Comparing different approaches in robotic-assisted surgery for unicompartmental knee arthroplasty: outcomes at a short-term follow-up of MAKO versus NAVIO system.

The popularity of unicompartmental knee arthroplasty (UKA) continues to grow among orthopaedic surgeons and robotic surgery may be helpful in obtaining a precise placement of the prosthetic components, thanks to the meticulous intra-operative computer study for simulating the prosthetic positioning. This may lead to longer implant survivorship as well as a reduction in intermediate and long-term prosthetic complications, despite the initial greater costs than those of manual UKA. In this preliminary study, from January 2017 and October 2017, 18 patients underwent UKA with MAKO robotic system assistance and 10 patients received UKA with NAVIO robotic system assistance. The two groups were homogeneous by age, BMI, degree of osteoarthritis involvement, and postoperative program. Patients were followed both clinically (Numeric Rating Scale NRS and Knee Injury Osteoarthritis Outcome Scores KOOS) and radiographically. At the end term follow up (2 years), no significant difference was observed for NRS and KOOS as well as for clinical parameters as an active range of motion. A significant discrepancy was detected regarding the duration of the surgery and time of using the robotic system, that appeared to be longer in the NAVIO group than that of MAKO group, likely due to the specific technical aspects that characterize these two different robotic systems. The main finding of this study is that favorable clinical and radiographical results may be obtained using a robotic approach (MAKO or NAVIO) for UKA positioning at a short follow up. Due to the lack of significant clinical differences observed between the two groups of patients at end term follow up, the "concept" of a robotic approach, more than a specific patented system, may be considered the key element for improving UKA technique and it is likely that in the near future the choice of a single specific robotic system will still be a "surgeon's preference". The results of the study add scientific evidence regarding the effective improvement of UKA results using different robotic approaches. They also show possible economic sustainability of this therapeutic strategy related to the optimal patients' performance obtained at short term follow up, suggesting that the robotic assistance may really become a key element for better long-term survivorship of unicompartmental knee arthroplasty.

When math meets surgery: how to improve femoral interference screw alignment in ACL reconstruction. A cadaveric study.

Transtibial femoral tunnel drilling is still an alternative technique in ACL reconstruction. Femoral interference screw divergence is a potential pitfall associated with transtibial tunnel technique, as angles greater than 15° jeopardize graft fixation. Our mathematical model theorizes the proper degrees of knee flexion during femoral screw insertion and the correct screwdriver position to obtain a minimal divergence of the screw in the femoral tunnel. The cadaveric study confirms our method. Mathematical model: using rototranslation matrices, a correlation is demonstrated between the ACLtibial- guide angle, the knee flexion, and the screwdriver position. A theoretical minimal divergence between femoral interference screw and the femoral tunnel is obtainable following these assumptions: 1) knee hyperflexion during femoral screw insertion is obtained adding a flexion corresponding to the ACL-tibial-guide angle to the flexion while drilling the femoral tunnel; 2) screwdriver position (through the AM portal) is kept parallel to tibial plateau at a rotation of 15° medial to tibial sagittal plane. Cadaveric study: 24 cadaver knees were used. The transtibial tunnel was drilled with an 8 mm drill bit with the help of an ACL tibial guide set at 55°. To simulate femoral tunnel direction, a 2.4 mm K. wire was drilled through the femur with a transtibial 7 mm offset femoral drill guide. To simulate the femoral screw direction, a second 2.4 mm K. wire was drilled from the femoral entry point of the first wire through the femur, with a cannulated screwdriver. Screwdriver direction and knee flexion during the simulation were obtained following two different methods: GROUP A (mathematical model group, 12 knees), screwdriver direction and knee flexion were calculated following the mathematical model; in GROUP B (control group, 12 knees), knee hyperflexion and screwdriver medialization were manually obtained by a senior surgeon. The divergence between the femoral interference screw and the femoral tunnel was identified as the angle formed by the two wires, measured on the plane formed by the direction of the wires. Mean divergence angles between the K. wires were significantly different (p< 0.05) between the groups: GROUP 1 (mathematical rule): 7.25° (SD 2.2); GROUP 2 (free-hand technique): 17.3° (SD 2.9). Our study shows that a minimal divergence between the femoral tunnel and the screwdriver can be achieved simply by following a mathematical rule for correct intraoperative knee flexion and screwdriver position without the need for any specialized instrumentation. Namely, during femoral interference screw insertion through the anteromedial portal: 1) the correct knee flexion is the sum between the knee flexion angle while drilling the transtibial femoral tunnel AND the ACL tibial guide angle used during tibial tunnel drilling; 2) Correct screwdriver position is parallel to the tibial plateau, engaging the femoral tunnel with a position of 15° medial to tibial sagittal plane. This simple concept has clinical relevance in helping the surgeons in obtaining an optimal alignment between the femoral tunnel and the femoral interference screw during transtibial ACL reconstruction. Furthermore, following the assumptions of this study, a starting knee flexion angle around 70° during femoral tunnel drilling seems preferable for ACL reconstruction when the transtibial tunnel technique is used. Indeed, because ACL-tibial-guide angles range commonly from 50° to 60° and in vivo, the maximal intraoperative knee flexion attainable is 130°, a starting knee flexion around 70° is optimal to allows for adding flexion angles up to 60° before reaching the physiological limit value of 130°.

