Imaging biobanks: operational limits, medical-legal and ethical reflections.

The extraordinary growth of health technologies has determined an increasing interest in biobanks that represent a unique wealth for research, experimentation, and validation of new therapies. "Human" biobanks are repositories of various types of human biological samples. Through years the paradigm has shifted from spontaneous collections of biological material all over the world to institutional, organized, and well-structured forms. Imaging biobanks represent a novel field and are defined by European Society of Radiology as: "organized databases of medical images, and associated imaging biomarkers shared among multiple researchers, linked to other biorepositories". Modern radiology and nuclear medicine can provide multiple imaging biomarkers, that express the phenotype related to certain diseases, especially in oncology. Imaging biobanks, not a mere catalogue of bioimages associated to clinical data, involve advanced computer technologies to implement the emergent field of radiomics and radiogenomics. Since Europe hosts most of the biobanks, juridical and ethical framework, with a specific referral to Italy, is analyzed. Linking imaging biobanks to traditional ones appears to be a crucial step that needs to be driven by medical imaging community under clear juridical and ethical guidelines.

Gender Violence During the Three Ages of Life and the Impact of the Covid-19 Pandemic: A Review.

Children, women, and older people suffer different types of violence, which appears to have been exacerbated during the COVID-19 pandemic and the relative lockdown. The aim of this study is to analyze the literature about gender violence and abuse in the different ages of life and during the COVID-19 lockdown. Data were obtained from an electronic literature search using various online sources such as PubMed, Google Scholar, Science Direct and Web of Science. The terms "child abuse" were the most frequently used, followed in frequency by "gender violence," "femicide," and, lastly, "elderly abuse." The first studies considered gender-based violence as a purely physical problem, then, progressively, the analysis focused on the psychological point of view of the issue. There was a greater number of studies in 2020 about violence in comparison with previous years. The social and scientific attention to gender-based violence appeared to be very poor, especially in the case of older people abuse. It is necessary to increase general attention to the topic to correctly identify each form of abuse and to be able to take care of the subjects most at risk.

Cure indicators and prevalence by stage at diagnosis for breast and colorectal cancer patients: A population-based study in Italy.

People alive many years after breast (BC) or colorectal cancer (CRC) diagnoses are increasing. This paper aimed to estimate the indicators of cancer cure and complete prevalence for Italian patients with BC and CRC by stage and age. A total of 31 Italian Cancer Registries (47% of the population) data until 2017 were included. Mixture cure models allowed estimation of net survival (NS); cure fraction (CF); time to cure (TTC, 5-year conditional NS >95%); cure prevalence (who will not die of cancer); and already cured (prevalent patients living longer than TTC). 2.6% of all Italian women (806,410) were alive in 2018 after BC and 88% will not die of BC. For those diagnosed in 2010, CF was 73%, 99% when diagnosed at stage I, 81% at stage II, and 36% at stages III-IV. For all stages combined, TTC was >10 years under 45 and over 65 years and for women with advanced stages, but ≤1 year for all BC patients at stage I. The proportion of already cured prevalent BC women was 75% (94% at stage I). Prevalent CRC cases were 422,407 (0.7% of the Italian population), 90% will not die of CRC. For CRC patients, CF was 56%, 92% at stage I, 71% at stage II, and 35% at stages III-IV. TTC was ≤10 years for all age groups and stages. Already cured were 59% of all prevalent CRC patients (93% at stage I). Cancer cure indicators by stage may contribute to appropriate follow-up in the years after diagnosis, thus avoiding patients' discrimination.

Is there a lesser value type of violence? Older people abuse: "The silence of the lambs".

The World Health Organization (WHO) describes gender violence as a real global health problem with a major impact not only on the victims' physical and mental health, but also on the economics of the National Health System. Gender-based violence has been also extended to all types of subjects defined as fragile: children, elderly, women, men and disabled people. Older people abuse, more frequent in women, is a far less socially debated issue, with many forms: physical, sexual, psychological, abandonment, neglect, economic-financial, pharmaceutical, discriminatory, institutional. An electronic literature research was carried out search using the keywords "elderly abuse" on various online sources. The research showed low number of results and little attention to this topic in the scientific literature. The paper highlights how the theme of older people abuse is little reported and not adequately addressed in scientific literature and in real life, being a form of violence certainly underestimated by the public.

