Antonio Grossich, the doctor and the irredentist.

The routine use of iodine tincture in medicine represents a turning point in the history of surgical procedures. It was the Istrian doctor Antonio Grossich (1849-1926) who first defined and applied the best formula and demonstrated to the world its superiority over other antiseptics. Although his was a life guided by medicine and the steadfast translation of his political ideals into practice, Grossich's achievements were somewhat obscured by his active involvement in the Istrian irredentism of the first decades of the wentieth century.

Caring for children with cancer evacuated from Ukraine: The patients' perception.

BACKGROUND AND AIMS: Since the beginning of the war in Ukraine on February 24, 2022, many pediatric oncology centers welcomed evacuated patients. To better understanding the needs of patients and families arriving at two Lombardy hospitals in the period March to November 2022, an anonymous questionnaire investigated the families' backgrounds, feelings, and impressions about hospitality and care. METHODS: Twenty questions investigated how patients had reached Italy, from whom they had received help (logistically/financially); the emotions regarding their status as war refugees; the knowledge, expectations, and opinions about Italy and Italians; the quality of medical care received and the relationships with the healthcare staff; lastly, suggestions to improve assistance. RESULTS: The questionnaires were completed by 19/32 patients/parents in November 2022 in two different pediatric-oncology centers. Most families had reached Italy (58%) and received medical care (95%) with the help of charities and the Italian Public Health Care System. A significant majority (69%) expressed satisfaction with the assistance provided. The Italian population demonstrated remarkable warmth, for 95% exhibiting friendliness and for 58% generosity. An improvement in their stay could be linked with the positive outcome of their children's cancer (15%), achieving complete family reunification (15%), the cessation of the conflict (10%), and the overcoming of language barriers (10%). CONCLUSIONS: Providing care for children from another country, not only grappling with the trauma of fleeing their homeland but also battling cancer, is an immense undertaking. It demands a diverse range of efforts and resources to ensure a positive and fulfilling outcome for this experience.

[Rare disease in the age of artificial intelligence.] / Ammalarsi di una patologia rara in tempi di intelligenza artificiale.

INTRODUCTION: The text examines the impact of artificial intelligence (AI) in the context of rare diseases, exploring how patients turn to AI resources for health information, especially in situations where doctor-patient communication is limited. The article features the case of a doctor specializing in clinical psychology and psychotherapy, diagnosed with thymoma and Good's syndrome, who uses AI resources during his illness. METHODS: The capabilities of five chatbots based on Large Language Models (LLMs), such as GPT-3.5, GPT-4, Bing Chat, Google Bard, and Anthropic Claude are explored. The AIs were queried on various aspects of the disease, from pre-diagnosis and diagnosis to therapeutic, psychological, and caregiver management issues. The responses were evaluated by five experts based on criteria such as: accuracy, relevance, coherence, clarity, practical utility, ethical considerations, empathy, and capacity to respond to questions and concerns. RESULTS: The results indicate consistency in the evaluators' assessments, with generally high scores across all dimensions. Particularly, systems like Bard and GPT-4 received high ratings in terms of information accuracy and the ability to respond to questions and concerns. Bing and Claude were appreciated for their empathy and tone. Overall, the AI systems' responses were considered appropriate, respectful of ethics and privacy, and useful in the clinical context. DISCUSSION: The article emphasizes the importance of understanding the reliability and precision of responses provided by AI systems in the clinical field. Although these systems offer high-quality responses, there is significant variability in their performance. Healthcare professionals must be aware of these differences and use such tools cautiously. AI can provide support in some aspects of care but cannot replace genuine human empathy and understanding. Integrating AI into clinical practice presents potential but also challenges, particularly the possibility of providing incorrect information. CONCLUSIONS: The AI systems demonstrate the ability to provide useful advice on clinical and psychological issues, but their use requires caution. It is crucial to distinguish the benefits of AI for patients from the challenges it presents for healthcare professionals. As AI technology continues to evolve, it is essential that its integration into the clinical field is accompanied by continuous research and evaluations, to ensure safe and effective use in the healthcare sector.

