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Simple Summary: In recent years, liquid biopsy has been introduced as a new method for the detection and management of cancer, but the studies on oral squamous cell carcinoma (OSCC) are lacking conclusive evidence. The aim of this study was to evaluate the expression of six circulating salivary and plasmatic miRNAs (-21, -31, -138, -145, -184, and -424) as diagnostic biomarkers in patients affected by OSCC and by oral potentially malignant disorders (OPMDs). Our results showed that liquid biopsy from saliva may be a useful tool for the identification of these biomarkers; in particular, miR-138 and miR-424 showed decreased expression levels in saliva samples in OSCC and OPMD patients compared to healthy controls. The introduction of liquid biopsy in daily clinical practice could revolutionize the approach to oral lesions by allowing the mass screening, stratification and monitoring of patients at risk, the monitoring of the response to treatment and the early identification of any recurrences. This study aims to evaluate the expression of salivary and plasmatic miRNAs as diagnostic biomarkers in patients with oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). A total of 25 patients were divided into three groups, according to their diagnosis: OSCC patients (n = 14); OPMDs patients (n = 6); and healthy controls (n = 5). At the time at diagnosis/enrolment, patients underwent salivary and plasmatic collection. The expression of miRNA -21, -31, -138, -145, -184, and -424 were evaluated by real-time PCR. An F-test and ANOVA test were performed to evaluate the miRNA levels (significance at p < 0.05). By comparing miRNA expression levels from saliva, a statistically significant difference emerged in the expression of miR-138 and miR-424 between the three groups (p < 0.05). In particular, these two miRNAs showed decreased expression levels in saliva samples from OSCC and OPMD patients compared to those from healthy controls. On the other hand, miRNA expression levels in plasma were low in all the groups, and no statistically significant differences were found. Overall, our results showed that liquid biopsy from saliva may be a useful tool for the identification of diagnostic molecular biomarkers in OSCC and OPMDs. [ABSTRACT FROM AUTHOR]

Background: Even if robotic assisted total knee arthroplasty (RATKA) is a widely used technique, there is still a gap of knowledge about whether this technology is effective in improving the patient utility. This measure is of paramount importance for conducting cost effectiveness analysis. The aim of this study was to compare the utility measure derived from self-reported outcomes questionnaires in patients who underwent RATKA compared to patients who underwent the manual surgery. Methods: We compared 72 patients operated with a robotic technique with 70 operated with traditional technique. The utility data were collected with the WOMAC (Western Ontario and McMaster University Osteoarthritis index) self-administrated questionnaire that investigates pain, stiffness and functionality of the patients, an then mapped to a utility value through a validated transforming function. We performed three surveys: the first one before the intervention (t0), the second one 1 year after the surgery (t1) and the third one at the 2 year follow up (t2). Results: we observed higher utility values in both groups. In detail, the mean utility score in the RATKA group increased from 0.37 to 0.71 (t1) and 0.78 (t2), while in the conventional group it increased from 0.41 to 0.78 (t1) and 0.78 (t2). The fixed effect coefficients of t1 and t2 were found to be 0.37 and 0.363 (p < 0.001 for both). The coefficient of the robotic technique, along with its interaction with the t1 and t2 time effect was non-significant. Conclusions: Even if at t1 the utility of patient who underwent RATKA were lower, at longer follow up (t2) we found no significant difference compared to traditional technique, leaving the superiority of robotic assisted technique yet to be proved. Our results may be useful for calculating the gained or lost Quality Adjusted Life Years (QALYs), so that the health care system (or an insurance company) could make an appropriate decision whether to fund the robotic approach or not, after a careful assessment of the incremental costs incurred. [ABSTRACT FROM AUTHOR]

Most researchers have assessed cognitive functions in post-COVID-19 patients by means of screening tools and found cognitive sequelae in addition to anxiety, stress, depression, and a reduced quality of life (QoL). This study was aimed at investigating cognitive and psychological sequelae in patients admitted to the intensive care unit (ICU) six months (t6) and one year (t12) after discharge from the hospital, the impact of critical illness on well-being and QoL, and the protective role of cognitive reserve (CR). Twenty-three ICU patients underwent an extensive neuropsychological test battery at t6 and t12; a healthy control group underwent the same evaluation. Patient scores were compared with control scores: patients reported significantly lower scores in visual–spatial functions, both at t6 (U = 122; p = 0.033) and at t12 (U = 70; p = 0.003), and higher levels of anxiety (U = 126; p = 0.043) and depression (U = 97; p = 0.005) at t6; the levels of anxiety decreased at t12, while only depression symptoms persisted (U = 99.5; p = 0.025). Regarding the QoL, patients obtained lower scores in the physical component of QoL, both at t6 (U = 72; p = 0.008) and at t12 (U = 56.5; p = 0.005). Few and moderate correlations emerged between isolated cognitive functions and CR and the length of hospital stay. The results suggest a prevalent visual–spatial involvement, the medium- and long-term persistence of psychological sequelae, and a reduced QoL in ICU patients. [ABSTRACT FROM AUTHOR]