Child Abuse: Adherence of Clinical Management to Guidelines for Diagnosis of Physical Maltreatment and Neglect in Emergency Settings.

Child maltreatment is a phenomenon of great importance due to the significant socio-health implications related to it. Purpose of the study is assessing compliance child abuse clinical management with guidelines and suggest corrective actions to avoid false negative or false positive judgments. The data come from 34 medical records of child victims of suspected abuse hospitalized in a pediatric clinic. We examined diagnostic and medico-legal management through the analysis of pediatric, dermatological, ophthalmological (including fundus examination), and gynecological (only in some cases) consultations, brain and skeletal imaging, laboratory tests (with reference to the study of hemostasis), and medico-legal advice. Of 34 patients, the average age was 23 months, ranging from 1 month to 8 years. The judgment was positive for abuse for 20 patients and negative for 12 patients; in two cases it was not possible to express a conclusive judgment. Two children died because of the injuries sustained. We underline the need of clinical-diagnostic standardized protocols, coroner in emergency settings, short-distance follow-up, social worker support. We also suggest objectifying in a descriptive way (using a common and repeatable language) and with photographic documentation the results of all the investigations carried out, to evaluate signs of physical maltreatment and neglect.

A COVID Dilemma: How to Manage Pregnancies in Case of Severe Respiratory Failure?

To date, the impact of the COVID-19 pandemic on the world's health, economics and politics is still heavy, and efforts to mitigate virus transmission have caused remarkable disruption. From the early onset of the pandemic, generated by SARS-CoV-2 spread, the scientific community was aware of its impact on vulnerable individuals, including pregnant women. The purpose of this paper is to highlight scientific pitfalls and ethical dilemmas emerging from management of severe respiratory distress in pregnant women in order to add evidence to this topic through an ethical debate. In the here-presented paper, three cases of severe respiratory syndrome are analyzed. No specific therapeutic protocol was available to guide physicians in a cost-benefit balance, and unequivocal conduct was not a priori suggested from scientific evidence. However, vaccines' advent, viral variants lurking on the horizon and other possible pandemic challenges make it necessary to maximize the experience gained through these difficult years. Antenatal management of pregnancies complicated by COVID-19 infection with severe respiratory failure is still heterogeneous and ethical concerns must be pointed out.

Trends in Liver Cancer Incidence and Survival in Italy by Histologic Type, 2003-2017.

(1) Background: Liver cancer in Italy is characterised by one of the highest incidence rates worldwide outside of Asia coupled with comparatively favourable survival figures. The objective of this study was to evaluate the most recent epidemiologic trends of the disease. (2) Methods: Thirteen cancer registries covering a population of about 12,740,000 (21% of the national population) made available the records of 35,574 cases registered between 2003 and 2017. Trends in age-standardised (Europe 2013) incidence rates were analysed using the results of age-drift models. Trends in survival were analysed using 1-year, 2-year, 5-year and 10-year net survival (NS) and 5|1-year and 5|2-year conditional NS. (3) Results: Over the study period, the average annual incidence rates per 100,000 persons were 29.4 (men) and 9.4 (women) for total liver cancer; 14.6 and 3.5 for hepatocellular carcinoma (HCC); 1.8 and 1.1 for intrahepatic cholangiocarcinoma (ICC); and 13.0 and 4.8 for the 'other liver cancer types' group. The incidence of total liver cancer and HCC decreased significantly for both sexes. For total liver cancer, the estimated average annual percent change was -1.6% among men and -2.1% among women. For HCC, the change was -1.3% among men and -2.7% among women. ICC followed an opposite trend. For men, the risk of HCC had two peaks, one in the birth cohorts of 1928 and 1933 and another, more moderate peak in the cohort of 1958. Men and women exhibited comparable improvements in both early and mid-term conditional NS from HCC. In 2013-2017, 5-year NS was 28.9% (95% CI: 27.3%; 30.6%) for men and 30.1% (95% CI: 26.9%; 33.5%) for women. The uptrend in survival from ICC was less pronounced and was weakly significant, with a 5-year NS in 2013-2017 of 13.9% (95% CI: 10.8%; 17.3%) for men and 17.4% (95% CI: 13.5%; 21.7%) for women. (4) Conclusions: The opposite incidence trends of HCC and ICC confirm a pattern observed in other populations. The generalised, albeit slow, improvement in survival from HCC indicates a trend towards earlier detection coupled with improvements in treatments.

