HER2 expression and genOmic characterization of rESected brain metastases from colorectal cancer: the HEROES study.

BACKGROUND: Little is known about prognostic factors of brain metastases (BM) from colorectal cancer (CRC). HER2 amplification/overexpression (HER2+) was previously described; its impact on prognosis remains uncertain. METHODS: In the translational study HEROES, extensive molecular analysis was performed on primary CRC (prCRC) and their matched resected BM by means of NGS comprehensive genomic profiling and HER2 status as assessed by immunohistochemical/ in situ hybridization. Count of tumour-infiltrating lymphocytes (TILs) was also performed. PRIMARY OBJECTIVE: to describe the molecular landscape of paired BM/prCRC. SECONDARY OBJECTIVES: to search for new prognostic biomarkers of outcome after BM resection: intracranial-only Progression-Free Survival (BM-iPFS), Progression-Free Survival (BM-PFS), and Overall Survival (BM-OS). RESULTS: Out of 22 patients having paired samples of prCRC and BM, HER2+ was found on 4 (18%) BM, 3 (75%) of which also HER2+ in matched prCRC. Lower tumour mutation burden (HR 3.08; 95%CI 1.06-8.93; p = 0.0386) and HER2-negative BM (HER2neg) (HR 7.75;95%CI 1.97-30.40; p = 0.0033) were associated with longer BM-iPFS; HER2neg BM (HR 3.44; 95%CI 1.03-11.53; p = 0.0449) and KRASmut BM (HR 0.31; 95%CI 0.12-0.80; p = 0.0153) conferred longer BM-PFS. Longer BM-OS was found in pts with TILs-enriched (≥1.6/HPF) BM (HR 0.11; 95%CI0.01-0.91; p = 0.0403). CONCLUSIONS: This study shows HER2+ enrichment in both BM and their prCRC. TILs-enriched BM conferred better BM-OS.

Sudden death in a case of recurrent Takotsubo syndrome.

Herein we report an unusual case of sudden death occurring in a 65 year old woman during a minor oral surgery. The subject, who had a medically treated anxiety, had a history of two reversible left ventricle dysfunction episodes consistent with recurrent Takotsubo Syndrome that had occurred seven and six years before, respectively. She also suffered from moderate, well treated post-menopausal systemic hypertension. Post-mortem examination showed apical biventricular ballooning of the heart with no cardiac rupture, coronary artery lesion or other cardiac/extra-cardiac disease. Toxicological tests and forensic investigations excluded unnatural causes of death, including pharmacological or iatrogenic causes related to medical malpractice. Only non-specific contraction bands and mild hypertrophy were observed by histology in the left ventricle myocytes. Takotsubo syndrome is usually an acute and reversible heart failure syndrome with acute left ventricle apex ballooning, no coronary artery disease or other macroscopic or microscopic cardiac changes; physical or emotional stress are well known triggering factors. Nevertheless, recurrent forms, major cardiac adverse events and even sudden death may occur in a minority of cases, meaning that a diagnosis of Takotsubo syndrome must be considered in cases of sudden death and in forensic investigations.

What do cancer patients experience of the simultaneous care clinic? Results of a cross-sectional study on patient care satisfaction.

