"Heal the sick": Health status and caregiving during the 17th-18th century in Northern Italy (St. Biagio cemetery, Ravenna).

OBJECTIVE: The study of health-related care provision in archeology gives important indications on the culture and community organization of past populations. This study aims to assess the health status of the skeletal assemblage recovered from the burial site of St. Biagio (Ravenna, 17th-18th Centuries); next, we identified likely instances of need for and receipt of caregiving in response to the condition, to examine evidence of community attitudes toward disease and disability. MATERIALS AND METHODS: The skeletal assemblage is composed of 133 individuals in a generally good state of preservation. Sex and age-at-death were estimated through classical anthropological methods. Health status was inferred through the biological index of frailty (BIF) and paleopathological analysis was performed through macroscopic and radiographic investigations. The "bioarcheology of care" approach was applied to individuals who showed evidence of impairment and disability. RESULTS: The skeletal assemblage of St. Biagio was equally represented by males and females (50% males), with a higher percentage of adults (83.4%) than subadults (10.5%), and this is reflected in the high life expectancy at birth (40.3 years). No significant differences in health status emerged between age groups and sexes, with a generally high percentage of joint diseases, antemortem trauma, and infectious diseases. Evidence of care and compassion was found in some individuals with a high degree of impairment or disability, as in the case of probable Angelman syndrome. DISCUSSION: This study provided important insights into the biological and social aspects of an Early Modern population in Northern Italy, showing that people with functional and/or visible abnormalities were probably cared for in life and were presumably considered full members of the society.

Real-World Retrospective Study into the Effects of Oral Semaglutide (As a Switchover or Add-On Therapy) in Type 2 Diabetes.

(1) Background: Oral semaglutide represents the first oral GLP-1 RA approved for the treatment of type 2 diabetes mellitus (T2DM). This real-world retrospective study aimed at evaluating its effectiveness and tolerability in the treatment of patients with T2DM when patients switched from a glucose-lowering agent to it and when it was added to the usual therapy. (2) Methods: Adult patients with T2DM taking oral semaglutide and followed in the ASUGI Diabetes Center were identified with the use of electronic medical records between October 2022 and May 2023. (3) Results: A total of 129 patients were recruited. The median follow-up was 6 months. Be it as a switchover or as an add-on therapy, oral semaglutide significantly reduced HbA1c and BMI. Switching from DPPIV inhibitors to oral semaglutide was associated with a significant reduction in HbA1c and BMI, switching from SGLT2 inhibitors was associated with a significant reduction in HbA1c, and switching from sulphonylureas was associated with a significant reduction in BMI. The median HbA1c change was associated with baseline HbA1c. SBP significantly decreased in the add-on group. Oral semaglutide was well tolerated. (4) Conclusions: This study shows that in the real-world setting, oral semaglutide is effective and safe as a switchover or as an add-on therapy for the treatment of T2DM.

Assessing the Impact of COVID-19 Prevention Measures on Adolescent Growth in Italy.

COVID-19 infection has caused increased morbidity and mortality worldwide. Several strategies have been adopted around the world to prevent its spread. Italy underwent a long lockdown for face-to-face educational activities, which were replaced with online classes. This longitudinal study aimed to analyze the effects of COVID-19 prevention measures on physical growth and body image perception in a sample of Italian adolescents who experienced the pandemic-induced lockdown in 2020. In particular, we wished to ascertain how lifestyle changes had affected their growth rates and health. Special attention was paid to increases in adiposity indicators (BMI, waist circumference, waist-to-height ratio) and weight caused by reduced physical activity, and consequent possible dissatisfaction with body image. We assessed the impact of school closures by comparing the annual growth rate and body image perception changes of adolescents (n = 60; age = 11.3 ± 0.4 years) who experienced this isolation with those in the following years who did not experience these restrictions (n = 68; age = 11.4 ± 0.3 years). As a consequence of the lockdown, our results indicate a greater annual growth rate in weight and other indices of adiposity (p < 0.05). As the virus is continuing to evolve and propagate, larger population studies can verify and confirm our findings. In promoting health policy to prevent the ongoing prevalence of obesity in adolescents, an accurate assessment of whether the increase in obesity rates during the pandemic is to be considered a temporary trend is highly recommended.

Orange Peel Biomass-derived Carbon Supported Cu Electrocatalysts Active in the CO2 -Reduction to Formic Acid.

