVA; for variables with abnormal distribution, the nonparametric test Mann-Whitney U was adopted. The distribution of dichotomous variables was analyzed by chi-square test, and statistical significance was calculated by Fisher exact test., Results: The study included 199 patients, of whom 156 underwent staged and 43 simultaneous bilateral THA. A total of 44 patients developed complications (21 systemics, 12 locals, and 20 postoperative anemia). There were no significant differences regarding local (simultaneous 5% vs. staged 6%; p = 0.999) or systemic complications (simultaneous 14% vs. staged 10%; p = 0.408). Only the incidence of postoperative anemia was significantly higher in simultaneous group compared with staged group (p = 0.003). There were no significant differences in FJS between the two groups (p = 0.258)., Conclusion: No differences in local or systemic complications nor readmission rates were observed following simultaneous or staged bilateral THA. Simultaneous bilateral THA is non-inferior to staged implants in terms of safety and patient satisfaction., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Chronic low back pain (LBP) represents a leading cause of absenteeism from work. An accurate knowledge of complex interactions is essential in understanding the difficulties of return to work (RTW) experienced by workers affected by chronic LBP. This study aims to identify factors related to chronic LBP, the worker, and the psycho-social environment that could predict and influence the duration of an episode of sick leave due to chronic LBP.Studies reporting the relation between prognostic factors and absenteeism from work in patients with LBP were included. The selected studies were grouped by prognostic factors. The results were measured in absolute terms, relative terms, survival curve, or duration of sick leave. The level of evidence was defined by examining the quality and the appropriateness of findings across studies in terms of significance and direction of relationship for each prognostic factor.A total of 20 studies were included. Prognostic factors were classified in clinical, psycho-social, and social workplace, reaching a total of 31 constructs. Global conditions with less favorable repercussions on worker's lives resulted in a delay in time to RTW. Older age, female, higher pain or disability, depression, higher physical work demands, and abuse of smoke and alcohol have shown strong level of evidence for negative outcomes.High global health well-being, great socioeconomic status, and good mental health conditions are decisive in RTW outcomes. Interventions that aim at RTW of employee's sick-listed with LBP should focus on psycho-social aspects, health behaviors, and workplace characteristics., (© 2024. The Author(s).)

PGAP2 gene has been known to be the cause of "hyperphosphatasia, mental retardation syndrome-3" (HPMRS3). To date, 14 pathogenic variants in PGAP2 have been identified as the cause of this syndrome in 24 patients described in single-case reports or small clinical series with pan-ethnic distribution. We aim to present a pediatric PGAP2 -mutated case, intending to further expand the clinical phenotype of the syndrome and to report our experience on a therapeutic approach to drug-resistant epilepsy.We present the clinical, neuroradiological, and genetic characterization of a Caucasian pediatric subject with biallelic pathogenic variants in the PGAP2 gene revealed by next generation sequencing analysis.We identified a subject who presented with global developmental delay and visual impairment. Brain magnetic resonance imaging showed mild hypoplasia of the inferior cerebellar vermis and corpus callosum and mild white matter reduction. Laboratory investigations detected an increase in alkaline phosphatase. At the age of 13 months, he began to present epileptic focal seizures with impaired awareness, which did not respond to various antiseizure medications. Electroencephalogram (EEG) showed progressive background activity disorganization and multifocal epileptic abnormalities. Treatment with high-dose pyridoxine showed partial benefit, but the persistence of seizures and the lack of EEG amelioration prompted us to introduce ketogenic diet treatment.Our case provides a further phenotypical expansion of HPMRS3 to include developmental and epileptic encephalopathy. Due to the limited number of patients reported so far, the full delineation of the clinical spectrum of HPMRS3 and indications for precision medicine would benefit from the description of new cases and their follow-up evaluations., Competing Interests: None declared., (Thieme. All rights reserved.)

