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Adolescents on the autism spectrum may experience challenges with multiple domains of communication that impact their quality of life. Both music therapists and speech-language pathologists (SLPs) implement activities to address these challenges. Empirical evidence suggests that incorporating music into treatment can be an effective way to improve communication. The purpose of this article is to provide suggestions for music therapists assisting adolescents on the autism spectrum to improve their communication skills and ways to collaborate with SLPs in doing so. In this paper, we discuss interprofessional collaborative models (e.g., interdisciplinary, transdisciplinary) and competencies (e.g., coordination, adaptability), as well as music-based clinical experiences that appeal to adolescents, and target improvement of communication skills for learners with complex communication needs.

Objective Serous tubal intraepithelial carcinoma (STIC) is currently considered the precursor lesion of pelvic high-grade serous carcinoma. The management of STIC diagnosed after risk-reducing salpingo-oophorectomy (RRSO) in women with BRCA1–2 variants remains unclear. The aim of our study was to evaluate the incidence of STIC, serous tubal intraepithelial lesions (STIL) and occult invasive cancer (OC) and to determine the long-term outcomes of these patients. Methods We conducted a retrospective study of patients with BRCA 1–2 variants who underwent RRSO between January-2010 and Dicember-2020 at the Clinic of Gynaecology of University of Padova. Inclusion criteria: women with a negative pelvic examination at the last screening prior to RRSO, patients with fallopian tubes analysed using the SEE-FIM protocol. Exclusion criteria: patients with a positive gynaecologic screening or with ovarian/tubal cancer prior to RRSO. Results We included 153 patients. STICs were diagnosed in 4 patients (2.6%) and STILs in 6 patients (3.9%). None of the patients with STIC underwent restaging surgery or adjuvant chemotherapy; all patients were followed closely every 6 months. None of the patients developed primary peritoneal carcinomas (PPCs) with a median FUP of 54.5 months (15–106). OC was diagnosed in 3 patients (2%). All patients with OC underwent staging surgery, and one patient developed a peritoneal carcinoma (PC) after 18 months by staging surgery. Conclusion(s) The incidence of STIC, STIL and OC after RRSO in BRCA1–2 variants was low. Our results demonstrated that long-term close surveillance in patients diagnosed with STIC should be considered a possible management strategy.

Objectives/hypothesis The accurate diagnostic assessment of clinically relevant human papillomavirus (HPV) infections in patients with head and neck squamous cell carcinoma represents an urgent unmet medical need. The aim of this study was to determine feasibility, accuracy, and clinical significance of HPV16/18 E6 oncoprotein detection on cytological specimens from oropharyngeal squamous cell carcinoma (OPSCC) and neck lymph node metastasis of SCC from unknown primary tumor (CUP) via a protein immunochromatographic assay. Study design Cross-sectional study. Methods Cytological specimens from primary tumor and neck metastases were collected from 34 patients with OPSCC or CUP and applied to a lateral flow format test that detects HPV16 and HPV18 E6 oncoproteins. E6 oncoprotein positivity or negativity in these specimens was compared to the specimens' "HPV-driven" reference status, defined by presence of HPV-DNA in combination with p16INK4a overexpression and/or HPV E6 seropositivity. Results Eighteen of 29 OPSCC (62%) and three of five CUP (60%) were HPV-driven according to our reference method. The E6 oncoprotein lateral flow test had a sensitivity of 94% (95% CI: 70%-100%) and a specificity of 100% (95% CI: 66%-100%) on primary tumor, and a sensitivity of 88% (95% CI: 64%-99%) and a specificity of 100% (95% CI: 74%-100%) on neck metastases. Test agreement between the E6 lateral flow test and the clinical reference method, HPV-DNA plus p16INK4a was excellent, both for primary lesion and neck metastases. Conclusions We found the detection of HPV16/18 E6 oncoproteins to be a feasible, highly reliable, and low-invasive method to assess "HPV-driven" status in OPSCC and CUP. Level of evidence II Laryngoscope, 131:1042-1048, 2021.

Medulloblastoma is an embryonal neuroepithelial tumor that affects mainly childhood and more rarely adults. Medulloblastoma occurring as multiple nodules at diagnosis is a rare and tricky presentation. Here, we describe the case of a previously healthy 47-year-old woman with multiple posterior fossa cerebellar tumors. Histological, immunohistochemical, and molecular analyses were performed to best characterize the two excised lesions. The histopathological analysis revealed different variants of medulloblastoma in the excised nodules, one being extensive nodularity, rare in adults, and the other desmoplastic/nodular with areas of anaplasia. Immunostains and molecular analysis classified both nodules as SHH medulloblastoma. Adult medulloblastoma is extremely rare. Important differences exist between adult medulloblastoma and medulloblastoma arising in children and infants. Such differences are in location, distribution of histological variants and of molecular subgroups, survival rates, and therapeutic options. An extensive morphological and molecular characterization of such rare tumors is necessary to choice the best-tailored therapy.