The main objectives of the present prospective clinical study were to evaluate the survival and success rates of implant-supported zirconia single crowns fabricated with a full digital workflow for the rehabilitation of mono- and bilateral agenesis of maxillary lateral incisors after 2 years of clinical function; biological and technical parameters affecting the prosthetic restorations were recorded, as well as the patient-satisfaction score. Twenty-two patients showing mono- or bilateral agenesis of the maxillary lateral incisors were included in this study, and a total of 30 narrow-diameter implants were inserted. Thirty screw-retained monolithic cubic zirconia single crowns with internal connections were fabricated. Objective outcome evaluations were performed by means of the Functional Implant Prosthodontic Score, whereas the patient-satisfaction score was evaluated using Visual Analog Scales. Descriptive statistics were performed and the Kaplan–Meier analysis was run to analyze time-to-event data. After 2 years of clinical function, the overall FIPS found in the present study was 9.2, whereas the average patient-satisfaction score was 8.7. The Kaplan–Meier analysis at the 2-year follow-up reported a cumulative survival rate of 100% and a cumulative success rate of 93.3%. The implant-prosthetic rehabilitation with a full digital workflow proved to be an effective and reliable procedure for the functional and aesthetic treatment of the agenesis of maxillary lateral incisors in the short-term. Clinical investigations with wider sample populations and longer observational follow-ups could be useful to validate, in the long-term, the clinical outcomes of the present prospective clinical study. [ABSTRACT FROM AUTHOR]

Background: Neonatal cerebral stroke includes a range of focal and multifocal ischemic and hemorrhagic brain lesions, occurring in about one of 3000 live births. More than 50% of children with neonatal stroke develop adverse outcomes, mainly unilateral cerebral palsy. Asymmetries in segmental movements at three months have been proven to be an early sign of CP in infants with unilateral brain damage. Recognition of additional early signs could enhance prognostic assessment and enable an early and targeted intervention. Aim: The aim of the study was to assess early signs of CP in infants with arterial cerebral stroke through the General Movements Assessment and the Motor Optimality Score—Revised (MOS-R). Method: Twenty-four infants born at term (12 females and 12 males) diagnosed with ACS, and 24 healthy infants (16 females and 8 males) were assessed. The GMs (fidgety movements) and MOS-R were assessed from videos recorded at 11–14 weeks of post-term age. Cognitive and motor outcomes were assessed at 24 months using the Griffiths III developmental quotient and Amiel-Tison neurological examination. The gross motor function classification system expanded and revised (GMFCS-E&R) was adopted to categorize CP. Results: Among infants with ACS, 21 (87.5%) developed unilateral CP. Most of them showed non-disabling CP (14 had GMFCS-E&R grade 1 [66.6%], 6 grade 2 [28.6%], and 1 grade 5 [4.8%]). Fidgety movements (FMs) were absent in 17 (70.8%), sporadic in 4 (16.7%) infants, and normal in 3 (12.5%). Segmental movement asymmetry was found in 22/24 (91.7%). According to the MOS-R, motor items (kicking, mouth movements), postural patterns (midline centered head, finger posture variability), and movement character (monotonous and stiff) were statistically different among infants with ACS and healthy infants. The MOS-R median global score was lower in the group with ACS compared to the control group (6 vs 26; p < 0.01). FMs, segmental movement asymmetry, and MOS-R global score were significantly correlated with abnormal outcome. MOS-R global scores less than or equal to 13 had 100% specificity and sensitivity in predicting GMFCS-E&R grade ≥ 2 CP in infants with ACS. Conclusions: The rate of CP was high among infants with ACS, but in most cases it showed low GMFCS-E&R grades. The study highlighted a significant correlation between MOS-R, together with absent FMs and unilateral CP in infants with ACS. Moreover, the MOS-R showed high sensitivity and specificity in the prediction of CP. Combined assessment of FMs and MOS-R could help to better identify infants at high risk of developing UCP in a population of infants with ACS. Early identification of precocious signs of unilateral CP is fundamental to providing an early individualized intervention. [ABSTRACT FROM AUTHOR]

Attention deficit hyperactivity disorder (ADHD) is among the most prevalent disorders in children and is frequently linked with motor difficulties that can impact both daily motor tasks and overall developmental trajectories. The objective of this study was to analyse the association between gross motor skills and ADHD symptoms. Using a cross-sectional research design, data were collected from a sample of primary school children (N = 2677; mean age = 8.58 years, SD = 1.49 years). The Gross Motor Development-3 Test (TGMD-3) was employed to assess participants' gross motor skills, whereas the ADHD Rating Scale (SDAI), completed by teachers, evaluated ADHD symptoms through two subscales: inattention and impulsivity/hyperactivity. The results revealed an association between motor development and ADHD symptoms, with greater proficiency in gross motor skills correlating with lower symptoms reported on the SDAI. Logistic regression analyses indicated that the TGMD-3 was significantly associated with the risk of ADHD in matched samples of at-risk children and controls. The evaluation of gross motor development proves to be a useful tool for monitoring global development, paying attention to any critical issues, particularly in relation to the variables of inattention and hyperactivity. [ABSTRACT FROM AUTHOR]

