Diagnostic Approach to Acute Liver Failure in Children: A Position Paper by the SIGENP Liver Disease Working Group.

Acute liver failure (ALF) is a clinical condition characterized by the abrupt onset of coagulopathy and biochemical evidence of hepatocellular injury, leading to rapid deterioration of liver cell function. In children, ALF has been characterized by raised transaminases, coagulopathy, and no known evidence of pre-existing chronic liver disease; unlike in adults, the presence of hepatic encephalopathy is not required to establish the diagnosis. Although rare, ALF has a high mortality rate without liver transplantation (LT). Etiology of ALF varies with age and geographical location, although it may remain indeterminate in a significant proportion of cases. However, identifying its etiology is crucial to undertake disease-specific management and evaluate indication to LT. In this position statement, the Liver Disease Working Group of the Italian Society of Gastroenterology, Hepatology and Nutrition (SIGENP) reviewed the most relevant studies on pediatric ALF to provide recommendations on etiology, clinical features and diagnostic work-up of neonates, infants and children presenting with ALF. Recommendations on medical management and transplant candidacy will be discussed in a following consensus conference.

Increase of renal resistive index and mineral metabolism disorder in patients with acute coronary syndrome with preserved renal function.

OBJECTIVE: Coronary artery disease is one of the first causes of death in the Western world; for this reason, it is essential to identify new, systemic, non-invasive and low-cost cardiovascular risk markers. The acute coronary syndrome includes ST-Elevation Myocardial Infarction (STEMI) and Non-ST-Elevation Myocardial Infarction (NSTEMI), based on ECG findings. We aimed to evaluate Renal Resistive Index (RRI) as a marker of cardiovascular risk and assess the associations with other cardiovascular risk factors (metabolic indexes, mineral metabolism disorders and endothelial dysfunction and atherosclerosis markers) in STEMI and NSTEMI patients. PATIENTS AND METHODS: Clinical, laboratory and instrumental examinations as metabolic and inflammation indexes, markers of atherosclerosis and endothelial dysfunction (renal function, mineral metabolism disorders, inflammation indexes, Intima Media Thickness (IMT), Ankle Brachial Pressure Index, Left Ventricular Mass Index, Relative Wall Thickness) were performed. RESULTS: Eighty-one patients with STEMI and NSTEMI were enrolled. We showed a significant positive correlation between RRI and age (p<0.01), intact parathyroid hormone (p<0.01) and IMT (p<0.01), as well as a significant negative correlation between RRI and body surface area (BSA) (p=0.02), estimated Glomerular Filtration Rate (eGFR) (p<0.01), serum calcium (p<0.01) and 25-hydroxy-vitamin D (p=0.03). Moreover, we found a significant correlation between RRI and male patients (p<0.01), coronary artery disease history (CAD) (p=0.049), hypertension (p=0.025) and left ventricular eccentric hypertrophy (LVEH) (p=0.047). CONCLUSIONS: Our study showed an association between RRI and the main traditional and non-traditional cardiovascular risk factors involved in atherosclerosis pathogenesis, such as age, BSA, hypertension, male sex, CAD history, mineral metabolism disorders and LVEH, in patients with preserved renal function. Moreover, we found a significant correlation between RRI and eGFR, suggesting that RRI could be useful in the evaluation of both renal function and progression of renal damage, even in an early stage with a conserved or only slightly reduced kidney function. We also showed a significant correlation with some markers of systemic atherosclerosis such as IMT and LVEH. For a more precise assessment of prognosis and cardiovascular risk in patients with high cardiovascular mortality, we suggest performing a systematic RRI evaluation, considering the non-invasive nature of the procedure, its reproducibility, easy execution, and low costs.

Cortical plasticity after hand prostheses use: Is the hypothesis of deafferented cortex "invasion" always true?