Rehabilitation protocol after simultaneous anterior cruciate ligament reconstruction and high tibial osteotomy: introducing the concept of the individualized approach.

Postoperative rehabilitation after simultaneous anterior cruciate ligament reconstruction and opening wedge high tibial osteotomy is a complex concept. Different osteotomy techniques, extremely selected patients, high expectations in returning to previous sport activities, and the different individual physical profile and performances make traditional chronological criteria impractical and unfeasible. This study presents a novel rehabilitation in which functional objective criteria are considered the key factors for standardizing a 4-step protocol. Each step is "individualized", based on the patient's response to the healing processes and to the different training phases, allowing for a safe return to sports competitions. This definitively implies a strict collaboration between patient, surgeon, physician and physiotherapists, as well as thorough and detailed patient education. Due to the high versatility of these new rehabilitation concepts, the application of the "individualized" steps described in this study may be broadened to include different sports medicine knee injuries that may benefit from a specific, detailed and carefully patient-centered rehabilitation project.

Eosinophilic cytoplasmic inclusions in type 2 papillary renal cell carcinoma.

A case of a patient with type 2 papillary renal cell carcinoma with eosinophilic cytoplasmatic inclusions is presented. About 50% of tumor cells were characterized by a well-circumscribed intra-cytoplasmatic round-to-oval or irregular inclusion/globule. Inclusions were 7-30 micron in diameter. They were glassy and pale to slightly eosinophilic in color in hematoxylin and eosin, were stained red by trichrome and were negative for periodic acid-Schiff reaction. Immunohistochemically, globules were negative for PAX8, epithelial membrane antigen, Carbonic Anhydrase IX, pan-cytokeratin (AE1/AE3), CD10, S100 protein, α-smooth-muscle actin, cytokeratin 7 and cytokeratin 34ßE12. Glassy hyaline globules were not detected in any adjacent normal kidney cells. The presence of eosinophilic cytoplasmic inclusions in renal cell carcinoma, especially in papillary renal cell carcinoma, has been rarely emphasized in the literature. In this article, we review similar cases in the literature and discuss the nature of eosinophilic globules.

Copy number variants analysis in a cohort of isolated and syndromic developmental delay/intellectual disability reveals novel genomic disorders, position effects and candidate disease genes.

BACKGROUND: Array-comparative genomic hybridization (array-CGH) is a widely used technique to detect copy number variants (CNVs) associated with developmental delay/intellectual disability (DD/ID). AIMS: Identification of genomic disorders in DD/ID. MATERIALS AND METHODS: We performed a comprehensive array-CGH investigation of 1,015 consecutive cases with DD/ID and combined literature mining, genetic evidence, evolutionary constraint scores, and functional information in order to assess the pathogenicity of the CNVs. RESULTS: We identified non-benign CNVs in 29% of patients. Amongst the pathogenic variants (11%), detected with a yield consistent with the literature, we found rare genomic disorders and CNVs spanning known disease genes. We further identified and discussed 51 cases with likely pathogenic CNVs spanning novel candidate genes, including genes encoding synaptic components and/or proteins involved in corticogenesis. Additionally, we identified two deletions spanning potential Topological Associated Domain (TAD) boundaries probably affecting the regulatory landscape. DISCUSSION AND CONCLUSION: We show how phenotypic and genetic analyses of array-CGH data allow unraveling complex cases, identifying rare disease genes, and revealing unexpected position effects.