Purpose: The exponential increase in total hip arthroplasty (THA) has led to acute and chronic surgery-related complications. Common chronic and local complications are represented by hip ossification (HO). The aim of our study was to assess the clinical and radiological correlates of patients undergoing surgical removal of heterotopic ossifications after THA and the possible association between HO and prosthetic joint infection., Methods: Data of 26 patients who underwent surgical removal of periprosthetic calcifications after THA from 2000 to 2022 were analyzed and compared with characteristics of 156 subjects without HO., Results: The preoperative radiographs of patients showed a high-grade Brooker, 3 or 4, later reduced to 1 or 2 in the postoperative radiographs. Ten (38.5%) patients underwent radiotherapy prophylaxis, administered as a single dose 24 h before surgery. In 19 (73%) patients, pharmacological prophylaxis with indomethacin was added in the 30 postoperative days. Only one patient who underwent radiotherapy had a recurrence, while new ossifications were found in three patients without prophylaxis (11.5%). Intraoperative cultures were performed for suspected periprosthetic infection in 8 study group patients. In logistic regression, the presence of HO was significantly and inversely associated with the ASA score (OR = 0.27, 95% CI = 0.09-0.82; P = 0.021) after adjusting., Conclusion: Surgical HO removal in symptomatic patients with high-grade disease produces good clinical and radiographic results. Radiotherapy was a good perioperative and preventive strategy for recurrence, also associated with NSAIDs and COX-2 inhibitors., (© 2023. The Author(s) under exclusive licence to SICOT aisbl.)

The etiology of post-arthroscopic osteonecrosis of the knee (PAONK) is still unknown. The aims of this systematic review were to analyze the main characteristics of patients who developed osteonecrosis after arthroscopy. We considered for inclusion in the review case reports, case series, retrospective and prospective clinical trial, that involved patients who developed osteonecrosis of the knee within 1 year of arthroscopy for meniscal lesion or anterior cruciate ligament rupture with or without chondropathy. In all cases, there was a pre-operative magnetic resonance imaging that excluded the presence of osteonecrosis. We used the MINORS criteria to estimate the risk of bias. A total of 13 studies that involved 125 patients were included in the review. Only 14 out of 55 patients performed the pre-operative MRI after the "window period", which we considered 6 weeks between the onset of symptoms and positive MRI findings. A diagnosis of PAONK was made for 55 patients within 1 year of surgery. Of these, 29% was treated conservatively, while 71% repeated surgery. Osteonecrosis after knee arthroscopy is a reality and surgeon shouldn't underestimate the persistence or re-emergence of symptoms after arthroscopy. It may be due to subchondral insufficiency fractures in osteopenic bone, without evidence of necrosis. However, there are not elements enough to differentiate clinical and radiological characteristics of PAONK from SPONK. Terminology should be simplified, distinguishing subchondral insufficiency fractures of the knee as a precursor of primary osteonecrosis of the knee., (© 2023. The Author(s), under exclusive licence to Istituto Ortopedico Rizzoli.)

Background: Arthroscopic partial meniscectomy (APM) is widely applied for the treatment of degenerative meniscal lesions in middle-aged patients; however, such injury is often associated with mild or moderate osteoarthritis and has been reported by MRI in asymptomatic knees. Previous studies suggested, in most patients, a lack of benefit of surgical approach over conservative treatment, yet many controversies remain in clinical practice. Our aims were to assess the functional and pain scores between exercise therapy and arthroscopic surgery for degenerative meniscal lesions and to evaluate the methodological quality of the most recent systematic reviews (SRs)., Methods: Two authors independently searched PubMed and Google Scholar for SRs comparing the outcome (in knee pain and functionality) of arthroscopic treatment and exercise therapy or placebo for degenerative meniscal lesions. The timeframe set was from 2009 to 2019 included., Results: A total of 13 SRs were selected. Two reviewers independently assessed the methodological quality of each paper using the AMSTAR 2 tool: seven scored as "moderate," four obtained a "low" grade while the remaining two were evaluated as "critically low." SRs agreed that in middle-aged patients with degenerative meniscal lesions arthroscopic surgery appears to grant no long-term improvement in pain and function over exercise therapy or placebo., Conclusions: Conservative treatment based on physical therapy should be the first-line management. However, most SRs revealed subgroups of patients that fail to improve after conservative treatment and find relief when undergoing surgery. In the future, randomized controlled trials, evidence should be looked for that APM can be successful in case of the unsatisfactory results after physical therapy., (© 2022. The Author(s).)

Background: The appropriate surgical treatment option for young and active patients undergoing shoulder arthroplasty for arthritis remains questionable. Pyrolitic carbon (pyrocarbon) has been shown to improve implant longevity and decrease wear when in contact with cartilage or bone. The present systematic review aimed to evaluate clinical and radiological outcomes as well as the survivorship of pyrocarbon shoulder implants., Methods: The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. A systematic search was performed using the MEDLINE, EMBASE and Cochrane Library databases. All the studies dealing with the use of pyrolitic shoulder implants were pooled, data of interest were extracted and statistically analyzed through meta-analysis., Results: A total of 9 studies were included for a total of 477 shoulders treated. The overall mean rate of survival of the implants was 93.4 ± 5.8% and 80% ± 26.5% at 2 years and final follow up, respectively, while resulting 82.4% ± 22.1% and 92.3% ± 3.5% for PISA (pyrocarbon interposition shoulder arthroplasty) and hemi-arthroplasty/hemi-resurfacing, respectively., Conclusions: Pyrolitic carbon shoulder implants showed good survivorship and clinical outcomes at an early to early-midterm follow-up. More studies and better-designed trials are needed in order to enrich the evidence on long-term outcomes and comparison with other shoulder replacement options for young and active patients., Level of Evidence: IV., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