Medico-Legal Issues in Cremation: Comparative Analysis of International Legislation.

Cremation has seen a constant increase in popularity all around the world. Because of its extensively destructive nature, however, a series of medico-legal issues arise concerning identification, forensic autopsy, external examination, histological, toxicological and genetic exams to be performed not in the immediacy of death. The aim of this study is to compare the international legislation on cremation, seeking the response of various countries to their medico-legal issues. Several affinities but also some differences were found. Similarities include the need for a certificate by a medical examiner excluding any medico-legal issues and non-natural causes of death and the expression of consent to cremation given by the deceased when still alive otherwise by relatives. Significant differences were found in German law, which provides for a second medical examination prior to cremation and in Italian law providing for the medical examiner to collect biological samples from the body and store them for a minimum of ten years for any future purpose of justice. The Italian approach could give a plausible solution to the medico-legal issues raised by cremation with the imperative premise, however, we need to look deeply into its privacy and consent implications, cost-benefits rate, sample collection and storage protocol.

[Update of survival of cancer patients in Italy: geographical comparisons and focus on patients with cancers targeted by screening programmes, childhood cancers, and smoking-associated cancers]. / Aggiornamento della sopravvivenza dei pazienti con tumore in Italia: confronti geografici e focus su pazienti con tumori oggetto di screening, pediatrici e associati al fumo.

OBJECTIVES: to update the Italian estimates of survival for patients with a paediatric cancer, tobacco smoke-associated cancers, and cancers targeted by screening; to assess geographical differences. DESIGN: population-based descriptive study. SETTING AND PARTICIPANTS: incident cancer cases diagnosed in 2010-2014, with follow-up to 2018, from 17 Italian cancer registries (covering 31% of the national population; 43% of the population residing in the North-Centre of the country and 8% of the population living in the South and Islands). MAIN OUTCOME MEASURES: age-standardized 5-year net survival (NS) by cancer site or type, sex, age, and geographical area. RESULTS: NS of patients aged ≥15 years with breast, prostate, colorectal, and lung cancers was higher in the North-Centre than in the South and Islands. The overall survival of people diagnosed with cancer in childhood (0-14 years) was 84.3%, with similar values among the geographical macro-areas and between males and females. Women with breast cancer within the current target age of the screening programmes and those in the younger age groups (45-49 years) show similar survival values; the same is true for women with colorectal cancer. In both cases, survival decreased in the age groups after the age of cessation of screening programmes. Survival of patients with tobacco smoke-associated cancers varies according to cancer site (from 11.1% for patients with pancreatic cancer to 79.7% for those with bladder cancer). For most cancer sites, women have higher survival than men. CONCLUSIONS: for adults, a geographical survival gap persists. The results may contribute to the debate on extending the target age for screening programmes and to support initiatives to encourage tobacco smoking cessation even after cancer diagnosis. For patients who receive a cancer diagnosis in childhood, survival similar to highest values internationally.

Diquat Poisoning: Care Management and Medico-Legal Implications.

