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Abstract Recently, the safety and efficacy of gene therapy were evaluated in patients with Crigler-Najjar syndrome (CNS). Although it is a promising curative option for CNS, many doubts still persist about its long-term efficacy and safety. Furthermore, there is a risk of overlooking several unresolved problems still present in current clinical practice. This letter is a call for action on crucial open issues that remain nowadays an unmet need in the management of CNS patients.

Obtaining a proper position for total hip arthroplasty components is a crucial aspect of implant performance and consequently of patient outcomes. Restoring the original hip center and maintaining the limb length are key factors in reaching the optimal implant positioning. The aim of this study was to assess the accuracy and safety of a computed dynamic analysis system that, through patient-specific guides, tries to improve implant positioning and functional orientation according to patients’ spinopelvic mobility and anatomy. A total of 100 consecutive patients were prospectively enrolled. All patients received an Optimized Positioning System dynamic hip preoperative planning schedule. A CT scan protocol follow-up analysis was performed 6 months after surgery. The mean deviations from the planned acetabular inclination and anteversion were 4.3° and 3.8°, respectively. In total, 98% of cases were within ± 10° of the Lewinnek safe zone, both for inclination and anteversion. The height of osteotomy deviated, on average, 1.6 mm. In total, 100% of cases were included within 4 mm of osteotomy. Patient-specific and laser-guided instrumentation was found to be safe and accurately reproduced dynamic planning in terms of the component orientation, osteotomy level, leg length and offset.

Wilson’s disease (WD) with acute onset poses a diagnostic challenge because it is clinically indistinguishable from other acute liver diseases. In addition, serum ceruloplasmin and urinary copper excretion, the first-line diagnostic tools for WD, can show false positive results in the case of acute liver failure, and the diagnostic role of genetic analysis is limited by the time required to perform it. In the case of fulminant onset, there is a clear indication of liver transplantation. “New Wilson Index” is frequently used to discriminate between patients who need liver transplantation versus those who can be successfully managed by medical treatment, but its reliability remains controversial. Timely referral of patients with acute liver failure due to WD may be a key factor in improving patient survival. Although liver transplant very often represents the only chance for such patients, maximum effort should be made to promote survival with a native liver. The management of these aspects of WD is still a matter of debate and will be the subject of this review.

Background. The success of orthotopic liver transplantation as a life-saving treatment has led to new indications and a greater competition for organ grafts. Pediatric patients with acute liver-related crises can benefit from orthotopic liver transplantation, but organ availability in the limited time can be a major obstacle. Crossing ABO blood group barriers could increase the organs available to such patients Methods. From November 2010 to June 2015, 176 children aged 0.2−to18 y were transplanted in the King Faisal Specialist Hospital and Research Center. Out of those, 19 children were transplanted across blood group barriers (ABO incompatible). The underlying diseases were biliary atresia (n = 6); progressive familial intrahepatic cholestasis type 2 (n = 4); Crigler-Najjar syndrome (n = 3); hepatoblastoma (n = 2); and urea cycle disorder, Caroli disease, cryptogenic cirrhosis, and neonatal sclerosing cholangitis (n = 1 each). Immunosuppression consisted of basiliximab, mycophenolate, tacrolimus, and steroids. Pretransplant prophylactic plasmapheresis, high-dose immunoglobulins, and rituximab were not administered. Results. The grafts were from living donors (n = 17) and deceased donors (n = 2). Living donor morbidity was nil. The recipient median age was 21 mo (5−70 mo). After a median follow-up of 44 mo, 2 recipients (10%) died because of sepsis, 1 because of uncontrolled acute myeloid leukemia. The overall rejection rate was 7%, and no grafts were lost because of antibody-mediated rejection (AMR). HLA matching was 3.8 of 6 (A, B, DR), and there were 2 patients presented with acute cellular rejection, 1 patient with AMR, and 1 patient with biliary strictures. Conclusions. ABO incompatible liver transplantation is a feasible and life-saving option even with antibody and B-cell depletion-free protocol without increasing the risks for AMR. We speculate that this excellent result is most likely because of presence of relatively low titer ABO isoagglutinins and the high HLA match compatibility caused by habit of longstanding interfamilial marriages as typical of Saudi Arabia.

