Being a technician during COVID-19: a qualitative cross-sectional survey on the experiences of clinical neurophysiology technicians.

BACKGROUND: During the Sars-CoV-2 virus pandemic, Italy faced an unrivaled health emergency. Its impact has been significant on the hospital system and personnel. Clinical neurophysiology technicians played a central role (but less visibly so compared to other healthcare workers) in managing the COVID-19 pandemic. This research aims to explore the experiences of clinical neurophysiology technicians during the pandemic and contribute to the debate on the well-being of healthcare workers on the front line. METHODS: We implemented a cross-sectional survey across Italy. It contained questions that were open-ended for participants to develop their answers and acquire a fuller perspective. The responses were analyzed according to the framework method. RESULTS: One hundred and thirty-one responses were valid, and the following themes were generated: technicians' experiences in their relationship with patients, technicians' relationship with their workgroup and directors, and technicians' relationship with the context outside of their work. The first theme included sub-themes: fear of infection, empathy, difficulty, a sense of obligation and responsibility, anger, and sadness. The second theme contained selfishness/solidarity in the workgroup, lack of protection/collaboration from superiors, stress, and distrust. The last theme included fear, stress/tiredness, serenity, sadness, and anger. CONCLUSION: This study contributes to building a humanized perspective for personnel management, bringing attention to the technical work of healthcare professionals in an emergency and the emotional and relational dimensions. These are the starting points to define proper, contextually adequate support.

Laser-Evoked Potentials to Pudendal Stimulation in Healthy Subjects: A Pilot Study.

PURPOSE: Laser-evoked potentials (LEPs) are useful neurophysiological tools for investigating the A-delta sensory peripheral fibers and the central nociceptive pathway. The current investigation aims to obtain normative values of LEPs via pudendal nerve stimulation in healthy adult volunteers. METHODS: Laser-evoked potentials were recorded in 16 men and 22 women, 22 to 75 years of age, using neodymium and yttrium and aluminum and perovskite laser bilateral stimulation to the pudendal nerve-supplied skin and the dorsal surface of the hands and feet. We assessed the perceptive threshold, latency, and amplitude of the N1 component and main vertex N2-P2 complex. The relationship between gender, age, height, and site of stimulation was statistically analyzed. RESULTS: Both in men and in women, laser perceptive threshold increased from genitalia to foot and from hand to foot (P ≤ 0.001). N1 and N2-P2 latencies progressively increased from pudendal area to hand to foot (P ≤ 0.008). N1 and N2-P2 complex LEP amplitudes progressively decreased from hand to genitalia to foot (P ≤ 0.04). The latencies of N1 component and N2-P2 complex of LEPs correlated with body height, whereas the amplitude of the N2-P2 complex correlated negatively with age; no correlations were observed between the latencies and amplitudes with gender. CONCLUSIONS: This study provides normative data on pudendal LEPs versus hand and foot LEPs. Incorporation of pudendal LEPs into clinical practice could provide a valuable neurophysiological tool for the study of pelvic pain syndromes.

Locally advanced paranasal sinus carcinoma: A study of 30 patients.

Sinonasal carcinomas (SNcs) are rare neoplasms arising from the paranasal sinuses and nasal cavity. Although these tumours have a heterogeneous histology, they are commonly diagnosed as a locally advanced disease and are associated with a poor prognosis. The present retrospective study reviewed 30 patients with locally advanced SNc, who were treated with surgery followed by chemoradiotherapy or radiotherapy, or radiotherapy with or without concomitant chemotherapy between January 1999 and January 2013 at the Department of Radiation Therapy, University of Naples 'Federico II' (Naples, Italy). A total of 19 patients were treated with upfront surgery followed by adjuvant radio- or chemoradiotherapy (group A), while the remaining 11 patients received exclusive radiotherapy with or without concomitant chemotherapy (group B). Concurrent cisplatin-based chemotherapy (100 mg/m2, days 1, 22 and 43 for 3 cycles) was administered to 34% of patients in group A and 55% of patients in group B. At a median follow-up of 31 months, 33.3% of patients were alive. Cause-specific survival (CSS) and progression-free survival (PFS) times were 32 and 12 months, respectively. No difference in CSS rate was observed between the two treatment groups. Univariate analysis determined that disease stage was the only factor that significantly affected CSS (P=0.002) and PFS (P=0.0001) rates. Acute and chronic toxicities were mild, with only 23.3% of patients reporting G1-2 side effects and no treatment-related blindness. The present study reported moderate activity and efficacy of surgery followed by adjuvant radio- or chemoradiotherapy, and exclusive radiotherapy with or without chemotherapy in this poor prognosis category of patients.

Short-course radiotherapy in elderly patients with early stage non-melanoma skin cancer: a phase II study.

