Long-term clinical results and MRI changes after autologous chondrocyte implantation in the knee of young and active middle aged patients.

BACKGROUND: Autologous chondrocyte implantation (ACI) represents a valid surgical option for symptomatic full-thickness chondral lesions of the knee. Here we report long-term clinical and MRI results of first-generation ACI. MATERIALS AND METHODS: Fifteen patients (mean age 21.3 years) underwent first-generation ACI for symptomatic chondral defects of the knee between 1997 and 2001. The mean size of the lesions was 5.08 cm(2) (range 2-9 cm(2)). Patients were evaluated using the International Knee Documentation Committee (IKDC) Knee Examination Form, the Tegner Activity Scale, and the Knee Injury and Osteoarthritis Outcome Score (KOOS). High-resolution MRI was used to analyze the repair tissue with nine variables (the MOCART scoring system). RESULTS: The mean follow-up period was 148 months (range 125-177 months). ACI resulted in substantial improvements in all clinical outcome parameters, even as much as 12 years after implantation. A significant decrease in the MOCART score was recorded at final measurement. Reoperation was required in 2 patients; failure was caused by partial detachment of the graft in both cases. CONCLUSION: Autologous chondrocyte implantation is an effective and durable solution for the treatment of large, full-thickness cartilage and osteochondral lesions, even in young and active middle-aged patients. High-resolution MRI is a useful and noninvasive method for evaluating the repaired tissue. LEVEL OF EVIDENCE: IV.

Muscle fiber type disproportion (FTD) in a family with mutations in the LMNA gene.

INTRODUCTION: Mutations in the lamin A/C protein cause laminopathies, a heterogeneous group of disorders that include recessive axonal neuropathy (CMT2B1), Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy (LGMD), dilated cardiomyopathy with conduction defect, and different forms of lipodystrophy and progeria. METHODS: We provide clinical, histopathological, muscle imaging, and cardiac features of a family with heterozygous mutation in the LMNA gene. RESULTS: We identified heterozygous mutations (c.80C> T; pT27I) in the LMNA gene in 3 family members who had the LGMD phenotype with onset in their early thirties and cardiac conduction defects or dilated cardiomyopathy. Interestingly, muscle biopsies showed changes consistent with fiber type disproportion (FTD). CONCLUSIONS: Fiber type disproportion has been reported only anecdotally in muscle biopsies of patients with LMNA mutations. Our report further supports this association and suggests inclusion of molecular testing for LMNA in the differential diagnosis of myopathies with FTD due to the risk for life threatening events.

F-18 FDG PET/CT quantization parameters as predictors of outcome in patients with diffuse large B-cell lymphoma.

AIM: We evaluated the prognostic significance of standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) obtained by F-18 FDG PET/CT (PET/CT) in patients with diffuse large B-cell Lymphomas (DLBCL) presenting intermediate IPI score. MATERIAL AND METHODS: Fifty-two patients (61 ± 13 yr) underwent PET/CT before the first-line chemotherapy. The mean SUVmax value, the summed MTV (cm(3) ; 42% threshold), and the cumulative TLG (g) were registered. The patients were followed up 18 months thereafter (range 3-41 months). The PET/CT results were compared to the event-free survival (EFS). RESULTS: At univariate analysis, SUVmax and lactate dehydrogenase (LDH) levels were predictive, but discordantly. The Kaplan-Meier survival analysis for SUVmax showed a significant better EFS in patients presenting higher values as compared to those having lesser (P = 0.0002, HR 0.13). Summed MTV and cumulative TLG were not suitable for predicting EFS. CONCLUSION: Despite the availability of new tools for the quantitative assessment of disease activity on PET/CT, the SUVmax rather than MTV and TLG remains the only predictor for EFS in DLBCL patients. The magnitude of glycolytic activity rather than the amount of metabolically active burden holds a predominant value for determining the response to chemotherapy in DLBCL.

Imiglucerase, cholecalciferol, and bone-diet in skeletal health management of type I Gaucher disease patients: a pilot study and systematic review.