SARS-CoV-2 very often causes kidney involvement through various mechanisms including: acute tubular injury, virus cell invasion, vascular damage due to hypercoagulability and finally dysregulation of the immune system. Even though there are no pathognomonic morphologic features that can rule out or confirm direct damage by SARS-CoV-2, the latest literature suggests that there may be some association. SARS-CoV-2 infection represents a poor prognostic factor, regardless of pulmonary involvement. We report a challenging case with complex renal biopsy findings suggestive of collapsing glomerulopathy and focal proliferative IgA-dominant glomerulonephritis in a patient affected by active hepatitis C virus (HCV), SARS-CoV-2 infection and personal history of cocaine abuse., (© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.)

The primary aim of this systematic review is to evaluate how postural balance and visual system are related in cross-eyed patients. The secondary goal is to assess the benefits of eye realignment on motor skills and body balance. Analyzing two different approaches: surgical or conservative, a systematic literature search was conducted using PubMed-Medline, Google Scholar and Cochrane Central in order to identify randomized controlled trials, case series and case-control studies which contained clinical evaluation of balance in strabismic patients as well as re-evaluation after surgery or conservative treatments via posturography to evaluate surface, length and mean speed of the center of pressure (CoP). A total of 11 studies were included in this review. The MINORS score is used to assess the methodological quality of the included studies, and its mean value was 12.8 for non-comparative studies and 17.5 for comparative studies. The postural balance was lower in strabismic patients compared with the control group, with statically higher value (p < 0.05) of surface, length and mean speed of the CoP in the study group. All patients show improvement in stability after surgery, as surface, length and mean speed of the CoP decreased after surgery in all the studies with statistical significance (p < 0.05)., (© 2022. The Author(s), under exclusive licence to Istituto Ortopedico Rizzoli.)

Objectives: Autosomic recessive mutations in the PIGN gene have been described in less than 30 subjects to date, in whom multiple congenital anomalies combined with severe developmental delay, hypotonia, epileptic encephalopathy, and cerebellar atrophy have been described as crucial features. A clear-cut neuroradiological characterization of this entity, however, is still lacking. We aim to present three pediatric PIGN mutated cases with an in-depth evaluation of their brain abnormalities., Methods: We present the neuroradiological, clinical, and genetic characterization of three Caucasian pediatric subjects with pathogenic/likely pathogenic variants in the PIGN gene revealed by Next Generation Sequencing analysis., Results: We identified three subjects (two siblings, one unrelated case) presenting with encephalopathy with early-onset epilepsy, hypotonia, and severe global developmental delay. No additional severe multiple congenital anomalies were detected. Neuroradiological evaluation showed extensive quantitative reduction of white matter, severe and progressive cortical atrophy, with frontal predominance and an anteroposterior gradient, combined with cerebellar and brainstem atrophy., Conclusions: Our findings broaden and systematize the neuroradiological spectrum of abnormalities in PIGN related encephalopathy. Furthermore, our dataset confirms that mutations in PIGN gene appear to be pan-ethnic and represent an underestimated cause of early-onset encephalopathy., Competing Interests: Declaration of competing interest The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article., (Copyright © 2021 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Visual experience is crucial for the development of neural processing. For example, alpha activity development is a vision-dependent mechanism. Indeed, studies report no alpha activity is present in blind adults. Nevertheless, studies have not investigated the developmental trajectory of this activity in infants and children with blindness. Here, we hypothesize that the difference in neural activity of blind compared to sighted subjects is: absent at birth, progressive with age, specifically occipital and linked to a gradual motor impairment. Therefore, we consider spectral power of resting-state EEG and its association with motor impairment indices, in blind subjects and in sighted controls between 0 and 11 years of age. Blind subjects show posterior alpha activity during the first three years of life, although weaker and slower maturing compared to sighted subjects. The first great differentiation between blind and sighted subjects occurs between 3 and 6 years of age. Starting in this period, reduced alpha activity increases the probability of motor impairment in blind subjects, likely because of impaired perception/interaction. These results show that visual experience mediates the neural mechanisms generating alpha oscillations during the first years of life, suggesting that it is a sensitive period for the plasticity of this process., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In patients with knee osteoarthritis, when only medial or lateral compartment of the knee is involved, unicompartimental knee arthroplasty (UKA) is a reliable option for addressing the symptoms and restore function. The main aim of the present review is to systematically collect the available evidence concerning the return to sport activity in the elderly patients after UKA. An electronic search was carried out on the following databases; Pubmed-Medline, Cochrane central, and Scopus, searching for randomized controlled trials, prospective cohort studies, retrospective case-control studies, and case series. Data concerning the evaluation of the return to sport (RTS) and of functional outcomes in the elderly patients after UKA surgery. MINORS score was used to assess the risk of methodological biases. Odds ratios and raw proportions were used to report the pooled effect of UKA on the return to sport in comparative and non-comparative studies, respectively. Same level RTS in elderly patients was of 86% (pooled return proportion 0.86, 95%CI 0.78, 0.94), showing also better relative RTS and time to RTS of patients undergoing UKA, in comparison to those undergoing TKA. Sport-specific RTS showed that higher return rates were observed for low-impact sports, whereas high-impact sports prevented a full return to activities. UKA is a valid and reliable option for elderly patients to satisfactorily resume their sport practice, especially for low impact activities. The rate of return to sports following UKA is higher than TKA.