Introduction/Background* Serous Tubal Intraepithelial Carcinoma (STIC) is a non-invasive subtype of high-grade serous carcinoma (HGSC), usually located at the tubo-peritoneal junction and currently considered the precursor lesion of HGSC. The management of STIC diagnosed after Risk-Reducing Salpingo-Oophorectomy (RRSO) in women with BRCA-carriers remains unclear. The aim of our study was to evaluate the incidence of STIC, serous tubal intraepithelial lesions (STIL) and Occult-Cancer (OC) in patients submitted to RRSO and determine the long-term outcomes of these patients. Methodology We conducted an observational retrospective study on patients with BRCA 1-2 mutation who undergone RRSO between January-2010 to Dicember-2020 at the Gynaecology Clinic of Padua. Inclusion criteria: (i) women with a negative pelvic examination prior to RRSO (ii) fallopian tubes analyzed using the Sectioning and Extensively Examining the Fimbriated (SEE-FIM) protocol. Exclusion criteria: patients with a positive gynecologic screening or with ovarian/tubal cancer prior to RRSO. We collected data about age, menopausal status, history of breast carcinoma, pre-operative CA-125 levels, transvaginal-ultrasound features before surgery, and follow up (FUP) information after RRSO, specifically with CA-125 and gynecologic examination. Result(s)* We included 153 patients: baseline characteristics (table 1). STICs was diagnosed in 4 (2.6%) and STILs in 6 (3.9%) patients. None patients with STIC and STIL underwent a restaging surgery or adjuvant chemotherapy; all patients were followed closely every 6 months with transvaginal-ultrasound and CA-125. None of them developed peritoneal carcinoma (PC) or primary peritoneal carcinomas (PPC) with a median FUP of 54.5 months (15-106) and 57,5 months (12-82) in patients with STIC and STIL, respectively. OC was diagnosed in 3 patients (2%) and they underwent a staging-surgery; one patient developed a recurrence with PC after 18 months by staging surgery. Conclusion* Considering the low incidence of OC-STIC-STIL, our data support the importance of RRSO in patients with BRCA 1-2 mutations for reducing the risk of ovarian cancer and for detecting the lesions in early stage. The management of patients with isolated STIC that is aimed to decreases the rates of subsequent PPC and PC. Our results demonstrated that a long-term close surveillance in patients with STIC should be considered a possible management strategy.

We conducted a screening analysis to assess the presence of a characteristic extracellular circulating microRNAs (ci-miRNAs) profile in Behcet's syndrome (BS). Total RNA was extracted from platelets-free plasma (PFP) samples obtained from 16 BS patients and 18 healthy controls. Ci-miRNAs profiling was conducted by using dedicated Agilent microarray hybridization and data extraction technology. Statistical analysis of data extracted from microarray scanning revealed the deregulation of 36 ci-miRNAs, which turned out be differentially expressed between BS patients and healthy controls. Detailed experimental methods and data analysis were described here. The raw and normalized microarray data were deposited into Gene Expression Omnibus (GEO) under accession number {"type":"entrez-geo","attrs":{"text":"GSE145191","term_id":"145191"}}GSE145191.

BACKGROUND Maximum safe resection for eloquent areas glioblastomas is the greatest tumor resection achievable without causing neurological deficits. This study aims to assess, through quantitative volumetric analysis, the outcomes of patients with eloquent areas glioblastomas and correlate the extent of resection (EOR), based on MRI T1-contrast enhanced (CE) and T2- fluid-attenuated inversion recovery (FLAIR) sequences, with patient outcomes and overall survival. METHODS We prospectively collected and analyzed patients with a diagnosis of primary GBM located in an eloquent area operated between January 2012 and April 2018. We examined 295 consecutive patients' records with GBM and identified 82 eloquent GBMs who met inclusion criteria. We stratified our patients by type of treatment - awake surgery (AS) and general anesthesia (GA) craniotomies. The kind of treatment was correlated with EOR, focusing on exeresis over the limit of the contrast-enhanced signal intensity, including both T1-CE and T2-FLAIR MRI signal alterations. RESULTS The overall mean EOR value was higher in AS than in GA on T1-CE (p-value: 0.010) and T2-Flair MRI images (p-value: 0.007). Also, patients who had at least 30% of T2-FLAIR signal resection (EOR ≥ 30%) had a significantly lower risk of death and recurrence (p-value: 0.020), independent of residual T1-CE tumor volume. CONCLUSIONS Extensive T2-Flair resection and AS improve overall survival and reduce risk of recurrence while simultaneously minimizing surgical and medical complications among patients with GBMs in eloquent areas.