End-of-Life transfusion support at hospice and pediatric oncology unit: Bridging the gap between benefits and therapeutic alliance.

OBJECTIVES: Although transfusion support is commonly used in oncological palliative care, there is still a paucity of literature. We examined the transfusion support provided in the terminal stage of the disease and compared the approach at a pediatric oncology unit and a pediatric hospice. CASE DESCRIPTION: This case series analyzed patients treated at the Fondazione IRCCS Istituto Nazionale dei Tumori di Milano (INT)'s pediatric oncology unit who died between January 2018 and April 2022. We compared these with those who died at the VIDAS hospice and analyzed the number of complete blood counts taken in a patient's last 14 days of life, and the number of transfusions performed in the same period.We analyzed 44 patients (22 in pediatric oncology unit; 22 in hospice) in total. Twenty-eight complete blood counts were performed (7/22 patients at the hospice; 21/22 patients at the pediatric oncology unit). Nine patients were given transfusions, three at the hospice, six at our pediatric oncology unit (24 transfusions in total): 20 transfusions at the pediatric oncology unit, four at the hospice. In total 17/44 patients were given active therapies in the last 14 days of life: 13 at the pediatric oncology unit, four at the pediatric hospice. Ongoing cancer treatments did not correlate with a greater likelihood of receiving a transfusion (p=0.91). CONCLUSIONS: The hospice's approach was more conservative than the pediatric oncology one. In the in-hospital setting, the need for a transfusion cannot always be decided on by a combination of numerical values and parameters alone. The family's emotional-relational response must be considered too.

The Use of Psychotropic Medication in Pediatric Oncology for Acute Psychological and Psychiatric Problems: Balancing Risks and Benefits.

Severe acute behavioral and emotional problems represent one of the most serious treatment-related adverse effects for children and adolescents who have cancer. The critical and severe nature of these symptoms often makes necessary the use of psychotropic drugs. A working group composed of experts in multiple disciplines had the task of creating an agreement regarding a management plan for severe acute behavioral and emotional problems (SABEPs) in children and adolescents treated for cancer. To obtain global information on the use of psychotropic drugs in pediatric oncology, the working group first developed and mailed a 15-item questionnaire to many Italian pediatric oncology centers. Overall, an evident lack of knowledge and education regarding the use of psychotropic medications for the treatment of SABEPs was found. Thus, by referring to an adapted version of the Delphi method of consensus and standard methods for the elaboration of clinical questions (PICOs), the working group elaborated evidence-based recommendations for psychotropic drugs in the pediatric oncology setting. Furthermore, based on a thorough multivariate analysis of needs and difficulties, a comprehensive management flow was developed to optimize therapeutic interventions, which allows more accurate and efficient matching of the acute needs of patients while guiding treatment options.

Palliative sedation in paediatric solid tumour patients: choosing the best drugs.

OBJECTIVES: Cancer remains the leading cause of mortality by disease in childhood in high-income countries. For terminally ill children, care focuses on quality of life, and patient management fundamentally affects grieving families. This paper describes our experience of palliative sedation (PS) for children with refractory symptoms caused by solid tumours, focusing on the drugs involved. METHODS: We retrospectively collected data on all children treated for cancer who died at the pediatric oncology unit of the Fondazione IRCCS Istituto Nazionale dei Tumori between January 2016 and December 2020. RESULTS: Of the 29 patients eligible for the study, all but 4 received PS. Midazolam was always used, combined in 16 cases with other drugs (mainly classic neuroleptics, alpha-2 agonists and antihistamines). Throughout the period of PS and on the day of death, patients with sarcoma were given higher doses of midazolam and morphine, and more often received combinations of drugs than patients with brain tumours. Sarcoma causes significant symptoms, while brain tumours require less intensive analgesic-sedative therapies because they already impair a patient's state of consciousness. CONCLUSIONS: Optimising pharmacological treatments demands a medical team that knows how drugs (often developed for other indications) work. Emotional and relational aspects are important too, and any action to lower a patient's consciousness should be explained to the family and justified. Parents should not feel like helpless witnesses. Guidelines on PS in paediatrics could help, providing they acknowledge that a child's death is always a unique case.