Hip and knee replacement is an effective treatment for symptomatic, end-stage hip and knee osteoarthritis, aiming to relieve pain and restore joint function. Several postoperative rehabilitation protocols and physical activities are proposed in routine clinical practice. However, their effect on clinical outcome and implant revision in patients undergoing joint replacement is still unclear. A systematic review of the literature was performed through a comprehensive search on online databases including Pubmed-Medline, Cochrane central, and Google scholar. We included all the available studies on postoperative physical activity and rehabilitation protocols after total knee and total hip arthroplasty in patients older than 65 years. The primary endpoint was to evaluate the effect of physical activity and rehabilitation on clinical outcome; the secondary outcome was to determine the effect on patients' quality of life (QoL) and implant survival. Although the heterogeneity of the rehabilitation protocols and outcome measures did not allow to draw definitive conclusions, most studies suggested that aquatic therapy, ergometer cycling, and fast-track protocols have a beneficial effect on muscle strength, gait speed, and main clinical scores after total hip arthroplasty. Similarly, enhanced rehabilitation protocols produced an improvement in primary and secondary outcomes after total knee arthroplasty.

Total hip arthroplasty (THA) and total knee arthroplasty (TKA) represent two of the most common procedures in orthopedic surgery. The growing need to avoid physical impairment in elderly patients undergoing this kind of surgery puts the focus on the possibility to undertake a preoperative physical activity program to improve their fit and physical health at the time of surgery. A systematic review has been carried out with online databases including PubMed-Medline, Cochrane Central and Google Scholar. The aim was to retrieve available evidence concerning preoperative physical activity and exercise, before total knee or total hip arthroplasty in patients older than 65 years, and to clarify the role of this practice in improving postoperative outcomes. Results of the present systematic analysis showed that, for TKA, most of the studies demonstrated a comparable trend of postoperative improvement of Visual Analogue Scale (VAS), range of movement (ROM) and functional scores, and those of quality of life. There is insufficient evidence in the literature to draw final conclusions on the topic. Prehabilitation for patients undergoing TKA leads to shorter length of stay but not to an enhanced postoperative recovery. Concerning THA, although currently available data showed better outcomes in patients who underwent prehabilitation programs, there is a lack of robust evidence with appropriate methodology.

Blocking interactions between PD-1 and PD-L1 opens a new era of cancer treatment involving immunity modulation. Although most immunotherapies use monoclonal antibodies, small-molecule inhibitors offer advantages. To facilitate development of small-molecule therapeutics, we implemented a rapid approach to characterize the binding interfaces of small-molecule inhibitors with PD-L1. We determined its interaction with a synthetic macrocyclic peptide by using two mass spectrometry-based approaches, hydrogen-deuterium exchange and fast photochemical oxidation of proteins (FPOP), and corroborated the findings with our X-ray structure of the PD-L1/macrocycle complex. Although all three approaches show that the macrocycle binds directly to PD-L1 over the regions of residues 46-87 and 114-125, the two protein footprinting approaches show additional binding at the N-terminus of PD-L1, and FPOP reveals some critical binding residues. The outcomes not only show the binding regions but also demonstrate the utility of MS-based footprinting in probing protein/ligand inhibitory interactions in cancer immunotherapy.