Introduction A dura mater substitute in decompressive craniectomies must protect the brain while providing a dissection plane between the cortex and myocutaneous layer. The human amniotic membrane (AM) has anti-inflammatory, wound healing, and differentiation properties. We tested AM properties as a dural substitute by comparing the outcomes to biological ones. Methods We prospectively collected data on 25 patients who randomly underwent decompressive craniectomy with lyophilized AM patches and 25 in which biological substitutes were utilized between 2015 and 2019. The AM was laid with the epithelial side facing the brain because of the anti-adhesive proprieties, while the chorion facing the myocutaneous flap. We collected data on demographics, neurological status, comorbidities, and surgical outcomes. Additionally, we created a score – dura mimicking score– and reviewed postoperative imaging and pathological specimens. Results The majority (96%) of AM grafts were integrated into native dura. Thirteen patients scored as excellent and 11 good on our “dura mimicking score”, showing tissue integration ability but no cerebral cortex adhesion. The histopathological analysis showed that AM had thick plates of dense fibrous tissue with small reactive vessels, reactive fibroblasts, and lymphocytes infiltrate. The AM group's first outcomes were not different from the biological substitute patients but higher integration rate to the dura and less adhesion to the myocutaneous flap in AM patients. Conclusions We documented the anti-adhesive, protective, and integrative properties of AM dural substitute patches in patients who underwent decompressive craniectomies, comparing the intraoperative differences and postoperative outcomes to biological dural substitutes.

The reasons why a specific subset of glioblastoma (GBM) patients survive longer than others is still unclear. This study analyzed a cohort of long-term and very-long-term GBM survivors to determine which genetic alterations or patient's characteristics influence survival time.We retrospectively reviewed a cohort of GBM patients treated at our institution over the last 20 years, stratifying patients in three groups: those with a survival time ≥ 36 months and 120 months (LTS), ≥120 months (VLTS), and 36 months, respectively. Clinical (age, sex, focality, resection degree, Karnofsky performance status), and immunohistochemical and molecular data (Ki-67 expression and multiple genes alterations) were collected. We then utilized principal component analysis, logistic regression, and Cox proportional hazard models to identify those variables associated with survival.Younger age at presentation (HR = 0.36, 95% CI 0.21-0.67, p = .001), and MGMT promoter [(MGMTp), methylated, HR = 0.57, CI 0.34-0.96, p = .034) were associated with higher odds of VLTS survival. The multivariate analysis showed how the combination of younger age (50 years), Ki-67 10%, and the coexistence of TERTp not mutated, MGMTp methylated, and IDH1/2 mutated in the same patient are also associated with higher odds of survival (HR = 0.10, CI 0.01-0.74, p = .025).We confirmed younger age at presentation and MGMTp methylation as the only independent factors associated with VLTS. The exceptional survival of our VLTS patients is probably associated with different, still understudied, gene mutations, or with the coexistence of multiple factors.

Meningeal solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) had been combined into a single classification until 2016. Recurrence and metastases rates are still understudied, especially for spinal SFT/HPCs. Here, we describe CNS SFT/HPCs and predictors for recurrence, metastases, and death, in spinal and intracranial SFT/HPCs, separately. We collected data from studies with patient-level data available on primary SFT/HPCs from multiple online databases. Clinico-demographic data, surgical outcomes, recurrence, metastases, and death rates were abstracted. We used logistic and Cox regression models to identify predictors for recurrence, metastases, and death for spinal and intracranial SFT/HPCs. Twenty-nine studies (368 patients) were included. Higher histological grade and subtotal resection were associated with recurrence (p values