(Epi)genotype-phenotype correlations in Beckwith-Wiedemann syndrome: a paradigm for genomic medicine.

Beckwith-Wiedemann syndrome (BWS) is the commonest overgrowth cancer predisposition disorder and represents a model for human imprinting dysregulation and tumorigenesis. BWS features can variably combine and present a widely variable range of severity in the phenotypic expression. This wide spectrum is paralleled at molecular level by complex (epi)genetic defects on chromosome 11p15.5 leading to disrupted expression of imprinted genes controlling growth and cellular proliferation. In this review, we outline the spectrum of clinical manifestations of BWS analyzing their (epi)genotype-phenotype correlations. The differences observed in the phenotypic profiles of BWS molecular subtypes allow a composite view of this syndrome with implications on clinical care, diagnosis, follow-up, and management, and provide directions for future disease monitoring.

Fetal growth patterns in Beckwith-Wiedemann syndrome.

We provide data on fetal growth pattern on the molecular subtypes of Beckwith-Wiedemann syndrome (BWS): IC1 gain of methylation (IC1-GoM), IC2 loss of methylation (IC2-LoM), 11p15.5 paternal uniparental disomy (UPD), and CDKN1C mutation. In this observational study, gestational ages and neonatal growth parameters of 247 BWS patients were compared by calculating gestational age-corrected standard deviation scores (SDS) and proportionality indexes to search for differences among IC1-GoM (n = 21), UPD (n = 87), IC2-LoM (n = 147), and CDKN1C mutation (n = 11) patients. In IC1-GoM subgroup, weight and length are higher than in other subgroups. Body proportionality indexes display the following pattern: highest in IC1-GoM patients, lowest in IC2-LoM/CDKN1C patients, intermediate in UPD ones. Prematurity was significantly more prevalent in the CDKN1C (64%) and IC2-LoM subgroups (37%). Fetal growth patterns are different in the four molecular subtypes of BWS and remarkably consistent with altered gene expression primed by the respective molecular mechanisms. IC1-GoM cases show extreme macrosomia and severe disproportion between weight and length excess. In IC2-LoM/CDKN1C patients, macrosomia is less common and associated with more proportionate weight/length ratios with excess of preterm birth. UPD patients show growth patterns closer to those of IC2-LoM, but manifest a body mass disproportion rather similar to that seen in IC1-GoM cases.

COX-2 expression is predictive for early relapse and aromatase inhibitor resistance in patients with ductal carcinoma in situ of the breast, and is a target for treatment.

BACKGROUND: Stratification of patients for treatment of ductal carcinoma in situ (DCIS) is suboptimal, with high systemic overtreatment rates. METHODS: A training set of 95 tumours from women with pure DCIS were immunostained for proteins involved in cell survival, hypoxia, growth factor and hormone signalling. A generalised linear regression with regularisation and variable selection was applied to a multiple covariate Cox survival analysis with recurrence-free survival 10-fold cross-validation and leave-one-out iterative approach were used to build and test the model that was validated using an independent cohort of 58 patients with pure DCIS. The clinical role of a COX-2-targeting agent was then tested in a proof-of-concept neoadjuvant randomised trial in ER-positive DCIS treated with exemestane 25 mg day(-1)± celecoxib 800 mg day(-1). RESULTS: The COX-2 expression was an independent prognostic factor for early relapse in the training (HR 37.47 (95% CI: 5.56-252.74) P=0.0001) and independent validation cohort (HR 3.9 (95% CI: 1.8-8.3) P=0.002). There was no significant interaction with other clinicopathological variables. A statistically significant reduction of Ki-67 expression after treatment with exemestane ± celecoxib was observed (P<0.02) with greater reduction in the combination arm (P<0.004). Concomitant reduction in COX-2 expression was statistically significant in the exemestane and celecoxib arm (P<0.03) only. CONCLUSIONS: In patients with DCIS, COX-2 may predict recurrence, aiding clinical decision making. A combination of an aromatase inhibitor and celecoxib has significant biological effect and may be integrated into treatment of COX2-positive DCIS at high risk of recurrence.