Simple Summary: Rehabilitation might play a crucial role in malignant pleural mesothelioma (MPM), but its role is still debated in MPM patients. The intervention comprised multidisciplinary educational sessions, physical rehabilitation, and respiratory physiotherapy. Feasibility was evaluated based on dropout rates, adherence to the rehabilitation program, safety, and patient-reported outcomes. In light of the current evidence, we have conducted a pilot study to assess the feasibility of tailored pulmonary rehabilitation in terms of physical and respiratory function in MPM. Twelve patients were initially enrolled, with seven completing the study. High adherence to physical (T1: 93.43%, T2: 82.56%) and respiratory (T1: 96.2%, T2: 92.5%) rehabilitation was observed, with minimal adverse events reported. Patient satisfaction remained high throughout the study (GPE scores at T1: 1.83 ± 1.17; T2: 2.0 ± 1.15), with improvements noted in physical function, pain management, and health-related quality of life. Despite its promising outcomes, further research with larger samples is warranted to validate its efficacy and integrate rehabilitation as a component into the multidisciplinary management of MPM. Malignant pleural mesothelioma (MPM) represents a significant health burden, with limited treatment options and poor prognosis. Despite advances in pharmacological and surgical interventions, the role of rehabilitation in MPM management remains underexplored. This study aims to assess the feasibility of a tailored pulmonary rehabilitation intervention addressing physical and respiratory function in MPM patients. A prospective pilot study was conducted on surgically treated MPM patients referred to a cardiopulmonary rehabilitation service. The intervention comprised multidisciplinary educational sessions, physical rehabilitation, and respiratory physiotherapy. Feasibility was evaluated based on dropout rates, adherence to the rehabilitation program, safety, and patient-reported outcomes. Twelve patients were initially enrolled, with seven completing the study. High adherence to physical (T1: 93.43%, T2: 82.56%) and respiratory (T1: 96.2%, T2: 92.5%) rehabilitation was observed, with minimal adverse events reported. Patient satisfaction remained high throughout the study (GPE scores at T1: 1.83 ± 1.17; T2: 2.0 ± 1.15), with improvements noted in physical function, pain management, and health-related quality of life. However, some issues, such as time constraints and lack of continuous supervision, were reported by participants. This pilot study demonstrates the feasibility and potential benefits of a tailored pulmonary rehabilitation intervention in MPM patients. Despite its promising outcomes, further research with larger samples is warranted to validate its efficacy and integrate rehabilitation as a component into the multidisciplinary management of MPM. [ABSTRACT FROM AUTHOR]

Background: Music Therapy (MT) is a non-pharmacological, art-based intervention that employs music experiences within a therapeutic alliance to attend to clients' physical, emotional, cognitive, and social requirements. This is the first study aiming at investigating the impact of MT on the psychological facets of children suffering from cancer. Methods: The study, combining the AQR and m-YPAS assessment tools, evaluated behavioral, sound–musical, and interactive parameters in pediatric oncology patients undergoing MT sessions during hospitalization. Fifty patients admitted to the Paediatric Oncology and Haematology Unit at Policlinico S. Orsola Hospital in Bologna, Italy, were enrolled, irrespective of their treatment regimen. Data collection occurred on the first day of the MT session between 3 p.m. and 5 p.m., with observations conducted by independent observers. In addition to traditional statistical analysis, network analysis was used to explore the combined interactions of all parameters, effectively discerning the distinctive roles played by each one during therapy sessions and their influence on all others. Results: Network analysis highlighted distinct patterns of interactions among parameters during the various sessions, emphasizing the role of positive emotions and a calm setting, the child's ability to take the initiative in sessions, their sense of agency, and the parent's role in guiding them. Significant differences were recorded at each time point between all variables considered. Conclusions: The results of this innovative study may pave the way for future multicenter studies aimed at further exploring the role of MT in children undergoing both curative and palliative treatments for cancer. [ABSTRACT FROM AUTHOR]

Background and aim: First, to compare somatosensory evoked potentials (SEPs) in preterm newborns without major brain injury studied at term equivalent age (TEA) with a term historical control group. Second, to investigate the impact of pain exposure during the first 28 days after birth on SEPs. Third, to evaluate the association between SEPs and Bayley-III at 2 years corrected age (CA). Methods: Infants born at <32 weeks' gestational age (GA) were studied with continuous-SEPs. First, SEP differences between preterm and term infants were analyzed. Second, regression analyses were conducted to explore the association between SEPs and painful procedures, and then between SEPs and neurodevelopment. Results: 86 preterm infants were prospectively enrolled. Preterm infants exhibited prolonged N1 latencies, central conduction times (CCTs), lower N1-P1 amplitudes, and more recurrently abnormal SEPs compared to term infants. Higher pain exposure predicted longer N1 latency and slower CCT (all p < 0.005), adjusting for clinical risk factors. Younger GA and postmenstrual age (PMA) at SEP recording were associated with longer N1 latency and lower N1-P1 amplitude (all p < 0.005). A normal SEP at TEA positively predicted cognitive outcome at 2 years CA (p < 0.005). Conclusion: Pain exposure and prematurity were risk factors for altered SEP parameters at TEA. SEPs predicted cognitive outcome. [ABSTRACT FROM AUTHOR]