Dietary Isoflavone Aglycons from Soy Germ Pasta Improves Reproductive Performance of Aging Hens and Lowers Cholesterol Levels of Egg Yolk.

This study compared dietary isoflavone aglycones with the glycoside conjugates in a novel model of postmenopausal status, the aging domestic hen (Gallus gallus domesticus), to determine the effects on reproductive performance, cholesterol levels, and nutritional quality of eggs laid. Hens, 18 mo old, were randomized into four groups (n = 10/group) and fed for 28 d a conventional poultry corn/soymeal diet (Control), or diets supplemented with isoflavone glycosides from soy germ (diet A), isoflavone aglycons from a soy germ pasta (diet B), or conventional pasta lacking isoflavones (diet C). The egg-laying rate was recorded daily, plasma isoflavones and cholesterol were measured, and the nutritional composition of the eggs was determined. Egg-laying declined over a 4-week period in hens in the Control group and those fed isoflavone glycosides (diets A and C), whereas hens fed isoflavone aglycons (diet B) significantly increased their egg-laying efficiency. The total egg count and egg yield were significantly higher in hens fed isoflavone aglycons, and their plasma cholesterol concentrations were lower and the eggs laid had a 30% lower yolk cholesterol content. None of these effects were observed with diets containing similar levels of isoflavone glycosides. These studies recapitulate the clinical effects of soy germ pasta enriched with isoflavone aglycons and lend support to the greater efficacy of a diet rich in isoflavone aglycons.

How ten-years of reirradiation for paediatric high-grade glioma may shed light on first line treatment.

PURPOSE: Recurrence incidence for paediatric/adolescent high-grade glioma (HGG) exceeds 80%. Reirradiation (reRT) palliates symptoms and delays further progression. Strategies for reRT are scarce: we retrospectively analysed our series to develop rational future approaches. METHODS: We re-evaluated MRI + RT plans of 21 relapsed HGG-patients, accrued 2010-2021, aged under 18 years. All underwent surgery and RT + chemotherapy at diagnosis. Pathologic/molecular re-evaluation allowed classification based on WHO 2021 criteria in 20/21 patients. Survival analyses and association with clinical parameters were performed. RESULTS: Relapse after 1st RT was local in 12 (7 marginal), 4 disseminated, 5 local + disseminated. Re-RT obtained 8 SD, 1 PR, 1PsPD, 1 mixed response, 10 PD; neurological signs/symptoms improved in 8. Local reRT was given to 12, followed again by 6 local (2 marginal) and 4 local + disseminated second relapses in 10/12 re-evaluated. The 4 with dissemination had 1 whole brain, 2 craniospinal irradiation (CSI), 1 spine reRT and further relapsed with dissemination and local + dissemination in 3/four assessed. Five local + disseminated tumours had 3 CSI, 1 spine reRT, further progressing locally (2), disseminated (1), n.a. (1). Three had a third RT; three were alive at 19.4, 29, 50.3 months after diagnosis. Median times to progression/survival after re-RT were 3.7 months (0.6-16.2 months)/6.9 months (0.6-17.9 months), improved for longer interval between 1st RT and re-RT (P = 0.017) and for non-PD after reRT (P < 0.001). First marginal relapse showed potential association with dissemination after re-RT (P = 0.081). CONCLUSIONS: This is the biggest series of re-RT in paediatric HGG. Considering the dissemination observed at relapse, our results could prompt the investigation of different first RT fields in a randomized trial.

The hidden side of Santiago Ramon y Cajal.