Abstract Background Caroli disease (CD, OMIM #600643) is a rare autosomal recessive disorder characterized by polycystic segmental dilatation of the intrahepatic bile ducts and extreme variability in age of onset and clinical manifestations. When congenital hepatic fibrosis is associated with the polycystic dilatation of the biliary tract, the condition is referred as Caroli syndrome. The disease is thought to be caused by pathogenic variants in the PKHD1 gene (OMIM *606702). Method We report the clinical, biochemical, and molecular characterization of three patients with a clinical suspicion of CS belonging to two different families. The genetic screening was performed using a target custom panel and sequencing was performed on Illumina platform. Results Genetic analysis revealed the presence of rare variants in the PKHD1 gene of the analyzed patients. In the first case, and his younger sister, two pathogenic variants (c.2702A>C and c.4870C>T) were found to be associated with a hepatic phenotype at clinical onset, followed by renal disease probably age‐related; while in the second case, one pathogenic variant (c.5879C>G) and a complex allele with uncertain clinical significance [c.3407A>G; c.8345G>C; c.8606C>A] were found to be associated with a severe hepatic phenotype. Conclusion The identification of the genetic causes of the disease and their relationship with the clinical phenotype could have a favorable impact on clinical management and complication prevention.

Intestinal failure-associated liver disease (IFALD) is a progressive liver disease complicating intestinal failure (IF). It is a preventable and reversible condition, but at the same time, a potential cause of liver cirrhosis and an indication to combined or non-combined liver and small bowel transplantation. The diagnostic criteria are not yet standardized, so that its prevalence varies widely in the literature. Pathophysiology seems to be multifactorial, related to different aspects of intestinal failure and not only to the long-term parenteral nutrition treatment. The survival rates of children with IF have increased, so that the main problems today are preventing complications and ensuring a good quality of life. IFALD is one of the most important factors that limit long-term survival of patients with IF. For this reason, more and more interest is developing around it and the number of published articles is increasing rapidly. The purpose of this narrative review was to focus on the main aspects of the etiology, pathophysiology, management, prevention, and treatment of IFALD, based on what has been published mainly in the last 10 years. Controversies and current research gaps will be highlighted with the aim to pave the way for new project and high-quality clinical trials.

Kasai portoenterostomy (KP) plays a crucial role in the treatment of biliary atresia (BA). The aim is to correlate MRI quantitative findings of native liver survivor BA patients after KP with a medical outcome. Thirty patients were classified as having ideal medical outcomes (Group 1; n = 11) if laboratory parameter values were in the normal range and there was no evidence of chronic liver disease complications; otherwise, they were classified as having nonideal medical outcomes (Group 2; n = 19). Liver and spleen volumes, portal vein diameter, liver mean, and maximum and minimum ADC values were measured; similarly, ADC and T2-weighted textural parameters were obtained using ROI analysis. The liver volume was significantly (p = 0.007) lower in Group 2 than in Group 1 (954.88 ± 218.31 cm3 vs. 1140.94 ± 134.62 cm3); conversely, the spleen volume was significantly (p < 0.001) higher (555.49 ± 263.92 cm3 vs. 231.83 ± 70.97 cm3). No differences were found in the portal vein diameter, liver ADC values, or ADC and T2-weighted textural parameters. In conclusion, significant quantitative morpho-volumetric liver and spleen abnormalities occurred in BA patients with nonideal medical outcomes after KP, but no significant microstructural liver abnormalities detectable by ADC values and ADC and T2-weighted textural parameters were found between the groups.

Hepatic hydrothorax (HH) represents a rare complication of portal hypertension among adult cirrhotic patients. Here, we describe a pediatric case of HH, observed in a biliary atresia infant. The child presented with recurrent right-sided pleural effusion, after a successful Kasai portoenterostomy with restoration of bile flow and without overt signs of hepatic failure. Recurrence of HH led the patient to liver transplant despite a low pediatric end-stage liver disease value. Although rare, HH can also occur in children and should be suspected in patients with portal hypertension and respiratory distress. HH may be an indication for liver transplantation.

Neonatal cholestasis (NC) may be due to multiple surgical and non-surgical causes, some of which are potentially fatal. The list of potential causes of NC is long, and the systematic search for each of them is challenging in infants, especially when overt signs of underlying disease are lacking. Endocrinological diseases as causes of NC are rare and sometimes misdiagnosed. We report the case of an infant with prolonged cholestatic jaundice due to adrenal insufficiency suspected because of a single episode of hypoglycemia occurring at birth in the absence of clinical signs of adrenal impairment. Clinical exome analysis identified a new homozygous variant in MC2R gene as a putative responsible for familial glucocorticoid deficiency (FGD). Adrenal insufficiency should always be considered in all cholestatic infants, even in the absence of specific symptoms, since early recognition and treatment is essential to prevent life-threatening events.