Acute chemical intoxication represents one of the major causes of Emergency Room admittance, and possible errors in diagnosis are extremely frequent, especially when patients present generic and non-specific symptoms. Diquat, a bipyridyl class of herbicides, exerts high intrinsic toxicity as a consequence of free oxygen radicals, leading to cellular death and organ dysfunctions. Following ingestion, with the major source of absorption for suicidal purposes, the chemical induces local irritating effects; systemic symptoms appear later, while specific symptoms can occur in the following 48 h. A smoker and hypertensive 50-year-old man arrives at the E.R., reporting that an episode of herbicide inhalation occurred few hours earlier. Physical examination evidenced alkalosis with hypoxemia, leucocytosis, mild hyperglycaemia and moderate increase in creatine kinase and myoglobin. Despite blood creatine kinase and myoglobin values that were higher than normal, he was prescribed with hydration and anti-pain therapy. During the night, the man left the hospital; he returned the next morning at 8:45 a.m., with cardiorespiratory arrest, medium fixed non-reactive mydriasis, diffused cyanosis of the skin and of the mucous membranes, as well as imperceptible pulse and peripheral pressure. Despite resuscitation attempts, the patient died at 9:30 a.m.; the body was immediately transferred to the morgue. Autopsy and toxicological analyses were carried out nine days later, evidencing paraquat ingestion for suicidal purposes. GC/MS analyses to verify the presence of diquat were performed on body fluids and gastric and colon contents; all specimens resulted positive, thus confirming the cause of death as herbicide ingestion (blood diquat concentration of 1.2 mg/L; more than twice the minimum to observe a systemic poisoning). The procedure followed for patient management resulted to be not in line with the provisions of both guidelines and good clinical practices. Staff did not perform clinical-diagnostical monitoring of the patient's condition or ask for more specific analyses (i.e., serum creatine phosphokinase monitoring). This misconduct led to a decrease in the patient's chances to survive.

Long-Term Follow-up of the Italian Flexible Sigmoidoscopy Screening Trial.

BACKGROUND: Recent reports showed that the protective effect of flexible sigmoidoscopy (FS) screening was maintained up to17 years, although differences were reported by sex. OBJECTIVE: To assess long-term reduction of colorectal cancer (CRC) incidence and mortality after a single FS screening. DESIGN: Parallel randomized controlled trial. (ISRCTN registry number: 27814061). SETTING: 6 centers in Italy. PARTICIPANTS: Persons aged 55 to 64 years expressing interest in having FS screening if invited, recruited from 1995 to 1999 and followed until 2012 (incidence) and 2014 to 2016 (mortality). INTERVENTION: Eligible persons were randomly assigned (1:1 ratio) to either the once-only FS screening group or control (usual care) group. MEASUREMENTS: Incidence and mortality rate ratios (RRs) and rate differences. RESULTS: A total of 34 272 persons (17 136 in each group) were included in the analysis; 9911 participants had screening in the intervention group. Median follow-up was 15.4 years for incidence and 18.8 years for mortality. Incidence of CRC was reduced by 19% (RR, 0.81 [95% CI, 0.71 to 0.93]) in the intention-to-treat (ITT) analysis, comparing the intervention with the control group, and by 33% (RR, 0.67 [CI, 0.56 to 0.81]) in the per protocol (PP) analysis, comparing participants screened in the intervention group with the control persons. Colorectal cancer mortality was reduced by 22% (RR, 0.78 [CI, 0.61 to 0.98]) in the ITT analysis and by 39% (RR, 0.61 [CI, 0.44 to 0.84]) in the PP analysis. Incidence of CRC was statistically significantly reduced among both men and women. Colorectal cancer mortality was statistically significantly reduced among men (ITT RR, 0.73 [CI, 0.54 to 0.97]) but not among women (ITT RR, 0.90 [CI, 0.59 to 1.37]). LIMITATION: Self-selection of volunteers from the general population sample targeted for recruitment may limit generalizability. CONCLUSION: The strong protective effect of a single FS screening for CRC incidence and mortality was maintained up to 15 and 19 years, respectively. PRIMARY FUNDING SOURCE: Italian Association for Cancer Research, Italian National Research Council, Istituto Oncologico Romagnolo, Fondo "E. Tempia," University of Milan, and Local Health Unit ASL-Torino.

Risk of thyroid as a first or second primary cancer. A population-based study in Italy, 1998-2012.