OBJECTIVE: To study motor cortex plasticity after a period of training with a new prototype of bidirectional hand prosthesis in three left trans-radial amputees, correlating these changes with the modification of Phantom Limb Pain (PLP) in the same period. METHODS: Each subject underwent a brain motor mapping with Transcranial Magnetic Stimulation (TMS) and PLP evaluation with questionnaires during a six-month training with a prototype of bidirectional hand prosthesis. RESULTS: The baseline motor maps showed in all three amputees a smaller area of muscles representation of the amputated side compared to the intact limb. After training, there was a partial reversal of the baseline asymmetry. The two subjects affected by PLP experienced a statistically significant reduction of pain. CONCLUSIONS: Two apparently opposite findings, the invasion of the "deafferented" cortex by neighbouring areas and the "persistence" of neural structures after amputation, could vary according to different target used for measurement. Our results do not support a correlation between PLP and motor cortical changes. SIGNIFICANCE: The selection of the target and of the task is essential for studies investigating motor brain plasticity. This study boosts against a direct and unique role of motor cortical changes on PLP genesis.

Gastrointestinal symptoms and digestive comorbidities in an Italian cohort of patients with COVID-19.

OBJECTIVE: The Coronavirus Disease 2019 (COVID-19) pandemic mainly involves respiratory symptoms, though gastrointestinal (GI) symptoms are increasingly being recognized. In this context, the presence of comorbidities appears to be associated with adverse outcomes. However, the role of digestive manifestations is not yet well defined. The primary aim of this study was to assess the prevalence of GI symptoms and digestive comorbidities in a cohort of patients with COVID-19 compared to controls. The secondary aim was to determine the association of GI-symptoms and digestive comorbidities with clinical outcomes. PATIENTS AND METHODS: Inpatients with COVID-19 and controls with similar symptoms and/or radiological findings were enrolled. Symptoms at admission and throughout hospitalization were collected as they were comorbidities. The measured clinical outcomes were mortality, intensive care unit admission and cumulative endpoint. RESULTS: A total of 105 patients were included: 34 with COVID-19 and 71 controls. At admission, the prevalence of GI symptoms among COVID-19 patients was 8.8%. During hospitalization, the frequency of GI symptoms was higher in patients with COVID-19 than in controls (p=0.004). Among patients with COVID-19, the mortality and a cumulative endpoint rates of those with GI symptoms were both lower than for those without GI symptoms (p=0.016 and p=0.000, respectively). Finally, we found digestive comorbidities to be associated with a milder course of COVID-19 (p=0.039 for cumulative endpoint). CONCLUSIONS: Our results highlighted the non-negligible frequency of GI symptoms in patients with COVID-19, partly attributable to the therapies implemented. In addition, the presence of GI symptoms and digestive comorbidities is associated with better outcomes. Most likely, digestive comorbidities do not hinder the host's immune response against SARS-COV-2, and the occurrence of GI symptoms might be linked to a faster reduction of the viral load via the faecal route.

Assessment of neurological manifestations in hospitalized patients with COVID-19.

BACKGROUND AND PURPOSE: The objective of this study was to assess the neurological manifestations in a series of consecutive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients, comparing their frequency with a population hospitalized in the same period for flu/respiratory symptoms, finally not related to SARS-CoV-2. METHODS: Patients with flu/respiratory symptoms admitted to Fondazione Policlinico Gemelli hospital from 14 March 2020 to 20 April 2020 were retrospectively enrolled. The frequency of neurological manifestations of patients with SARS-CoV-2 infection was compared with a control group. RESULTS: In all, 213 patients were found to be positive for SARS-CoV-2, after reverse transcriptase polymerase chain reaction on nasal or throat swabs, whilst 218 patients were found to be negative and were used as a control group. Regarding central nervous system manifestations, in SARS-CoV-2-positive patients a higher frequency of headache, hyposmia and encephalopathy always related to systemic conditions (fever or hypoxia) was observed. Furthermore, muscular involvement was more frequent in SARS-CoV-2 infection. CONCLUSIONS: Patients with COVID-19 commonly have neurological manifestations but only hyposmia and muscle involvement seem more frequent compared with other flu diseases.

Oral health conditions in Wilson's disease patients: A clinical diagnostic study.

