Novel Variant in ANO5 Muscular Dystrophy: Identification by Whole Genome Sequencing and Quad Analysis.

BACKGROUND: The phenotypic spectrum of ANO5 muscle disease ranges widely from elevated creatine kinase (CK) levels in the serum of asymptomatic individuals to progressive muscular dystrophy. Due to overlapping clinical features among muscular dystrophies, the diagnosis of ANO5 muscle disease is established by molecular genetic tests. Early diagnosis is crucial for the clinical management of symptoms and to mitigate cardiac and musculoskeletal complications. METHODS: Quad-joint analysis was performed on whole genome sequencing (WGS) data obtained from an 18-year-old female with mild myalgia and elevated CK and her unaffected parents and sister. The phenotype-driven analysis was performed to prioritize genomic alterations related to the phenotype. The zygosity-based analysis investigated compound heterozygous and de novo status for all variants. RESULTS: The quad-joint WGS analysis revealed a novel pathogenic heterozygous variant, ANO5:c.1770_1773del (p.Phe593Metfs*15), that was paternally inherited. A second and known pathogenic heterozygous variant, ANO5:c.148C>T (p.Arg50*), was also present that was maternally inherited. The genome finding led to the diagnosis of autosomal recessive ANO5 muscle disease and an early personalized clinical management for the patient regarding her cardiac and musculoskeletal health. CONCLUSIONS: This is the first report of the ANO5:c.1770_1773del variant in the literature. This report highlights the spectrum of ANO5 muscle disease and describes the role of quad-joint WGS in the early diagnosis and preventive clinical management of ANO5 muscle disease.

Diagnosis of Two Unrelated Syndromes of Prader-Willi and Calpainopathy: Insight from Trio Whole Genome Analysis and Isodisomy Mapping.

PURPOSE: An investigation for the co-occurrence of two unrelated genetic disorders of muscular dystrophy and Prader-Willi syndrome (PWS) (OMIM#176270) using joint whole genome sequencing (WGS). METHODS: Trio WGS joint analysis was performed to investigate the genetic etiology in a proband with PWS, prolonged muscular hypotonia associated hyperCKemia, and early-onset obesity. The parents were unaffected. RESULTS: Results showed maternal isodisomy uniparental disomy (UPD) in chromosome 15, expanding from 15q11.2 to 15q22.2, including PWS regions at 15q11.2-15q13. Maternal heterodisomy was detected from 15q22.2 to 15q26.3. A pathogenic variant, NM_000070.3(CAPN3):c.550del (p.Thr184fs), was identified at 15q15.1 in a heterozygous state in the mother that was homozygous in the proband due to maternal isodisomy. CONCLUSION: This is the first study of the concurrent molecular etiology of PWS and calpainopathy (OMIM#253600) in the same patient. This report highlights the utility of joint analysis and the need for the assessment of autosomal recessive disease in regions of isodisomy in patients with complex and unexplained phenotypes.

PRAME expression and its prognostic significance in invasive breast carcinoma.

OBJECTIVES: PRAME (PReferentially expressed Antigen in MElanoma) is a carcinoma testis antigen expressed in numerous tumour types. The aim of this study was to assess PRAME expression in different surrogate subtypes of breast carcinoma and its correlation with other prognostic factors. MATERIAL AND METHODS: A total of 220 cases of invasive breast carcinoma were selected and categorized according to ER, PgR, HER2 status, and Ki67 proliferation index in luminal A like, luminal B HER2+ like, luminal B HER2- negative like, HER2 positive like and triple-negative or basal-like. All cases were examined for PRAME expression by immunohistochemistry (IHC). RESULTS: A PRAME-high profile was detected in 53 (24,1 %) of all examined breast carcinoma samples. A significantly higher expression of PRAME was detected in HER2-positive carcinomas (50 %) and TN breast carcinomas (40,54 %) compared to ER-positive (luminal-like) subtype of breast carcinomas (3,38 % luminal A and 15,38 % luminal B). Percentage of PRAME positive tumour cells showed positive correlation with tumor size, Ki67 proliferation index, HER2 status, nuclear grade, TILs and presence of metastasis, and negative correlation with ER status and disease-free survival (DFS). CONCLUSION: Our study showed that HER2 positive and TN breast carcinomas more commonly express PRAME than ER positive carcinomas and that PRAME expression shows positive correlation with certain prognostic factors, however PRAME wasn't revealed as an independent prognostic factor in our study. The importance of PRAME expression in breast carcinoma lies in its potential use as an immunotherapeutic target, particularly in patients with limited therapeutic options.

Complications of Percutaneous Vertebroplasty: A Pictorial Review.