BACKGROUND: Veneto Institute of Oncology has activated a simultaneous care outpatient clinic (SCOC) in which cancer patients with advanced-stage cancer are evaluated by oncologist and palliative care specialists. This cross-sectional study investigated patients' perceptions of the quality of this service. MATERIALS AND METHODS: An ad-hoc self-administered questionnaire, developed by SCOC team, was used to assess the satisfaction of patients admitted at SCOC consultation. The questionnaire, in addition to the socio-demographic questions, contains eight questions with the Likert scale: time dedicated, feel listened to, feel understood, feel free to speak openly and to express doubts and concerns, feeling about information and indication received, level of empathy of health care and quality of the relationship, level of professional/quality of performance and utility of consultation, and one open-ended question. The questionnaire has been proposed to all 174 consecutively admitted patients at SCOC. RESULTS: One hundred and sixty-two patients filled in the questionnaire: 66.7% were male, median age was 71 years, 88.3% had metastatic disease. The time dedicated to SCOC consultation was judged more than adequate (55%) or adequate (35%) by 90% of subjects. Patients completely satisfied about being listened to were 92.5%, with 80.9% being completely satisfied with understanding of their issues and 92% with the freedom to speak and express doubts. Usefulness of the SCOC was rated as excellent by 40% and good by 54.4% of patients. No statistically significant differences were observed in the responses to the questions by gender, age (< or ≥70 years old) and type of tumor. CONCLUSION: Our study shows high levels of satisfactions after SCOC consultation in advanced cancer subjects. Patients' feedback confirmed that SCOC model was effective in helping them during their treatment journey and decision at the end of life. This study encouraged us to enhance our practice of SCOC consultation. IMPLICATIONS FOR PRACTICE: A joint evaluation of patients living with cancer by oncologist and palliative care team (SCOC-embedded model), has shown to enhance patients' experience/satisfaction with care-such as listening, understanding, receiving information, symptom control, and decision about future, independently of age, gender, and kind of tumor.

Advanced Non-Clear Cell Renal Cell Carcinoma Treatments and Survival: A Real-World Single-Centre Experience.

BACKGROUND: Non-clear cell renal cell carcinoma (nccRCC) is a heterogeneous group of cancer. Treatment recommendations are extrapolated from ccRCC and lack solid evidence. Here, we review advanced nccRCC patients treated at our institute. PATIENTS AND METHODS: We collected retrospective data on all advanced nccRCC pts treated at the Istituto Oncologico Veneto from January 2008. We compared overall response rate (ORR), progression free survival (PFS) and overall survival (OS) according to histological subtypes and type of systemic treatments. Kaplan-Meier method, log-rank test and Cox regression were used to estimate and compare PFS and OS. RESULTS: Of 1370 RCC patients, 289 had a diagnosis of nccRCC and 121 were eligible for the analysis. Fifty-three pts showed papillary histology (pRCC), 15 chromophobe; 37 unclassified RCC (NOS-RCC), 16 other histologies. Pts with chromophobe and other hystologies showed poorer survival rates compared to pRCC and NOS-RCC (mOS 10.7 vs. 20.7 vs. 30.7, p = 0.34). Pts treated with combination regimens achieved a better OS (30.7 vs. 13.7, p = 0.10), PFS (12.7 vs. 6.4, p = 0.10) and ORR (42.4% vs. 13.9%, p = 0.002) than those treated with monotherapy. IMDC and Meet-URO score retained their prognostic value. CONCLUSION: Our retrospective real-life cohort of advanced nccRCC patients shows that immunotherapy-based combinations could improve ORR, PFS and OS compared to TKI monotherapy. Prospective trials for nccRCC patients utilizing novel therapies are ongoing and their results eagerly awaited.

Actionable molecular alterations in newly diagnosed and recurrent IDH1/2 wild-type glioblastoma patients and therapeutic implications: a large mono-institutional experience using extensive next-generation sequencing analysis.

BACKGROUND: Next-generation sequencing (NGS) panels enable the identification of alterations in cancer-related genes. This may guide a molecularly targeted strategy for the treatment of glioblastoma (GBM). MATERIAL AND METHODS: We retrospectively analysed data obtained using FoundationOne®CDx in a large cohort of IDH1/2 wild-type GBM. We aimed to 1) identify potentially actionable molecular alterations at diagnosis and/or recurrence based on ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) defined categories of targetability, 2) understand the clinical implications of NGS in terms of access to and activity of targeted therapies. RESULTS: In 442 samples, an NGS profile was available in 98.2%. The median time from diagnosis to NGS profiling was 7.4 months (interquartile range (IQR): 3.4-13.2). Although about half of the patients had at least one actionable molecular alteration, only 3.4% of them were classified as ESCAT IB-IC and 6.7% as ESCAT IIB. Only 36 patients (10.5%) received personalised treatment in clinical trials or as off-label/compassionate use from second-line (median line 3). Most patients did not receive targeted therapy due to clinical deterioration/death (49.6%). Patients treated with dabrafenib/trametinib (9 patients) had the highest disease control rate of 77% and an objective response rate of 22%, with a median progression-free survival (PFS) of 5.2 months. No complete/partial responses were seen with the other regimens. 4/9 (44.4%) patients on anti-BRAF/anti-MEK, 2/4 patients (50%) on erdafitinib and 1/1 patient on capmatinib had a PFS ratio > 1.3. One recurrent GBM patient with ROS1-GOCP fusion maintained a complete response for 11.3 months on entrectinib. CONCLUSIONS: Our study demonstrated the feasibility of NGS in GBM samples. As the number of clinically relevant targets was limited and only a small group of GBM patients were treated with targeted therapy, NGS testing should be performed in the context of clinical trials. Our results support the activity of anti-BRAF/anti-MEK, while for the other agents prospective study results are needed to draw solid conclusions.