AIM: The aims of this study were: To evaluate oral health conditions, oral health behaviours and eating habits in Wilson's disease (WD) patients; to assess the possible relationship between oral health status and long-term pharmacological therapies undertaken. METHODS: Sixty WD patients were selected and their data were compared to those of an age-matched control group of 62 subjects. Clinical examinations were carried out and a questionnaire on oral health behaviours and eating habits was submitted to both groups. WD patients were interviewed on long-term pharmacological therapies undertaken. Statistical analysis was performed. RESULTS: The mean DMFT value was 3.75±4.65 in the WD group and 2.81±4.65 in the control group. The difference in the mean DMFT value between the two groups was not statistically significant. Modified Dental Enamel Defects (DDE) Index showed significantly higher values in WD group than in control group. No statistical differences in Visible Plaque Index (VPI), Gingival Bleeding Index (GBI) and malocclusions were observed between groups. In relation to the questionnaire, the differences between groups were statistically significant for: dental visits in a year; brushing teeth after a snack; drinking soft beverages; using mouthwash. For WD patients no statistical correlation between oral health status and long-term pharmacological therapies undertaken was observed. CONCLUSION: WD patients did not show worse oral health conditions than the control group, despite worse oral health behaviours and eating habits. Nerveless, WD patients showed higher presence of dental enamel defects. Finally, for WD group oral health status was not correlated to the long-term pharmacological therapies.

Clinical characteristics and outcome of patients with autoimmune encephalitis: clues for paraneoplastic aetiology.

BACKGROUND AND PURPOSE: Autoimmune encephalitis (AE) represents a complex syndrome with diverse clinical manifestations and therapeutic outcomes. The aim of this study was to report the clinical characteristics and the long-term outcome of patients with paraneoplastic and idiopathic AE. METHODS: All patients with subacute encephalopathy admitted to the Neurology Department of our Institution from January 2012 to May 2019 were consecutively enrolled. Patients' serum and cerebrospinal fluid were tested for neural-specific autoantibodies by indirect immunofluorescence assays on mouse brain, rat neurons, cell-based assays and immunoblots. Outcome was assessed by the modified Rankin Scale score. RESULTS: From 107 adult patients with subacute encephalopathy, 50 patients were finally diagnosed with AE. Neural antibodies (Abs) were detected in 45/50 patients (90%). Leucine-rich glioma-inactivated protein 1 immunoglobulin G was the most frequent (6/50, 12%) Ab specific to neural surface antigens detected in adults with AE. Paraneoplastic encephalitis was diagnosed in 16/50 patients (32%). The presence of bilateral temporal lobe lesions on magnetic resonance imaging and cerebrospinal fluid restricted oligoclonal bands was associated with a higher probability to detect cancer at the time of AE diagnosis. All patients with Abs to neural surface antigens had a good outcome at last follow-up. Severe disability at AE onset and the lack of long-term immunosuppression predicted a poor outcome. CONCLUSIONS: Leucine-rich glioma-inactivated protein 1 immunoglobulin G was the most frequent Ab detected. Patients with bilateral temporal lobe lesions and oligoclonal bands have a higher probability to harbour an occult tumour. In these patients, a strict surveillance and monitoring for cancer detection is recommended.

Early diagnosis of Alzheimer's disease: the role of biomarkers including advanced EEG signal analysis. Report from the IFCN-sponsored panel of experts.

Alzheimer's disease (AD) is the most common neurodegenerative disease among the elderly with a progressive decline in cognitive function significantly affecting quality of life. Both the prevalence and emotional and financial burdens of AD on patients, their families, and society are predicted to grow significantly in the near future, due to a prolongation of the lifespan. Several lines of evidence suggest that modifications of risk-enhancing life styles and initiation of pharmacological and non-pharmacological treatments in the early stage of disease, although not able to modify its course, helps to maintain personal autonomy in daily activities and significantly reduces the total costs of disease management. Moreover, many clinical trials with potentially disease-modifying drugs are devoted to prodromal stages of AD. Thus, the identification of markers of conversion from prodromal form to clinically AD may be crucial for developing strategies of early interventions. The current available markers, including volumetric magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebral spinal fluid (CSF) analysis are expensive, poorly available in community health facilities, and relatively invasive. Taking into account its low cost, widespread availability and non-invasiveness, electroencephalography (EEG) would represent a candidate for tracking the prodromal phases of cognitive decline in routine clinical settings eventually in combination with other markers. In this scenario, the present paper provides an overview of epidemiology, genetic risk factors, neuropsychological, fluid and neuroimaging biomarkers in AD and describes the potential role of EEG in AD investigation, trying in particular to point out whether advanced analysis of EEG rhythms exploring brain function has sufficient specificity/sensitivity/accuracy for the early diagnosis of AD.

Re-revision total hip arthroplasty: Epidemiology and factors associated with outcomes.

