Early skeletal outcomes after hematopoietic stem and progenitor cell gene therapy for Hurler syndrome.

Mucopolysaccharidosis type I Hurler (MPSIH) is characterized by severe and progressive skeletal dysplasia that is not fully addressed by allogeneic hematopoietic stem cell transplantation (HSCT). Autologous hematopoietic stem progenitor cell-gene therapy (HSPC-GT) provides superior metabolic correction in patients with MPSIH compared with HSCT; however, its ability to affect skeletal manifestations is unknown. Eight patients with MPSIH (mean age at treatment: 1.9 years) received lentiviral-based HSPC-GT in a phase 1/2 clinical trial (NCT03488394). Clinical (growth, measures of kyphosis and genu velgum), functional (motor function, joint range of motion), and radiological [acetabular index (AI), migration percentage (MP) in hip x-rays and MRIs and spine MRI score] parameters of skeletal dysplasia were evaluated at baseline and multiple time points up to 4 years after treatment. Specific skeletal measures were retrospectively compared with an external cohort of HSCT-treated patients. At a median follow-up of 3.78 years after HSPC-GT, all patients treated with HSPC-GT exhibited longitudinal growth within WHO reference ranges and a median height gain greater than that observed in patients treated with HSCT after 3-year follow-up. Patients receiving HSPC-GT experienced complete and earlier normalization of joint mobility compared with patients treated with HSCT. Mean AI and MP showed progressive decreases after HSPC-GT, suggesting a reduction in acetabular dysplasia. Typical spine alterations measured through a spine MRI score stabilized after HSPC-GT. Clinical, functional, and radiological measures suggested an early beneficial effect of HSPC-GT on MPSIH-typical skeletal features. Longer follow-up is needed to draw definitive conclusions on HSPC-GT's impact on MPSIH skeletal dysplasia.

Spontaneous extracapsular parathyroid adenoma hemorrhage: when surgery is required?

PURPOSE: Spontaneous bleeding is a rare but serious complication of parathyroid adenomas and few cases were reported in the literature. Clinical manifestations and treatment may vary but sometimes an immediate surgery is required. In other cases a conservative approach can be preferred based on clinical stability and patients' conditions. The purpose of this work is to describe our case and to carry out a review of the current literature on this topic. METHODS: We reported a case of a parathyroid adenoma hemorrhage in an elderly patient describing its management. Moreover, a literature review of 57 cases was carried out, with the aim of collecting data about the most involved parathyroid gland and identifying the most correct management based on clinical manifestations and chosen treatments. RESULTS: The patients had an age between 29 and 81 years (mean 56.9 ± 16.4 years). Forty-four patients were females (77.2%), whereas 12 were males (21.8%). Based on clinical severity, age, comorbidities and calcemic status, three possible scenarios were identified, each with a recommended management. CONCLUSIONS: In parathyroid adenoma hemorrhages a careful clinical assessment is crucial to identify emergency conditions requiring immediate intubation, tracheostomy or neck exploration. Elderlies and comorbid patients have a higher risk of perioperative complications and indication for surgery should be evaluated case by case: whenever feasible, a conservative approach should be preferred in these subjects, especially in those with a stable course and without hypercalcemia-related symptoms.

Uncommon Site of Metastasis and Prolonged Survival in Patients with Anaplastic Thyroid Carcinoma: A Systematic Review of the Literature.

Anaplastic thyroid carcinoma (ATC) is a very rare, highly aggressive malignant thyroid tumor with an overall survival from 3 to 5 months in most of the cases. Even the modern and intensive treatments seem not to be enough to provide a cure, also for the resectable ones, and the role of chemotherapy is still unclear but does not seem to prolong survival. Nevertheless, some patients survive longer and have a better outcome, even in the presence of metastasis, than what the literature reports. We present the case of a 64-year-old female affected by ATC, treated on February 2018 with surgery followed by chemoradiation. One year after surgery, the patient developed a subcutaneous recurrence that was radically resected and is still alive 29 months after the diagnosis. We propose a systematic review of the literature to deepen the knowledge of the prognostic factors of ATC with the aim to recognize and select the patients with a better outcome, even if metastatic, and to describe a very uncommon site of metastatization.

A Comparative Evaluation of 3 Different Free-Form Deformable Image Registration and Contour Propagation Methods for Head and Neck MRI: The Case of Parotid Changes During Radiotherapy.