Chronic school absenteeism is a common problem in childhood and adolescence, and it is frequently observed in patients with somatic symptom and related disorders (SSRDs). This study aimed to determine whether and to what extent the presence of school absenteeism may be a risk factor for the diagnosis of SSRDs in hospitalised patients. This matched cohort study included children and adolescents aged between 8 and 17 years, admitted to the paediatric ward of the IRCCS Burlo Garofolo in Trieste from 2021 to 2023, who were divided into two groups, the first including children with at least 15 days of absence from school for medical reasons and the second including children with regular school attendance, matched to the former group by age and sex. We consecutively enrolled 70 patients, 35 in the absentee group and 35 in the control group. In the absentee group, 30/35 (85.7%) patients were diagnosed with an SSRD, while in the control group, 1/35 (2.9%) was diagnosed with an SSRD. The absentee group had a 30-fold higher risk of being diagnosed with SSRDs than the control group (RR = 30 [95% CI = 4.3–208]; p < 0.001). This study shows that in hospitalised children, a history of school absenteeism of more than two weeks is an important risk factor for the diagnosis of SSRDs. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has emerged as the primary global health challenge of the new millennium. Understanding its impact on health systems and learning from these experiences are crucial for improving system resilience against future health crises. This paper examines hospitalizations related to COVID-19 in Italy from 2020 to 2021, with a specific focus on the costs associated with these admissions. Design and methods: This is a retrospective, population-based study of Italian hospitalizations of patients diagnosed with COVID-19 during the 2020–2021 period, using data extracted from the National Hospital Discharge Registry. The outcome variables considered include hospital admissions, costs, and length of stay. Results: In Italy, hospitalizations for COVID-19 totaled 357,354 in 2020 and 399,043 in 2021, with the transfer rate being three times higher than that of other patients. Hospitalizations were predominantly concentrated in the northern regions, especially during the first year. Mortality rates increased with age, while hospitalization rates peaked in the youngest and oldest age groups. The financial impact of COVID-19 hospitalizations was approximately €3.1 billion in 2020 and €3.6 billion in 2021. The cost per admission was around €8000 for standard care and €24,000 for intensive therapy in both years. Conclusion: Conducting a cost-benefit analysis of implementing a protective pad around the entire health system, which leverages networks of family doctors and nurses connected in real-time, could be an important step in strengthening health system resilience. [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening condition that affects 1.2 million children annually. Although there are several criteria for diagnosing this condition, signs are often nonspecific, and identifying sepsis is challenging. In this context, presepsin (P-SEP) seems to be a promising new biomarker since its plasma levels increase earlier than other sepsis-related proteins and its measurement is faster. We enrolled 157 minors who presented to the Pediatric Emergency Department of Agostino Gemelli Hospital with fever and suspected sepsis. Biochemical, anamnestic, and clinical data were collected. Viral agents were identified as the causative factor in 64 patients, who had an average P-SEP value of 309.04 pg/mL (SD ± 273.2), versus an average P-SEP value of 526.09 pg/mL (SD ± 657) found in 27 bacterial cases (p value: 0.0398). Four cases of overt sepsis had an average P-SEP value of 3328.5 pg/mL (SD ± 1586.6). The difference in P-SEP levels in viral versus bacterial infections was found to be statistically significant; therefore, P-SEP may have a central role in the evaluation of febrile children, helping clinicians distinguish between these two etiologies. Furthermore, amongst the cases of confirmed sepsis, P-SEP was always greater than 2000 pg/mL, while C-reactive protein and procalcitonin values appeared lower than what was considered significant. [ABSTRACT FROM AUTHOR]

Background: The SARS-CoV-2 pandemic has significantly affected the pediatric population. Long-term sequelae (Long COVID-19) may particularly involve the central nervous system, with possible effects on psychological well-being and quality of life (QoL), aspects that were already influenced by the restrictive measures and general social impact of the pandemic. Methods: We conducted a cross-sectional survey that aims at investigating the neuropsychological effects and the QoL impairment of SARS-CoV-2 on a cohort of children and adolescents in the Abruzzo region (Italy). A questionnaire was submitted to caregivers with the help of the PEDIATOTEM platform. A control group of healthy subjects was also included to distinguish between the effects of infection from the general influence of the pandemic. Results: A total of 569 subjects responded: 396 COVID-19 patients (99 of whom had Long COVID-19) and 111 controls. After the pandemic, when compared with the COVID-19 group, the controls reported significantly increased appetite, sleeping habits, and time spent remotely with friends and a reduction in physical activity and time spent in person with friends. A significant higher rate of controls asked for psychological/medical support for emotional problems. On the other hand, the Long COVID-19 group showed more fatigue and emotional instability with respect to non-Long-COVID-19 subjects. No differences in QoL results (EuroQOL) were found between the COVID-19 patients and controls, while the Long-COVID-19 subgroup showed significantly higher rates of pain/discomfort and mood instability, as confirmed by the analysis of variation of responses from the pre-COVID-19 to the post-COVID-19 period. Conclusions: Among COVID-19 patients, neuropsychological and QoL impairment was more evident in the Long COVID-19 subgroup, although emotional and relational issues were also reported by uninfected patients, with a growing request for specialist support as a possible consequence of social restriction. [ABSTRACT FROM AUTHOR]