Skeletal anomalies represent a characteristic feature of type 1 Gaucher disease (GD1). Here we evaluated the impact of an integrated therapy comprising enzyme-replacement therapy (ERT), cholecalciferol, and a normocalcemic-normocaloric-hyposodic diet (bone diet) on bone health in GD1 patients. We also performed a systematic review to compare our results with available data. From January 1, 2015 to February 28, 2019, all GD1 patients referred to Federico II University were enrolled and treated with the integrated therapy. Bone turnover markers and bone mineral density (BMD) were evaluated at baseline (T0) and after 24 months (T24). We enrolled 25 GD1 patients, all showing 25-hydroxy vitamin D (25OHD) levels < 50 nmol/l (hypovitaminosis D) at T0. Response to cholecalciferol treatment was effective, showing a direct relationship between 25OHD levels before and after treatment. At T0, 2 GD1 patients showed fragility fractures, 5 the Erlenmeyer flask deformity, 3 osteonecrosis, and 7 a BMD Z-score ≤ -2. Overall, GD1 patients with bone anomalies showed higher C-terminal telopeptide levels compared with those without bone anomalies. No new bone anomalies occurred during 2 years of follow-up. At T24, BMD remained stable across the entire study cohort, including in patients with bone anomalies. The systematic review showed that our study is the first that evaluated all bone health parameters. Hypovitaminosis D is prevalent in GD1 patients. The response to cholecalciferol treatment was effective but different to healthy subjects and in patients with metabolic bone disorders. Integrated therapy including ERT, cholecalciferol, and bone diet guarantees bone health.

New developments in magnetic resonance imaging of the nail unit.

The evolution of dedicated magnetic resonance imaging (MRI) musculoskeletal equipment allows new sequences and better images of the nail unit. The use of MRI has modified the imaging strategies used in treating inflammatory arthritis. In the case of psoriatic arthritis (PsA), the MRI study of the nail unit identifies nail involvement, which appears as an initial lesion for the induction of distal phalanx damage and consequently of distal interphalangeal joint arthritis. All patients with psoriasis, even in the absence of a clinically evident onychopathy, show characteristic MRI changes in the nail. This evidence could have a practical diagnostic value, because MRI study of the nail could document diagnosis in patients with undifferentiated spondyloarthropathies who have a barely evident psoriasis. We discuss the advantages and problems related to the use of low-field and high-field MRI in the study of the nail unit of patients with PsA.

Liver-Directed Adeno-Associated Virus-Mediated Gene Therapy for Mucopolysaccharidosis Type VI.

BACKGROUND: Mucopolysaccharidosis type VI (MPS VI) is an inherited multisystem lysosomal disorder due to arylsulfatase B (ARSB) deficiency that leads to widespread accumulation of glycosaminoglycans (GAG), which are excreted in increased amounts in urine. MPS VI is characterized by progressive dysostosis multiplex, connective tissue and cardiac involvement, and hepatosplenomegaly. Enzyme replacement therapy (ERT) is available but requires life-long and costly intravenous infusions; moreover, it has limited efficacy on diseased skeleton and cardiac valves, compromised pulmonary function, and corneal opacities. METHODS: We enrolled nine patients with MPS VI 4 years of age or older in a phase 1/2 open-label gene therapy study. After ERT was interrupted, patients each received a single intravenous infusion of an adeno-associated viral vector serotype 8 expressing ARSB. Participants were sequentially enrolled in one of three dose cohorts: low (three patients), intermediate (two patients), or high (four patients). The primary outcome was safety; biochemical and clinical end points were secondary outcomes. RESULTS: The infusions occurred without severe adverse events attributable to the vector, meeting the prespecified end point. Participants in the low and intermediate dose cohorts displayed stable serum ARSB of approximately 20% of the mean healthy value but returned to ERT by 14 months after gene therapy because of increased urinary GAG. Participants in the high-dose cohort had sustained serum ARSB of 30% to 100% of the mean healthy value and a modest urinary GAG increase that did not reach a concentration at which ERT reintroduction was needed. In the high-dose group, there was no clinical deterioration for up to 2 years after gene therapy. CONCLUSIONS: Liver-directed gene therapy for participants with MPS VI did not have a dose-limiting side-effect and adverse event profile; high-dose treatment resulted in ARSB expression over at least 24 months with preliminary evidence of disease stabilization. (Funded by the Telethon Foundation ETS, the European Commission Seventh Framework Programme, and the Isaac Foundation; ClinicalTrials.gov number, NCT03173521; EudraCT number, 2016-002328-10.)

Atypical dermoid cyst of the ovary during pregnancy: A multi-modality diagnostic approach.

We report a case of a sixth-month-pregnant 37-year-old woman with abdominal pain with the presence of a dermoid cyst of the left ovary. The diagnostic work-up required a multi-modality imaging approach. In particular, US and MR examinations were initially performed but resulted with an inconclusive outcome of a final diagnosis. Hence, a CT scan was successively used to formulate lesion characterization. Thus, integrated imaging approach would be recommended.

Magnetic resonance imaging of nail unit in psoriatic arthritis.