The role of nanoliposomal irinotecan plus fluorouracil/leucovorin in the continuum of care of patients with metastatic pancreatic ductal adenocarcinoma.

BACKGROUND: The NAPOLI-I trial showed better outcome of nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) compared to 5-FU/LV in patients with advanced pancreatic ductal adenocarcinoma cancer (advPDAC) progressed to gemcitabine-based therapy. This study aims to explore the real-world efficacy and safety of 5-FU/LV-nal-IRI. METHODS: This is a retrospective multicenter analysis including advPDAC patients receiving 5-FU/LV-nal-IRI after failure of gemcitabine-based therapy. Survival analyses were performed using Kaplan-Meier method, univariate and multivariate analyses by Cox regression. RESULTS: A total of 296 patients (median age 64.4 years, ECOG PS ≥1 in 56% of cases) were treated at 11 Italian institutions between 2016 and 2018. 34% of them underwent primary tumor resection, and 79% received gemcitabine-nabpaclitaxel as first line. 5-FU/LV-nal-IRI was administered as second-line in 73% of cases. Objective response and disease control rate were 12% and 41%, respectively. Treatment was well tolerated with dose reductions in 50% of patients but no one permanent discontinuation; the commonest grade ≥3 toxicities were neutropenia (14%) and diarrhea (12%). Median PFS and OS from 5-FU/LV-nal-IRI initiation was 3.2 and 7.1 months, respectively. CONCLUSIONS: These real-world data confirm the 5-FU/LV-nal-IRI efficacy and safety in advPDAC patients progressed to gemcitabine-based therapy, with outcomes comparable to NAPOLI-1, even in a less-selected population and with more modern therapeutic algorithm.

Patient Reported Outcomes, Paternity, Relationship, and Fertility in Testicular Cancer Survivors: Results from a Prospective Observational Single Institution Trial.

Purpose: Testicular cancer (TC) is the most common solid tumor in young adults. 95% of patients are cured, but they may experience late adverse effects (anxiety, fear of recurrence, and sexual dysfunction) with an impact on daily life. We attempted to assess Patient Reported Outcomes (PROMs), long-term sexual disorders, and difficulties in achieving fatherhood in a cohort of TC survivors, as well as their possible correlation with previous cancer treatments. Methods: Different questionnaires, such as the Impact of Cancer (IOC) and the Body Image Scale (BIS), were used to investigate the distinct areas of the PROMs. International Index of Erectile Function (IIEF15) and the Premature Ejaculation Diagnostic Tool (PEDT) focused on sexuality and fertility. Patients were prospectively recruited between February 2020 and February 2022. Results: 144 participants completed all the questionnaires. Results showed a good QoL, a moderate fear of TC recurrence, a good satisfaction with their personal body image, low incidence of premature ejaculation and erectile dysfunction. 19.5% of patients who had a testicular implant reported general dissatisfaction. Only 18% of patients had unsuccessfully attempted fatherhood, while the majority had not yet tried, and 23.4% succeeded. A low percentage of patients used procedures assisted reproduction and adoption. Conclusion: This trial supports the use of various questionnaires as a multifactorial tool capable of investigating all the aspects of long-term cancer survivorship. The assessment of medical and psychosocial sequelae is an essential part of patient care and is important for the development of a comprehensive care plan for TC survivors.