Abstract Background Pseudo-ascites is a very rare condition in children and remains a challenging diagnosis. Targeted imaging may be helpful, but a high index of clinical suspicion is often necessary to guide the investigations, as pseudo-ascites may efficiently mimic true ascites. To date, still many cases of pseudo-ascites suffer diagnostic and therapeutic delay, and some are only diagnosed during surgical exploration. We report the case of a patient with a late laparoscopic diagnosis of pseudo-ascites. We retrospectively review our patient’s imaging findings and suggest new characteristic features which may help differentiate pseudo-ascites from true ascites. Case presentation A 7-month-old infant was referred for a progressive abdominal distention. Physical examination and initial ultra-sonographic findings evoked free ascites. An extensive diagnostic workup was then performed and was negative for hepatic, renal, cardiac, intestinal, pancreatic, inflammatory or infectious diseases, malignancy and congenital metabolic disorders. Pseudo-ascites was evoked and dedicated ultra-sonographic and magnetic resonance studies were repeated but could not confirm this diagnosis. Symptomatic diuretic treatment with spironolactone and furosemide was then started. A temporary and limited effect was noted but, with time, repeated paracenteses were necessary as the abdominal distention progressed causing discomfort and breathing difficulty. Last, because the patient’s quality of life deteriorated, a peritoneal-venous shunting was proposed; as the operation started with a diagnostic laparoscopy, a benign giant cystic mesenteric lymphangioma was identified and totally excised. The resolution of symptoms was immediate and the patient remained symptom-free throughout the subsequent observation period that lasted more than 1 year. Conclusions Increased awareness about pseudo-ascites is necessary, as the diagnosis is often overlooked, and treatment delayed. Targeted imaging may be helpful, as some specific, although not pathognomonic, features exist which may aid in the diagnosis.

Myasthenia gravis (MG) with symptoms limited to eye muscles [ocular MG (OMG)] is a rare disease. OMG incidence varies according to ethnicity and age of onset. In recent years, both an increase in incidence rate, particularly in the elderly, and a lower risk for secondary generalization may have contributed to the growing disease prevalence in Western countries. OMG should be considered in patients with painless ptosis and extrinsic ophthalmoparesis. Though asymmetric muscle involvement and symptom fluctuations are typical, in some cases, OMG can mimic isolated cranial nerve paresis, internuclear ophthalmoplegia, and conjugate gaze palsy. Diagnostic confirmation can be challenging in patients negative for anti-acetylcholine receptor and anti-muscle-specific tyrosine kinase antibodies on standard radioimmunoassay. Early treatment is aimed at relieving symptoms and at preventing disease progression to generalized MG. Despite the absence of high-level evidence, there is general agreement on the efficacy of steroids at low to moderate dosage; immunosuppressants are considered when steroid high maintenance doses are required. The role of thymectomy in non-thymoma patients is controversial. Prolonged exposure to immunosuppressive therapy has a negative impact on the health-related quality of life in a proportion of these patients. OMG is currently excluded from most of the treatments recently developed in generalized MG.

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.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system (CNS) primarily affecting the optic nerves and spinal cord, but also involving other regions of the CNS including the area postrema, periaqueductal gray matter, and hypothalamus. Knowledge related to pediatric manifestations of NMOSD has grown in recent years, particularly in light of newer information regarding the importance of not only antibodies to aquaporin 4 (AQP4-IgG) but also myelin oligodendrocyte glycoprotein (MOG-IgG) in children manifesting clinically with this syndrome. In this review, we describe the current state of the knowledge related to clinical manifestations, diagnosis, and chronic therapies for children with NMOSD, with emphasis on literature that has been published in the last 5 years. Following the review, we propose recommendations for the assessment/follow up clinical care, and treatment of this population.