AIM: To evaluate outcome of an accelerated radiotherapy (RT) regimen in elderly patients with an early stage non-melanoma skin cancer (NMSC). METHODS: Total RT dose was 30 Gy in 5 Gy fractions in six consecutive days. RESULTS: Thirty-one patients were enrolled. Fourteen were aged ≥80 years. Acute skin and observed late toxicity were exclusively of grade 1. Thirty patients showed a complete response (median follow-up 30 months). Two-year actuarial local control was 93.2%. The cosmetic result was mostly judged as good or excellent. CONCLUSIONS: Short-course RT in elderly NMSC patients produces >90% local control of disease.

Volumetric intensity modulated arc therapy for stereotactic body radiosurgery in oligometastatic breast and gynecological cancers: feasibility and clinical results.

In the present study, the preliminary results of the first stereotactic body radiosurgery (SRS) experience with volumetric intensity modulated arc therapy (VMAT) in oligometastatic breast and recurrent gynecological tumors (OBRGT) are reported in terms of feasibility, toxicity and efficacy. Patients were treated in a head-first supine treatment position on a customized body frame immobilization shell. SRS-VMAT treatment plans were optimized using the ERGO++ treatment planning system. Response assessment was performed 8-12 weeks after treatment by morphologic imaging modalities, or if feasible, also by functional imaging. Thirty-six lesions in 24 consecutive patients (median age, 63 years; range, 40-81) were treated: 13.9% had primary or metastatic lung lesions, 30.5% had liver metastases, 36.1% had bone lesions, 16.7% had lymph node metastases and 2.8% had a primary vulvar melanoma. The median dose was 18 Gy (BED2 Gy, α/ß: 10=50.4 Gy), the minimal dose was 12 Gy (BED2 Gy, α/ß: 10=26.4 Gy) and the maximal dose was 28 Gy (BED2 Gy, α/ß: 10=106.4 Gy). Seven patients (29.2%) experienced acute toxicity, which however was grade 2 in only 1 case. Moreover, only 3 patients (12.5%) developed late toxicity of which only 1 was grade 2. Objective response rate was 77.7% including 16 lesions achieving complete response (44.4%) and 12 lesions achieving partial response (33.3%). The median duration of follow-up was 15.5 months (range, 6-50). Recurrence/progression within the SRS-VMAT treated field was observed in 6 patients (total lesions=7) with a 2-year inside SRS-VMAT field disease control expressed on a per lesion basis of 69%. Recurrence/progression of disease outside the SRS-VMAT field was documented in 15 patients; the 2-year outside SRS-VMAT field metastasis­free survival, expressed on a per patient basis, was 35%. Death due to disease was documented in 6 patients and the 2-year overall survival was 58%. Although the maximum tolerated dose was not reached, SRS-VMAT resulted in positive early clinical results in terms of tumor response, local control rate and toxicity.

A large de novo 9p21.3 deletion in a girl affected by astrocytoma and multiple melanoma.

BACKGROUND: Association of melanoma, neural system tumors and germ line mutations at the 9p21 region in the CDKN2A, CDKN2B and CDKN2BAS genes has been reported in a small number of families worldwide and described as a discrete syndrome in melanoma families registered as a rare disease, the melanoma-astrocytoma syndrome. CASE PRESENTATION: We here studied two young patients developing melanoma after radiotherapy for astrocytoma, both reporting lack of family history for melanoma or neural system tumors at genetic counselling. Patient A is a girl treated for anaplastic astrocytoma at 10 years and for multiple melanomas on the scalp associated to dysplastic nevi two years later. Her monozygotic twin sister carried dysplastic nevi and a slow growing, untreated cerebral lesion. Direct sequencing analysis showed no alterations in melanoma susceptibility genes including CDKN2A, CDK4, MC1R and MITF or in TP53. By microsatellite analysis, multiplex ligation-dependent probe amplification, and array comparative genomic hybridization a deletion including the CDKN2A, CDKN2B and CDKN2BAS gene cluster was detected in both twin sisters, encompassing a large region at 9p21.3 and occurring de novo after the loss of one paternal allele.Patient B is a boy of 7 years when treated for astrocytoma then developing melanoma associated to congenital nevi on the head 10 years later: sequencing and multiplex ligation-dependent probe amplification revealed a normal profile of the CDKN2A/CDKN2B/CDKN2BAS region. Array comparative genomic hybridization confirmed the absence of deletions at 9p21.3 and failed to reveal known pathogenic copy number variations. CONCLUSIONS: By comparison with the other germ line deletions at the CDKN2A, CDKN2B and CDKN2BAS gene cluster reported in melanoma susceptible families, the deletion detected in the two sisters is peculiar for its de novo origin and for its extension, as it represents the largest constitutive deletion at 9p21.3 region identified so far.In addition, the two studied cases add to other evidence indicating association of melanoma with exposure to ionizing radiation and with second neoplasm after childhood cancer. Melanoma should be considered in the monitoring of pigmented lesions in young cancer patients.

