MRI in the evaluation of facial dermal fillers in normal and complicated cases.

OBJECTIVES: To ascertain by MRI the presence of filler injected into facial soft tissue and characterize complications by contrast enhancement. METHODS: Nineteen volunteers without complications were initially investigated to study the MRI features of facial fillers. We then studied another 26 patients with clinically diagnosed filler-related complications using contrast-enhanced MRI. TSE-T1-weighted, TSE-T2-weighted, fat-saturated TSE-T2-weighted, and TIRM axial and coronal scans were performed in all patients, and contrast-enhanced fat-suppressed TSE-T1-weighted scans were performed in complicated patients, who were then treated with antibiotics. Patients with soft-tissue enhancement and those without enhancement but who did not respond to therapy underwent skin biopsy. Fisher's exact test was used for statistical analysis. RESULTS: MRI identified and quantified the extent of fillers. Contrast enhancement was detected in 9/26 patients, and skin biopsy consistently showed inflammatory granulomatous reaction, whereas in 5/17 patients without contrast enhancement, biopsy showed no granulomas. Fisher's exact test showed significant correlation (p < 0.001) between subcutaneous contrast enhancement and granulomatous reaction. Cervical lymph node enlargement (longitudinal axis >10 mm) was found in 16 complicated patients (65 %; levels IA/IB/IIA/IIB). CONCLUSIONS: MRI is a useful non-invasive tool for anatomical localization of facial dermal filler; IV gadolinium administration is advised in complicated cases for characterization of granulomatous reaction. KEY POINTS: • MRI is a non-invasive tool for facial dermal filler detection and localization. • MRI-criteria to evaluate complicated/non-complicated cases after facial dermal filler injections are defined. • Contrast-enhanced MRI detects subcutaneous inflammatory granulomatous reaction due to dermal filler. • 65 % patients with filler-related complications showed lymph-node enlargement versus 31.5 % without complications. • Lymph node enlargement involved cervical levels (IA/IB/IIA/IIB) that drained treated facial areas.

High-resolution, handheld camera use for occult breast lesion localization plus sentinel node biopsy (SNOLL): a single-institution experience with 186 patients.

BACKGROUND: Sentinel node and occult lesion localization (SNOLL) calls for a combination of two specific procedures: intraoperative detection of sentinel lymph node (SLN) via gamma probe and radioguided occult lesion localization (ROLL). This applies to nonpalpable invasive breast cancer or high-grade in situ carcinoma. As opposed to standard techniques, today's handheld gamma cameras enable intraoperative scintigraphic images. METHODS: A cohort (N = 186) of consecutive patients with breast cancer was subjected to radioguided conservative surgery (quadrantectomy and SLN biopsy), using a standard gamma probe and a high-resolution handheld camera. Intraoperative SLN frozen section was also performed. RESULTS: Neoplastic lesions were removed in 99.4% of all patients, and SLN biopsy was achieved in 99%. Of the 137 patients with invasive cancer, SLN metastasis was confirmed in 21. In 12% of patients, a second operation was required for close or tumor-positive surgical margins. DISCUSSION: This combination of procedures represents an improvement in the surgical management of occult breast carcinomas and is the method of choice for accurate tumor localization and SLN biopsy. Handheld cameras have the potential to become highly useful intraoperative aids.

Diagnosis and management of dermal filler complications in the perioral region.

BACKGROUND: Lip augmentation with injectable materials is a popular aesthetic procedure. When complications occur, patients often ignore which material was implanted, thus making subsequent treatments difficult. This study aims to present the diagnosis and management of dermal filler complications in the perioral region. STUDY DESIGN: The Medical charts of 26 patients with filler complications in the oral region were reviewed. All patients were submitted to High Frequency Ultrasound, often complemented by Magnetic Resonance Imaging (MRI) and White Blood Cell Scintigraphy, to evaluate filler characteristics and complication types. Antibiotic, corticosteroid or surgical treatment was therefore planned. RESULTS: Imaging always identified dermal fillers in the oral region, distinguishing among infections, fibrosis, granulomatous inflammation and product migration. Nine patients received surgery, ten received medical treatments, six received both, and one refused treatment. Eighty percent of the patients presented an improvement after three- year follow-up. CONCLUSIONS: Complications of oral region fillers are similar in clinical presentation but differ in etiology, therefore necessitating different clinical approaches. Imaging techniques add useful information for treatment planning.

Identification of a short ACE2-derived stapled peptide targeting the SARS-CoV-2 spike protein.

The design and synthesis of a series of peptide derivatives based on a short ACE2 α-helix 1 epitope and subsequent [i - i+4] stapling of the secondary structure resulted in the identification of a 9-mer peptide capable to compete with recombinant ACE2 towards Spike RBD in the micromolar range. Specifically, SARS-CoV-2 Spike inhibitor screening based on colorimetric ELISA assay and structural studies by circular dichroism showed the ring-closing metathesis cyclization being capable to stabilize the helical structure of the 9-mer 34HEAEDLFYQ42 epitope better than the triazole stapling via click chemistry. MD simulations showed the stapled peptide being able not only to bind the Spike RBD, sterically interfering with ACE2, but also showing higher affinity to the target as compared to parent epitope.