Sex Differences in Cutaneous Melanoma: Incidence, Clinicopathological Profile, Survival, and Costs.

Background: This study aims to provide a comprehensive overview of sex-related characteristics of cutaneous malignant melanoma (CMM), with special reference to its incidence, clinicopathological profile, overall survival, and treatment-related costs. Methods: This retrospective cohort study included all 1,279 CMM patients who were registered in 2015 in the Veneto Cancer Registry (a population-based registry including all 4,900,000 regional residents). The by-sex comparisons included tumor stage and site, histological subtype, and other clinical-pathological variables. A Cox regression analysis was used to test the association between sex and survival, adjusting for the main covariates. Treatment costs were calculated by linking patients with several administrative regional databases. Results: Age-specific incidence rates were significantly higher for men among people >50 years old. For men, the trunk was the most common primary site (59.3%), whereas for women the lower limbs (32.1%) were the most common primary site, followed by the trunk (31.8%), which was lower than for men (p < 0.001). At presentation, the frequency of early stage CMM was higher among women, who also featured a significantly lower risk of death (p = 0.016), after adjusting for covariates. Men also incurred higher costs for melanoma treatment in the first year after their diagnosis. Conclusions: Among younger adults, CMM was more common in women, whereas among older adults, it was more common in men. Sex also influences patients' histopathological characteristics at diagnosis. Women had better overall survival after adjusting for demographic, pathological, and clinical profiles. The costs of treatment were also lower for women with CMM.

Cause of Death in Charred Bodies: Reflections and Operational Insights Based on a Large Cases Study.

Our study aims to demonstrate the experience of analyzing fully or partially charred corpses to offer a proper implementation protocol for determining the cause of death. In this study, we present a total of 103 cases obtained from the University of Rome La Sapienza and the University of Pisa archives. All cases were classified based on the extent and severity of burns using a visual method. We divided all cases into two groups. The first group included grade I-II burns (21 cases) without the need for identification. The second group (82 cases) included injuries worse than grade burns II, so all cases were analyzed using an analytical method. For each case, we have documented which of the following analyses have been used and the corresponding findings: inspection, autopsy examination, imaging examination, genetic and toxicological examinations, and histological examination. The results describe the main diagnostic findings and show that only the application of all the above systematic analyses can provide greater accuracy and reliability in describing the causes of death or solving problems, such as identification. In conclusion, we propose an available protocol that defines the main steps of a complete diagnostic pathway that pathologists should follow daily in studying charred bodies.

Malignant Melanoma: Direct Costs by Clinical and Pathological Profile.

INTRODUCTION: A number of studies have examined the impact of tumor stage on direct health care costs of patients with melanoma. This study aimed to investigate the association between the direct costs for melanoma and the patients' clinical and histological characteristics. METHODS: The present analysis included 1368 patients diagnosed with melanoma in 2017 in the Veneto Region (northeast Italy) and recorded in a regional population-based melanoma registry. The costs were assessed taking monthly and total direct costs into account. Log-linear multivariable analysis was used to identify the clinical and histological cost drivers, focusing on monthly and total direct costs per patient incurred during the first 2 years after a patient's diagnosis. RESULTS: On multivariable analysis, besides the stage of melanoma, also the presence of mitoses (> 2) was associated with higher monthly direct costs [odds ratio (OR) 1.55, 95% confidence interval (CI) 1.15-2.08, p = 0.004] in respect to cases with 0-2 mitoses. Vertical growth was associated with higher costs compared with radial growth (OR 1.28, 95% CI 1.00-1.64, p = 0.055). Moreover, the association between the absence of tumor-infiltrating lymphocytes (TILs) and higher monthly direct costs reached statistical significance (OR 1.31, 95% CI 1.05-1.64, p = 0.017). There were no differences in monthly direct costs by patients' sex or age, ulceration, or tumor site. CONCLUSION: This study showed that not only tumor stage but also other clinical and histopathologic characteristics have an impact on the direct monthly and total costs of treating melanoma. Further studies on the cost-effectiveness of the various options for managing this disease should take these variables into account, as well as tumor stage, as cost drivers.