INTRODUCTION: The epidemiology of re-revision total hip arthroplasty (THA) is not yet well-understood. We aim to investigate the epidemiology and risk-factors that are associated with re-revision THA. METHODS: 288 revision THA were analyzed between 1/2012 and 12/2013. Patients who underwent two or greater revision THA were included. Hips with first-revision due to periprosthetic joint infection (PJI) were excluded. Failure was defined as reoperation. RESULTS: 51 re-revision patients were available. Mean age was 59.6 (±14.2 years), 32 (67%) females, average BMI of 28.8 (±5.4), and median ASA 2 (23; 55%). The most common re-revision indications were acetabular component loosening (15; 29%), PJI (13; 25%) and instability (9; 18%). The most common indications for first revision in the re-revision population were acetabular component loosening (11; 27%), polyethylene wear (8; 19%) and instability (8; 19%). There was an increased risk of re-revision failure if the re-revision involved exchanging only the head and polyethylene liner (RR = 1.792; p = 0.017), instability was the first-revision indication (RR = 3.000; p < 0.001), and instability was the re-revision indication (RR = 1.867; p = 0.038). If isolated femoral component revision was indicated during the re-revision, there was a decreased risk of failure (RR = 0.268, p = 0.046). 1-year re-revision survival was 54% (23/43). DISCUSSION: Acetabular component loosening, instability, and PJI were the most common indications for re-revision. Revision due to instability is a recurrent problem that leads to re-revision failure. There was a higher infection rate in the re-revision population compared to published revision PJI. A better understanding of the indications and patient factors that are associated with re-revision failures can help align surgeon and patient expectations in this challenging population.

Lateral meniscal cysts: long-term clinical and radiological results of a partial meniscectomy and percutaneous decompressive needling.

INTRODUCTION: The aim of this study was to describe clinical and radiological long-term results of an arthroscopic partial meniscectomy associated with an outside-in decompressive needling of the cyst for lateral parameniscal cyst. METHODS: Eighteen patients with symptomatic parameniscal cysts treated between April 2002 and September 2009 were retrospectively included in the study. All patients underwent arthroscopic partial meniscectomy (preserving peripheral rim) and needling of the cyst using a 20-gauge needle. Pre- and post-operative IKDC, Tegner, and Lysholm scores were used to evaluate clinical results. Radiological results were obtained from pre- and post-operative radiographies and post-operative MRI scans. Both supine and weight bearing MRI examinations were performed. Kellgren-Lawrence and WORMS scales were used to evaluate osteoarthritis development of the knee. RESULTS: The mean follow-up period was 11.6 ± 2.6 years (range 7-15). Horizontal lesions were found in 56% of patients. All patients fully recovered. Mean Lysholm scores passed from mean pre-operative value 52 ± 16.9 to post-operative 85 ± 11.9 (P < 0.01) and mean IKDC scale score changed from 49.5 ± 14.7 to 67 ± 23.5 (P < 0.01). Mean Tegner scores did not change significantly. Post-operative radiographies showed a Kellgren-Lawrence scale grade 0 in six patients (33%), a grade I in eight (44%), a grade II in three (17%), and a grade III in one patient (6%). No patients were found with a Kellgren-Lawrence scale grade IV. No significant differences with pre-operative radiographies were found (chi-square = 1.867; df = 3; P = 0.60) in osteoarthritis development of the knee. Reported WORMS scores had an average of 12.4 ± 5.1. No recurrence of any cysts was observed. DISCUSSION: Different treatments for lateral meniscal cysts have been proposed, but proper management of the cyst is still controversial. The results of this study suggest that the outside-in needling of the cyst associated with partial meniscectomy is a highly effective, simple, and repeatable technique. Excellent clinical outcomes were reported at a mean follow-up of 11.6 ± 2.6 years (range 7-15). Imaging evaluation showed no significant evolution to osteoarthritis of the knee. CONCLUSIONS: Partial arthroscopic meniscectomy associated with percutaneous decompressive needling of the cyst wall under arthroscopic visualization showed positive clinical and radiological long-term results. Neither traditional radiographies nor innovative standing MRIs showed findings of osteoarthritis.

Subgroup comparison according to clinical phenotype and serostatus in autoimmune encephalitis: a multicenter retrospective study.