Effect of fortification on the osmolality of human milk.

BACKGROUND: It is known that human milk fortifiers (HMF) increases osmolality of human milk (HM) but some aspects of fortification have not been deeply investigated. Our aim was to evaluate the effect of fortification on the osmolality of donor human milk (DHM) and mother's own milk (MOM) over 72 h of storage using two commercial fortifiers and medium-chain triglycerides (MCT) supplementation. METHODS: Pasteurized DHM and unpasteurized preterm MOM were fortified with 4% PreNAN FM85, 4% PreNAN FM85 plus 2% MCT, or 4% Aptamil BMF. Osmolality was measured in unfortified DHM and MOM and, moreover, just after fortification (T0), and after 6 (T6), 24 (T24) and 72 h (T72) to determine the effect of mixing and storage. RESULTS: Unfortified DHM and MOM did not show changes of osmolality. Fortification increased osmolality of DHM and MOM without changes during the study period, except for Aptamil BMF which increased osmolality of MOM. The addition of MCT to fortified human milk (FHM) did not affect its osmolality. CONCLUSIONS: Changes of osmolality in the 72 h following fortification of both DHM and MOM did not exceed the safety values supporting the theoretically possibility of preparing 72 h volumes of FHM. Supplementation with MCT of FHM does not change osmolality suggesting that increasing energy intake in preterm infants via this approach is safe.

The utility of high-frequency ultrasound in dermal filler evaluation.

Aim of this study is to describe the use of high-frequency ultrasound to ascertain the site, quantity, and type of filler injected in the soft tissue of the face, with respect to reliability of the procedure and the analysis costs. Between December 2006 and August 2010, 80 subjects aged 25 to 65 years, who underwent facial filler augmentation, were submitted to high-frequency sonography. Of total, 42 patients (22 after temporary filler and 20 after permanent filler) were healthy and satisfied of the treatment, and 38 patients sought consultation for filler-related problems. The nature of the injected filler was known in 86.25% of the patients, whereas it was unknown in 13.75% of the patients. Besides 4 patients, previously treated with temporary products, in which no foreign material was detected, high-frequency sonography was able to identify and quantify the presence of filler in the soft tissue of 97% of patients. Moreover, it was possible to detect inflammatory reaction (that were often silent), granulomas, and recognize the presence of diverse fillers in the same area. Ultrasonography has proved to be a useful, inexpensive, noninvasive tool for the identification of the site, quantity, and often even nature of the filler injected.

High-frequency sonography of temporary and permanent dermal fillers.

BACKGROUND: Dermal fillers are used widely; some have a permanent effect, whereas others are temporary. The aim of this study is to describe the ultrasonographic features of permanent and temporary fillers injected into patients for cosmetic purposes. MATERIALS AND METHODS: Between December 2006 and April 2009, 36 subjects, aged 25-45, who had received lips or nasolabial fold filler augmentation, were enrolled for a high-frequency sonographic examination by a blinded investigator. The criteria for exclusion were a history of autoimmunity, infection, neoplastic diseases or episodes of local reactions to the injected filler. Twenty patients underwent a sonographic exam after the injection of a temporary filler (collagen or hyaluronic acid) by FRG; the rest were enrolled among patients seeking a consultation for further cosmetic reasons, but had been treated with an identifiable filler before. RESULTS: It was always possible to identify the filler at the site of injection. Seldom was it possible to discover a silent inflammatory reaction, otherwise unsuspected. The sonographic images differed according to the temporary or the permanent nature of the filler. CONCLUSION: Ultrasonography has proved to be a useful, non-invasive tool for the identification of the presence and type of the filler injected.

Beyond BRCA1 and BRCA2: Deleterious Variants in DNA Repair Pathway Genes in Italian Families with Breast/Ovarian and Pancreatic Cancers.

The 5-10% of breast/ovarian cancers (BC and OC) are inherited, and germline pathogenic (P) variants in DNA damage repair (DDR) genes BRCA1 and BRCA2 explain only 10-20% of these cases. Currently, new DDR genes have been related to BC/OC and to pancreatic (PC) cancers, but the prevalence of P variants remains to be explored. The purpose of this study was to investigate the spectrum and the prevalence of pathogenic variants in DDR pathway genes other than BRCA1/2 and to correlate the genotype with the clinical phenotype. A cohort of 113 non-BRCA patients was analyzed by next-generation sequencing using a multigene panel of the 25 DDR pathways genes related to BC, OC, and PC. We found 43 unique variants in 18 of 25 analyzed genes, 14 classified as P/likely pathogenic (LP) and 28 as variants of uncertain significance (VUS). Deleterious variants were identified in 14% of index cases, whereas a VUS was identified in 20% of the probands. We observed a high incidence of deleterious variants in the CHEK2 gene, and a new pathogenic variant was detected in the RECQL gene. These results supported the clinical utility of multigene panel to increase the detection of P/LP carriers and to identify new actionable pathogenic gene variants useful for preventive and therapeutic approaches.