We report a green, wet chemistry approach towards the production of C-supported Cu electrocatalysts active in the CO2 reduction to formic acid. We use citrus peels as a C support precursor and as a source of reducing agents for the Cu cations. We show that orange peel is a suitable starting material compared to lemon peel for the one-pot hydrothermal synthesis of Cu nanostructures affording better Cu dispersion as well as productivity and selectivity towards formic acid. We rationalize this finding in terms of the beneficial chemical composition of the orange peel, which favors both the reduction of the Cu precursor as well as the carbon matrix. This work demonstrates new viable opportunities for the reuse of citrus waste on a rational basis.

Cemiplimab in an Elderly Frail Population of Patients With Locally Advanced or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Center Real-Life Experience From Italy.

BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer whose incidence is growing parallel to the lengthening of the average lifespan. Cemiplimab, an antiPD-1 monoclonal antibody, is the first approved immunotherapy for patients with locally advanced CSCC (laCSCC) or metastatic CSCC (mCSCC) thanks to phase I and II studies showing high antitumor activity and good tolerability. Nevertheless, at present, very few data are available regarding cemiplimab in real-life experience and in frail, elderly, and immunosuppressed patients as well as regarding biomarkers able to predict response so as to guide therapeutic choices. PATIENTS AND METHODS: We built a retroprospective cohort study including 30 non-selected patients with laCSCC (25) and mCSCC (five) treated with cemiplimab from August 2019 to November 2020. Clinical outcomes, toxicity profile, and correlations with disease, patients, and peripheral blood parameters are explored. RESULTS: The median age was 81 years (range, 36-95), with 24 males and five patients having an immunosuppressive condition, while the frailty prevalence was 83% based on index derived from age, Eastern Cooperative Oncology Group performance status, and Charlson Comorbidity Index. We reported 23 responses (76.7%) with nine complete responses (30%). A statistically significant higher response rate was observed in head and neck primary tumors and in patients with hemoglobin level >12 g/dl. No difference was observed with respect to frailty, median age, sex, and body mass index. The baseline low neuthophil/lymphocyte ratio and low platelet/lymphocyte ratio resulted to be also correlated with a better response. Moreover, lymphocyte, neutrophil, and monocyte behaviors had an opposite trend in responders and non-responders. An overall response was reported in four of five immunosuppressed patients. Seventeen patients (57.6%) have an ongoing response and are still alive. Six responders had interrupted treatment (two for toxicity and four for personal choice) but maintained their response. The treatment was well tolerated by the majority of patients. The most common adverse events were fatigue in seven patients (23.3%) and skin toxicity in 10 patients (33.3%), including pruritus in six patients, rash in three patients, and bullous erythema in one patient. CONCLUSIONS: In our real-life experience, cemiplimab showed a high antitumor activity with acceptable safety profile similar to those in trials with selected patients. Moreover, its antitumor activity resulted to be not impaired in very elderly patients and in those with immunocompromised status.

The Management of Oligoprogression in the Landscape of New Therapies for Metastatic Melanoma.

Background: A limited degree of progression after a response to treatment is labelled as oligoprogression and is a hot topic of metastatic melanoma (MM) management. Rogue progressive metastases could benefit from local treatment, which could allow the continuation of ongoing systemic therapy, also known as treatment beyond progression (TBP). Methods: We retrospectively reviewed 214 selected MM patients who developed oligoprogression during treatment with v-Raf murine sarcoma viral oncogene homolog B (BRAF)/mitogen-activated-extracellular signal-regulated kinase (MEK) or programmed cell death protein 1 (PD-1) inhibitors and received a local treatment continuing TBP. We performed univariate and multivariable analyses to assess the association between therapy outcomes and a series of clinical and biological features. Results: We identified 27 (10%) oligoprogressed patients treated locally with surgery (14), radiosurgery (11), and electrochemotherapy (2). TBP included PD-1 inhibitors (13) and BRAF/MEK inhibitors (14). The median progression-free survival post oligoprogression (PFSPO) was 14 months (5-19 95% confidence interval (C.I.)). In the univariate analysis, a significantly longer PFSPO was associated with complete response (CR), Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, neutrophils/lymphocytes ratio (N/L) <2, and progression-free survival (PFS) at oligoprogression >11 months. Nevertheless, in the multivariable analysis, only CR and N/L <2 were found to be associated with longer PFSPO. Conclusions: In selected patients, local treatments contribute to controlling oligoprogression for a long time, allowing the continuation of systemic treatment and prolongation of overall survival (OS). Increasing biological and clinical knowledge is improving the accuracy in identifying patients to apply for local ablative therapies.