Cutaneous Melanoma in Alpine Population: Incidence Trends and Clinicopathological Profile.

Previous studies associated high-level exposure to ultraviolet radiation with a greater risk of cutaneous malignant melanoma (CMM). This study focuses on the changing incidence of CMM over time (from 1990 to 2017) in the Veneto region of Northeast Italy, and its Alpine area (the province of Belluno). The clinicopathological profile of CMM by residence is also considered. A joinpoint regression analysis was performed to identify significant changes in the yearly incidence of CMM by sex and age. For each trend, the average annual percent change (AAPC) was also calculated. In the 2017 CMM cohort, the study includes a descriptive analysis of the disease's categorical clinicopathological variables. In the population investigated, the incidence of CMM has increased significantly over the last 30 years. The AAPC in the incidence of CMM was significantly higher among Alpine residents aged 0-49 than for the rest of the region's population (males: 6.9 versus 2.4; females 7.7 versus 2.7, respectively). Among the Alpine residents, the AAPC was 3.35 times greater for females aged 0-49 than for people aged 50+. The clinicopathological profile of CMM was significantly associated with the place of residence. Over three decades, the Veneto population has observed a significant increase in the incidence of CMM, and its AAPC. Both trends have been markedly more pronounced among Alpine residents, particularly younger females. While epidemiology and clinicopathological profiles support the role of UV radiation in CMM, the young age of this CMM-affected female population points to other possible host-related etiological factors. These findings also confirm the importance of primary and secondary prevention strategies.

Left atrial remodeling in heart failure: the role of sphericity index (the SPHERICAT-HF study).

Left atrial sphericity index (LASI) is an echocardiographic index easily obtained; its use in patients with heart failure (HF) has never been investigated so far. This single-centre study aimed to investigate the usefulness of LASI in an unselected cohort of patients hospitalized for acute HF, and its potential correlation with the amino-terminal portion of pro-B-type natriuretic peptide (NT-proBNP) levels and with New York Heart Association (NYHA) functional class. Ninety-four consecutive HF patients underwent a transthoracic echocardiogram with a detailed study of the left atrium (LA) including LASI (calculated from the apical four-chamber view as the ratio between the transverse and longitudinal diameters), and blood tests (including NT-proBNP) on the same day. Median age was 75.5 (interquartile range-IQR 62-82) years and 55% were males, 58.5% had a NYHA class III-IV, and median NT-proBNP was 3284 (IQR 1215-7055) pg/ml. The LA was dilated in 94%, and median biplane LA volume index was 62 ml/m2. Patients with advanced NYHA class showed more advanced LA remodeling. Mean LASI was 0.78 ± 0.09 and did not correlate with NT-proBNP levels (r 0.03; p 0.75) or with patient NYHA class (R2 0.011; p 0.287). None of the echocardiographic indices of LA structural and functional remodeling proved to be independently associated with a high NYHA class on multivariate regression analysis. In conclusion, LA remodeling is almost invariably present in patients with HF. LASI does not correlate with NT-proBNP levels or with NYHA functional class. Further studies are needed to describe the complex patterns of atrial remodeling in HF.

Impact of Wide Local Excision on Melanoma Patient Survival: A Population-Based Study.