Alongside his anatomical studies, which laid the foundations of modern neuroanatomy, Santiago Ramón y Cajal also showed a lively interest in studying dreams, hypnosis, and the world of the paranormal. On his travels to worlds far removed from anatomy, Cajal sometimes strove to find potential neuroanatomical explanations for the phenomena he encountered, while at other times he simply allowed himself to be carried along by his curiosity, with no preconceptions. His investigations in such diverse spheres of knowledge and human behavior are an exceptional example of a scientific epoch that has since disappeared.

Get up, stand up: Alongside adolescents and young adults with cancer for their right to be forgotten.

Adolescent and young adult cancer survivors may experience various forms of social difficulties years or even decades after completing their cancer treatments. This article will hopefully help the Italian national project dedicated to adolescents and young adults with cancer promoting political and legal solutions to stop discrimination and supporting the right to be forgotten.

A Textual Analysis for Understanding the Relations and the Identity Construction in Adolescent Oncology Patients: Retrospective Personal Views in Order to Educate Health Professionals.

Patient input is critical for all aspects of value-based healthcare design. This contribution describes the following: the specifics of communications with doctors regarding the disease in adolescents and young adults with cancer; the patients' thoughts, emotions and changes in self-perception; "other meanings" taking shape along the treatment pathway; and reacting modes to the disease and treatments. Thirty-five Italian AYA patients in follow-up (age 18-24) were involved in a plenary interview on the cited aspects of their oncological experience. The answers were analyzed by MADIT (Analysis Methodology of Computerized Textual Data) with the software SPAD. MADIT allowed us to perform text analysis, describe the graphical outcomes and discuss the results. Respondents took a first-person perspective and their personal narrative recall had objective and unequivocal connotations. Experience was narrated mainly by maintenance repertoires that fix the reality of disease, its treatments and personal identity. The account focused on the tumor and on an agreed approach to it. The time "after" was described as a distressing space that defines them. Making sense of the events was considered a significant help. Professionals need to focus on the discursive repertoires of communication with which the inner and outer reality are built. Lastly, these patients required a two-way dialogue throughout the entire caring process.

Managing Care during the COVID-19 Pandemic: The Point of View and Fears of Pediatric Cancer Patients' Families.

(1) Background: When the COVID-19 pandemic arrived, changes had to be made to several management aspects at our Pediatric Oncology Unit. We investigated how the families perceived these changes. (2) Methods: Two questionnaires were developed at the Pediatric Oncology Unit of the Istituto Nazionale dei Tumori in Milan in order to explore how the pandemic had affected the experience of patients who had been or were being treated at our hospital, as well as their families. These questionnaires were administered to three groups of individuals. (3) Results: Between July and October 2020, 120 questionnaires were administered to parents of patients. The impact of school closures and the impossibility of attending sports and social activities outside the hospital were regarded as important, and it was reported that 77.5% of parents judged social distancing to have affected their children. Regarding the changes introduced in the management of the ward and outpatient clinic, most parents' opinions were positive. Differences in the opinions expressed by Groups 2 and 3 were statistically significant on the topics of relationships in the ward and staff workload. The aspect most negatively affected by the pandemic was the support that patients' parents were able to give each other. Regardless of whether patients were treated before the pandemic or after the first lockdown, all parents indicated strong degrees of satisfaction with the care received and the organizational arrangements. (4) Conclusions: The results of our study point us in the right direction to further improve our daily work and better respond to the needs of our patients and their families.

Playing cards designed by young cancer patients with the Youth Project in Milan.

This short piece briefly describes a creative project undertaken by a group of adolescent and young adult cancer patients as part of our Youth Project (a scheme dedicated to young cancer patients with the dual aim of optimizing medical aspects of their care and promoting a holistic approach to their needs, including the organization of artistic activities). In this project, young cancer patients designed their personalized playing cards, with kings receiving chemo, queens wearing bandanas, jacks dressed as nurses, and jokers as doctors. The playing cards, with the patients' own words, contain a little bit of these young cancer patients' stories in them.