Simple Summary: This analysis of the ARISE study, a multicenter observational cohort trial, is based on a modern statistical approach, integrating the Least Absolute Shrinkage and Selection Operator algorithm and the Classification and Regression Tree analysis. The results of this study show significant shortcomings in pain management for breast cancer patients undergoing radiotherapy, particularly highlighting that younger patients and those with non-neoplastic pain, especially in southern and central Italy, experience even poorer pain management. This research underscores the urgent need for tailored pain management strategies in breast cancer patients, taking into account patient age, pain type, and geographic disparities to enhance care quality and outcomes for subjects across different regions. Background: The primary objective of this study was to assess the adequacy of analgesic care in radiotherapy (RT) patients, with a secondary objective to identify predictive variables associated with pain management adequacy using a modern statistical approach, integrating the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and the Classification and Regression Tree (CART) analysis. Methods: This observational, multicenter cohort study involved 1387 patients reporting pain or taking analgesic drugs from 13 RT departments in Italy. The Pain Management Index (PMI) served as the measure for pain control adequacy, with a PMI score < 0 indicating suboptimal management. Patient demographics, clinical status, and treatment-related factors were examined to discern the predictors of pain management adequacy. Results: Among the analyzed cohort, 46.1% reported inadequately managed pain. Non-cancer pain origin, breast cancer diagnosis, higher ECOG Performance Status scores, younger patient age, early assessment phase, and curative treatment intent emerged as significant determinants of negative PMI from the LASSO analysis. Notably, pain management was observed to improve as RT progressed, with a greater discrepancy between cancer (33.2% with PMI < 0) and non-cancer pain (73.1% with PMI < 0). Breast cancer patients under 70 years of age with non-cancer pain had the highest rate of negative PMI at 86.5%, highlighting a potential deficiency in managing benign pain in younger patients. Conclusions: The study underscores the dynamic nature of pain management during RT, suggesting improvements over the treatment course yet revealing specific challenges in non-cancer pain management, particularly among younger breast cancer patients. The use of advanced statistical techniques for analysis stresses the importance of a multifaceted approach to pain management, one that incorporates both cancer and non-cancer pain considerations to ensure a holistic and improved quality of oncological care. [ABSTRACT FROM AUTHOR]

The EASY-NET network program (NET-2016-02364191)—effectiveness of audit and feedback (A&F) strategies to improve health practice and equity in various clinical and organizational settings), piloted a novel and more structured A&F strategy. This study compared the effectiveness of the novel strategy against the sole periodic dissemination of indicators in enhancing the appropriateness and timeliness of emergency health interventions for patients diagnosed with acute myocardial infarction (AMI) and ischemic stroke in the Lazio Region. The efficacy of the intervention was assessed through a prospective quasi-experimental design employing a pre- and post-intervention (2021–2022) comparison with a control group. Participating hospitals in the Lazio Region, where professional teams voluntarily engaged in the intervention, constituted the exposed group, while the control group exclusively engaged in routine reporting activities. Effectiveness analysis was conducted at the patient level, utilizing regional health information systems to compute process and outcome indicators. The effectiveness of the intervention was evaluated using difference-in-difference models, comparing pre- and post-intervention periods between exposed and control groups. Estimates were calculated in terms of the difference in percentage points (PP) between absolute risks. Sixteen facilities for the AMI pathway and thirteen for the stroke pathway participated in the intervention. The intervention yielded a reduction in the proportion of 30-day readmissions following hospitalization for ischemic stroke by 0.54 pp in the exposed patients demonstrating a significant difference of −3.80 pp (95% CI: −6.57; −1.03; 5453 patients, 63.7% cases) in the exposed group compared to controls. However, no statistically significant differences attributable to the implemented A&F intervention were observed in other indicators considered. These results represent the first evidence in Italy of the impact of A&F interventions in an emergency setting, utilizing aggregated data from hospitals involved in the Lazio Region's emergency network. [ABSTRACT FROM AUTHOR]

Previous research has highlighted the positive impact of greater health-related quality of life (Hr-QoL) and subjective well-being (SWB) on chronic diseases' severity and progression. There is a paucity of studies investigating the long-term trajectories of these variables among hypertensive patients. The present study aims to investigate the relationships between psychological variables (Type A and D personality, locus of control—LoC, self-esteem, and trait anxiety) with SWB and Hr-QoL in patients with hypertension and comorbid metabolic syndrome. A total of 185 volunteer patients (130 males, 70.3%; mean age 54 ± 10.93) were enrolled. Patients filled out measures of Hr-QoL and SWB, LoC, and self-esteem at three time points—Type A and D behaviors and anxiety measures only at baseline. Analyses were run through two-level hierarchical mixed models with repeated measures (Level 1) nested within participants (Level 2), controlling for sociodemographic and clinical confounders. Neither Hr-QoL nor SWB changed over time. Patients with greater self-esteem and internal LoC (and lower external LoC) increased their SWB and Hr-QoL up to 1-year follow-up. A greater Type A behavior and trait anxiety at baseline predicted a longitudinal increase in most of the dependent variables. Results suggest that it could be useful to tailor interventions targeting specific variables to increase Hr-QoL and SWB among hypertensive patients. [ABSTRACT FROM AUTHOR]

The removable partial denture, despite new technologies and new materials, continues to play a significant role in clinical dental practice. The purpose of the following study was to evaluate the design of new retention devices in Kennedy class II scenarios. For the study of "lamellar" retentive devices, four prosthetists were chosen. According to inclusion and exclusion criteria, prosthetists selected 16 patients (8 women and 8 men) whose upper arches had to be rehabilitated using a removable partial prosthesis. The results showed that the parameters taken into consideration, such as satisfaction, stability, aesthetics, and retention, had an average score that was higher than 3.30 (range 1–4), with an average standard deviation of 0.6225 in the four parameters, indicative that the data were relatively homogeneous and coherent. In conclusion, we can state that the skeletonized prosthesis with lamellar retentions, designed for Kennedy class II scenarios, has shown high acceptance in selected patients. [ABSTRACT FROM AUTHOR]