Background: The most common procedure to manage a torn anterior cruciate ligament (ACL) is surgical reconstruction. Primary repair of the ACL is returning on the forefront in the management of acute ACL, aiming to be less invasive and preserve the original ligament. Several techniques have been reported; the present systematic review investigates the clinical outcomes of ACL primary repair in adults., Sources of Data: Following an electronic search through Medline, Cochrane and Google Scholar databases, articles of interest were retrieved and evaluated, including case series, retrospective studies, case-control studies and randomized controlled trials. The main outcome data were extracted and summarized in tables and text. The methodology of the studies was assessed using the Coleman methodology score (CMS)., Areas of Agreement: Of the articles included, one was of level I, two of level III and the remaining of level IV. The direct intraligamentary stabilization technique was the most widely and accurately reported technique, with acceptable success and improvement of functional outcomes. The CMS averaged 58.75 (range 48 to 69), with no significant association with year of publication (Pearson's regression r = -0.397, P = 0.207)., Areas of Controversy: Concerning stump sutures and suture anchors repair, although leading to good results, also in comparison with ACL reconstruction, no sufficient evidence was available to support these techniques., Growing Points: The overall good results were reported also for other techniques are not supported by adequate evidence. More and better trials are required to improve our knowledge and understanding in this controversial area., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: To understand the role of camptocormia (increased kyphosis) and postural alteration in Parkinson's disease in the development of shoulder pathology, with a special concern for adhesive capsulitis and shoulder stiffness., Methods: A preliminary online search was carried out, with combination of keywords including "Parkinson," "Shoulder stiffness," "Frozen shoulder," "Adhesive capsulitis," "Postural alteration," "Camptocormia". The retrieved papers were screened by title and abstract and those considered relevant to the aim of the review were read in full text and included. Relevant information were extracted and reported into text., Results: Due to a severe impairment of posture, patients affected by PD show an increased thoracic kyphosis (camptocormia) and decreased mobility of the trunk that can yield a humeroacromial impingement syndrome and capsulitis, resulting in inflammation of the bursa, shoulder pain and reduction of movement. Furthermore, kinematic of the shoulder is allowed by the combined movement of the humerus, the scapula, the clavicle, the thoracic wall and thoracic spine. The thoracic spine and wall mobility are severely impaired in the parkinsonian patient, thus limiting the shoulder motion., Conclusion: The postural alteration observed in PD is the primum movens for shoulder pathology, since anterior tilt of the scapula, which occurs with the increment of thoracic kyphosis, yields to a subacromial impingement. A closed loop is then created, as the rigidity of the shoulder causes further alteration in the posture, which worsens the impingement syndrome and so on.

Osteoarthritis (OA) of the knee is one of the most relevant and debilitating health problems. Obesity represents one of the major risk factor for early development of OA. In the obese population, knee replacement should be delayed and eventually avoided and prefer conservative treatments including intrarticular hyaluronic acid (HA) viscosupplementation. In the present clinical randomized trial, we present a comparison between two groups of 24 obese patients which were randomized to be treated with two intrarticular injections of hybrid (low and high molecular weight) hyaluronic acid (Group A) or two injections of high molecular weight hyaluronic acid (Group B). Patients were followed-up through to 6 months and assessed though IKDC and KOOS scores, pain was evaluated with VAS. All patients reported a significant improvement when compared to baseline value in all outcome measures. At 3-month follow-up, IKDC had significantly improved in patients of Group A, compared to Group B (53.1±1.9 vs 51.4±2.4, p=0.0079) and the same for KOOS (52.1±2.0 vs 50.1±2.9, p=0.010). Furthermore, the difference in KOOS was persistently significant at 6-month follow-up (54.7±2.3 vs 51.7±4.9, p=0.014). The VAS reduced significantly more in Group A at 3 months (3.7±0.5 vs 5.2±0.7, p less than 0.001). In an obese population, where basal inflammatory pattern increases symptoms of OA and conservative treatment is recommended, HA viscosupplementation improved function and pain of the knee. The treatment with hybrid HA showed better outcomes than high molecular weight HA in obese patients. The combination of the anti-inflammatory action of low molecular weight HA on chondrocytes and the biomechanical role of high molecular weight HA might explain the different results.