"Based on a true story" podcast: a journey into the world of young patients with cancer.

This article describes a creative project undertaken by a group of adolescent and young adult patients with cancer as part of the Milan's Youth Project, a scheme dedicated to young patients with cancer with the dual aim of optimizing medical aspects of their care and promoting a holistic approach to their needs. The project was based on audio recordings and focused on the theme of "the journey," such as a holiday or an adventure, or as a metaphor of the cancer experience. The podcast installments were published on the main streaming platforms. Talking about their disease and how they feel is of importance for young patients to process their feelings surrounding the cancer experience and to find the inner resources they need to facilitate coping.

Fertility Counseling in Survivors of Cancer in Childhood and Adolescence: Time for a Reappraisal?

Genetic predisposition could have an important role in the pathogenesis of cancers in children and adolescents. A recent study by our group showed that, among female survivors of cancers in childhood and adolescence, the proportion of cases involving a possible genetic predisposition was sizable (at least one in five). Our sample is too small to be representative of the general population, but it gave us an opportunity to reappraise this issue. Women with a genetic predisposition can transmit the risk of cancer to their offspring, and their awareness of this may influence their reproductive and fertility preservation choices. In our experience, a predisposition to cancer receives little attention in the fertility counseling and decision-making process unless a patient already has a definitive molecular diagnosis of a hereditary cancer syndrome. We feel it is essential to empower women on this issue, particularly as there are ways to overcome the problem, including preimplantation genetic testing (PGT-M) in definitively diagnosed cases, egg donation and adoption. In the context of fertility counseling for survivors of cancer in childhood and adolescence who have reached adulthood, the risk of transmitting a predisposition to cancer should be discussed with patients, if relevant and desired.

Ugo Cerletti, Pathologica and electroconvulsive therapy.

Ugo Cerletti was the inventor of the electroconvulsive therapy (ECT) adopted in 1938 to treat schizophrenia. He had a robust education in anatomical pathology, which also left its mark on the journal Pathologica. Although his name is associated with several important moments and breakthroughs in the history of medicine, Ugo Cerletti's reputation has partly suffered from the same fate as his treatment. Electroshock was initially widely adopted, partly because of its low cost and relatively easy application, but with the advent of psychoactive drugs in the 1950s and 1960s, it subsequently came under ferocious criticism. Its fall from grace also affected to some extent the man who had invented it, though this seems hard to justify today.

Children and adolescent solid tumours and high-intensity end-of-life care: what can be done to reduce acute care admissions?

Despite improvements in survival, cancer remains the leading cause of non-accidental death in children and adolescents, who risk receiving high-intensity end-of-life (HI-EOL) care. OBJECTIVE: To analyse treatments for relapses (particularly in the last weeks of life), assess their impact on the EOL, identify patients most likely to receive HI-EOL care and examine whether palliative care services can contain the intensity of EOL care. METHODS: This retrospective study involved patients treated at the paediatric oncology unit of the Istituto Nazionale Tumori in Milan who died between 2018 and 2020. The primary outcome was HI-EOL care, defined as: ≥1 session of intravenous chemotherapy <14 days before death; ≥1 hospitalisation in intensive care in the last 30 days of life and ≥1 emergency room admission in the last 30 days of life. RESULTS: The study concerned 68 patients, and 17 had HI-EOL care. Patients given specific in-hospital treatments in the last 14 days of their life more frequently died in hospital. Those given aggressive EOL care were less likely to die at home or in the hospice. Patients with central nervous system (CNS) tumours were more likely to have treatments requiring hospitalisation, and to receive HI-EOL care. CONCLUSION: These results underscore the importance of considering specific treatments at the EOL with caution. Treatments should be administered at home whenever possible.The early activation of palliative care, especially for fragile and complicated patients like those with CNS cancers, could help families cope with the many problems they face.