Clinical and Antitumor Immune Responses in Relapsed/Refractory Follicular Lymphoma Patients after Intranodal Injections of IFNα-Dendritic Cells and Rituximab: a Phase I Clinical Trial.

PURPOSE: This study was aimed at evaluating the feasibility, safety, immunologic and clinical responses in patients with follicular lymphoma treated with monocyte-derived dendritic cells generated in the presence of IFNα and GM-CSF (IFN-DC) in combination with low doses of rituximab. PATIENTS AND METHODS: Firstly, we analyzed in vitro and in vivo the immunologic properties of IFN-DC against follicular lymphoma. Thus, we performed a phase I trial in 8 patients with refractory and relapsed follicular lymphoma based on sequential intranodal injections of low-dose of rituximab and unloaded IFN-DC and report the safety, clinical, and immunologic results of the enrolled patients. RESULTS: Preclinical studies indicated that IFN-DC can synergize with rituximab leading to increased cytotoxicity and T-cell tumor infiltration. The clinical evaluation showed that the combined treatment was totally safe. The overall response rate was 50%, PET-negative complete response rate 37%, and remission is still ongoing in 2/4 of responding patients (median follow-up 26 months, range 11-47). Notably, following the combined therapy all patients showed induction/enhancement of T-cell responses by CD107 degranulation or IFNγ ELISPOT assay against patient-specific tumor IGHV sequences. CONCLUSIONS: These results represent the proof-of-principle on the effectiveness of unloaded IFN-DC in inducing durable clinical responses and promoting induction of tumor-specific peripheral T cells, thus suggesting the occurrence of an effective endogenous antitumor vaccination. The overall findings indicate that some unique properties of IFN-DC can be successfully exploited to induce/enhance antitumor responses, thus representing a valuable antitumor strategy for novel and more effective combination therapies in patients with cancer.

Rapid detection of copy number variations and point mutations in BRCA1/2 genes using a single workflow by ion semiconductor sequencing pipeline.

Molecular analysis of BRCA1 (MIM# 604370) and BRCA2 (MIM #600185) genes is essential for familial breast and ovarian cancer prevention and treatment. An efficient, rapid, cost-effective accurate strategy for the detection of pathogenic variants is crucial. Mutations detection of BRCA1/2 genes includes screening for single nucleotide variants (SNVs), small insertions or deletions (indels), and Copy Number Variations (CNVs). Sanger sequencing is unable to identify CNVs and therefore Multiplex Ligation Probe amplification (MLPA) or Multiplex Amplicon Quantification (MAQ) is used to complete the BRCA1/2 genes analysis. The rapid evolution of Next Generation Sequencing (NGS) technologies allows the search for point mutations and CNVs with a single platform and workflow. In this study we test the possibilities of NGS technology to simultaneously detect point mutations and CNVs in BRCA1/2 genes, using the OncomineTM BRCA Research Assay on Personal Genome Machine (PGM) Platform with Ion Reporter Software for sequencing data analysis (Thermo Fisher Scientific). Comparison between the NGS-CNVs, MLPA and MAQ results shows how the NGS approach is the most complete and fast method for the simultaneous detection of all BRCA mutations, avoiding the usual time consuming multistep approach in the routine diagnostic testing of hereditary breast and ovarian cancers.

Cytological diagnostic features of late breast implant seromas: From reactive to anaplastic large cell lymphoma.

Late breast implant seroma may be the presentation of a breast implant-associated anaplastic large cell lymphoma (BI-ALCL), which claims for a prompt recognition. However, BI-ALCL diagnosis on fine-needle aspiration (FNA) might be challenging for pathologists lacking experience with peri-implant breast effusions. Sixty-seven late breast implant seromas collected by FNA from 50 patients were evaluated by Papanicolaou smear stain and immunocytochemistry on cell blocks. A diagnostic algorithm based on the cellular composition, cell morphology and percentage of CD30+ cells was developed. Histological evaluation of the corresponding peri-prosthetic capsules was also performed. Most of the effusions (91% of the samples) were classified as reactive and 9% as BI-ALCL. In the BI-ALCL cases, medium-to-large atypical cells expressing CD30 represented more than 70% of the cellularity, whereas in in the reactive effusions CD30+ elements were extremely rare (<5%) and consisted of non-atypical elements. The reactive effusions were categorized into three patterns: i) acute infiltrate with prominent neutrophilic component (33% of the samples); ii) mixed infiltrate characterized by a variable number of neutrophils, lymphocytes and macrophages (30% of the samples); iii) chronic infiltrate composed predominantly of T lymphocytes or macrophages with only sporadic granulocytes (37% of the samples). The inflammatory cytological patterns were consistent with the histology of the corresponding capsules. Our results indicate that cytological analysis of late breast implant effusions, supported by the knowledge of the heterogeneous cytomorphological spectrum of late seromas, is a valuable approach for the early recognition of BI-ALCL.