Hemidiaphragm Paralysis after Robotic Prostatectomy: Medical Malpractice or Unforeseeable Event?

The authors present a case of suspected malpractice linked to the onset of hemidiaphragm paralysis after robot-assisted radical prostatectomy (RARP). The approach to the case is shown from a medico-legal point of view. It is demonstrated how, after a thorough review of the literature, this was not a case of medical malpractice but an unforeseeable event. This paper aims at contributing to the very few reports dealing with the onset of hemidiaphragm paralysis after RARP, thus fostering clinical knowledge of these rare events and meanwhile providing useful data for the medico-legal handling in case of alleged negligence of surgeons.

Combining dental and skeletal evidence in age classification: Pilot study in a sample of Italian sub-adults.

BACKGROUND: Dental and skeletal maturation have proved to be reliable evidence for estimating age of children and prior studies and internationally accredited guidelines recommend to evaluate both evidence in the same subject to reduce error in age prediction. Nevertheless the ethical and legal justification of procedures that imply a double exposition of children stands as a relevant issue. This study aims to evaluate the accuracy of age estimation provided by a combination of skeletal and dental methods applied in the same sample of children. MATERIALS AND METHODS: The sample consisted of 274 orthopantomographies and left hand-wrist X-rays of Italian children, (aged between 6 and 17years) taken on the same day. Greulich and Pyle's (GP), Tanner-Whitehouse's version 3 (TW3) and Willems' (W) and the Demirjian's (D) methods were respectively applied for estimating skeletal and dental age. A combination of skeletal and dental age estimates through Linear Discriminant Analysis (LDA) is proposed to obtain a classifier respect to an age threshold. RESULTS: The combination of D and TW3 obtained an improvement of accuracy in classifying female subjects respect to the 12years threshold respect to the original methods (from about 77% using either original methods to 83.3% combining TW3+D) as well as a consistent reduction of false positives rate (from 17% to 21% for original methods to 5.6% with TW3+D). For males the LDA classifier (based on TW3 and W) enable a small improvement in accuracy, whilst the decreasing of false positives was as noticeable as for females (from 17.6 to 14.1% for original methods to 6.2% combining TW3+W). CONCLUSIONS: Although the study is influenced by the limited size and the uneven age distribution of the sample, the present findings support the conclusion that age assessment procedures based on both dental and skeletal age estimation can improve the accuracy and reduce the occurrence of false positives.

Pulmonary Cement Embolism After Kyphoplasty.

Pulmonary polymethylmethacrylate (PMMA) cement embolism after kyphoplasty (KP) surgery is a quite frequent event as well as the pulmonary embolization of central venous catheter fragment. This report shows the case of a subject who, after KP, developed pulmonary embolism and who underwent thoracic surgery. After hospital discharge, the subject advanced a claim for damages toward the hospital where he was operated, complaining sensation of tenderness at the chest surgical scar and esthetic damage. To understand the nature of the embolism (either central venous catheter fragment or cement), chemical investigations were then ordered. Spectrometry identified the PMMA cement used for KP. When doubts rise about the origin of the embolized material, chemical investigations may reveal important data not only for clinical but also for forensic purposes.

The Claims Management Committees trial: experience of an Italian hospital of the National Health System.

INTRODUCTION: In Italy, health care is mainly financed by earmarked central and regional taxes, with regions receiving their allocated share of resources from the National Health Fund. The Council of the Tuscany Region in 2009 began an experimentation aimed to enforce the extrajudicial conciliation. The Council established the Claims Management Committees (CMC) for civil liability in the Tuscan Health Service. The CMC trial provides that the damages are compensated directly by the hospital, removing the cost of liability insurance. The aim of this study is to collect and compare the liability-insurance-period and the CMC trial-period. MATERIALS AND METHODS: Data were derived from the management claims database of the Health Directorate of the Careggi Hospital in Florence between 2006 and 2012. Two main periods are considered for the comparison of data: 2006-2007-2008 during the insurance management and 2010-2011-2012 during the CMC trial. RESULTS: During the insurance management period, the total expenditure was equal to the €14,846,334.44 paid in the 3-year period. The total expenditure during the CMC trial 3-years period was equal to €7.076.370,75. Under the CMC management, we observed a marked decrease in the recourse to legal action in the face of a substantial maintenance of the number of claims opened for each year. The CMC trial showed a greater speed in setting claims for damages. DISCUSSION AND CONCLUSIONS: Under CMC management, a greater and more diligent efficiency is matched by a lower economic outlay. The use of the direct management of damage compensation may be an important tool for risk management, thus guaranteeing the recourse to targeted and appropriate interventions.