The use of magnetic resonance imaging (MRI) has modified the imaging strategies of inflammatory arthritides. In psoriatic arthritis (PsA), MRI study of the nail unit identifies nail involvement that appears as the initial lesion for induction of distal phalanx damage and consequently of distal interphalangeal joint arthritis. All psoriatic patients, also in the absence of a clinically evident onychopathy, show characteristic MRI changes of the nail. This evidence could have practical diagnostic value because MRI study of the nail could document diagnosis in patients with undifferentiated spondyloarthropathies who have barely evident psoriasis. We discuss the advantages and problems related to the use of low- and high-field MRI in the study of the nail unit of patients with PsA.

The role of imaging in the skeletal involvement of mucopolysaccharidoses.

This article discusses the role of imaging modalities including radiography, multi-detector computed tomography, magnetic resonance imaging, and ultrasound in diagnosing and monitoring skeletal abnormalities in mucopolysaccharidoses (MPS). The advantages and disadvantages of these different imaging tools will be discussed, along with their feasibility in this class of patients. As the musculoskeletal involvement is common to all MPS and is one of the main reasons for seeking medical attention, an increased awareness among paediatricians, rheumatologists, orthopaedists, radiologists, and other musculoskeletal specialists on the possible spectrum of abnormalities observed could facilitate a timely diagnosis, an appropriate severity evaluation, and better management.

Spleen enlargement following recombinant human granulocyte colony-stimulating factor administration for peripheral blood stem cell mobilization.

BACKGROUND AND OBJECTIVES: Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is widely used to mobilize peripheral blood stem cells (PBSC) for autologous or allogeneic transplants. Such treatment may cause spleen enlargement; exceptionally, spontaneous spleen rupture has been reported. We investigated changes in spleen size during stem cell mobilization. DESIGN AND METHODS: We evaluated spleen size, comparing palpation with ultrasound (US)-evaluated longitudinal diameter and volume, in 13 healthy donors and 22 patients with a hematological malignancy who were undergoing PBSC mobilization with rhG-CSF-including regimens. RESULTS: Intraobserver and interobserver variability of US-calculated spleen volume was very low; the correlation between the volume calculated by US and that measured by 3-dimensional computed tomography was excellent. During mobilization, spleen enlargement was detected by palpation in 17% of subjects, by US-measured longitudinal diameter in 60%, and by US-calculated volume in 91%. The median increase in spleen volume was 300 mL (range, 54-820; p<0.001) in healthy donors and 135 mL (range, 0-413; p=0.004) in the group of patients; the enlargement correlated with white blood cell count elevation (p=0.016) but not with circulating CD34+ cells. One month after the last administration of rhG-CSF, the median decrease was 160 mL (range, 35-800) in healthy donors and 58 mL (range, 0-310) in patients. INTERPRETATION AND CONCLUSIONS: When evaluated by sensitive methods, rhG-CSF caused spleen enlargement in almost all individuals treated. US-calculated volume proved to be an excellent method, much better than longitudinal diameter, for detecting non-palpable splenomegaly induced by rhG-CSF.

Discovertebral erosions in patients with enteropathic spondyloarthritis.

OBJECTIVE: Magnetic resonance imaging (MRI) is considered the modality of choice for the diagnosis of spondyloarthropathy (SpA)-related spondylodiscitis, or discovertebral erosions (DE). Our aim was to analyze the prevalence and the clinical features of DE in patients with enteropathic SpA (EA) using MRI. METHODS: We evaluated 72 patients with EA and 43 controls for the study. All patients and controls underwent rheumatological and gastroenterological clinical examinations, and demographic features were recorded. For each patient, these factors were also recorded: duration of inflammatory bowel disease and arthritis from onset to enrollment, history of viral and bacterial infections, and occurrence of previous major trauma to the spine. These scores were taken: Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Harvey-Bradshaw Index, and the Simple Clinical Colitis Activity Index. All subjects had MRI of the spine. RESULTS: On the basis of inclusion criteria, 43 patients with EA were included in the study. Twenty-three had axial EA (axEA) and 20 had axial and peripheral subset EA (overlap subset or peripheral type 3; axphEA). Twenty-two patients with EA (15/7 axEA/axphEA) showed DE (30.55%; p < 0.001). DE was significantly more prevalent in axEA subjects than in the overlap subset (p < 0.001). In axEA, DE had a significant direct correlation with arthritis duration (r = 0.546, p = 0.007). Patients with DE showed BASDAI, BASMI, and BASFI scores significantly higher than patients without DE (p < 0.001). CONCLUSION: We found a high prevalence of DE among patients with EA (30.55%), confirming that DE is an important characteristic aspect of SpA. We found a high prevalence in patients in the axphEA subset (31.82%), suggesting that DE could be a characterizing feature of the overlap subset.

Accuracy of sonographic volume measurements of kidney transplant.