BACKGROUND AND PURPOSE: Autoimmune encephalitides (AE) include a spectrum of neurological disorders whose diagnosis revolves around the detection of neuronal antibodies (Abs). Consensus-based diagnostic criteria (AE-DC) allow clinic-serological subgrouping of AE, with unclear prognostic implications. The impact of AE-DC on patients' management was studied, focusing on the subgroup of Ab-negative-AE. METHODS: This was a retrospective multicenter study on patients fulfilling AE-DC. All patients underwent Ab testing with commercial cell-based assays (CBAs) and, when available, in-house assays (immunohistochemistry, live/fixed CBAs, neuronal cultures) that contributed to defining final categories. Patients were classified as Ab-positive-AE [N-methyl-d-aspartate-receptor encephalitis (NMDAR-E), Ab-positive limbic encephalitis (LE), definite-AE] or Ab-negative-AE (Ab-negative-LE, probable-AE, possible-AE). RESULTS: Commercial CBAs detected neuronal Abs in 70/118 (59.3%) patients. Testing 37/48 Ab-negative cases, in-house assays identified Abs in 11 patients (29.7%). A hundred and eighteen patients fulfilled the AE-DC, 81 (68.6%) with Ab-positive-AE (Ab-positive-LE, 40; NMDAR-E, 32; definite-AE, nine) and 37 (31.4%) with Ab-negative-AE (Ab-negative-LE, 17; probable/possible-AE, 20). Clinical phenotypes were similar in Ab-positive-LE versus Ab-negative-LE. Twenty-four/118 (20.3%) patients had tumors, and 19/118 (16.1%) relapsed, regardless of being Ab-positive or Ab-negative. Ab-positive-AE patients were treated earlier than Ab-negative-AE patients (P = 0.045), responded more frequently to treatments (92.3% vs. 65.6%, P < 0.001) and received second-line therapies more often (33.3% vs. 10.8%, P = 0.01). Delays in first-line therapy initiation were associated with poor response (P = 0.022; odds ratio 1.02; confidence interval 1.00-1.04). CONCLUSIONS: In-house diagnostics improved Ab detection allowing better patient management but was available in a patient subgroup only, implying possible Ab-positive-AE underestimation. Notwithstanding this limitation, our findings suggest that Ab-negative-AE and Ab-positive-AE patients share similar oncological profiles, warranting appropriate tumor screening. Ab-negative-AE patients risk worse responses due to delayed and less aggressive treatments.

Characterization of multi-channel intraneural stimulation in transradial amputees.

Although peripheral nerve stimulation using intraneural electrodes has been shown to be an effective and reliable solution to restore sensory feedback after hand loss, there have been no reports on the characterization of multi-channel stimulation. A deeper understanding of how the simultaneous stimulation of multiple electrode channels affects the evoked sensations should help in improving the definition of encoding strategies for bidirectional prostheses. We characterized the sensations evoked by simultaneous stimulation of median and ulnar nerves (multi-channel configuration) in four transradial amputees who had been implanted with four TIMEs (Transverse Intrafascicular Multichannel Electrodes). The results were compared with the characterization of single-channel stimulation. The sensations were characterized in terms of location, extent, type, and intensity. Combining two or more single-channel configurations caused a linear combination of the sensation locations and types perceived with such single-channel stimulations. Interestingly, this was also true when two active sites from the same nerve were stimulated. When stimulating in multi-channel configuration, the charge needed from each electrode channel to evoke a sensation was significantly lower than the one needed in single-channel configuration (sensory facilitation). This result was also supported by electroencephalography (EEG) recordings during nerve stimulation. Somatosensory potentials evoked by multi-channel stimulation confirmed that sensations in the amputated hand were perceived by the subjects and that a perceptual sensory facilitation occurred. Our results should help the future development of more efficient bidirectional prostheses by providing guidelines for the development of more complex stimulation approaches to effectively restore multiple sensations at the same time.

Methods for analysis of brain connectivity: An IFCN-sponsored review.

