Different Molecular Signatures in Magnetic Resonance Imaging-Staged Facioscapulohumeral Muscular Dystrophy Muscles

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies and is characterized by a non-conventional genetic mechanism activated by pathogenic D4Z4 repeat contractions. By muscle Magnetic Resonance Imaging (MRI) we observed that T2-short tau inversion recovery (T2-STIR) sequences identify two different conditions in which each muscle can be found before the irreversible dystrophic alteration, marked as T1-weighted sequence hyperintensity, takes place. We studied these conditions in order to obtain further information on the molecular mechanisms involved in the selective wasting of single muscles or muscle groups in this disease

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Tracking muscle wasting and disease activity in facioscapulohumeral muscular dystrophy by qualitative longitudinal imaging

Abstract Background Facioscapulohumeral muscular dystrophy (FSHD) is one of the most frequent late‐onset muscular dystrophies, characterized by progressive fatty replacement and degeneration involving single muscles in an asynchronous manner. With clinical trials at the horizon in this disease, the knowledge of its natural history is of paramount importance to understand the impact of new therapies. The aim of this study was to assess disease progression in FSHD using qualitative muscle magnetic resonance imaging, with a focus on the evolution of hyperintense lesions identified on short‐tau inversion recovery (STIR+) sequences, hypothesized to be markers of active muscle injury. Methods One hundred genetically confirmed consecutive FSHD patients underwent lower limb muscle magnetic resonance imaging at baseline and after 365 ± 60 days in this prospective longitudinal study. T1 weighted (T1w) and STIR sequences were used to assess fatty replacement using a semiquantitative visual score and muscle oedema. The baseline and follow‐up scans of each patient were also evaluated by unblinded direct comparison to detect the changes not captured by the scoring system. Results Forty‐nine patients showed progression on T1w sequences after 1 year, and 30 patients showed at least one new STIR+ lesion. Increased fat deposition at follow‐up was observed in 13.9% STIR+ and in only 0.21% STIR‐ muscles at baseline (P < 0.001). Overall, 89.9% of the muscles that showed increased fatty replacement were STIR+ at baseline and 7.8% were STIR+ at 12 months. A higher number of STIR+ muscles at baseline was associated with radiological worsening (odds ratio 1.17, 95% confidence interval 1.06–1.30, P = 0.003). Conclusions Our study confirms that STIR+ lesions represent prognostic biomarkers in FSHD and contributes to delineate its radiological natural history, providing useful information for clinical trial design. Given the peculiar muscle‐by‐muscle involvement in FSHD, MRI represents an invaluable tool to explore the modalities and rate of disease progression

Magnetic Resonance Imaging in a large cohort of facioscapulohumeral muscular dystrophy patients: pattern refinement and implications for clinical trials

OBJECTIVE: therapeutic perspectives raised attention on the development of instruments to accurately evaluate the degree of pathology in patients with facioscapulohumeral muscular dystrophy. We aimed to analyze the type and extent of muscle involvement on MRI in a large cohort of patients representative of the broad clinical spectrum of this disease. METHODS: pelvic and lower limb muscle MRI scans of 269 symptomatic individuals and 19 non-penetrant gene carriers were assessed. Comparative analysis of the upper girdle scan in 181 of these subjects was also performed. RESULTS: we found a peculiar susceptibility and resistance of particular muscles. Combined involvement of abdominal and hamstring muscles with iliopsoas sparing is common in facioscapulohumeral muscular dystrophy (67% of the patients). Adductor longus and/or rectus femoris, whose involvement can go clinically undetected, are often typically affected in early disease (69% of patients below age 45). The extent of lesions on lower limb MRI showed a high correlation with overall clinical severity. One-fourth of the non-penetrant gene carriers showed abnormalities on MRI. Hyperintensities on short-tau inversion recovery sequences, markers of active disease, were found in muscles without signs of fatty replacement in 35% of patients, representing early lesions. INTERPRETATION: Our large-scale cross-sectional data provides preliminary evidence for the usefulness of MRI in clinical trials, and sets the baseline for longitudinal studies. Muscle MRI can be also used for distinguishing facioscapulohumeral muscular dystrophy from other myopathies in selected cases. Finally, our results are consistent with a model that configures facioscapulohumeral muscular dystrophy as a "muscle-by-muscle" diseas

Novel dominant mutation in BIN1 gene causing mild centronuclear myopathy revealed by myalgias and CK elevation

We present the clinical, morphological and molecular data of an Italian family with centronuclear myopathy, carrying a novel pathogenic mutation of BIN1 gene in heterozygous state, consistent with autosomal dominant inheritance. The proband, a 56-years-old man suffered of lower limbs myalgia and slight CK elevation. Clinical examination revealed no muscle weakness, short stature, mild symmetric eyelid ptosis, scapular winging, ankle retraction and well-developed muscles. Muscle biopsy showed nuclear centralization and clustering, deep sarcolemmal invaginations and type 1 fibers hypotrophy. Muscle MRI revealed fatty infiltration of posterior legs compartments, lumbar paraspinal and serratus muscles. By sequencing BIN1 , we identified a heterozygous pathogenic mutation [c.107C>A (p.A36E)], and we demonstrate that the mutation strongly impairs the membrane tubulation property of the protein. One affected sister with similar phenotype carried the same mutation. Our findings expand the clinical, morphological and genetic spectrum of the autosomal dominant CNM associated with BIN1 mutations

Deep brain stimulation in Parkinson's disease: a comparison of accuracy and clinical outcomes of frame-based, frameless and frameless fiducial-less techniques

Background: The effectiveness of deep brain stimulation (DBS) for Parkinson's disease (PD) depends on implantation accuracy. DBS initially employed a stereotactic frame (frame-based, FB), but technological advancements led to the development of less invasive methods based on fiducial markers (F + F) or intraoperative imaging (F-F). This study compares the accuracy and efficacy of three DBS-STN implantation techniques. Methods: This retrospective study involved 18 patients with PD who underwent bilateral STN DBS between 2018 and 2023. Patients were divided into three groups: FB (n = 6), F + F (n = 7), and F-F (n = 5). Postoperative CT and preoperative MRI fusion were used to evaluate electrode accuracy via deviations from planned targets in x, y, z axes, and calculate the radial error (RE) and vector error (VE). We analyzed Unified Parkinson's Disease Rating Scale (UPDRS) III scores in four "on/off medication-stimulation" combinations, LEDD, and disease stage before DBS, and 3 and 12 months post-DBS. Results: No statistically significant differences were observed between the three methods in|Δx| (FB = 1.30 ± 0.91; F + F = 1.05 ± 0.93; F-F = 1.33 ± 1.09&nbsp;mm),|Δy| (FB = 0.95 ± 0.98; F + F = 1.11 ± 1.17; F-F = 1.28 ± 1.14&nbsp;mm), RE (FB = 1.82 ± 0.29; F + F = 1,71 ± 0,36; F-F = 1,91 ± 1,49&nbsp;mm) and VE (FB = 3,14 ± 0,35&nbsp;mm; F + F = 4,92 ± 0,54&nbsp;mm; F-F = 4,42 ± 1,22&nbsp;mm). All groups demonstrated significant UPDRS III (&gt; 50%) and LEDD reduction (&gt; 40%) at 12 months, with no intergroup differences. Conclusions: The study concludes that all three techniques provide equivalent accuracy and clinical efficacy. Centers should select DBS-STN methods based on available resources and expertise