Prospective neoadjuvant analysis of PET imaging and mechanisms of resistance to Trastuzumab shows role of HIF1 and autophagy.

BACKGROUND: Although Trastuzumab has improved survival of HER2+ breast cancer patients, resistance to the agent pre-exists or develops through the course of therapy. Here we show that a specific metabolism and autophagy-related cancer cell phenotype relates to resistance of HER2+ breast cancer to Trastuzumab and chemotherapy. METHODS: Twenty-eight patients with locally advanced primary breast cancer were prospectively scheduled to received one cycle of Trastuzumab followed by a new biopsy on day 21, followed by taxol/Trastuzumab chemotherapy for four cycles before surgery. FDG PET/CT scan was used to monitor tumour response. Tissue samples were immunohistochemically analysed for metabolism and autophagy markers. RESULTS: In pre-Trastuzumab biopsies, the LC3A+/HER2+ cell population was correlated with HIF1α expression (P=0.01), while GLUT1 and LC3B expression were correlated with Ki67 proliferation index (P=0.01 and P=0.01, respectively). FDG PET tumour dimensions before therapy were correlated with LC3B expression (P=0.005). Administration of Trastuzumab significantly reduced clinical and PET-detected tumour dimensions (P<0.01). An inverse association of tumour response with the percentage of cells expressing HIF1α at baseline was documented (P=0.01). Administration of Trastuzumab resulted in a decrease of the proliferation index (P=0.004), GLUT1 (P=0.04) and HER2 (P=0.01) expression. In contrast, the percentage of LC3A+/HER2+ cells was increased (P=0.01). High baseline HIF1α expression was the only parameter associated with poorer pathological response to preoperative chemotherapy (P=0.001). CONCLUSIONS: As the HER2+/LC3A+ phenotype, which often overexpresses HIF1α, is a major subpopulation increasing after therapy with Trastuzumab, LC3A- and HIF1α-targeting therapies should be investigated for the augmentation of anti-HER2 therapy efficacy.

Assessment of energy-saving strategies and operational costs in full-scale membrane bioreactors.

The energy-saving strategies and operational costs of stand-alone, hybrid, and dual stream full-scale membrane bioreactors (MBRs) with capacities ranging from 1100 to 35,000 m(3) day(-1) have been assessed for seven municipal facilities located in Northeast Spain. Although hydraulic load was found to be the main determinant factor for the energy consumption rates, several optimisation strategies have shown to be effective in terms of energy reduction as well as fouling phenomenon minimization or preservation. Specifically, modifications of the biological process (installation of control systems for biological aeration) and of the filtration process (reduction of the flux or mixed liquor suspended solids concentration and installation of control systems for membrane air scouring) were applied in two stand-alone MBRs. After implementing these strategies, the yearly specific energy demand (SED) in flat-sheet (FS) and hollow-fibre (HF) stand-alone MBRs was reduced from 1.12 to 0.71 and from 1.54 to 1.12 kW h(-1) m(-3), respectively, regardless of their similar yearly averaged hydraulic loads. The strategies applied in the hybrid MBR, namely, buffering the influent flow and optimisation of both biological aeration and membrane air-scouring, reduced the SED values by 14%. These results illustrate that it is possible to apply energy-saving strategies to significantly reduce MBR operational costs, highlighting the need to optimise MBR facilities to reconsider them as an energy-competitive option.

A high resolution deletion map of human chromosome Xp22.

We have developed a 32-interval deletion panel for human chromosome Xp22 spanning about 30 megabases of genomic DNA. DNA samples from 50 patients with chromosomal rearrangements involving Xp22 were tested with 60 markers using a polymerase chain reaction strategy. The ensuing deletion map allowed us to confirm and refine the order of previously isolated and newly developed markers. Our mapping panel will provide the framework for mapping new sequences, for orienting chromosome walks in the region and for projects aimed at isolating genes responsible for diseases mapping to Xp22.

Loss-of-function mutations in the EGF-CFC gene CFC1 are associated with human left-right laterality defects.