The use of rituximab (RTX), an anti-CD20 monoclonal antibody (Ab), in refractory myasthenia gravis (MG) is associated with a better response in patients with Abs to the muscle-specific tyrosine kinase (MuSK) than in other MG subgroups. Anti-MuSK Abs are mostly IgG4 with proven pathogenicity and positive correlation with clinical severity. The rapid and sustained response to RTX may be related to MuSK Ab production by short-lived Ab-secreting cells derived from specific CD20+ B cells. Here, we investigated the long-term effects of RTX in nine refractory MuSK-MG patients with a follow-up ranging from 17 months to 13 years. In patients’ sera, we titrated MuSK-specific IgG (MuSK-IgG) and MuSK-IgG4, along with total IgG and IgG4 levels. Optimal response to RTX was defined as the achievement and maintenance of the status of minimal manifestations (MM)-or-better together with a ≥ 50% steroid reduction, withdrawal of immunosuppressants, and no need for plasma-exchange or intravenous immunoglobulin. After a course of RTX, eight patients improved, with optimal response in six, while only one patient did not respond. At baseline, MuSK-IgG and MuSK-IgG4 serum titers were positive in all patients, ranging from 2.15 to 49.5 nmol/L and from 0.33 to 46.2 nmol/L, respectively. MuSK Abs mostly consisted of IgG4 (range 63.80–98.86%). RTX administration was followed by a marked reduction of MuSK Abs at 2–7 months and at 12–30 months (p < 0.02 for MuSK-IgG and p < 0.01 for MuSK-IgG4). In patients with a longer follow-up, MuSK Ab titers remained suppressed, paralleling clinical response. In the patient who achieved long-term complete remission, MuSK-IgG4 was no longer detectable within 2 years, while MuSK-IgG remained positive at very low titers up to 10 years after RTX. In the patient who did not respond, MuSK-IgG and MuSK-IgG4 remained unchanged. In this patient series, total IgG and IgG4 transiently decreased (p < 0.05) at 2–7 months after RTX. The different trends of reduction between MuSK-IgG4 and total IgG4 after RTX support the view that short-lived Ab-secreting cells are the main producers of MuSK Abs. The ratio between short-lived Ab-secreting cells and long-lived plasma cells may influence the response to RTX, and B-cell severe depletion may reduce self-maintaining autoimmune reactivity.

Adverse clinical events in primary sclerosing cholangitis (PSC) happen too slowly to capture during clinical trials. Surrogate endpoints are needed, but no such validated endpoints exist for children with PSC. We evaluated the association between gamma glutamyltransferase (GGT) reduction and long‐term outcomes in pediatric PSC patients. We evaluated GGT normalization (< 50 IU/L) at 1 year among a multicenter cohort of children with PSC who did or did not receive treatment with ursodeoxycholic acid (UDCA). We compared rates of event‐free survival (no portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or liver‐related death) at 5 years. Of the 287 children, mean age of 11.4 years old, UDCA was used in 81% at a mean dose of 17 mg/kg/day. Treated and untreated groups had similar GGT at diagnosis (314 versus 300, P= not significant [NS]). The mean GGT was reduced at 1 year in both groups, with lower values seen in treated (versus untreated) patients (99 versus 175, P= 0.002), but 5‐year event‐free survival was similar (74% versus 77%, P= NS). In patients with GGT normalization (versus no normalization) by 1 year, regardless of UDCA treatment status, 5‐year event‐free survival was better (91% versus 67%, P< 0.001). Similarly, larger reduction in GGT over 1 year (> 75% versus < 25% reduction) was also associated with improved outcome (5‐year event‐free survival 88% versus 61%, P= 0.005). Conclusion:A GGT < 50 and/or GGT reduction of > 75% by 1 year after PSC diagnosis predicts favorable 5‐year outcomes in children. GGT has promise as a potential surrogate endpoint in future clinical trials for pediatric PSC.

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.

Fever and pain are challenging symptoms in children and adolescents and are common reasons for consultations in primary care and hospital. Paracetamol and ibuprofen are currently the only recommended drugs for treating fever in Italy, but the therapeutic approaches are discrepant in the different settings. In Italy, paracetamol and ibuprofen are the most prescribed analgesics for acute mild–moderate pain in children; however, their use is often inappropriate in that fever is over-treated and pain is under-treated. An Italian board of experts analyzed the motivations for the misalignment between daily practice and guidelines of fever and acute mild–moderate pain management of the territory and hospitals. The expert opinion consensus process underscored the appropriate use of paracetamol and ibuprofen according to clinical scenarios, patients’ profiles, and the safety features of the drugs. Although patients’ profiles can indicate different benefits from paracetamol or ibuprofen, critical issues of fever and acute mild–moderate pain management persist in primary care and hospitals. These expert opinion consensus statements can be an across-the-board tool to harmonize the routine practice between the territory and hospitals, especially under special conditions (at-risk for dehydration, coagulation disorder patients, etc.). It can also promote educational activity about fever and acute mild–moderate pain management to enhance the milestones already achieved by Italian pediatricians.

