Strain Elastography in Invasive Lobular Carcinoma

Breast cancer remains the second cause of mortality in women, even if the mortality rates linked to it have drastically dropped at the present time. Invasive lobular carcinoma (ILC) accounts for 5–15% of the breast cancers and it is the second most encountered type among invasive carcinomas. There has been reported a high rate for bilateral lesions (6–47%), multifocality/multicentricity (21%), all affecting ILC overall survival. Due to its nonspecific symptoms and to the fact that it does not invoke a vigorous desmoplastic response and has a low likelihood of producing calcifications, the ILC tends to be insidious on mammography. Contrast enhanced MRI has the lowest false negative rate in detecting ILC and it is the most accurate method of determining the lesion extension, though it is expensive and not widely available. Therefore, the ultrasound (US) plays a significant role in the diagnosis of ILC. US elastography imaging (EI) individualizes malignant breast lesions with high sensitivity and specificity. Recent studies suggested that US elastography can even diagnose lobular cancers that have benign findings on conventional imaging. Goal: present various US aspects and exemplify the added diagnostic value of strain elastography—how it may change the BIRADS category and further therapeutic management

Mutations in the COL1A1 and COL1A2 genes associated with osteogenesis imperfecta (OI) types I or III

Although over 85% of osteogenesis imperfecta (OI) cases are associated with mutations in the procollagen type I genes (COL1A1 or COL1A2), no hot spots for the mutations were associated with particular clinical phenotypes. Eight patients that were studied here, diagnosed with OI by clinical standards, are from the Polish population with no ethnic background indicated. Previously unpublished mutations were found in six out of those eight patients. Genotypes for polymorphisms (Sp1 - rs1800012 and PvuII - rs412777), linked to bone formation and metabolism were determined. Mutations were found in exons 2, 22, 50 and in introns 13 and 51 of the COL1A1 gene. In COL1A2, one mutation was identified in exon 22. Deletion type mutations in COL1A1 that resulted in OI type I had no effect on collagen type I secretion, nor on its intracellular accumulation. Also, a single base substitution in I13 (c.904-9 G>T) was associated with the OI type I. The OI type III was associated with a single base change in I51 of COL1A1, possibly causing an exon skipping. Also, a missense mutation in COL1A2 changing Gly→Cys in the central part of the triple helical domain of the collagen type I molecule caused OI type III. It affected secretion of the heterotrimeric form of procollagen type I. However, no intracellular accumulation of procollagen chains could be detected. Mutation in COL1A2 affected its incorporation into procollagen type I. The results obtained shall help in genetic counseling of OI patients and provide a rational support for making informed, life important decisions by them and their families

Comparative two time-point proteome analysis of the plasma from preterm infants with and without bronchopulmonary dysplasia

Background: In this study, we aimed to analyze differences in plasma protein abundances between infants with and without bronchopulmonary dysplasia (BPD), to add new insights into a better understanding of the pathogenesis of this disease. Methods: Cord and peripheral blood of neonates (≤ 30 weeks gestational age) was drawn at birth and at the 36th postmenstrual week (36 PMA), respectively. Blood samples were retrospectively subdivided into BPD(+) and BPD(−) groups, according to the development of BPD. Results: Children with BPD were characterized by decreased afamin, gelsolin and carboxypeptidase N subunit 2 levels in cord blood, and decreased galectin-3 binding protein and hemoglobin subunit gamma-1 levels, as well as an increased serotransferrin abundance in plasma at the 36 PMA. Conclusions: BPD development is associated with the plasma proteome changes in preterm infants, adding further evidence for the possible involvement of disturbances in vitamin E availability and impaired immunological processes in the progression of prematurity pulmonary complications. Moreover, it also points to the differences in proteins related to infection resistance and maintaining an adequate level of hematocrit in infants diagnosed with BPD

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

The Role of US in Depicting Axillary Metastasis in High-Risk Breast Cancer Patients