Adhesive capsulitis (AC) is a common pathological condition of the shoulder characterized by painful restriction of range of motion (ROM) of the glenohumeral joint. Currently, no consensus has been reached regarding the best treatment. Hyaluronic acid (HA) injection is a safe procedure that can result in significant improvement in active and passive ROM, alleviating pain and improving shoulder function. We systematically reviewed current literature in order to evaluate the best evidence about the effectiveness of intra-articular HA injection for the treatment of primary AC. We searched Medline, CINAHL, Embase, Google Scholar and Cochrane Library. We selected studies comparing clinical outcomes of patients treated with HA in association or not with conventional therapy. Seven studies were evaluated: 2 uncontrolled randomized studies and 5 prospective randomized clinical trials with level of evidence I. Clinical outcome measures used included, among other, ROM, Visual Analogic Scale (VAS) pain scores, Constant score, Activity of daily living, Shoulder Pain and Disability Index (SPADI), American Shoulder and Elbow Surgeons (ASES) and Japanese Orthopedic Association Score (JOA score). Improvement was noted in terms of ROM, constant scores and pain in patients affected by AC treated with intra-articular HA injections. When compared with cortisone intra-articular injection, HA has equivalent clinical outcomes and ROM. The heterogeneity of treatments used in the studies reviewed, makes it difficult to draw a definite conclusion on the subject. HA injections do not seem to determine the final outcomes directly compared with conventional treatments. However, they could play an important role for early mobilization in the initial stages, during which, due to pain and inflammation, the patient keeps the shoulder immobilized for a long time, determining the direct cause of AC. Numerous variables, including use of lidocaine, different HA and AC stages, could influence the results and deserve to be accounted for in future investigations.

Meniscal extrusion (ME) has shown to play a critical but still unclear role in osteoarthritis (OA) development. ME has been described as an important risk factor in the progression of knee OA, as it is involved in the thinning of articular cartilage, joint space narrowing, spontaneous osteonecrosis of the knee and subchondral bone marrow lesions. Meniscal damage of any degree of severity could cause ME in both compartments, but it is commonly associated with severe meniscal tears or root tears mainly in the medial meniscus. Magnetic resonance imaging is the most commonly used imaging modality in the assessment of ME, while ultrasonography may represent a valid alternative with high sensitivity and specificity. Conservative treatment for ME includes physical therapy and rehabilitation to maintain range of motion, corticosteroid injections and intra-articular injections of hyaluronic acid to provide short-term relief of knee pain. The goal of this study is to review standards of current diagnosis and treatment of ME and its relationship to knee OA.

Encephalopathy with status epilepticus during sleep (ESES) is an epileptic encephalopathy, as defined by the International League Against Epilepsy (ILAE) Task Force on Classification and Terminology, that is, a condition in which the epileptic processes themselves are believed to contribute to the disturbance in cerebral function. Clinical manifestations of ESES are heterogeneous: apart from different seizure types, they consist in combinations of cognitive, motor, and behavioural disturbances associated with a peculiar electroencephalographic pattern of paroxysmal activity significantly activated during slow sleep, which culminates in a picture of continuous spikes and waves during sleep (CSWS). The pathophysiological mechanisms underlying this condition are still incompletely understood. Establishing a clear-cut correlation between EEG abnormalities and clinical data, though interesting, is very complex. Computer-assisted EEG analyses especially if combined with functional magnetic resonance imaging (EEG-fMRI) and metabolic neuroimaging have recently emerged as useful approaches to better understand the pathophysiological processes underlying ESES. Treatment of ESES is not just limited to seizures control but it should be focused on controlling neuropsychological outcome through an improvement of the continuous epileptiform activity. General agreement on treatment guidelines is still lacking. Implementation of new techniques might allow a better understanding of the pathophysiology of ESES and could enhance therapeutics options.

Objective: To investigate visual habituation - a measure of visual cortical excitability - in photosensitive patients in pediatric age and compare the findings with a matched sample with idiopathic generalized epilepsies without photosensitivity and with normally developing children., Methods: We presented a full-field black-and-white checkerboard pattern, at 3 reversal/s with 100% contrast binocularly for 600 consecutive trials and measured the N75-P100 and P100-N145 pattern-reversal visual evoked potential inter-peak amplitudes and N75, P100, N145 latencies for the six blocks of 100 responses. As a measure of habituation we used the slope of the linear regression line of the N75-P100 and P100-N145 peak-to-peak amplitudes. The slope of the linear regression line of the N75-P100 and P100-N145 latencies was also analyzed., Results: Statistical analysis revealed significant differences between the three groups in the slope index of N75-P100 PR-VEP amplitude, with increased or constant amplitude in the PS group compare to the IGE and ND across the six blocks., Conclusions: Our results support the notion that photosensitivity is associated with altered control of excitatory and inhibitory cortical processes. The causal relationship between habituation deficit and photo-paroxysmal response needs to be further investigated with longitudinal studies., Significance: This study supports the hypothesis that suppression of PR-VEP is a sensitive intermediate phenotype, which discriminates patients with photosensitivity from those with generalized epilepsies in pediatric age., (Copyright © 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Hypothalamic hamartoma is a rare developmental non-neoplastic malformation, often characterised by early onset gelastic seizures and later progressive cognitive and behavioural deterioration. In this case study, we have examined a child who presented with an atypical onset of benign paroxysmal gaze deviation between two to three months of age. The patient subsequently developed gelastic seizures at age 13. Based on the observation that hypothalamic hamartomas do not involve any functional region involved in eye motility, we speculate that both gaze deviation and gelastic seizures are a manifestation of the epileptogenic nature of the hypothalamic hamartoma. [Published with video sequences].