PURPOSE: To validate and compare the deformable image registration and parotid contour propagation process for head and neck magnetic resonance imaging in patients treated with radiotherapy using 3 different approaches-the commercial MIM, the open-source Elastix software, and an optimized version of it. MATERIALS AND METHODS: Twelve patients with head and neck cancer previously treated with radiotherapy were considered. Deformable image registration and parotid contour propagation were evaluated by considering the magnetic resonance images acquired before and after the end of the treatment. Deformable image registration, based on free-form deformation method, and contour propagation available on MIM were compared to Elastix. Two different contour propagation approaches were implemented for Elastix software, a conventional one (DIR_Trx) and an optimized homemade version, based on mesh deformation (DIR_Mesh). The accuracy of these 3 approaches was estimated by comparing propagated to manual contours in terms of average symmetric distance, maximum symmetric distance, Dice similarity coefficient, sensitivity, and inclusiveness. RESULTS: A good agreement was generally found between the manual contours and the propagated ones, without differences among the 3 methods; in few critical cases with complex deformations, DIR_Mesh proved to be more accurate, having the lowest values of average symmetric distance and maximum symmetric distance and the highest value of Dice similarity coefficient, although nonsignificant. The average propagation errors with respect to the reference contours are lower than the voxel diagonal (2 mm), and Dice similarity coefficient is around 0.8 for all 3 methods. CONCLUSION: The 3 free-form deformation approaches were not significantly different in terms of deformable image registration accuracy and can be safely adopted for the registration and parotid contour propagation during radiotherapy on magnetic resonance imaging. More optimized approaches (as DIR_Mesh) could be preferable for critical deformations.

Erdheim-Chester disease: imaging-guided therapeutic approach.

Erdheim-Chester disease (ECD) is a rare form of systemic non-Langerhans cell histiocytosis with characteristic bone involvement. However, extraskeletal involvement occurs in approximately half of the patients. Because of its protean findings, the diagnosis of ECD is often delayed; thus, a clinical suspicion may prompt specific imaging studies to recognize suggestive signs of organ involvement. In this study, a case of a patient with ECD with representative progressive multisystemic involvement has been reported; although the final diagnosis was confirmed by histologic analysis, imaging studies with almost pathognomonic findings guided the diagnostic process and prompted different therapeutic approaches according to the localization of the disease.

MRI of cardiomyopathy.

OBJECTIVE: The aims of this article are to present the main features of MRI of cardiomyopathy and to show selected images of cardiomyopathies. CONCLUSION: Cardiomyopathy is a frequent reason for cardiac MRI evaluation, which is now considered the most appropriate imaging technique for the diagnosis and follow-up of this wide range of myocardial diseases.

Elderly manifestation of non-compaction of the ventricular myocardium.

Non-compaction of the ventricular myocardium (NCVM) is a rare disorder of myocardial morphogenesis usually diagnosed in paediatric age associated with high mortality rates. Among reported cases, NCVM has been described in only six patients > or = 70 years. We describe the case of a 74-year-old male with NCVM involving the left ventricle, representing one of the oldest patients ever reported in the literature. Of note, this case was characterized by late appearance of NCVM and rapid deterioration of clinical conditions. The wide age range of symptom onset from prenatal to geriatric age supports the hypothesis that NCVM is a multifactorial rather than a simple congenital disorder.

Delayed gadolinium-enhanced cardiac magnetic resonance in patients with chronic myocarditis presenting with heart failure or recurrent arrhythmias.

OBJECTIVES: We evaluated the effectiveness of contrast-enhanced cardiac magnetic resonance (CE-CMR) in detecting chronic myocarditis (CM). BACKGROUND: Chronic myocarditis represents a common evolution of acute myocarditis. Although CE-CMR has been revealed to be effective in identifying areas of myocardial damage in acute myocarditis, its role in the diagnosis of chronic myocardial inflammation has not yet been investigated. METHODS: Twenty-three patients with CM underwent CE-CMR and endomyocardial biopsy (EMB). Chronic myocarditis was defined by the presence of: 1) chronic (>6 months) heart failure symptoms and/or repetitive ventricular arrhythmias; 2) no history of recent flu-like symptoms or infections; and 3) histologic evidence of active myocarditis (AM) or borderline myocarditis (BM) according to Dallas criteria. Contrast-enhanced cardiac magnetic resonance included black-blood T2-weighted (BBT2w) images without and with fat saturation and delayed three-dimensional T1 turbo field-echo inversion-recovery sequences obtained 15 min after gadolinium injection. RESULTS: Histology showed AM in 14 patients and BM in 9 patients. FatSat BBT2w revealed the presence of edema in five (36%) patients with AM but not in BM patients. Areas of late enhancement (LE) were observed in 12 (84%) subjects with AM and in 4 (44%) cases with BM. A mid-wall LE pattern was the most frequent finding in both groups while a subepicardial distribution of LE was observed only in patients with AM. CONCLUSIONS: Contrast-enhanced cardiac magnetic resonance identified areas of myocardial inflammation in up to 70% of patients with biopsy-proven CM. We suggest that CE-CMR may be a useful non-invasive diagnostic tool in patients with CM, and it may indicate and even guide the execution of left ventricular EMB with relevant prognostic and therapeutic implications.