The functional positioning of components in a total hip arthroplasty (THA) and its relationship with individual lumbopelvic kinematics and a patient’s anatomy are being extensively studied. Patient-specific kinematic planning could be a game-changer; however, it should be accurately delivered intraoperatively. The main purpose of this study was to verify the reliability and accuracy of a patient-specific instrumentation (PSI) and laser-guided technique to replicate preoperative dynamic planning. Thirty-six patients were prospectively enrolled and received dynamic hip preoperative planning based on three functional lateral spinopelvic X-rays and a low dose CT scan. Three-dimensional (3D) printed PSI guides and laser-guided instrumentation were used intraoperatively. The orientation of the components, osteotomy level and change in hip length and offset were measured on postoperative CT scans and compared with the planned preoperative values. The length of surgery was compared with that of a matched group of thirty-six patients who underwent a conventional THA. The mean absolute deviation from the planned inclination and anteversion was 3.9° and 4.4°, respectively. In 92% of cases, both the inclination and anteversion were within +/− 10° of the planned values. Regarding the osteotomy level, offset change and limb length change, the mean deviation was, respectively, 1.6 mm, 2.6 mm and 2 mm. No statistically significant difference was detected when comparing the planned values with the achieved values. The mean surgical time was 71.4 min in the PSI group and 60.4 min in the conventional THA group (p < 0.05). Patient-specific and laser-guided instrumentation is safe and accurately reproduces dynamic planning in terms of the orientation of the components, osteotomy level, leg length and offset. Moreover, the increase in surgical time is negligible.

Abstract Background Several studies have recently shown better restoration of normal knee kinematics and improvement of rotator knee stability after reconstruction with higher femoral tunnel obliquity. The aim of this study is to evaluate tunnel obliquity, length, and posterior wall blowout in single-bundle anterior cruciate ligament (ACL) reconstruction, comparing the transtibial (TT) technique and the out–in (OI) technique. Materials and methods Forty consecutive patients operated on for ACL reconstruction with hamstrings were randomly divided into two groups: group A underwent a TT technique, while group B underwent an OI technique. At mean follow-up of 10 months, clinical results and obliquity, length, and posterior wall blowout of femoral tunnels in sagittal and coronal planes using computed tomography (CT) scan were assessed. Results In sagittal plane, femoral tunnel obliquity was 38.6 ± 10.2° in group A and 36.6 ± 11.8° in group B (p = 0.63). In coronal plane, femoral tunnel obliquity was 57.8 ± 5.8° in group A and 35.8 ± 8.2° in group B (p = 0.009). Mean tunnel length was 40.3 ± 1.2 mm in group A and 32.9 ± 2.3 mm in group B (p = 0.01). No cases of posterior wall compromise were observed in any patient of either group. Clinical results were not significantly different between the two groups. Conclusions The OI technique provides greater obliquity of the femoral tunnel in coronal plane, along with satisfactory length of the tunnel and lack of posterior wall compromise. Level of evidence II, prospective study.

Introduction. Intra-articular ganglion cysts of the knee joint are rare and mostly incidental findings in magnetic resonance imaging (MRI) or arthroscopy. Posterior cruciate ligament (PCL) ganglion cyst in a child is an extremely rare finding, and to the best of our knowledge, only one case has been described in the literature. We report a case of a large intra-articular ganglion cyst of the knee arising from the PCL in an autistic child. Case Presentation. An 8-year-old Caucasian boy affected by autism presented with nontraumatic knee pain. His parents, observing child’s gait, reported recurrent limp while walking, sometimes accompanied by knee locking. Clinical examination was hindered by the noncompliance of the patient and revealed painful limitation of terminal flexion and extension. MRI scans showed a large ganglion cyst located in the intercondylar notch. Arthroscopy confirmed an intrasubstance PCL ganglion cyst, extending both anteriorly and posteriorly. Complete excision of the cyst was performed, with full recovery of the child and no recurrence. Conclusion. In pediatric patients with pain or limited knee range of motion, physicians should consider the possibility of a ganglion cyst arising from the PCL, despite its rarity. Arthroscopic excision is a safe and effective procedure that guarantees a complete recovery of the patient with the lowest rate of recurrence.