Using Biacore's new regenerateable streptavidin capture (CAP) sensor chips, we investigated a number of biotinylation conditions for target ligands. We explored standard amine as well as the less commonly used carboxyl biotinylation methods. We illustrate the time scales required for efficient biotinylation as well as the hazards of overbiotinylation. We evaluated a range of desalting methods, including spin columns, dialysis membranes, and filters. Finally, we tested the effects of common buffer components, such as Tris and glycerol, on the biotinylation process. Together, our results serve as a general guide of the steps to consider when minimally biotinylating a target ligand., (Copyright 2010 Elsevier Inc. All rights reserved.)

Movement disorders are rarely described in association with the "continuous spikes and waves during slow sleep (CSWS)" EEG pattern. We report the case of a young girl affected by an epileptic encephalopathy who, from the age of seven years and four months, has twice presented a movement disorder affecting the right arm, manifesting on awakening and disappearing by early afternoon. Sleep EEG during these periods showed continuous, high-amplitude, diphasic spikes and slow waves over the left hemisphere. Association of clobazam, valproic acid and, on the second occasion, ethosuccimide led to disappearance of the above-described EEG picture and associated motor symptoms. Neurophysiological investigations excluded other possible aetiologies. In view of this, and of the close relationship between the EEG picture and clinical course, we interpret the patient's impairment as "motor neglect" secondary to the continuous electrical activity recorded during sleep over the left hemisphere and involving the associative areas. This electrical activity in sleep, may be regarded as a "functional lesion" whose clinical consequences can be correlated with the site of the abnormalities.[Published with video sequences].

Continuous spikes and waves during slow sleep (CSWSS) is a well-known EEG pattern that can be associated with cognitive and behavioural deterioration. We present the long-term neuropsychological follow-up and nosological considerations of five patients who developed CSWSS during childhood. All five of our patients presented CSWSS, although the duration and severity of this pattern varied. The outcome was of three basic types: acquired frontal dementia, language deficits and normal. Four of our patients were initially diagnosed with Landau-Kleffner syndrome but have had markedly diverse outcomes in terms of the severity and type of compromise. Our data suggest that the initial diagnosis, according to current nosological categories, has almost no prognostic significance, while the length and the age of onset of CSWSS, the site of epileptiform activity and the individual neuropsychological profile are more useful for identifying the long-term outcome of patients with CSWSS.

Continuous spikes and waves during slow sleep (CSWS) are a well-known EEG pattern that can be associated with cognitive and behavioural deterioration. We present the long-term clinical, neuropsychological and EEG follow-up of two patients who developed CSWS during childhood. In both the CSWS onset was followed immediately by rapid cognitive and behavioural deterioration. Later the CSWS fragmented or fluctuated and the spike-wave discharges diminished and this was associated with progressive clinical improvement. At the same time bilateral frontal EEG abnormalities appeared awake and in sleep. After the initial period of rapid cognitive and linguistic improvement both patients stabilised. The latest neuropsychological assessment showed a frontal syndrome. The presence of frontal EEG abnormalities superimposed on CSWS, their persistence after CSWS resolution and, in addition, the finding of subtle frontal-type neuropsychological alterations early in recovery may indicate poor long-term outcome.