The goal of this paper is to examine existing methods to study the "Human Brain Connectome" with a specific focus on the neurophysiological ones. In recent years, a new approach has been developed to evaluate the anatomical and functional organization of the human brain: the aim of this promising multimodality effort is to identify and classify neuronal networks with a number of neurobiologically meaningful and easily computable measures to create its connectome. By defining anatomical and functional connections of brain regions on the same map through an integrated approach, comprising both modern neurophysiological and neuroimaging (i.e. flow/metabolic) brain-mapping techniques, network analysis becomes a powerful tool for exploring structural-functional connectivity mechanisms and for revealing etiological relationships that link connectivity abnormalities to neuropsychiatric disorders. Following a recent IFCN-endorsed meeting, a panel of international experts was selected to produce this current state-of-art document, which covers the available knowledge on anatomical and functional connectivity, including the most commonly used structural and functional MRI, EEG, MEG and non-invasive brain stimulation techniques and measures of local and global brain connectivity.

Surgical approach significantly affects the complication rates associated with total hip arthroplasty.

AIMS: A variety of surgical approaches are used for total hip arthroplasty (THA), all with reported advantages and disadvantages. A number of common complications can occur following THA regardless of the approach used. The purpose of this study was to compare five commonly used surgical approaches with respect to the incidence of surgery-related complications. PATIENTS AND METHODS: The electronic medical records of all patients who underwent primary elective THA at a single large-volume arthroplasty centre, between 2011 and 2016, with at least two years of follow-up, were reviewed. After exclusion, 3574 consecutive patients were included in the study. There were 1571 men (44.0%) and 2003 women (56.0%). Their mean age and body mass index (BMI) was 63.0 years (sd 11.8) and 29.1 kg/m2 (sd 6.1), respectively. Data gathered included the age of the patient, BMI, the American Society of Anesthesiologists (ASA) score, estimated blood loss (EBL), length of stay (LOS), operating time, the presence of intra- or postoperative complications, type of complication, and the surgical approach. The approaches used during the study were posterior, anterior, direct lateral, anterolateral, and the northern approach. The complications that were recorded included prolonged wound drainage without infection, superficial infection, deep infection, dislocation, aseptic loosening, and periprosthetic fracture. Finally, the need for re-operation was recorded. Means were compared using analysis of variance (ANOVA) and Student's t-tests where appropriate and proportions were compared using the chi-squared test. RESULTS: A total of 248 patients had 263 complications related to the surgery, with an incidence of 6.94%. The anterior approach had the highest incidence of complications (8.5% (113/1329)) and the posterior approach had the lowest, at 5.85% (97/1657; p = 0.006). Most complications were due to deep infection (22.8%), periprosthetic fracture (22.4%), and prolonged wound drainage (21.3%). The rate of dislocation was 0.84% (14/1657) with the posterior approach and 1.28% (17/1329) with the anterior approach (p = 0.32). CONCLUSION: Overall, THA has a relatively low complication rate. However, the surgical approach plays a role in the incidence of complications. We found that the posterior approach had a significantly lower overall complication rate compared with the anterior approach, with an equal dislocation rate. Periprosthetic fracture and surgical site infection contributed most to the early complication rates. Cite this article: Bone Joint J 2019;101-B:646-651.

2019 Frank Stinchfield Award: A comparison of prosthetic joint infection rates between direct anterior and non-anterior approach total hip arthroplasty.

AIMS: We studied the impact of direct anterior (DA) versus non-anterior (NA) surgical approaches on prosthetic joint infection (PJI), and examined the impact of new perioperative protocols on PJI rates following all surgical approaches at a single institution. PATIENTS AND METHODS: A total of 6086 consecutive patients undergoing primary total hip arthroplasty (THA) at a single institution between 2013 and 2016 were retrospectively evaluated. Data obtained from electronic patient medical records included age, sex, body mass index (BMI), medical comorbidities, surgical approach, and presence of deep PJI. There were 3053 male patients (50.1%) and 3033 female patients (49.9%). The mean age and BMI of the entire cohort was 62.7 years (18 to 102, sd 12.3) and 28.8 kg/m2 (13.3 to 57.6, sd 6.1), respectively. Infection rates were calculated yearly for the DA and NA approach groups. Covariates were assessed and used in multivariate analysis to calculate adjusted odds ratios (ORs) for risk of development of PJI with DA compared with NA approaches. In order to determine the effect of adopting a set of infection prevention protocols on PJI, we calculated ORs for PJI comparing patients undergoing THA for two distinct time periods: 2013 to 2014 and 2015 to 2016. These periods corresponded to before and after we implemented a set of perioperative infection protocols. RESULTS: There were 1985 patients in the DA group and 4101 patients in the NA group. The overall rate of PJI at our institution during the study period was 0.82% (50/6086) and decreased from 0.96% (12/1245) in 2013 to 0.53% (10/1870) in 2016. There were 24 deep PJIs in the DA group (1.22%) and 26 deep PJIs in the NA group (0.63%; p = 0.023). After multivariate analysis, the DA approach was 2.2 times more likely to result in PJI than the NA approach (OR 2.2 (95% confidence interval 1.1 to 3.9); p = 0.006) for the overall study period. CONCLUSION: We found a higher rate of PJI in DA versus NA approaches. Infection prevention protocols such as use of aspirin, dilute povidone-iodine lavage, vancomycin powder, and Gram-negative coverage may have been positively associated with diminished PJI rates observed for all approaches over time. Cite this article: Bone Joint J 2019;101-B(6 Supple B):2-8.