Percutaneous vertebroplasty is a minimally invasive treatment technique for vertebral body compression fractures. The complications associated with this technique can be categorized into mild, moderate, and severe. Among these, the most prevalent complication is cement leakage, which may insert into the epidural, intradiscal, foraminal, and paravertebral regions, and even the venous system. The occurrence of a postprocedural infection carries a notable risk which is inherent to any percutaneous procedure. While the majority of these complications manifest without symptoms, they can potentially lead to severe outcomes. This review aims to consolidate the various complications linked to vertebroplasty, drawing from the experiences of a single medical center.

The Use of Contrast-Enhanced Ultrasound (CEUS) in the Evaluation of the Neonatal Brain.

In recent years, advancements in technology have allowed the use of contrast-enhanced ultrasounds (CEUS) with high-frequency transducers, which in turn, led to new possibilities in diagnosing a variety of diseases and conditions in the field of radiology, including neonatal brain imaging. CEUSs overcome some of the limitations of conventional ultrasounds (US) and Doppler USs. It allows the visualization of dynamic perfusion even in the smallest vessels in the whole brain and allows the quantitative analysis of perfusion parameters. An increasing number of articles are published on the topic of the use of CEUSs on children each year. In the area of brain imaging, the CEUS has already proven to be useful in cases with clinical indications, such as hypoxic-ischemic injuries, stroke, intracranial hemorrhages, vascular anomalies, brain tumors, and infections. We present and discuss the basic principles of the CEUS and its safety considerations, the examination protocol for imaging the neonatal brain, and current and emerging clinical applications.

Calcium-Sensing Receptor Expression in Breast Cancer.

The calcium-sensing receptor (CaSR) plays a crucial role in maintaining the balance of calcium in the body. Altered signaling through the CaSR has been linked to the development of various tumors, such as colorectal and breast tumors. This retrospective study enrolled 79 patients who underwent surgical removal of invasive breast carcinoma of no special type (NST) to explore the expression of the CaSR in breast cancer. The patients were categorized based on age, tumor size, hormone receptor status, HER2 status, Ki-67 proliferation index, tumor grade, and TNM staging. Immunohistochemistry was conducted on core needle biopsy samples to assess CaSR expression. The results revealed a positive correlation between CaSR expression and tumor size, regardless of the tumor surrogate subtype (p = 0.001). The expression of ER exhibited a negative correlation with CaSR expression (p = 0.033). In contrast, a positive correlation was observed between CaSR expression and the presence of HER2 receptors (p = 0.002). Increased CaSR expression was significantly associated with lymph node involvement and the presence of distant metastasis (p = 0.001 and p = 0.038, respectively). CaSR values were significantly higher in the patients with increased Ki-67 (p = 0.042). Collectively, higher CaSR expression in breast cancer could suggest a poor prognosis and treatment outcome regardless of the breast cancer subtype.

Breast Cancer Surrogate Subtype Classification Using Pretreatment Multi-Phase Dynamic Contrast-Enhanced Magnetic Resonance Imaging Radiomics: A Retrospective Single-Center Study.

This study aimed to explore the potential of multi-phase dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) radiomics for classifying breast cancer surrogate subtypes. This retrospective study analyzed 360 breast cancers from 319 patients who underwent pretreatment DCE-MRI between January 2015 and January 2019. The cohort consisted of 33 triple-negative, 26 human epidermal growth factor receptor 2 (HER2)-positive, 109 luminal A-like, 144 luminal B-like HER2-negative, and 48 luminal B-like HER2-positive lesions. A total of 1781 radiomic features were extracted from manually segmented breast cancers in each DCE-MRI sequence. The model was internally validated and selected using ten times repeated five-fold cross-validation on the primary cohort, with further evaluation using a validation cohort. The most successful models were logistic regression models applied to the third post-contrast subtraction images. These models exhibited the highest area under the curve (AUC) for discriminating between luminal A like vs. others (AUC: 0.78), luminal B-like HER2 negative vs. others (AUC: 0.57), luminal B-like HER2 positive vs. others (AUC: 0.60), HER2 positive vs. others (AUC: 0.81), and triple negative vs. others (AUC: 0.83). In conclusion, the radiomic features extracted from multi-phase DCE-MRI are promising for discriminating between breast cancer subtypes. The best-performing models relied on tissue changes observed during the mid-stage of the imaging process.

Early Assessment of Neoadjuvant Chemotherapy Response Using Multiparametric Magnetic Resonance Imaging in Luminal B-like Subtype of Breast Cancer Patients: A Single-Center Prospective Study.