All vertebrates display a characteristic asymmetry of internal organs with the cardiac apex, stomach and spleen towards the left, and the liver and gall bladder on the right. Left-right (L-R) axis abnormalities or laterality defects are common in humans (1 in 8,500 live births). Several genes (such as Nodal, Ebaf and Pitx2) have been implicated in L-R organ positioning in model organisms. In humans, relatively few genes have been associated with a small percentage of human situs defects. These include ZIC3 (ref. 5), LEFTB (formerly LEFTY2; ref. 6) and ACVR2B (encoding activin receptor IIB; ref. 7). The EGF-CFC genes, mouse Cfc1 (encoding the Cryptic protein; ref. 9) and zebrafish one-eyed pinhead (oep; refs 10, 11) are essential for the establishment of the L-R axis. EGF-CFC proteins act as co-factors for Nodal-related signals, which have also been implicated in L-R axis development. Here we identify loss-of-function mutations in human CFC1 (encoding the CRYPTIC protein) in patients with heterotaxic phenotypes (randomized organ positioning). The mutant proteins have aberrant cellular localization in transfected cells and are functionally defective in a zebrafish oep-mutant rescue assay. Our findings indicate that the essential role of EGF-CFC genes and Nodal signalling in left-right axis formation is conserved from fish to humans. Moreover, our results support a role for environmental and/or genetic modifiers in determining the ultimate phenotype in humans.

X-linked situs abnormalities result from mutations in ZIC3.

Vertebrates position unpaired organs of the chest and abdomen asymmetrically along the left-right (LR) body axis. Each structure comes to lie non-randomly with respect to the midline in an overall position designated situs solitus, exemplified in humans by placement of the heart, stomach and spleen consistently to the left. Aberrant LR axis development can lead to randomization of individual organ position (situs ambiguus) or to mirror-image reversal of all lateralized structures (situs inversus). Previously we mapped a locus for situs abnormalities in humans, HTX1, to Xq26.2 by linkage analysis in a single family (LR1) and by detection of a deletion in an unrelated situs ambiguus male (Family LR2; refs 2,3). From this chromosomal region we have positionally cloned ZIC3, a gene encoding a putative zinc-finger transcription factor. One frameshift, two missense and two nonsense mutations have been identified in familial and sporadic situs ambiguus. The frameshift allele is also associated with situs inversus among some heterozygous females, suggesting that ZIC3 functions in the earliest stages of LR-axis formation. ZIC3, which has not been previously implicated in vertebrate LR-axis development, is the first gene unequivocally associated with human situs abnormalities.

Case report: Gastroenterological management in a case of cardio-facio-cutaneous syndrome.

Background: cardio-facio-cutaneous syndrome is a rare genetic disorder affecting less than 900 people in the world. It is mainly characterized by craniofacial, dermatologic and cardiac defects, but also gastroenterological symptoms may be present, ranging from feeding difficulties to gastroesophageal reflux and constipation.In this report we describe a case of this syndrome characterized by severe feeding and growth difficulties, with a particular focus on the management of gastroenterological complications. Case presentation: the patient was a caucasian male affected by Cardio-Facio-Cutaneous syndrome who presented feeding difficulties already a few hours after birth. These symptoms worsened in the following months and lead to a complete growth arrest and malnutrition. He was first treated with a nasogastric tube placement. Subsequently, a laparoscopic Nissen fundoplication and a laparoscopic Stamm gastrostomy were performed. The child was fed with nocturnal enteral nutrition and diurnal oral and enteral nutrition. Eventually the patient resumed feeding validly and regained adequate growth. Conclusion: this paper aims to bring to light a complex rare syndrome that infrequently comes to the attention of the pediatricians and whose diagnosis is not always straightforward. We also highlight the possible complications under a gastroenterologic point of view. Our contribution can be helpful to the pediatrician in the first diagnostic suspect of this syndrome. In particular, it is worth highlighting that -in an infant with Noonan-like features- symptoms like suction or swallowing problems, vomiting and feeding difficulties should orient towards the diagnosis of a Cardio-facio-cutaneous syndrome. It is also important to stress that its related gastroenterological issues may lead to severe growth failure and therefore the role of the gastroenterologist is key to manage supplemental feeding and to establish whether a nasogastric or gastrostomic tube placement is necessary.