In this study, we examined the effects of memory training on cognitive function and depressive symptoms in a cohort of 794 healthy adults aged 50 years or older. Participants were divided into an active intervention group and a passive intervention group, with various cognitive measures assessed over a one-year period. Univariate analysis revealed that the active intervention group consistently outperformed the passive group in measures of memory self-perception (Memory Complaint Questionnaire—MACQ), depressive symptoms (Geriatric Depression Scale—GDS-4), verbal memory and recall ability (A3LP), and verbal fluency (VF). Significant differences in MACQ scores were observed between the two groups at all time points, indicating enhanced memory self-perception in the active group. GDS-4 scores consistently favored the active group, suggesting a reduction in depressive symptoms. A3LP scores demonstrated that the active group had better verbal memory and recall abilities. VF scores consistently favored the active group, indicating superior language skills and cognitive flexibility. Linear regression model and mixed linear regression model reinforced these findings, with highly significant interaction effects observed between the active/passive group, gender, age, education, and time. These effects were particularly pronounced for MACQ and A3LP scores, indicating the combined impact of these factors on memory self-perception and verbal memory. This study highlights the positive impact of memory training intervention on cognitive function and depressive symptoms in older adults and underscores the importance of considering gender, age, and education in cognitive interventions. Notably, these benefits persist for up to six months from the end of the program. The results provide valuable insights into cognitive changes in aging populations and suggest that tailored memory training programs can yield significant improvements. [ABSTRACT FROM AUTHOR]

Few studies have evaluated the effect of bovine lactoferrin (bLf) on reducing respiratory infections in preschool children. This randomized controlled trial evaluated the effect of bLf in preschool children with recurrent respiratory infections. Participants were randomly assigned bLf (n = 25) or control (n = 25). Outcomes included respiratory infection episodes (RIEs), symptom duration, school absence and medication. Fifty children aged 4.2 ± 0.1 years were included. During the active 4-month phase, median number of RIEs was reduced by 50% in the bLf group [1-episode, interquartile range (IQR): 0–2] vs. control (2, IQR: 1–3; p = 0.02). The proportion of participants with >3 RIEs was significantly lower in bLf (n = 1, 4%) vs. control (n = 7, 28%) with 80% lower odds of upper RIEs in the bLf arm (odds ratio: 0.20, 95% CI:0.06–0.74, p = 0.015). The duration of symptoms (3 vs. 6, p = 0.009) and days absent from school (3 vs. 6, p = 0.15) were lower in the active arm. Over the 2-month follow-up, no significant differences were observed between groups for infection episodes, symptom duration or school absence. However, bLf-treated children received significantly less corticosteroids over the entire 6-month study period (32% vs. 60%; p = 0.047). bLf supplementation significantly reduced the frequency and duration of RIEs in children with decreased corticosteroid use. [ABSTRACT FROM AUTHOR]

Introduction: Fever is among the most common reason for medical assessment and antibiotic prescription in practice. The aim of this study was to evaluate positive and negative predictive values of rapid nasopharyngeal swabs for respiratory pathogens to discriminate viral from bacterial infections. Methods: We prospectively tested children with signs and/or symptoms of infections (e.g., fever, cough, wheezing, suspected urinary tract infection) admitted to a paediatric department. Following discharge, clinical phenotypes were assigned defining a cohort of children having probable/certain viral infection, probable/certain bacterial infection, other inflammatory conditions or healthy controls. Results: In this study, 190 children were enrolled (50.5% females, median age 30.5 (8–86) months). In total, 102 patients (53.7%) were affected by respiratory viral infections, 16 (8.4%) by bacterial infections, 29 (15.3%) were healthy controls and 43 (22.6%) were affected by another pathological condition manifested with fever. In total, 84.3% of patients classified as viral infection tested positive for viruses, compared with 18.8% of patients with bacterial infection (p < 0.001), 18.6% of patients with other condition (p < 0.001) and 17.2% of control patients (p < 0.001). The positive predictive value of NPSs in the diagnosis of viral infection was 88.6% and the negative predictive value was 75.0%. Conclusion: Our findings suggest that rapid NPS tests for respiratory viruses are a useful tool to confirm viral infections in children with fever and improve antibiotic use. [ABSTRACT FROM AUTHOR]

Background: Despite the increasing interest in biologics for the management of allergic diseases, sparse real-world data are still available in the pediatric population. This study aimed to evaluate the early real-life efficacy and safety of omalizumab for patients with moderate-to-severe asthma and chronic spontaneous urticaria (CSU), and Dupilumab for patients with moderate-to-severe atopic dermatitis (AD). Methods: A prospective study enrolling children aged 6–18 years was designed to assess the efficacy and safety of biologic drugs at 16 weeks of treatment (T1). The effectiveness was measured using validated questionnaires (ACQ-5 for asthma, UAS7 for CSU, and EASI score for AD). Secondary outcome measures included reductions in inhaled corticosteroid (ICS) dosages, asthma-related hospitalizations/exacerbations, and quality of life (QoL) indicators (iNRS, sNRS, DLQI/cDLQI) for CSU and AD. Safety was expressed according to the descriptions of adverse events provided by EMA and FDA. Results: The study cohort consisted of eighteen children (mean age 12.9 ± 3.4 years). The omalizumab treatment significantly reduced ACQ-5 and UAS7 scores (p = 0.002 and p < 0.001, respectively). In patients with asthma, decreased ICS dosage and hospitalization/exacerbation rates were observed. QoL parameters significantly improved in CSU and AD patients. No severe adverse events were reported for either treatment. Conclusions: Our findings validate omalizumab and dupilumab as effective and safe therapeutic options for managing moderate-to-severe allergic diseases in children and adolescents. [ABSTRACT FROM AUTHOR]