BACKGROUND: The number of patients living after a cancer diagnosis is increasing, especially after thyroid cancer (TC). This study aims at evaluating both the risk of a second primary cancer (SPC) in TC patients and the risk of TC as a SPC. METHODS: We analyzed two population-based cohorts of individuals with TC or other neoplasms diagnosed between 1998 and 2012, in 28 Italian areas covered by population-based cancer registries. Standardized incidence ratios (SIRs) of SPC were stratified by sex, age, and time since first cancer. RESULTS: A total of 38,535 TC patients and 1,329,624 patients with other primary cancers were included. The overall SIR was 1.16 (95% CI: 1.12-1.21) for SPC in TC patients, though no increase was shown for people with follicular (1.06) and medullary (0.95) TC. SPC with significantly increased SIRs was bone/soft tissue (2.0), breast (1.2), prostate (1.4), kidney (2.2), and hemolymphopoietic (1.4) cancers. The overall SIR for TC as a SPC was 1.49 (95% CI: 1.42-1.55), similar for all TC subtypes, and it was significantly increased for people diagnosed with head and neck (2.1), colon-rectum (1.4), lung (1.8), melanoma (2.0), bone/soft tissue (2.8), breast (1.3), corpus uteri (1.4), prostate (1.5), kidney (3.2), central nervous system (2.3), and hemolymphopoietic (1.8) cancers. CONCLUSIONS: The increased risk of TC after many other neoplasms and of few SPC after TC questions the best way to follow-up cancer patients, avoiding overdiagnosis and overtreatment for TC and, possibly, for other malignancies.

Mepolizumab improves sino-nasal symptoms and asthma control in severe eosinophilic asthma patients with chronic rhinosinusitis and nasal polyps: a 12-month real-life study.

BACKGROUND: Severe eosinophilic asthma is frequently associated to chronic rhinosinusitis and nasal polyposis (CRSwNP) that contribute to poor asthma control. Mepolizumab is an anti-IL-5 monoclonal antibody, approved for the treatment of severe eosinophilic asthma. A limited number of studies have assessed the efficacy of mepolizumab on CRSwNP in severe asthmatics. We aim to evaluate the efficacy of mepolizumab on sino-nasal symptoms, polyp growth and asthma control in severe eosinophilic asthma patients with CRSwNP in real life. METHODS: In this study 44 severe eosinophilic asthma patients with CRSwNP were treated with mepolizumab (100 mg q4w) for 1 year. The following outcomes were assessed before (T0), after 6 (T6) and 12 months (T12) of treatment: sino/nasal outcome test (SNOT-22), Total Endoscopic Nasal Polyp Score (TENPS), %FEV1 (FEV1/FEV1 predicted) and Asthma control test (ACT). Blood eosinophil count, exhaled nitric oxide (FENO) and prednisone intake were measured. In a subgroup of patients, nasal cytology was performed before (T0), after 6 (T6) and after 12 months (T12) of treatment with mepolizumab. RESULTS: We reported a significant reduction of SNOT-22 [from 51.5 ± 21.2 at baseline (T0) to 31.70 ± 17.36 at T6 and 29.7 ± 21.5 at T12 (T0-T12 p < 0.001)] and a decrease of TENPS (from 2.88 ± 3.07 to 1.70 ± 2.37 and 1.77 ± 2.56 at T0, T6 and T12, respectively, T0-T12 p = 0.99). A significant improvement of %FEV1, ACT and a decrease in blood eosinophils and mean prednisone intake were also reported. No statistically significant decreasing trend was measured for FENO. Nasal cytology findings suggest a significant reduction of eosinophil percentage following mepolizumab treatment (from 16.8 ± 7.2% to 3.6 ± 6.2% and 0.8 ± 2.4% at T0, T6 and T12 respectively, T0 to T12: p < 0.001). CONCLUSIONS: Mepolizumab improves sino-nasal and asthma symptoms and reduces polyp growth in patients with severe eosinophilic asthma and concomitant CRSwNP in real life.The reviews of this paper are available via the supplemental material section.

Changes in life expectancy for cancer patients over time since diagnosis.