Aim of this study was to investigate whether octreotide, a synthetic somatostatin analogue that inhibits growth hormone, insulin and glucagon secretion and improves glycaemic control in insulin dependent diabetic patients was able to exert similar effects in insulin treated type 2 diabetic patients with chronic renal failure who have high plasma glucagon levels. For this purpose saline or octreotide was randomly administered by continuous subcutaneous infusion (100 mcg/daily) in addition to usual insulin treatment for 5 days to six type 2 insulin treated diabetic patients with chronic renal failure and to six type 2 patients with normal renal function, as a control group. At day 3 of insulin plus saline or insulin plus octreotide treatment, total glucose uptake and hepatic glucose production (HGP) were investigated during an euglycemic clamp; at day 5 GH, glucagon and C-peptide plasma levels were evaluated. Octreotide treatment lowered endogenous insulin secretion (evaluated by C-Peptide levels assay), GH and glucagon in all patients, but caused a significant reduction of daily insulin requirement (32 +/- 14 I.U. vs 41 +/- 19 I.U., P<0.02) only in patients with renal failure. HGP was significantly (P<0.05) lowered in patients with renal failure but glucose uptake remained unchanged. The lowering effect of octreotide on insulin requirement in diabetic patients with renal failure in spite of the contemporaneous inhibition on insulin secretion could be explained on the basis of the greater reduction of glucagon levels which are very elevated in these patients as compared to patients with normal renal function. The lowering of glucagon could decrease HGP and, consequently, insulin requirement.

We report the case of a child with benign partial epilepsy with centro-temporal spikes (BECT) in whom protrusion of the tongue stopped the interictal abnormalities, and describe the polygraphic EEG recording of a seizure which terminated upon voluntary protrusion of the tongue. We mention the close link between the post-central (somatosensory) cortex and pre-central (motor) cortex, and how the primary sensory area has direct access to the motor cortex. We also examine how a tactile stimulus may provoke the inhibition of an epileptic discharge.

Focal epileptiform abnormalities in awake children submitted to ventricular shunting are well described in the literature, but there are few reports about EEG patterns during sleep. We studied 20 children affected by hydrocephalus of various aetiology and submitted to shunting during the first year of life. We found focal abnormalities in all the children and in 95% of cases they were on the same side as the shunt; in 65% of cases they had an amplitude of 300 mV or more. During sleep there was activation of abnormalities in all subjects, and in 33% we found continuous spikes and waves during slow sleep (CSWS). We discuss the aetiology of CSWS and its possible role in causing the neuropsychological disturbances of our patients.

The results of an histochemical and microscopic study of the APUD cells carried on gastric biopsies are reported. Endocrine cell hyperplasia, microscopically detected, was particularly evident in atrophic gastritis (type A chronic gastritis) and adenomas. The presence of the APUD cells confirmed by electronmicroscopy, which revealed granules of 200 NM with a central nucleus and a membrane-separating electron-lucent ring, gives a further contribution to the hypothesis of a possible association between endocrine cell hyperplasia and intestinal metaplasia.

The authors, in the light of the data supplied by the literature, and through a careful analysis of their recent casuistry, based upon the observation of 48 cases of duodenal diverticula, propose a modern reviewing of the topic. After illustrating the etiopathogenetic, anatomo-pathological and clinical features of such disease, the Authors dwell upon the diagnostic and therapeutical problems involved, and point out the importance of a correct diagnostic iter and a consequent exact surgical indication. As a conclusion, they affirm the surgical treatment of duodenal diverticula, not exempt from risks, should be only reserved to cases rebellious to the medical treatment or severely complicate.

The authors show a case of acute intestinal stoppage due to Meckel's diverticulum. After some notices about embryogenesis, pathological anatomy and symptomatology of Meckel's diverticula, they point out the difficulty to reach the diagnosis of such disease, which almost always is only done subsequent to the appearance of complications, such as: intestinal stoppage, inflammation, ulceration, perforation, neoplasms, bleeding. In fact, the diagnosis of Meckel's diverticulum is exceptionally preoperative and difficult on the basis of the symptomatology only, for which the disease can be responsible, whereas it can be more easily placed thanks to the contribution of instrumental methods, such as: barium meal, opaque enema, scintigraphy with 99mNa pertechnetate, selective arteriography of upper mesenterial artery. The diagnosis is more frequently interoperative, in course of explorative laparotomy or performed for other indications. Then the Authors state their orientation about the treatment, which is surgical in all the complex cases of Meckel's diverticulum, with a mention of the different operative techniques, and, as a conclusion, confirm the necessity for the systematic research of the asymptomatic diverticulum, the removal of which represents the only prophylactic measure against a permanent possibility and dreadful complicative evolution of same.

A ten-year series of early gastric cancer is reported, stress being laid on the diagnostic and therapeutic problems associated with the condition. The importance of intensified mass screening programmes, particularly in populations at risk, is underlined to enable these potentially dangerous conditions to be treated in time.