In children, the factors that influence COVID-19 disease and its medium- and long-term effects are little known. Our investigation sought to evaluate the presence of comorbidity factors associated with respiratory long COVID manifestations in children and to study ultrasound abnormalities following SARS-CoV-2 infection. Children, who arrived at the 'Respiratory Diseases of Pediatric Interest Unit' at the Department of Woman, Child, and General and Specialized Surgery of the University of Campania 'Luigi Vanvitelli', were selected during the timeframe from September 2021 to October 2022. The children were diagnosed with a SARS-CoV-2 infection that occurred at least one month before the visit. All patients followed a COVID-19 follow-up protocol, developed by the Italian Society of Pediatric Respiratory Diseases (SIMRI), which included: collection of data regarding SARS-CoV-2 illness and history of known respiratory and allergic diseases; physical examination; BMI assessment; baseline spirometry and after bronchodilation test; six-minute walking test; and lung ultrasound (LUS). In a cohort of 104 participants with respiratory long COVID symptoms (64.7% male, average age 8.92 years), 46.1% had fever with other symptoms, and 1% required hospitalization. BMI analysis showed 58.4% of the cohort was overweight. The LUS was positive in 27.0% of cases. A significant BMI association was observed with COVID-19 symptoms and LUS score (p-value < 0.05). No associations were found with asthma or atopy. [ABSTRACT FROM AUTHOR]