Multimodality imaging of intraosseous ganglia of the wrist and their differential diagnosis.

Intraosseous ganglion (IOG) is the most frequently occurring bone lesion within the carpus and is often an incidental finding on radiographs obtained for other reasons. Two types of IOG have been described: an "idiopathic" form (or type I), the pathogenesis of which has not been completely clarified, and a "penetrating" form (or type II), caused by the intrusion of juxtacortical material (often a ganglion cyst of the dorsal soft tissue) into the cancellous bone compartment. The differential diagnosis for IOG is wide-ranging and complex, including lesions of posttraumatic (posttraumatic cystlike defects), degenerative (subchondral degenerative cysts), inflammatory [cystic rheumatoid arthritis, chronic tophaceous gout (CTG)], neoplastic (benign primary bone tumours and synovial proliferative lesions), ischaemic (Kienböck's disease or avascular osteonecrosis of the lunate) and metabolic (amyloidosis) origin. Multimodality imaging of IOGs is a useful diagnostic tool that provides complete morphological characterisation and differentiation from other intraosseous cystic abnormalities of the carpus. Thin-slice multidetector computed tomography (MDCT) can provide high-spatial-resolution images of the cortical and cancellous bone compartments, allowing detection of morphological findings helpful in characterising bone lesions, whereas magnetic resonance (MR) imaging can simultaneously visualise bone, articular surfaces, hyaline cartilage, fibrocartilage, capsules and ligaments, along with intra- and periarticular soft tissues.

Imaging studies of crystalline arthritides.

Gout, calcium pyrophosphate dihydrate (CPPD) deposition disease, and calcium hydroxyapatite deposition disease (HADD) are the three most common crystal-induced arthropathies. Multimodality imaging may help in their diagnosis, and is useful for a precise and comprehensive assessment and grading of the related osteoarticular damage. Plain film radiography, due to its low cost and wide availability, is the first imaging technique to be used in crystal deposition diseases, providing well-known and specific findings for CPPD deposition disease and HADD, while it may undergrade the early osteoarticular lesions in gouty patients. Ultrasonography (US) is a radiation-free approach that accurately depicts crystal deposits in cartilage, peri- and intra-articular soft tissues, but it does not give a panoramic view of the affected joints. Cross-sectional imaging techniques can examine crystal deposits in the spine and axial joints. CT has the potential to distinguish monosodium urate (MSU) crystals from calcium containing crystals, due to their different attenuation values. MRI may demonstrate synovitis, erosions and bone marrow edema in gouty patients and it may differentiate tophi from other soft tissue nodules due to its high contrast resolution and power of tissue characterization.

Brain Abnormalities in Patients with Germline Variants in H3F3: Novel Imaging Findings and Neurologic Symptoms Beyond Somatic Variants and Brain Tumors.

BACKGROUND AND PURPOSE: Pathogenic somatic variants affecting the genes Histone 3 Family 3A and 3B (H3F3) are extensively linked to the process of oncogenesis, in particular related to central nervous system tumors in children. Recently, H3F3 germline missense variants were described as the cause of a novel pediatric neurodevelopmental disorder. We aimed to investigate patterns of brain MR imaging of individuals carrying H3F3 germline variants. MATERIALS AND METHODS: In this retrospective study, we included individuals with proved H3F3 causative genetic variants and available brain MR imaging scans. Clinical and demographic data were retrieved from available medical records. Molecular genetic testing results were classified using the American College of Medical Genetics criteria for variant curation. Brain MR imaging abnormalities were analyzed according to their location, signal intensity, and associated clinical symptoms. Numeric variables were described according to their distribution, with median and interquartile range. RESULTS: Eighteen individuals (10 males, 56%) with H3F3 germline variants were included. Thirteen of 18 individuals (72%) presented with a small posterior fossa. Six individuals (33%) presented with reduced size and an internal rotational appearance of the heads of the caudate nuclei along with an enlarged and squared appearance of the frontal horns of the lateral ventricles. Five individuals (28%) presented with dysgenesis of the splenium of the corpus callosum. Cortical developmental abnormalities were noted in 8 individuals (44%), with dysgyria and hypoplastic temporal poles being the most frequent presentation. CONCLUSIONS: Imaging phenotypes in germline H3F3-affected individuals are related to brain features, including a small posterior fossa as well as dysgenesis of the corpus callosum, cortical developmental abnormalities, and deformity of lateral ventricles.