Purpose: The aim of this study is to evaluate the role of US in depicting axillary nodal disease in high-risk patients with and without pathogenic mutations. Methods: The retrospective study included consecutive high-risk breast cancer (BC) patients who underwent a multigene testing panel for hereditary cancers, pre-operative axillary US and breast/axillary surgery. The group was divided into patients with pathogenic mutations (PM group) and patients without PM. Statistical analyses were performed using GraphPad Prism by applying Chi-square and Fisher exact tests, with a reference p-value Results: Out of 190 patients with BC, 96 (51%) were negative and 94 (49%) were positive for PM as follows: 28 (25.5%) BRCA1, 16 (17%) BRCA2, 15 (16%) CHECK2, 14 (14%) RAD Group, 7 (7%) PALB, 6 (6%) NBN, 3 (3%) TP53 and ATM and 2 (2%) BARD1. US was positive in 88 of the patients, 36 with PM and 52 without PM. US and surgery (≥N1 stage) were both positive in 31 (62%) of PM patients and 44 (88%) of patients without genetic changes. There were 19 (61%) false negative US examinations in the PM group and 6 (13%) in the group without genetic changes, respectively. If the US is positive, there is a 2.6 times greater risk of positive nodes in PM patients (p-value p-value BRCA1/2 subgroup, there is 2.5 greater times risk of nodal disease if the US is positive (p-value = 0.001, 95%CI = 2.6–76). In patients without PM, US compared to surgery reached a sensitivity = 88, PPV = 84 and NPV = 86. Conclusion: US is more sensitive in depicting axillary nodal disease in high-risk patients without PM compared to PM patients. Furthermore, there are more false negative US examinations in PM patients, compared to surgery patients

Are Mutation Carrier Patients Different from Non-Carrier Patients? Genetic, Pathology, and US Features of Patients with Breast Cancer

The purpose of this study is to evaluate the relationship between the pathogenic/likely pathogenic mutations, US features, and histopathologic findings of breast cancer in mutation carriers compared to non-carrier patients. Methods: In this retrospective study, we identified 264 patients with breast cancer and multigene panel testing admitted to our clinic from January 2018 to December 2020. Patient data US findings, US assessment of the axilla, multigene panel tests, histopathology, and immunochemistry reports were reviewed according to the BI-RADS lexicon. Results: The study population was comprised of 40% pathogenic mutation carriers (BRCA1, BRCA2, CHEK2, ATM, PALB, TP 53, NBN, MSH, BRIP 1 genes) and 60% mutation-negative patients. The mean patient age was 43.5 years in the carrier group and 44 years in the negative group. Carrier patients developed breast cancer with benign morphology (acoustic enhancement, soft elastography appearance) compared to non-carriers (p &lt; 0.05). A tendency towards specific US features was observed for each mutation. BRCA1 carriers were associated with BC with microlobulated margins, hyperechoic rim, and soft elastography appearance (p &lt; 0.05). Estrogen receptor (ER)-negative tumors were associated with BRCA1, TP53, and RAD mutations, while BRCA2 and CHEK2 were associated with ER-positive tumors. Conclusions: Patients with pathogenic mutations may exhibit BC with benign US features compared to negative, non-carrier patients. BRCA1, TP53, and RAD carriers account for up to one third of the ER tumors from the carrier group. Axillary US performed worse in depicting involved lymph nodes in carrier patients, compared to negative patients

Typical and unusual sonoelastographic patterns of breast cystic lesions: impact on BI-RADS classification

Purpose: To describe the sonoelastographic appearance of breast cysts (simple, complicated-cysts with sedimentation and complex-cysts with internal solid parts). To assess the influence of sonoelastography on the BI-RADS classification of complicated cysts. Materials and Methods: A prospective study was conducted and all cysts diagnosed by the same radiologist between May 2007 and July 2008 in our breast unit were included. Each lesion was assessed according to BI-RADS and the Tsukuba elasticity score using a Hitachi 8500 US device. Cytology or histopathology was obtained for complicated and complex cysts. Results: 49 simple, 43 complicated and 14 complex cysts were detected. The elasticity patterns were divided into 4 categories: typical BGR (blue-green-red) pattern, appearance similar to that described for solid. lesions, variants of BGR, an inverse score of 3. The BGR pattern was predominant in breast cysts. Atypical elasticity patterns were mostly associated with complicated and complex cysts. BI-RADS classification of complicated cysts before and after elastography showed a statistically significant difference in terms of final category assessment (most of the complicated cysts were downgraded to BI-RADS 2 after elastography). Conclusion: Being aware of the wide spectrum of elastographic patterns of breast cysts and considering elastography when assessing the BI-RADS category of complicated cysts may lead radiologists to better patient management.Ziel: Ziel war die Beschreibung der sonoelastischen Darstellung von Mammazysten (einfache Zysten, komplizierte Zysten mit Sedimentation und komplexe Zysten mit soliden Anteilen) sowie die Beurteilung des Einflusses der Sonoelastografie auf die BI-RADS Klassifikation bei komplizierten Zysten. Material und Methoden: Zwischen Mai 2007 und Juli 2008 wurden prospektiv alle Patienten unseres Brustzentrums mit Mammazysten in eine Studie eingeschlossen. Die Untersuchungen wurden alle durch den gleichen Radiologen durchgeführt. Alle Läsionen wurde mittels BI-RADS und dem Tsukuba Score mit einem Hitachi 8500 US Gerät klassifiziert. Biopsien zur zytologischen oder histopathologischen Diagnostik wurden bei komplizierten und komplexen Zysten durchgeführt. Ergebnisse: 49 einfache, 43 komplizierte und 14 komplexe Zysten wurden untersucht. Die Elastizitätsmuster wurden in vier Kategorien eingeteilt: typisches BGR-Muster (BGR: blau-grün-rot), Muster ähnlich wie bei soliden Läsionen beschrieben, Varianten von BGR, und ein inverser Score 3. Das BGR-Muster wurde überwiegend in einfachen Zysten gefunden. Atypische Elastizitätsmuster wurden überwiegend bei komplizierten und bei komplexen Zysten gefunden. Die BI-RADS Klassifikation komplizierter Zysten war vor und nach Elastografie signifikant unterschiedlich hinsichtlich der endgültigen Zuordnung zu einer Kategorie (die meisten komplizierten Zysten wurden nach Elastografie auf BI-RADS 2 heruntergestuft). Schlussfolgerung: Die Kenntnis des großen Spektrums elastografischer Darstellungsmuster von Mammazysten und das Einbeziehen der Elastografie bei der BI-RADS Klassifikation komplizierter Zysten kann dem Radiologen ein besseres Patientenmanagement ermöglichen