PURPOSE: Sonographic measurement of renal volume is one of the parameters used in the diagnosis of renal transplant dysfunction and in follow-up of patients with renal transplant. The aim of this study was to compare the prolate ellipsoid formula with a new formula in calculating the volume of a transplanted kidney. METHODS: The renal volumes in 24 patients with a stable renal transplant were determined sonographically with the ellipsoid formula and via helical CT with the voxel-count method, which is the gold standard. A new formula that uses renal length and the cross-sectional area at the maximum transverse section has been evaluated in a small series of transplanted kidneys. RESULTS: Renal volume was underestimated with the sonographic ellipsoid formula and the new formula. The new formula yielded the lowest underestimation of the mean renal volume, and the measurements obtained with it were not significantly different from those obtained with CT. CONCLUSIONS: The use of sonography is appropriate for accurate calculation of renal volume, and the new formula that uses only 2 ultrasound parameters best represents the volume of a renal transplant.

Nail and distal interphalangeal joint in psoriatic arthritis.

OBJECTIVE: To study distal interphalangeal (DIP) joints in patients with psoriatic arthritis (PsA) with or without onychopathy, using magnetic resonance imaging (MRI). METHODS: Twenty-three patients with PsA (9/14 F/M, median age 47 yrs), 12 with onychopathy (2/10 F/M, median age 44 yrs) and 11 without (7/4 F/M, median age 52 yrs), and 10 control subjects (5/5 F/M, median age 43.2 yrs) were enrolled. MRI of nail and distal phalanx (DP) including examination of DIP joints was carried out. MRI was performed with a surface coil in a 1.5 T device. For each selected finger, both longitudinal and axial scans were performed. The involvement of nail, DP, and DIP joint was scored. RESULTS: Nail thickening with or without surface irregularity occurred in 95.7% of cases (100% with onychopathy and 90.9% without). MRI nail involvement was more frequent in patients with clinical evidence of onychopathy than in those without (p = 0.003). Similarly, 95.7% of patients showed MRI abnormalities of DP (100% with onychopathy and 90.9% without). MRI DP abnormalities were more marked in patients with clinical evidence of onychopathy than in those without (p = 0.009). Involvement of DIP joints was present in 34.8% of cases (58.3% with onychopathy and 9.1% without), and onychopathic patients showed marked MRI DIP joint involvement in 5 cases and mild in 2, while patients without onychopathy showed minimal changes in one case (p = 0.03). Considering the entire group of patients, MRI involvement of DIP joints was always associated with MRI DP changes, and in no case was it present alone. CONCLUSION: MRI nail involvement was present in almost all patients with PsA studied, even in those without clinically evident onychopathy. MRI involvement of DP always overlapped with nail involvement, since it was present in all psoriatic cases showing MRI nail involvement. In contrast, MRI DIP joint involvement was almost exclusively in a lower percentage of the patients with clinical nail involvement and was always associated with MRI DP changes. Our results suggest that DIP joint involvement is always secondary to nail and DP involvement.

Measurement of spleen volume by ultrasound scanning in patients with thrombocytosis: a prospective study.

Spleen size was assessed in 73 patients with thrombocytosis and in 15 healthy subjects, comparing palpation with ultrasonography (US) measurement of longitudinal diameter and volume. Intraobserver and interobserver variability for volume on US, checked in 12 patients, was very low. Correlation between spleen volume measured by US and that measured by computed tomography was excellent. Splenomegaly was detected by palpation in 25% of patients, by US assessment of longitudinal diameter in 33%, and by US assessment of volume in 52%. After diagnostic work-up, 54 patients had a diagnosis of essential thrombocythemia (ET), 4 of idiopathic myelofibrosis (IMF), and 15 of secondary thrombocytosis (ST). Spleen volume in patients with ST was in the normal range (138 +/- 47 mL) and was significantly lower than that in patients with ET or IMF (370 +/- 210 mL; P <.001). Thus, US-measured volume was the most sensitive method for identifying nonpalpable splenomegaly in patients with primary myeloproliferative diseases, and it may help in distinguishing these diseases from reactive disorders.

Giant cell tumor and Paget's disease of bone in one family: geographic clustering.

Giant cell tumor is a rare complication of Paget's disease of bone. Typically, this tumor occurs in the case of polyostotic disease and only in pagetic bones. This tumor rarely has been seen in multiple family members who have Paget's disease, although Paget's bone disease clearly has a hereditary component. Our report documents four cases of polyostotic Paget's bone disease complicated by benign giant cell tumor. In two patients, the giant cell tumor also was multifocal. All patients were from one family. They were born in Avellino and reside in Campania, a Southern Italian region. The ancestors of the patients with familial giant cell tumor in Paget's bone disease were born in the same geographic area. These data suggest that a combination of environmental and genetic factors could be responsible for linkage of the patients born in Avellino with this neoplasm that is highly unusual in patients with Paget's disease of bone.