SMARCB1 inactivation is a well-established trigger event in atypical teratoid/rhabdoid tumor. Recently, a role for SMARCB1 inactivation has emerged as a mechanism of clonal evolution in other tumor types, including rare brain tumors. We describe an unusual malignant intra-axial SMARCB1-deficient spindle cell desmoplastic neoplasm, occurring in a 6-year-old child with meningioangiomatosis and a long history of seizures. Striking features of the tumor were a storiform pattern and strong CD34 expression. Undifferentiated round cell areas with isolated rhabdoid cells showing high mitotic index and focal necrosis with INI1 expression loss were present. The meningioangiomatosis component showed few chromosomal imbalances, including chromosomal 22 monosomy (where SMARCB1 maps) and gain at 6q14.3. In addition to these abnormalities, the spindle cell desmoplastic neoplasm and its dedifferentiated SMARCB1-deficient component shared several other aberrations, including homozygous deletion at 9p21.3, losses at 1p, 3p, 3q, 10p, and 13q, gains and losses at 5p and 11p. In line with INI1 loss, the dedifferentiated component showed remarkably decreased levels of SMARCB1 transcript. The residual SMARCB1 allele was wildtype. Our findings suggest progression from the meningioangiomatosis to the malignant desmoplastic neoplasm through the occurrence of complex chromosomal abnormalities, and point to functional silencing of SMARCB1 in the dedifferentiation component.

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Background: Platinum-based drugs such as Cisplatin are commonly employed for cancer treatment. Despite an initial therapeutic response, Cisplatin treatment often results in the development of chemoresistance. To identify novel approaches to overcome Cisplatin resistance, we tested Cisplatin in combination with K+ channel modulators on colorectal cancer (CRC) cells. Methods: The functional expression of Ca2+-activated (KCa3.1, also known as KCNN4) and voltage-dependent (Kv11.1, also known as KCNH2 or hERG1) K+ channels was determined in two CRC cell lines (HCT-116 and HCT-8) by molecular and electrophysiological techniques. Cisplatin and several K+ channel modulators were tested in vitro for their action on K+ currents, cell vitality, apoptosis, cell cycle, proliferation, intracellular signalling and Platinum uptake. These effects were also analysed in a mouse model mimicking Cisplatin resistance. Results: Cisplatin-resistant CRC cells expressed higher levels of KCa3.1 and Kv11.1 channels, compared with Cisplatin-sensitive CRC cells. In resistant cells, KCa3.1 activators (SKA-31) and Kv11.1 inhibitors (E4031) had a synergistic action with Cisplatin in triggering apoptosis and inhibiting proliferation. The effect was maximal when KCa3.1 activation and Kv11.1 inhibition were combined. In fact, similar results were produced by Riluzole, which is able to both activate KCa3.1 and inhibit Kv11.1. Cisplatin uptake into resistant cells depended on KCa3.1 channel activity, as it was potentiated by KCa3.1 activators. Kv11.1 blockade led to increased KCa3.1 expression and thereby stimulated Cisplatin uptake. Finally, the combined administration of a KCa3.1 activator and a Kv11.1 inhibitor also overcame Cisplatin resistance in vivo. Conclusions: As Riluzole, an activator of KCa3.1 and inhibitor of Kv11.1 channels, is in clinical use, our results suggest that this compound may be useful in the clinic to improve Cisplatin efficacy and overcome Cisplatin resistance in CRC. Published version

Background: Platinum-based drugs such as Cisplatin are commonly employed for cancer treatment. Despite an initial therapeutic response, Cisplatin treatment often results in the development of chemoresistance. To identify novel approaches to overcome Cisplatin resistance, we tested Cisplatin in combination with K+ channel modulators on colorectal cancer (CRC) cells. Methods: The functional expression of Ca2+-activated (KCa3.1, also known as KCNN4) and voltage-dependent (Kv11.1, also known as KCNH2 or hERG1) K+ channels was determined in two CRC cell lines (HCT-116 and HCT-8) by molecular and electrophysiological techniques. Cisplatin and several K+ channel modulators were tested in vitro for their action on K+ currents, cell vitality, apoptosis, cell cycle, proliferation, intracellular signalling and Platinum uptake. These effects were also analysed in a mouse model mimicking Cisplatin resistance. Results: Cisplatin-resistant CRC cells expressed higher levels of KCa3.1 and Kv11.1 channels, compared with Cisplatin-sensitive CRC cells. In resistant cells, KCa3.1 activators (SKA-31) and Kv11.1 inhibitors (E4031) had a synergistic action with Cisplatin in triggering apoptosis and inhibiting proliferation. The effect was maximal when KCa3.1 activation and Kv11.1 inhibition were combined. In fact, similar results were produced by Riluzole, which is able to both activate KCa3.1 and inhibit Kv11.1. Cisplatin uptake into resistant cells depended on KCa3.1 channel activity, as it was potentiated by KCa3.1 activators. Kv11.1 blockade led to increased KCa3.1 expression and thereby stimulated Cisplatin uptake. Finally, the combined administration of a KCa3.1 activator and a Kv11.1 inhibitor also overcame Cisplatin resistance in vivo. Conclusions: As Riluzole, an activator of KCa3.1 and inhibitor of Kv11.1 channels, is in clinical use, our results suggest that this compound may be useful in the clinic to improve Cisplatin efficacy and overcome Cisplatin resistance in CRC.