Imaging of tophi with an extremity-dedicated MRI system.

OBJECTIVES: To describe the MRI features of gout tophi in the soft-tissues or joints of the limbs by low-field extremity-dedicated MRI. METHODS: Nine consecutive patients, 8M/1W, affected by chronic tophaceous gout were studied. Mean patients' age was 71.3±11.5 years, mean disease duration 98.1±44.9 months, and mean serum uric acid concentration 9.2±2.8 mg/L. Diagnosis was based on the ACR classification criteria for gout, and by identification of MSU crystals in the tophi and synovial fluid. Conventional radiograms and MRI with an extremity-dedicated system were obtained of the joint areas involved by tophi. RESULTS: At T1 weighted MRI images, all tophi showed a homogeneous intermediate signal intensity, similar to that of muscle. Conversely, in T2 weighted images, a wide spectrum of signal intensity patterns was observed. The pattern of contrast enhancement was variable from intense homogeneous to peripheral and heterogeneous. Capsulo-ligamentous structures were often thickened and degenerated and, on occasion, could be recognised as inhomogeneous, hypointense ribbon-shaped elements in the context of the tophus. In only two cases, tendons were infiltrated by tophaceous matter. Bone marrow oedema (BME) and erosions were seen in 8 out of 10 bones adjacent to tophi. CONCLUSIONS: The MRI appearance of gout tophi using an extremity-dedicated machine is similar to that described in the literature using whole body machines. BME adjacent to the tophus was a frequent finding. This technique may occasionally help in the differential diagnosis of nodules and in the follow-up of the disease. It also represents a useful tool to investigate the pathogenesis of gout and to better understand its clinical progression.

Prenatal features of Noonan syndrome: prevalence and prognostic value.

OBJECTIVE: Noonan syndrome (NS) is a common autosomal dominant developmental disorder, mainly characterized by congenital heart defects, short stature, and a variable degree of developmental delay. We have reviewed the prenatal findings in NS and we have correlated them with genotype and postnatal phenotype. METHODS: The cohort consisted of 47 patients with molecular diagnosis of NS. Prenatal and postnatal phenotypes were assessed by analysis of medical records, and clinical follow-up. Postnatal clinical phenotype, congenital heart disease, neuropsychomotor development, and growth pattern were arbitrarily scored in terms of severity. RESULTS: Mean age at diagnosis of NS was 7 years (ranging from birth to 38 years). Abnormal maternal serum triple screen was present in 36% of cases, nuchal translucency > 2.5 mm in 41%, polyhydramnios in 38% and fetal anomalies at prenatal ultrasonography in 21%. No statistical association was observed between prenatal findings and NS genotype or scores of postnatal clinical phenotype, congenital heart disease, neuropsychomotor development, or short stature. Presence of morphologic fetal anomalies at ultrasonography was associated with developmental delay/intellectual disabilities (p < 0.001) and juvenile myelomonocytic leukaemia (p = 0.006). CONCLUSIONS: Abnormal prenatal findings are frequent in NS pregnancies, though they are not specific and most are not useful for the prediction of the postnatal phenotype.

A knowledge-based control system for air-scour optimisation in membrane bioreactors.

Although membrane bioreactors (MBRs) technology is still a growing sector, its progressive implementation all over the world, together with great technical achievements, has allowed it to reach a mature degree, just comparable to other more conventional wastewater treatment technologies. With current energy requirements around 0.6-1.1 kWh/m3 of treated wastewater and investment costs similar to conventional treatment plants, main market niche for MBRs can be areas with very high restrictive discharge limits, where treatment plants have to be compact or where water reuse is necessary. Operational costs are higher than for conventional treatments; consequently there is still a need and possibilities for energy saving and optimisation. This paper presents the development of a knowledge-based decision support system (DSS) for the integrated operation and remote control of the biological and physical (filtration and backwashing or relaxation) processes in MBRs. The core of the DSS is a knowledge-based control module for air-scour consumption automation and energy consumption minimisation.