Mutations in COL1A1 and COL1A2 Genes Associated with Osteogenesis Imperfecta (OI) Types I or III.

Although over 85% of osteogenesis imperfecta (OI) cases are associated with mutations in the procollagen type I genes (COL1A1 or COL1A2), no hot spots for the mutations were associated with particular clinical phenotypes. Eight patients that were studied here, diagnosed with OI by clinical standards, are from the Polish population with no ethnic background indicated. Previously unpublished mutations were found in six out of those eight patients. Genotypes for polymorphisms (Sp1 - rs1800012 and PvuII - rs412777), linked to bone formation and metabolism were determined. Mutations were found in exons 2, 22, 50 and in introns 13 and 51 of the COL1A1 gene. In COL1A2, one mutation was identified in exon 22. Deletion type mutations in COL1A1 that resulted in OI type I had no effect on collagen type I secretion, nor on its intracellular accumulation. Also, a single base substitution in I13 (c.904-9 G>T) was associated with the OI type I. The OI type III was associated with a single base change in I51 of COL1A1, possibly causing an exon skipping. Also, a missense mutation in COL1A2 changing Gly→Cys in the central part of the triple helical domain of the collagen type I molecule caused OI type III. It affected secretion of the heterotrimeric form of procollagen type I. However, no intracellular accumulation of procollagen chains could be detected. Mutation in COL1A2 affected its incorporation into procollagen type I. The results obtained shall help in genetic counseling of OI patients and provide a rational support for making informed, life important decisions by them and their families

Primary Pericardial Synovial Sarcoma: A Case Report and Literature Review

We report a case of a 52-year-old woman who was referred to our institution with a superior vena cava syndrome and was investigated through echocardiography, CT and MRI revealing a well-defined, encapsulated pericardial mass. The pathology, correlated with the immunohistochemical analysis, concluded it was an extremely rare primary pericardial synovial sarcoma. The patient underwent surgery and chemotherapy with a 16-month disease-free survival and passed away after a contralateral aggressive relapse. Moreover, we discuss the role of each imaging modality together with their pericardial synovial sarcoma reported features

An iTRAQ-based quantitative proteomic analysis of plasma proteins in preterm newborns with retinopathy of prematurity

Purpose: Retinopathy of prematurity (ROP) is a vision-threatening complication of a premature birth, in which the etiology still remains unclear. Importantly, the molecular processes that govern these effects can be investigated in a perturbed plasma proteome composition. Thus, plasma proteomics may add new insights into a better understanding of the pathogenesis of this disease. Methods: The cord and peripheral blood of neonates (≤30 weeks gestational age) was drawn at birth and at the 36th postmenstrual week (PMA), respectively. Blood samples were retrospectively subdivided into ROP(+) and ROP(−) groups, according to the development of ROP. Results: The quantitative analysis of plasma proteome at both time points revealed 30 protein abundance changes between ROP(+) and ROP(−) groups. After standardization to gestational age, children who developed ROP were characterized by an increased C3 complement component and fibrinogen level at both analyzed time points. Conclusions: Higher levels of the complement C3 component and fibrinogen, present in the cord blood and persistent to 36 PMA, may indicate a chronic low-grade systemic inflammation and hypercoagulable state that may play a role in the development of ROP