Introduction: Promoting standardization and quality assurance (QA) in oncology on the strength of real-world data is essential to ensure better patient outcomes. Wide excision after primary tumor biopsy is a fundamental step in the therapeutic pathway for cutaneous malignant melanoma (CMM). The aim of this population-based cohort study is to assess adherence to wide local excision in a cohort of patients diagnosed with CMM and the impact of this recommended procedure on overall and disease-specific survival. Materials and Methods: This retrospective cohort study concerns CMM patients diagnosed in the Veneto region (north-east Italy) in 2017, included in the high-resolution Veneto Cancer Registry, and followed up through linkage with the regional mortality registry up until February 29th, 2020. Using population-level real-world data, linking patient-level cancer registry data with administrative records of clinical procedures may shed light on the real-world treatment of CMM patients in accordance with current guidelines. After excluding TNM stage IV patients, a Cox regression analysis was performed to test whether the completion of a wide local excision was associated with a difference in melanoma-specific and overall survival, after adjusting for other covariates. Results: No wide excision after the initial biopsy was performed in 9.7% of cases in our cohort of 1,305 patients. After adjusting for other clinical prognostic characteristics, Cox regression revealed that failure to perform a wide local excision raised the hazard ratio of death in terms of overall survival (HR = 4.80, 95% CI: 2.05-11.22, p < 0.001) and melanoma-specific survival (HR = 2.84, 95% CI: 1.04-7.76, p = 0.042). Conclusion: By combining clinical and administrative data, this study on real-world clinical practice showed that almost one in ten CMM patients did not undergo wide local excision surgery. Monitoring how diagnostic-therapeutic protocols are actually implemented in the real world may contribute significantly to promoting quality improvements in the management of oncological patients.

Simultaneous Care in Oncology: A 7-Year Experience at ESMO Designated Centre at Veneto Institute of Oncology, Italy.

Benefits of early palliative care referral in oncology are well-validated. At the Veneto Institute of Oncology-IRCCS, a simultaneous-care outpatient clinic (SCOC) has been active since 2014, where patients with advanced cancer are evaluated by an oncologist together with a palliative care team. We prospectively assessed SCOC patients' characteristics and SCOC outcomes through internal procedure indicators. Data were retrieved from the SCOC prospectively maintained database. There were 753 eligible patients. The median age was 68 years; primary tumor sites were gastrointestinal (75.2%), genitourinary (15.0%) and other sites (9.8%). Predominant symptoms were psychological issues (69.4%), appetite loss (67.5%) and pain (65.9%). Dyspnea was reported in 53 patients (7%) in the referral form, while it was detected in 226 patients (34.2%) during SCOC visits (p < 0.0001). Median survival of patients after the SCOC visit was 7.3 months. Survival estimates by the referring oncologist were significantly different from the actual survival. Psychological intervention was deemed necessary and undertaken in 34.6% of patients, and nutritional support was undertaken in 37.9% of patients. Activation of palliative care services was prompted for 77.7% of patients. Out of 357 patients whose place of death is known, 69.2% died at home, in hospice or residential care. With regard to indicators' assessment, the threshold was reached for 9 out of 11 parameters (81.8%) requested by the procedure. This study confirmed the importance of close collaboration between oncologists and palliative care teams in responding properly to cancer patients' needs. The introduction of a procedure with indicators allowed punctual assessment of a team's performance.

Simultaneous care in oncology: Assessment of benefit in relation to symptoms, sex, and age in 753 patients.

Background: Early activation of palliative care for patients with advanced cancer is central in the treatment trajectory. At the Veneto Institute of Oncology, a simultaneous-care outpatient clinic (SCOC) has been active since 2014, where patients are evaluated by an oncologist together with a palliative care team. Recently, we reported on consecutive patients admitted at SCOC from 2018 to 2021 in terms of appropriateness, process, and outcome indicators. Here, we report further analysis in the same group of 753 patients, evaluating other parameters and the correlation between symptom intensity, gender, age, and survival. Methods: SCOC data were retrieved from a prospectively maintained database. Results: Among the patients, 42.2% were women, and the median age was 68 years, with 46.7% of patients aged ≥70 years. The most prevalent disease type was gastrointestinal cancer (75.2%), and 90.9% of the patients had metastatic disease. The median score for the distress thermometer was 4; the vast majority of the patients (98.6%) reported physical problems, and 69.4% presented emotional issues. Younger women demonstrated a significantly greater median distress than other patients (p=0.0018). Almost all symptoms had a higher prevalence on the 0-3 Edmonton Symptom Assessment Scale (ESAS) score, except for fatigue. About 43.8% of the patients received systemic anticancer treatment (SAT) in the last 60 days of life, 15.0% of whom received SAT in the last month and 3.1% in the last 2 weeks. For some symptoms, women frequently had more ESAS >3. Pain and nausea were significantly less reported by older patients compared with younger adults. Men had a lower risk of having MUST score ≥ 2 (p=0.0311). Men and older patients showed a lower prognosis awareness (p=0.0011 and p=0.0049, respectively). Older patients received less SAT within the last 30 days of life (p=0.0006) and had death risk decreased by 20.0%. Conclusion: Our study identified two subgroups of patients with advanced cancer who require special attention and support due to important symptoms' burden detected by Patient Reported Outcome Measures tests: women and younger adults. These categories of patients require special attention and should be provided early access at SCOC. The role of an oncologist remains crucial to intercept all patients in need of early palliative care and balancing trade-offs of anticancer treatment in advanced metastatic disease.