Cost-effective peri-operative pain management: assuring a happy patient after total knee arthroplasty.

AIMS: The aim of this study was to determine the optimal regimen for the management of pain following total knee arthroplasty (TKA) by comparing the outcomes and cost-effectiveness of different protocols implemented at a large, urban, academic medical centre. PATIENTS AND METHODS: Between September 2013 and September 2015, we used a series of modifications to our standard regimen for the management of pain after TKA. In May 2014, there was a department-wide transition from protocols focused on femoral nerve blocks (FNB) to periarticular injections of liposomal bupivacaine. In February 2015, patient-controlled analgesia (PCA) was removed from the protocol while continuing liposomal bupivacaine injections. Quality measures and hospital costs were compared between the three protocols. RESULTS: The cohort being treated with PCA-less liposomal bupivacaine injections had a significantly higher percentage of patients who were discharged to their home (p = 0.010) and a significantly shorter length of stay (p < 0.001). Patient-reported Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) scores relating to pain being "well-controlled" and "overall pain management" also favoured this cohort (p = 0.214 and p = 0.463, respectively), in which cost was significantly lower compared with the other two cohorts (p = 0.005). CONCLUSION: The replacement of FNBs injections and the removal of PCAs, both of which are known to be associated with high rates of adverse outcomes, and the addition of liposomal bupivacaine periarticular injections to a multimodal pain regimen, led to improvements in many quality measures, HCAHPS pain scores, and cost-effectiveness. Cite this article: Bone Joint J 2018;100-B(1 Supple A):55-61.

Febrile infection-related epilepsy syndrome (FIRES) with super-refractory status epilepticus revealing autoimmune encephalitis due to GABAAR antibodies.

BACKGROUND: Febrile infection-related epilepsy syndrome (FIRES) has been described as an epileptic encephalopathy of unknown etiology affecting previously healthy children following febrile illness. Despite large investigations on autoimmune pathogenesis no membrane antibodies has been associated since now. CASE STUDY: We report a 13 years-old girl with negative history for neurological or autoimmune disease that developed at the sixth day of high fever a super-refractory status epilepticus. All investigations, including the most common antibodies related to immune-mediated encephalitis were negative. Seizures continued despite several therapeutic trials with anesthetics (midazolam, propofol) and antiepileptic agents as well as i.v. immunoglobulins but responded, at day 10 from the onset, to ketamine and high dose i.v. steroids. Due the high suspicion of autoimmune encephalitis we tested patient's CSF and plasma on mouse brain with positive response. We subsequently detected a high titre of GABAAR antibodies. After the resolution of the status epilepticus the patient achieved complete recovery of neurological functions. CONCLUSION: this is the first reported case of a FIRES-like condition due to autoimmune encephalitis mediated by GABAAR antibodies. Our case suggests that GABAAR antibodies should be investigated FIRES.

The association of pre-operative body pain diagram scores with pain outcomes following total knee arthroplasty.