The definition of the gene expression profile of genes encoding Ion Channels and Transporters (ICT-GEP) represents a novel and attracting aspect in cancer. We determined the ICT-GEP of Follicular Lymphoma (FL), and compared it with that of the more aggressive Diffuse Large B Cell Lymphoma (DLBCL). cDNA microarray data were collected both from patients enrolled for this study, and from public datasets. In FL the ICT-GEP indicated the overexpression of both the K+ channel encoding gene KCNN4, and SLC2A1, which encodes the Glut1 glucose transporter. SLC2A1 turned out to represent the hub of a functional network, connecting channels and transporters in FL. Relapsed FL patients were characterised by 38 differentially expressed ICT genes, among which ATP9A, SLC2A1 and KCNN4 were under-expressed, indicating a down-regulation of both excitability and glycolysis. A completely different profile of K+ channel encoding genes emerged in DLBCL accompanied by the over-expression of the fatty acid transporter-encoding gene SLC27A1 as well as of the metabolism regulator NCoR1. This indicates a change in excitability and a shift towards an oxidative metabolism in DLBCL. Overall, the ICT-GEP may contribute to identifying novel lymphoma biomarkers related to excitability and metabolic pathways, with particular relevance for drug resistant, relapsed FL.

A type of breast tumor histopathologically similar to the papillary thyroid carcinoma has been described and named “Breast tumor resembling the tall cell variant of papillary thyroid carcinoma.” Because breast is not an uncommon site for metastasis and about 5% of all such cases are of the thyroid origin, it is important to be aware of the existence of mammary tumors that can closely mimic a thyroid tumor representing a dangerous diagnostic pitfall that can also lead to unnecessary clinical investigations. Here, we describe a singular case of “Breast tumor resembling the tall cell variant of papillary thyroid carcinoma” showing an amazing macroscopic and microscopic resemblance with thyroid tissue harboring a papillary carcinoma.

Although multiple primary malignancies are relatively rare, they have increased in frequency over the last decades, partly because of advances in diagnosis and therapy. This report describes for the first time the case of a patient with past occupational exposure to asbestos and no family history of cancer who developed 2 rare primary malignancies: a cardiac sarcoma and a gliosarcoma 11 months later. Molecular-cytogenetic studies did not identify common lesions to these 2 rare metachronous sarcomas. The gliosarcoma was associated with monosomy 10 and underlying PTEN monoallelic loss, which has been recurrently observed. In the cardiac sarcoma, MDM2 amplification and CDKN2AB/9p21 biallelic deletion suggested intimal sarcoma. No causal relationship was found between cardiac sarcoma and asbestos exposure, although MDM2 abnormalities were linked to malignant mesothelioma.

Malignant mesothelioma is a primary neoplasm of the serosal membranes that usually presents with a diffuse pattern of growth. However, cases of localized mesotheliomas have been described. The predominant localization is the pleura; peritoneum and pericardium being rarer localizations. Only few cases of true intraparenchymal mesothelioma arising in organs such as liver, gonads, lung, and pancreas have been described. We report a case of an otherwise healthy 48-year-old man without asbestos exposure with a nodule of 3 cm in diameter, localized in the spleen, discovered incidentally at the ultrasonographic examination, for which histopathological and immunohistochemical findings were consistent with epithelioid mesothelioma: large round cells with eosinophil dense cytoplasm and macronucleoli and with immunohistochemical positivity for pancytokeratins, calretinin, Wilms tumor-1, and others markers of mesothelial differentiation. The diagnosis of localized intrasplenic epithelioid malignant mesothelioma was carried out. To the best of our knowledge, this is the first case of a localized intrasplenic mesothelioma published in the indexed literature.

Immunoglobulin G4 (IgG4)-related hypertrophic pachymeningitis, which is a focally or diffusely thickened dura mater and lymphoplasmacytic infiltration with increased IgG4 bearing plasma cells, is a rare disease, and cases involving the whole cervical spine are even rarer. Here, we describe a case of probable IgG4-related hypertrophic pachymeningitis involving the whole cervical spine and the auditory canals in an 18-year-old male. The patient, who had a history of paresthesia and had previously experienced weakness, presented with generalized tonic seizures. A decompressive laminectomy on cervical vertebrae was performed as a matter of urgency, removing intradural fibrous material. The patient responded well to treatment and was discharged walking independently, with no strength deficit to any of the 4 limbs, and with normal blood tests.