Prognosis for Cutaneous Melanoma by Clinical and Pathological Profile: A Population-Based Study.

INTRODUCTION: Among white people, the incidence of cutaneous malignant melanoma (CMM) has been increasing steadily for several decades. Meanwhile, there has also been a significant improvement in 5-year survival among patients with melanoma. This population-based cohort study investigates the five-year melanoma-specific survival (MSS) for all melanoma cases recorded in 2015 in the Veneto Tumor Registry (North-Est Italian Region), taking both demographic and clinical-pathological variables into consideration. METHODS: The cumulative melanoma-specific survival probabilities were calculated with the Kaplan-Meier method, applying different sociodemographic and clinical-pathological variables. Cox's proportional hazards model was fitted to the data to assess the association between independent variables and MSS, and also overall survival (OS), calculating the hazard ratios (HR) relative to a reference condition, and adjusting for sex, age, site of tumor, histotype, melanoma ulceration, mitotic count, tumor-infiltrating lymphocytes (TIL), and stage at diagnosis. RESULTS: Compared with stage I melanoma, the risk of death was increased for stage II (HR 3.31, 95% CI: 0.94-11.76, p=0.064), almost ten times higher for stage III (HR 10.51, 95% CI: 3.16-35.02, p<0.001), and more than a hundred times higher for stage IV (HR 117.17, 95% CI: 25.30-542.62, p<0.001). Among the other variables included in the model, the presence of mitoses and histological subtype emerged as independent risk factors for death. CONCLUSIONS: The multivariable analysis disclosed that older age, tumor site, histotype, mitotic count, and tumor stage were independently associated with a higher risk of death. Data on survival by clinical and morphological characteristics could be useful in modelling, planning, and managing the most appropriate treatment and follow-up for patients with CMM.

Finding the Victim of Abuse: A New Frontier of Physicians' Liability? Data From a Local Italian Experience on Minor Maltreatment.

Violence toward minors is a widespread phenomenon and effective programs are desperately needed to prevent it. Data from the literature showed that underreporting child/adolescents abuse has become a widespread phenomenon, exposing minors to additional harm from further potentially dangerous situations. It is proved that systematic screening and standardized procedures for minors presenting at emergency departments with the suspicion of abuse might increase the detection rate, reducing the risk of underreporting. In Italy a system of mandatory reporting is in place, and it is considered to be crucial in detecting abuse and preventing further harm to children. In this paper we report our experience with a regional (Tuscany) project named "Codice Rosa" (Pink code) introduced in 2014 with the aim to treat and protect the most vulnerable bracket of the population. We present data concerning the access of minors for suspected abuse at the emergency room of the local hospital, focusing on a case of omitted diagnosis leading to further violence episodes. According to our experience, since the introduction of the "Pink Code" there have been 43 cases of reported child abuse, with an increasing trend throughout these years (from 1 reported event in 2015 to 16 reported events in 2018). Despite the limited number of our population, the increasing trend in the reported events was particularly evident for bullying cases (n = 0 in 2015; n = 4 in 2018). Despite data are still limited, the procedure proved effective in preventing child abuse, though it could still be implemented. Minor abuse and maltreatment are important health issue globally which can lead to significant physical and psychological morbidity. Implementing knowledge of healthcare professionals on how to deal with child abuse and introducing educational programs on recognition, treatment and report of child abuse is mandatory not only to prevent missing diagnosis of child and minor maltreatment, but also to reduce the risk of professional liability on different bases.