This study aimed to evaluate the performance of multiparametric breast magnetic resonance imaging (mpMRI) for predicting response to neoadjuvant chemotherapy (NAC) in patients with luminal B subtype breast cancer. The prospective study included thirty-five patients treated with NAC for both early and locally advanced breast cancer of the luminal B subtype at the University Hospital Centre Zagreb between January 2015 and December 2018. All patients underwent breast mpMRI before and after two cycles of NAC. Evaluation of mpMRI examinations included analysis of both morphological (shape, margins, and pattern of enhancement) and kinetic characteristics (initial signal increase and post-initial behavior of the time-signal intensity curve), which were additionally interpreted with a Göttingen score (GS). Histopathological analysis of surgical specimens included grading the tumor response based on the residual cancer burden (RCB) grading system and revealed 29 NAC responders (RCB-0 (pCR), I, II) and 6 NAC non-responders (RCB-III). Changes in GS were compared with RCB classes. A lack of GS decrease after the second cycle of NAC is associated with RCB class and non-responders to NAC.

SHORT-TERM OUTCOMES OF PERCUTANEOUS RADIOFREQUENCY AND MICROWAVE ABLATION IN THE TREATMENT OF SMALL RENAL MASSES.

Although the gold standard in the management of kidney tumors is surgical treatment, thermal ablation methods are a viable therapeutic option for patients with small (<4 cm) renal masses who are poor surgical candidates. The aim of this study was to compare the technical success, primary efficacy and complication rate of percutaneous radiofrequency and microwave ablation in the treatment of small renal masses. A retrospective analysis of consecutive patients with small renal masses treated with radiofrequency or microwave ablation between December 2017 and January 2022 was conducted. Response to the ablative therapy was assessed on contrast-enhanced computed tomography examination after 3 months. Ablations of 44 kidney lesions were performed in 43 patients. Sixteen lesions were treated with radiofrequency and 28 with microwave ablation. Both methods were associated with high technical success (100%). Primary efficacy rates of radiofrequency and microwave ablation were 81.3% and 89.3%, respectively. Ablation-related complications were noted only in the patients treated with microwave ablation (18.5%), all of them being low grade (Clavien-Dindo 1 and 2). Radiofrequency and microwave ablation exhibited comparable efficacy in the treatment of small renal masses. Microwave ablation was associated with a comparatively higher number of complications.

Percutaneous CT-Guided Bone Lesion Biopsy for Confirmation of Bone Metastases in Patients with Breast Cancer.

We aimed to determine diagnostic accuracy of CT-guided bone lesion biopsy for the confirmation of bone metastases in patients with breast cancer and assessment of hormone receptor status in metastatic tissue. A total of 56 female patients with breast cancer that underwent CT-guided biopsy of suspected bone metastasis were enrolled in this retrospective study. Three different techniques were employed to obtain samples from various sites of skeleton. Collectively, 11 true negative and 3 false negative findings were revealed. The sensitivity of CT-guided biopsy for diagnosing bone metastases was 93.6%, specificity was 100% and accuracy was 94.8%. Discordance in progesterone receptor status and complete concordance in estrogen receptor status was observed. Based on our single-center experience, bone metastasis biopsy should be routinely performed in patients with breast cancer and suspicious bone lesions, due to the impact on further treatment.

Case Report: Advanced Skeletal Muscle Imaging in S-Adenosylhomocysteine Hydrolase Deficiency and Further Insight Into Muscle Pathology.

Introduction: S-Adenosylhomocysteine hydrolase deficiency (SAHHD) is a rare inherited multisystemic disease with muscle involvement as one of the most prominent and poorly understood features. To get better insight into muscle involvement, skeletal muscles were analyzed by magnetic resonance imaging (MRI) and MR spectroscopy (MRS) in three brothers with SAHHD in the different age group. Method: The study was based on analysis of MRI and MRS of skeletal muscles of the lower and the proximal muscle groups of the upper extremities in three SAHHD patients. Results: Three siblings presented in early infancy with similar signs and symptoms, including motor developmental delay. All manifested myopathy, more pronounced in the lower extremities and the proximal skeletal muscle groups, and permanently elevated creatine kinase. At the time of MRI and MRS study, the brothers were at the age of 13, 11, and 8 years, respectively. MRI revealed lipid infiltration, and the MRS curve showed an elevated muscle lipid fraction (higher peak of lipid), which increased with age, and was more prominent in the proximal skeletal muscles of the lower extremities. These results were consistent with muscle biopsy findings in two of them, while the third patient had no specific pathological changes in the examined muscle tissue. Conclusions: These findings demonstrate that an accessible and non-invasive method of MRI and MRS is useful for an insight into the extent of muscle involvement, monitoring disease progression, and response to treatment in SAHHD.

Diagnostic performance of digital breast tomosynthesis in female patients with nipple discharge.