Dosimetric predictors of asymptomatic heart valvular dysfunction following mediastinal irradiation for Hodgkin's lymphoma.

PURPOSE: To identify dose-heart-volume constraints that correlate with the risk of developing asymptomatic valvular defects (VD) in Hodgkin's lymphoma (HL) patients treated with three-dimensional radiotherapy (RT). PATIENTS AND METHODS: Fifty-six patients undergoing cytotoxic chemotherapy (CHT) and involved-field radiation treatment for HL were retrospectively analyzed. Electro-echocardiography was performed before CHT, after CHT, and after RT. For the entire heart, for right and left ventricle (RV, LV), right and left atrium (RA, LA) percentage of volume exceeding 5-30Gy in increment of 5Gy (V(x)), and dosimetric parameters were calculated using 1.6Gy fraction as reference. To evaluate clinical and dosimetric factors possibly associated with VD, univariate and multivariate logistic regression analyses were performed. RESULTS: At a median follow up of 70.5 months, 32.1% of patients developed VD (regurgitation and/or stenosis): 25.0% developed mitral, 5.4% developed aortic, and 14.3% tricuspid VD. In particular the percentage of LA exceeding 25Gy (LA-V(25)) and the percentage of LV exceeding 30Gy (LV-V(30)) correlated with mitral and aortic VD with an odds ratio (OR) of 5.7 (LA-V(25)>63.0% vs. LA-V(25)≤63.0%) and OR of 4.4 (LV-V(30)>25% vs. LV-V(30)≤25%), respectively. RV-V(30) correlated with tricuspid VD (OR=7.2, RV-V(30)>65% vs. RV-V(30)≤65%). CONCLUSION: LA-V(25), LV- and RV-V(30) prove to be predictors of asymptomatic alteration of valve functionality.

Cutaneous melanoma in childhood and adolescence shows frequent loss of INK4A and gain of KIT.

Childhood cutaneous melanoma is a rare disease with increasing incidence. It is not clear whether it differs from adult melanoma in etiology and clinical evolution. To genetically characterize childhood melanoma, 21 pediatric patients were studied by germ-line analysis of CDKN2A, CDK4, and MC1R genes. In addition, alterations in CDKN2A, c-Kit, BRAF, and NRAS genes were evaluated at the somatic level by direct gene sequencing, fluorescence in situ hybridization analysis, and immunohistochemistry. As a control group of susceptible patients, we studied patients from 23 melanoma-prone families. At the germ-line level, CDKN2A and MC1R gene variants were detected in 2/21 and 12/21 pediatric patients and in 9/23 and 19/22 in familial patients. At the somatic level, most lesions (9/14) from pediatric patients showed CDKN2A locus homozygous deletions and a null p16 immunophenotype, whereas most lesions (5/8) from familial patients were disomic and immunoreactive. A c-Kit low-polysomy profile seems to parallel CDKN2A homozygous deletions in pediatric melanoma whereas the single activating mutation observed segregates with familial patients. Loss of KIT protein expression was frequent (7/14) in pediatric melanomas, where metastatic cases were prevalent. BRAF(V600E) mutation occurred at a similar rate (approximately 50%) in lesions from pediatric and familial patients, whereas no NRAS mutations were detected.

Germline mutations of TP53 and BRCA2 genes in breast cancer/sarcoma families.

The genetic aetiology of familial aggregations of breast cancer and sarcomas has been elucidated only in part. In this study, 23 unrelated individuals from families with one case of sarcoma and at least one case of breast cancer were screened for mutations in the TP53, BRCA1 and BRCA2 genes. Families were classified according to their conformity to the criteria defining the Li-Fraumeni syndrome (LFS), Li-Fraumeni-like (LFL) syndrome and hereditary breast/ovarian cancer (HBOC). Germline TP53 mutations were identified in three instances (13%), including one LFS and two LFL families, while none of the non-LFS/non-LFL families had a TP53 mutation. Three cases (13%), including one with a TP53 mutation, carried BRCA2 mutations. Of these, two were observed in LFL/HBOC families and the other one in a non-LFS/non-LFL/HBOC family, while none of the non-HBOC families tested positive. These findings suggest that the screening of BRCA2, in addition to TP53, may be appropriate for the molecular characterisation of breast cancer/sarcoma families, with practical implications for counselling and clinical management.