Haplotypic structure of the X chromosome in the COGA population sample and the quality of its reconstruction by extant software packages.

BACKGROUND: The haplotypes of the X chromosome are accessible to direct count in males, whereas the diplotypes of the females may be inferred knowing the haplotype of their sons or fathers. Here, we investigated: 1) the possible large-scale haplotypic structure of the X chromosome in a Caucasian population sample, given the single-nucleotide polymorphism (SNP) maps and genotypes provided by Illumina and Affimetrix for Genetic Analysis Workshop 14, and, 2) the performances of widely used programs in reconstructing haplotypes from population genotypic data, given their known distribution in a sample of unrelated individuals. RESULTS: All possible unrelated mother-son pairs of Caucasian ancestry (N = 104) were selected from the 143 families of the Collaborative Study on the Genetics of Alcoholism pedigree files, and the diplotypes of the mothers were inferred from the X chromosomes of their sons. The marker set included 313 SNPs at an average density of 0.47 Mb. Linkage disequilibrium between pairs of markers was computed by the parameter D', whereas for measuring multilocus disequilibrium, we developed here an index called D*, and applied it to all possible sliding windows of 5 markers each. Results showed a complex pattern of haplotypic structure, with regions of low linkage disequilibrium separated by regions of high values of D*. The following programs were evaluated for their accuracy in inferring population haplotype frequencies: 1) ARLEQUIN 2.001; 2) PHASE 2.1.1; 3) SNPHAP 1.1; 4) HAPLOBLOCK 1.2; 5) HAPLOTYPER 1.0. Performances were evaluated by Pearson correlation (r) coefficient between the true and the inferred distribution of haplotype frequencies. CONCLUSION: The SNP haplotypic structure of the X chromosome is complex, with regions of high haplotype conservation interspersed among regions of higher haplotype diversity. All the tested programs were accurate (r = 1) in reconstructing the distribution of haplotype frequencies in case of high D* values. However, only the program PHASE realized a high correlation coefficient (r > 0.7) in conditions of low linkage disequilibrium.

Development of a heptaplex PCR system to analyse X-chromosome STR loci from five Italian population samples. A collaborative study.

Many X-chromosome short tandem repeats (X-STRs) have been validated for forensic use even if further studies are needed on allele frequencies and mutation rates to evaluate the extent of polymorphism in different populations and to establish reference databases useful for forensic applications and for anthropological studies. A single multiplex reaction of seven X-STRs, which includes the DXS6789, HUMARA, DXS10011, DXS7423, HPRTB, DXS6807, DXS101 loci, is presented and their allele frequency distribution in a large population sample including 556 subjects (268 females and 288 males) analysed by five forensic laboratories of Central and Northern Italy is shown. Our results demonstrate the feasibility of a single amplification/detection reaction involving seven markers of the X chromosome, which can be fruitfully used in complex kinship analysis.

Forensic entomology and the estimation of the minimum time since death in indoor cases.

Eight cases that occurred indoors in which the insects played an important role in the mPMI estimation are presented. The bodies of socially isolated people and old people living alone were discovered in central Italy between June and November. mPMI ranged from a few days to several weeks. Insects were collected during the body recovery and the postmortem. Climatic data were obtained from the closest meteorological stations and from measurements performed on the site. Sarcophagidae and Calliphoridae species were present in 75% of the cases with Lucilia sericata and Chrysomya albiceps collected in 50% of the cases. Chrysomya albiceps was always found in association with Lucilia species. Scuttle flies (Phoridae) were found in 37.5% of the cases, confirming the ability of these species in indoor body colonization. We show that if sealed environment may delay, the insect arrival dirty houses may create the environment where sarcosaprophagous insects are already present.