OBJECTIVE: Approximately 20% of total knee arthroplasty (TKA) recipients have suboptimal pain relief. We evaluated the association between pre-surgical widespread body pain and incomplete pain relief following TKA. METHOD: This prospective analysis included 241 patients with knee osteoarthritis (OA) undergoing unilateral TKA who completed questionnaires preoperatively and up to 12 months post-operatively. Questionnaires included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale and a body pain diagram. We derived the number of non-index painful body regions from the diagram. We used Poisson regression to determine the association between painful body regions identified preoperatively and both WOMAC pain at follow-up and improvement in pain as defined by the minimal clinically important difference (MCID). RESULTS: Mean subject age was 66 years (SD 9), and 61% were females. Adjusting for age, sex, co-morbid conditions, baseline pain, pain catastrophizing, and mental health, we found that more widespread body pain was associated with a higher likelihood of reporting 12-month WOMAC pain score >15 (relative risk [RR] per painful body region 1.39, 95% CI 1.18-1.63) and a greater likelihood of failing to achieve the MCID (RR 1.47, 95% CI 1.16-1.86).). Pain catastrophizing was an independent predictor of persistent pain and failure to improve by the MCID (RR 3.57, 95% CI 1.73-7.31). CONCLUSIONS: Pre-operative widespread pain was associated with greater pain at 12-months and failure to reach the MCID. Widespread pain as captured by the pain diagram, along with the pain catastrophizing score, may help identify persons with suboptimal TKA outcome.

Nanohydroxyapatite promotes the healing process in open-wedge high tibial osteotomy: A CT study.

BACKGROUND: The aim of this prospective and randomized study was to evaluate the effectiveness of adding nanohydroxyapatite (NHA) to heterologous bone graft in open wedge high tibial osteotomy (OWHTO) by measuring the bone density of the tibial osteotomy gap. METHODS: Twenty-seven patients (26 knees) were operated by OWHTO and randomly divided into two groups: pure graft group, in which the osteotomy gap was filled with only heterologous bone graft; nanohydroxyapatite group, in which the osteotomy gap was filled with heterologous bone graft and NHA. All patients underwent computed tomography (CT) examination within one week after operation (Time 0), and after two months (Time 1) and 12months (Time 2). CT volume acquired Hounsfield Units (HU) were calculated and the mean value of bone density on three planes was measured. RESULTS: At Time 0, the mineral density of the nanohydroxyapatite group appeared significantly higher compared with the pure graft group, due to the presence of NHA. At Time 1, the mineral density of the nanohydroxyapatite group had decreased relative to Time 0, while in the pure graft group it remained unchanged. At Time 2, the mineral density in the nanohydroxyapatite group had further decreased, reaching values close to the mineral density of normal bone. In contrast, in the pure graft group the mineral density had increased, probably due to the lack of reabsorption of the graft and the development of sclerosis in the osteotomy borders. CONCLUSIONS: The results of the present study show better osseointegration of the heterologous graft when nanohydroxyapatite is added.

Alpha Lipoic Acid (ALA) effects on subchorionic hematoma: preliminary clinical results.

OBJECTIVE: The clinic use of alpha Lipoic Acid (ALA) is linked to its capability to exert antioxidant effects and, more interestingly, to counteract the pathologic changes of complex networks of cytokines, chemokines and growth factors, restoring their physiological state. The aim of this randomized controlled clinical trial was to test the contribution of oral supplementation of ALA to the standard treatment with Progesterone vaginal suppositories, in healing subchorionic hematomas in patients with threatened miscarriage. Controls were administered only Progesterone suppositories. PATIENTS AND METHODS: Nineteen pregnant women in the first trimester of gestation, with threatened miscarriage and ultrasound evidence of subchorionic hematoma, were included in the trial and randomly divided in two groups: controls, treated with 400 mg Progesterone (200 mg 2 times per day), given by vaginal suppositories, and case study treated with the same Progesterone dosage, plus ALA, given orally at the dose of 600 mg (300 mg 2 times per day, DAV®, Lo.Li. Pharma srl, Italy). Sixteen patients completed the trial. Treatment was performed until complete resolution of the clinical picture. RESULTS: In both groups, the subjects improved significantly but, in general, a better and faster evolution in the major signs of threatened miscarriage was observed in the subjects treated with ALA and Progesterone. In these patients, the speed of resorption of subchorionic hematoma was significantly (p ≤ 0.05) superior compared to controls. The ALA and Progesterone group showed a faster decrease or disappearance of all symptoms than that observed in the control group, however the difference was not significant. CONCLUSIONS: These preliminary results suggest that ALA supplementation significantly contributes to speed up the process of restoration of physiological conditions in threatened miscarriage and ameliorates the medical conditions of both the mothers and the foetus, probably modulating the networks of cytokines, growth factors and other molecules.