Background: Periprosthetic joint infection (PJI) represents 25% of failed total knee arthroplasties (TKA). The European Knee Associates (EKA) formed a transatlantic panel of experts to perform a literature review examining patient-related risk factors with the objective of producing perioperative recommendations in PJI high-risk patients. Methods: Multiple databases (Pubmed/MEDLINE, EMBASE, Scopus, Cochrane Library) and recommendations on TKA PJI prevention measures from the International Consensus Meetings on PJI from the AAOS and AAHKS were reviewed. This represents a Level IV study. Results: Strong evidence was found on poor glycemic control, obesity, malnutrition, and smoking being all associated with increased rates of PJI. In the preoperative period, patient optimization is key: BMI < 35, diet optimization, Hemoglobin A1c < 7.5, Fructosamine < 292 mmol/L, smoking cessation, and MRSA nasal screening all showed strong evidence on reducing PJI risk. Intraoperatively, a weight-based antibiotic prophylaxis, accurate fluid resuscitation, betadine and chlorhexidine dual skin preparation, diluted povidone iodine solution irrigation, tranexamic acid administration, and monofilament barbed triclosan-coated sutures for soft tissues closure all represented effective prevention measures. In the postoperative period, failure to reach normalization of ESR, CRP, D-dimer, and IL-6 six weeks postoperatively suggested early PJI. Conclusion: The current recommendations from this group of experts, based on published evidence, support risk stratification to identify high-risk patients requiring implementation of perioperative measures to reduce postoperative PJI.

Background: Hereditary fructose intolerance (HFI) is a rare genetic disorder of fructose metabolism due to aldolase B enzyme deficiency. Treatment consists of fructose, sorbitol, and sucrose (FSS)-free diet. We explore possible correlations between daily fructose traces intake and liver injury biomarkers on a long-term period, in a cohort of young patients affected by HFI. Methods: Patients’ clinical data and fructose daily intake were retrospectively collected. Correlations among fructose intake, serum alanine aminotransferase (ALT) level, carbohydrate-deficient transferrin (CDT) percentage, liver ultrasonography, genotype were analyzed. Results: We included 48 patients whose mean follow-up was 10.3 ± 5.6 years and fructose intake 169 ± 145.4 mg/day. Eighteen patients had persistently high ALT level, nine had abnormal CDT profile, 45 had signs of liver steatosis. Fructose intake did not correlate with ALT level nor with steatosis severity, whereas it correlated with disialotransferrin percentage (R2 0.7, p < 0.0001) and tetrasialotransferrin/disialotransferrin ratio (R2 0.5, p = 0.0001). p.A150P homozygous patients had lower ALT values at diagnosis than p.A175D variant homozygotes cases (58 ± 55 IU/L vs. 143 ± 90 IU/L, p = 0.01). Conclusion: A group of HFI patients on FSS-free diet presented persistent mild hypertransaminasemia which did not correlate with fructose intake. Genotypes may influence serum liver enzyme levels. CDT profile represents a good marker to assess FSS intake.

Serological markers of Nuromyelitis Optica (NMO), an autoimmune disorder of the central nervous system, are autoantibodies targeting the astrocytic water channel aquaporin-4 (AQP4). We have previously demonstrated that the main epitopes for these autoantibodies (AQP4-IgG) are generated by the supramolecular arrangement of AQP4 tetramers into an Orthogonal Array of Particles (OAPs). Many tests have been developed to detect AQP4-IgG in patient sera but several procedural issues affect OAP assembly and consequently test sensitivity. To date, the protein based ELISA test shows the lowest sensitivity while representing a valid alternative to the more sensitive cell based assay (CBA), which, however, shows economic, technical and interpretation problems. Here we have developed a high perfomance ELISA in which native OAPs are used as the molecular target. To this aim a native size exclusion chromatography method has been developed to isolate integral, highly pure and AQP4-IgG-recognized OAPs from rat brain. These OAPs were immobilized and oriented on a plastic plate by a sandwich approach and 139 human sera were tested, including 67 sera from NMO patients. The OAP-ELISA showed a 99% specificity and a higher sensitivity (91%) compared to the CBA test. A comparative analysis revealed an end-point titer three orders of magnitude higher than the commercial ELISA and six times higher than our in-house CBA test. We show that CNS-extracted OAPs are crucial elements in order to perform an efficient AQP4-IgG test and the OAP-ELISA developed represents a valid alternative to the CBA currently used.