9p21 locus analysis in high-risk gastrointestinal stromal tumors characterized for c-kit and platelet-derived growth factor receptor alpha gene alterations.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are noncomplex sarcomas that often are due to c-kit-activating and platelet-derived growth factor receptor alpha gene (PDGFRalpha)-activating mutations and perturbations of their related signaling pathways. Molecular and cytogenetic findings have indicated correlations between tumor progression and high-risk GISTs with c-kit mutations, the overexpression of genes such as ezrin, and losses at 9p. In particular, it was reported recently that malignant GISTs showed alterations in the p16INK4a gene located at the 9p21 locus. METHODS: To assess the involvement of p14ARF and p15INK4b in addition to p16INK4a in GISTs, the authors undertook a molecular and cytogenetic study of the 9p21 locus. A series of 22 pre-Gleevec era, cryopreserved, high-risk GISTs that were characterized well in terms of KIT and PDGFRalpha receptors were investigated for mRNA expression, homozygous deletions, mutations, and promoter methylation of locus 9p21, in some instances complemented by fluorescent in situ hybridization studies. RESULTS: The results indicated the loss of p16INK4a mRNA expression in 41% of the GISTs, mainly due to the homozygous deletion of both the p16INK4a gene and the p14ARF gene (24%). No mutations were found, and promoter methylation (detected by means of methylation-specific polymerase chain reaction analysis in 27% of tumors) was restricted mainly to the p15INK4b gene (20%). It is noteworthy that, in all of the methylated GISTs, the epigenetic promoter alteration was coupled with mRNA expression. CONCLUSIONS: Alterations in the 9p21 locus were found cumulatively in 54% of the tumors in the current series and were represented mainly by the loss of tumor suppressor gene expression. The p16INK4a deletion, which always was coupled with p14ARF gene loss, seemed to be the most common 9p21 inactivation mechanism.

BRAF alterations are associated with complex mutational profiles in malignant melanoma.

To evaluate the mutational profiles associated with BRAF mutations in human melanoma, we have studied BRAF, RAS, PTEN, TP53, CDKN2A and CDK4 genes and their expression in melanoma lesions. Owing to the lack of sufficient material from fresh specimens, we employed short-term cell lines obtained from melanoma biopsies. In all, 41 melanoma obtained from eight primary lesions, 20 nodal, 11 cutaneous and two visceral metastases from patients with sporadic (n=31), familial (n=4) and multiple melanoma (n=2) were analysed. The results revealed novel missense mutations in the BRAF, PTEN, CDKN2A and CDK4 genes. Overall, activating mutations of BRAF and loss of functional p16 and ARF were detected in the majority of melanomas (29/41, 36/41 and 29/41, respectively), while PTEN alterations/loss, NRAS and TP53 mutations occurred less frequently (6/41, 6/41 and 10/41, respectively). In the resulting 12 mutational profiles, p16/ARF loss associated with mutated BRAFV599E was the most represented (n=15). In addition, TP53 and PTEN mutations were always accompanied with BRAF alterations, while PTEN loss was found in association with CDKN2A or TP53 mutations in the absence of BRAF activation. The p16/ARFDelta+BRAF/RAS profile was significantly associated with a longer survival, while complex mutational profiles were detected in highly aggressive disease and poor survival. These data support the existence of several molecularly defined melanoma groups which likely reflect different clinical/biological behaviour, thus suggesting that a more extensive molecular classification of melanoma would significantly impact its clinical management.

High prevalence of the G101W germline mutation in the CDKN2A (P16(ink4a)) gene in 62 Italian malignant melanoma families.

CDKN2A germline mutation frequency estimates are commonly based on families with several melanoma cases. When we started counseling in a research setting on gene susceptibility analysis in northern and central Italy, however, we mostly found small families with few cases. Here we briefly characterize those kindred, estimate CDKN2A/CDK4 mutation test yields, and provide indications on the possibility of implementing formal DNA testing for melanoma-prone families in Italy. In September 1995 we started genetic counseling in a research setting at our Medical Genetics Center. Screening for CDKN2A/CDK4 mutations was performed on families with two melanoma patients, one of whom was younger than 50 years at onset, the other complying with one of the following: 1) being a first-degree relative, 2) having an additional relative with pancreatic cancer, or 3) having multiple primary melanomas. Sixty-two of 67 (80%) melanoma cases met our criteria. Four previously described CDKN2A mutations (G101W, R24P, V126D, and N71S) were found in 21 of the 62 families (34%) with a high prevalence of G101W (18/21). The percentage of families with two melanoma cases/family harboring a mutation was low (7%, 2/27), but rose to 45% (9/20) if one of the melanoma patients carried multiple melanomas or if pancreatic cancer was present in that family. In the 15 families with three melanoma cases the presence of a mutation was higher (67%, 10/15) and reached 100% in the 4 families with four or more melanoma cases. Our results suggest that CDKN2A/CDK4 counseling-based mutational analysis may be reasonably efficient also for families with two melanoma cases, if one patient carries multiple melanomas or if pancreatic cancer is present in the family.