BACKGROUND: Nipple discharge is one of the most common symptoms related to the breast, but it is a presenting feature of breast cancer in 5%-12% of women. AIMS: The purpose of this study was to determine the diagnostic performance of digital breast tomosynthesis (DBT) in the evaluation of patients with nipple discharge and to compare it with mammography (MMG), ultrasound (US), and magnetic resonance imaging (MRI). METHODS AND RESULTS: This retrospective study included 53 patients with nipple discharge. All patients underwent DBT, and results were compared to MMG, breast US, and MRI. Radiological findings for each method were categorized according to BI-RADS classification: categories 1-2 were considered negative and categories 3-5 positive. If a tissue specimen was obtained, the final diagnosis was established based on the results of histopathological analysis; otherwise, a clinical follow-up was required for at least 2 years to confirm benign radiological findings. Measures of diagnostic accuracy of DBT, MMG, US, and MRI were calculated and compared. RESULTS: Final histopathological analysis revealed six malignant breast lesions, all of which were detected in patients with pathologic nipple discharge. DBT and MRI exhibited high sensitivity (100%) and high negative predictive value (100%) for the detection of breast cancer in patients with nipple discharge. DBT showed higher specificity compared to MRI (82.9% vs. 61.9%). Sensitivity and specificity of MMG were 83.3% and 76.6%, respectively. Breast US was determined to have a sensitivity of 66.7% and specificity of 57.5%. CONCLUSION: DBT exhibited higher specificity than MRI at the same level of sensitivity and negative predictive value. Therefore, the use of DBT should be considered as an alternative to MRI in the assessment of patients with nipple discharge.

Breast metastasis as the initial presentation of malignant pleural mesothelioma.

Metastatic involvement of the breast is far less common than primary breast carcinoma, comprising 0.5%-6.6% of all breast malignancies. Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with higher incidence among men, particularly smokers, strongly associated with asbestos exposure. The epithelioid type of MPM can represent a diagnostic pitfall in this setting, as it shows similar histologic features to primary breast carcinoma as well as other metastatic epithelioid malignancies. We report a rare case of breast metastasis of malignant pleural mesothelioma in a 61-year-old female.

Changes in total body surface area and the distribution of skin surfaces in relation to body mass index.

BACKGROUND: A correct estimation of total burn surface area is important since it is used for determining fluid resuscitation volumes, nutritional estimates and hospital admission criteria. Wallace's rule of nines is the most commonly used methods for this purpose. However, fat distribution is non-uniform and the total body surface area changes with obesity. The aim of this study was to determine if the rule of nines applies to all body mass index groups. METHODS: A total of 217 individuals were included in the study. The patients were divided into 4 groups according to their BMI (18.5-25kg/m2 (60 persons)), 25-29.9kg/m2 (61 individuals)), 30-34.9kg/m2 (55 persons)), >35kg/m2 (41 persons)). Each patient underwent a complete duel-energy X-ray absorptiometry body scan to determine the surface area (cm2) of the various regions of the body. RESULTS: We found no statistically significant variations between the Wallace body percentage distributions and our results in the men for all BMI ranges (head p=0.331, arms p=0.861, legs p=0.282, trunk p=0.696). In contrast, among women we found a statistically significant change in body surface area percentage distribution between the BMI groups and specific body regions (head p=0.000, legs p=0.000 and trunk p=0.001). CONCLUSION: The Wallace rule of nines is a quick and acceptable method for estimating the total burn surface area percentage in men of all BMI ranges. However, for women, a more accurate method of burn area estimation is required as proposed by our BMI adjusted charts.

Correlation of MRI features and pathohistological prognostic factors in invasive ductal breast carcinoma.

OBJECTIVE: The aim of this study was to correlate magnetic resonance imaging (MRI) features of invasive ductal carcinomas (IDC) with pathohistological prognostic factors. Such an association, if present, could have significant translational implications for early identification of aggressive types of breast cancer. MATERIALS AND METHODS: One hundred and fourteen consecutive women with IDC who underwent breast MRI within one month prior to surgery were included in this retrospective study. MRI features were analyzed and then interpreted with a Göttingen score (GS) that included morphological (shape, margins, and pattern of enhancement) and kinetic characteristics (initial signal increase and post-initial behavior of the time-signal intensity curve). Histological specimens were analyzed for tumor size, axillary lymph node status, histological grade, estrogen receptors (ER), progesterone receptors (PR), HER2, and Ki-67. RESULTS: By multivariate analysis, a smooth margin was a significant, independent predictor of a larger tumor size (p = 0.041), lymph node invasion (p = 0.013), and lower expression of ER (p = 0.022). High GS was a significant, independent predictor of a higher histological grade (p = 0.022) while round or oval shape of lesion was independent predictor of a higher PR expression (p = 0.027). CONCLUSION: A smooth margin of breast cancer on breast MRI was able to predict positive axillary lymph nodes, larger tumor size, and lower expression of ER. Except for a higher histological grade, GS was not able to predict other unfavorable prognostic factors, probably due to the fact that smooth margins were assigned fewer points than spiculated margins.