The aims of this study were to provide life expectancy (LE) estimates of cancer patients at diagnosis and LE changes over time since diagnosis to describe the impact of cancer during patients' entire lives. Cancer patients' LE was calculated by standard period life table methodology using the relative survival of Italian patients diagnosed in population-based cancer registries in 1985-2011 with follow-up to 2013. Data were smoothed using a polynomial model and years of life lost (YLL) were calculated as the difference between patients' LE and that of the age- and sex-matched general population. The YLL at diagnosis was highest at the youngest age at diagnosis, steadily decreasing thereafter. For patients diagnosed at age 45 years, the YLL was above 20 for lung and ovarian cancers and below 6 for thyroid cancer in women and melanoma in men. LE progressively increased in patients surviving the first years, decreasing thereafter, to approach that of the general population. YLL in the long run mainly depends on attained age. Providing quantitative data is essential to better define clinical follow-up and plan health care resource allocation. These results help assess when the excess risk of death from tumour becomes negligible in cancer survivors.

Late mortality and causes of death among 5-year survivors of childhood cancer diagnosed in the period 1960-1999 and registered in the Italian Off-Therapy Registry.

INTRODUCTION: Advances in paediatric oncology led to the increase in long-term survival, revealing the burden of therapy-related long-term side effects. We evaluated overall and cause-specific mortality in a large cohort of Italian childhood cancer survivors (CCSs) and adolescent cancer survivors identified through the off-therapy registry. MATERIALS AND METHODS: CCSs alive 5 years after cancer diagnosis occurring between 1960 and 1999 were eligible; the last follow-up was between 2011 and 2014. Outcomes were reported as standardised mortality ratios (SMRs) and absolute excess risks (AERs). RESULTS: Among 12,214 CCSs, 1113 (9.1%) deaths occurred. Survival at 35 years since diagnosis was 87% (95% confidence interval [CI]: 86-88) and at 45 years was 81% (95% CI: 77-84). CCSs had an 11-fold increased risk of death (SMR 95% CI: 10.7-12), corresponding to an AER of 48 (95% CI: 45-51). Mortality decreased by 60% for survivors treated most recently (1990-1999). The most frequent causes of death were recurrence of the original cancer (56%), a subsequent neoplasm (19%) and cardiovascular diseases (5.8%). Among those who survived at least 15 years after diagnosis, a secondary malignancy was the leading cause of death. CONCLUSIONS: This study confirms the impact of recent advances in anticancer therapy in reducing mortality, mainly attributable to recurrence but also to other causes. However, overall mortality continues to be higher than in the general population. A long-term follow-up is needed to prevent late mortality due to secondary neoplasms and non-neoplastic causes in CCSs.

Genetic Risk in Insurance Field.

The risk-delimiting tools available to insurance companies are therefore substantial and it is also possible to argue that a margin of uncertainty is a natural component of the insurance contract. Despite this, businesses look at the potential of predictive medicine, and in particular the growing understanding of genetic mechanisms that support many common diseases. In particular, the rapid development of genetics has led many insurance companies to glimpse in the predictive diagnosis of disease by genetic testing the possibility of extending the calculation of the individual risk of developing a particular disease to appropriate premiums or even denying insurance coverage.

Genetic Testing and Professional Responsibility: The Italian Experience.

Responsibility means responding to the damaging consequences of technical work and in this binding perspective the general principles of guilt in genetic diagnostics and related activities are not different from any other medical performance. Performing a genetic test however, especially when it has predictive characteristics, offers absolutely peculiar technical deontological issues. It is not and should not be considered as a mere habitual laboratory test but as a complex set of interactions that presupposes adequate information as a valid consensus to formalize absolutely in written form.

Genetic Testing: Ethical Aspects.

The aim of this article is to provide an analysis of the main issues related to the application of predictive medicine by analysing the most significant ethical implications. Genetic medicine is indeed a multidisciplinary matter that covers broad contexts, sometimes transversely. Its extreme complexity, coupled with possible perceived repercussions on an individual's life, involves important issues in the ethical, deontological and legal medical field. The aspects related to the execution of genetic testing have to be addressed at different levels, starting with the correct information about the "cognitive" meaning they intend (by forcefully disassociating it from the strange "preventive aspect") to the legal medical issues that can be aroused in the field of forensic pathology, medical responsibility and insurance. There is no doubt that in recent years, from the decoding of the human genome, genetic research has exponentially expanded with an equally exponential increase in its use in clinical practice and the ethical and social evolution of it.