Skeletal age estimation for forensic purposes: A comparison of GP, TW2 and TW3 methods on an Italian sample.

BACKGROUND: Paediatricians, radiologists, anthropologists and medico-legal specialists are often called as experts in order to provide age estimation (AE) for forensic purposes. The literature recommends performing the X-rays of the left hand and wrist (HW-XR) for skeletal age estimation. The method most frequently employed is the Greulich and Pyle (GP) method. In addition, the so-called bone-specific techniques are also applied including the method of Tanner Whitehouse (TW) in the latest versions TW2 and TW3. AIM: To compare skeletal age and chronological age in a large sample of children and adolescents using GP, TW2 and TW3 methods in order to establish which of these is the most reliable for forensic purposes. MATERIAL AND METHODS: The sample consisted of 307 HW-XRs of Italian children or adolescents, 145 females and 162 males aged between 6 and 20 years. The radiographies were scored according to the GP, TW2RUS and TW3RUS methods by one investigator. The results' reliability was assessed using intraclass correlation coefficient. Wilcoxon signed-rank test and Student t-test were performed to search for significant differences between skeletal and chronological ages. RESULTS: The distributions of the differences between estimated and chronological age, by means of boxplots, show how median differences for TW3 and GP methods are generally very close to 0. Hypothesis tests' results were obtained, with respect to the sex, both for the entire group of individuals and people grouped by age. Results show no significant differences among estimated and chronological age for TW3 and, to a lesser extent, GP. The TW2 proved to be the worst of the three methods. CONCLUSIONS: Our results support the conclusion that the TW2 method is not reliable for AE for forensic purpose. The GP and TW3 methods have proved to be reliable in males. For females, the best method was found to be TW3. When performing forensic age estimation in subjects around 14 years of age, it could be advisable to use and associate the TW3 and GP methods.

Age estimation for forensic purposes in Italy: ethical issues.

Age assessment in children and young adults is a relevant medicolegal issue due to the gradual increase of persons devoid of proper identification documents in European countries. Because of the illegal immigration and growing crime rates among children and adolescents, age estimation for forensic purposes is often required. The scientific research and the extensive experience of forensic experts in the last decades focused on the use of radiographic methods addressed to evaluate the degree of skeletal or dental development as the most accurate parameters to estimate the chronological age of children and adolescents. This paper analyzes the ethical issues related to age estimation procedures based on radiographic methods, showing how the ethical principles of beneficence, nonmalevolence, justice, and autonomy may be guaranteed during the execution of the age assessment in forensic practice. The procedure might be conducted in accordance with international guidelines and protocols, though they need a higher homogenization and standardization. A strong collaboration between various scientific societies of professionals (forensic odontologists, forensic pathologists, forensic anthropologist, radiologists, pediatricians, and psychologists), who have been involved in age estimation for years, is needed to reach this goal.

Armillaria mellea induces a set of defense genes in grapevine roots and one of them codifies a protein with antifungal activity.

Grapevine root rot, caused by Armillaria mellea, is a serious disease in some grape-growing regions. Young grapevines start to show symptoms of Armillaria root rot from the second year after inoculation, suggesting a certain degree of resistance in young roots. We used a suppression subtractive hybridization approach to study grapevine's reactions to the first stages of A. mellea infection. We identified 24 genes that were upregulated in the roots of the rootstock Kober 5BB 24 h after A. mellea challenge. Real-time reverse-transcriptase polymerase chain reaction analysis confirmed the induction of genes encoding protease inhibitors, thaumatins, glutathione S-transferase, and aminocyclopropane carboxylate oxidase, as well as phase-change related, tumor-related, and proline-rich proteins, and gene markers of the ethylene and jasmonate signaling pathway. Gene modulation was generally stronger in Kober 5BB than in Pinot Noir plants, and in vitro inoculation induced higher modulation than in greenhouse Armillaria spp. treatments. The full-length coding sequences of seven of these genes were obtained and expressed as recombinant proteins. The grapevine homologue of the Quercus spp. phase-change-related protein inhibited the growth of A. mellea mycelia in vitro, suggesting that this protein may play an important role in the defense response against A. mellea.