Simple Summary: The lung immune prognostic index (LIPI) is a valuable tool for reflecting the systemic inflammatory status by combining lactate dehydrogenase (LDH) levels and derived neutrophil/lymphocyte ratio (dNLR) values. In advanced non-small cell lung cancer, the LIPI score before starting PD-(L)1 checkpoint inhibitors can predict disease outcomes through three risk categories. Our hypothesis is that changes in the LIPI score during treatment can predict the likelihood of immune-related adverse events (irAEs). Interestingly, patients who experienced a shift towards a more favorable prognostic category in their LIPI score were at a significantly higher risk of developing irAEs. Furthermore, the dynamic variations in LIPI score provided prognostic insights into overall survival outcomes. In advanced cancer patients undergoing immune checkpoint blockade, the burden of immune-related adverse events (irAEs) is high. The need for reliable biomarkers for irAEs remains unfulfilled in this expanding therapeutic field. The lung immune prognostic index (LIPI) is a noninvasive measure of systemic inflammation that has consistently shown a correlation with survival in various cancer types when assessed at baseline. This study sought to determine whether early changes in the LIPI score could discriminate the risk of irAEs and different survival outcomes in advanced non-small cell lung cancer (NSCLC) patients receiving PD-(L)1 blockade-based therapies. We included consecutive patients diagnosed with metastatic NSCLC who received pembrolizumab, nivolumab, or atezolizumab as second-line therapy following platinum-based chemotherapy, or first-line pembrolizumab either alone or in combination with platinum-based chemotherapy. The LIPI score relied on the combined values of derived neutrophil/lymphocyte ratio (dNLR) and lactate dehydrogenase. Their assessment at baseline and after two cycles of treatment allowed us to categorize the population into three subgroups with good (LIPI-0), intermediate (LIPI-1), and poor (LIPI-2) prognosis. Between April 2016 and May 2023, we enrolled a total of 345 eligible patients, 165 (47.8%) and 180 (52.2%) of whom were treated as first- and second-line at our facility, respectively. After applying propensity score matching, we considered 83 relevant patients in each cohort with a homogeneous distribution of all characteristics across the baseline LIPI subgroups. There was a noticeable change in the distribution of LIPI categories due to a significant decrease in dNLR values during treatment. Although no patients shifted to a worse prognosis category, 20 (24.1%) transitioned from LIPI-1 to LIPI-0, and 7 (8.4%) moved from LIPI-2 to LIPI-1 (p < 0.001). Throughout a median observation period of 7.3 (IQR 3.9–15.1) months, a total of 158 irAEs (63.5%) were documented, with 121 (48.6%) and 39 (15.7%) patients experiencing mild to moderate and severe adverse events, respectively. Multivariate logistic regression analysis showed that the classification and changes in the LIPI score while on treatment were independent predictors of irAEs. The LIPI-0 group was found to have significantly increased odds of experiencing irAEs. Following a median follow-up period of 21.1 (95% CI 17.9–25.8) months, the multivariable Cox model confirmed LIPI categorization at any given time point as a significant covariate with influence on overall survival, irrespective of the treatment line. These findings suggest that reassessing the LIPI score after two cycles of treatment could help pinpoint patients particularly prone to immune-related toxicities. Those who maintain a good LIPI score or move from the intermediate to good category would be more likely to develop irAEs. The continuous assessment of LIPI provides prognostic insights and could be useful for predicting the benefit of PD-(L)1 checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Breast cancer treatments can elicit negative kinesiological side effects concerning both the posture and functional status of breast cancer survivors. As our body is functionally organized in myofascial meridians, physical exercise practice should favor a whole-body approach rather than a local one. The aim of the study was to investigate and compare the effects of two whole-body disciplines, i.e., adapted Nordic Walking and myofascial exercise, on the flexibility and strength performances in BCS. One hundred and sixty breast cancer survivors were trained three times per week for 12 weeks through adapted Nordic Walking or myofascial exercise. Handgrip, sit and reach, back scratch, and single leg back bridge tests and body composition were assessed at the beginning and completion of the training period. Linear mixed models showed no significant changes in body composition, whereas flexibility (p < 0.001), strength (p < 0.001), and muscle quality index (p = 0.003) changed independently from the treatment. When data modification has been analyzed according to sub-sample membership, no significant differences have been observed. Age, radiation therapy, and chemotherapy seem to have independent effects on several investigated variables. Twelve weeks of adapted myofascial exercise and Nordic Walking led to significant changes in flexibility, strength, and muscle quality in breast cancer survivors, with no apparent superiority of one approach over the other. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer patients frequently experience pain, impacting their quality of life. Unfortunately, pain management in those referred for radiotherapy (RT) is often insufficient, with limited research in this area. This study aimed to assess the adequacy and effectiveness of pain management and identify factors affecting them in cancer patients referred for RT. We observed 1042 cancer outpatients and found that 42.9% did not receive adequate pain management. Specifically, 72% of patients referred for palliative RT and 75% of those referred for curative RT experienced inadequate or ineffective analgesic therapy. Patients undergoing palliative RT, those with poorer general health, those with cancer-related pain, and those treated in Northern Italy had higher odds of receiving adequate pain management. Our findings highlight the need for educational and organizational strategies to address this issue and suggest that early palliative RT referral can improve pain management and treatment outcomes for cancer patients. Background: Pain is a prevalent symptom among cancer patients, and its management is crucial for improving their quality of life. However, pain management in cancer patients referred to radiotherapy (RT) departments is often inadequate, and limited research has been conducted on this specific population. This study aimed to assess the adequacy and effectiveness of pain management when patients are referred for RT. Moreover, we explored potential predictors of adequate pain management. Methods: This observational, prospective, multicenter cohort study included cancer patients aged 18 years or older who were referred to RT departments. A pain management assessment was conducted using the Pain Management Index (PMI), calculated by subtracting the pain score from the analgesic score (PMI < 0 indicated inadequate pain management). Univariate and multivariate analyses were performed to identify predictors of adequate pain management. Results: A total of 1042 cancer outpatients were included in the study. The analysis revealed that 42.9% of patients with pain did not receive adequate pain management based on PMI values. Among patients with pain or taking analgesics and referred to palliative or curative RT, 72% and 75% had inadequate or ineffective analgesic therapy, respectively. The odds of receiving adequate pain management (PMI ≥ 0) were higher in patients undergoing palliative RT (OR 2.52; p < 0.001), with worse ECOG-PS scores of 2, 3 and 4 (OR 1.63, 2.23, 5.31, respectively; p: 0.017, 0.002, 0.009, respectively) compared to a score of 1 for those with cancer-related pain (OR 0.38; p < 0.001), and treated in northern Italy compared to central and southern of Italy (OR 0.25, 0.42, respectively; p < 0.001). Conclusions: In this study, a substantial proportion of cancer patients referred to RT departments did not receive adequate pain management. Educational and organizational strategies are necessary to address the inadequate pain management observed in this population. Moreover, increasing the attention paid to non-cancer pain and an earlier referral of patients for palliative RT in the course of the disease may improve pain response and treatment outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is one of the most common oncological diseases among women in Western Countries and Italy as well. GIM 13-AMBRA is a patient journey study regarding how the prognosis of metastatic breast cancer patients has changed in the last decades as a result of the introduction of new drugs in clinical practice. This study also provides information regarding the different natural histories of breast cancer according to the presence or absence of hormone receptors and HER2 receptors. GIM 13-AMBRA is a longitudinal cohort study aimed at describing therapeutic strategies and the relative outcome parameters in 939 HER2-ve MBC patients. Taxanes–based regimens, or taxanes + targeted agents, mainly Bevacizumab, were the preferred first choice in both Luminal (30.2%) and TNBC (33.3%) patients. The median PFS1 was 12.5 months (95% CI 16.79–19.64), without any significant difference according to subtypes, while the median Time to first Treatment Change (TTC1) was significantly lower in TNBC patients (7.7 months—95% CI 5.7–9.2) in comparison to Luminal A (13.2 months, 95% CI 11.7–15.1) and Luminal B patients (11.8 months, 95% CI 10.3–12.8). PFS2 was significantly shorter in TNBC patients (5.5 months, 95% CI 4.3–6.5 vs. Luminal A—9.4, 95% CI 8.1–10.7, and Luminal B—7.7 95% CI 6.8–8.2, F-Ratio 4.30, p = 0.014). TTC2 was significantly lower in patients with TNBC than in those with the other two subtypes. The median OS1 was 35.2 months (95% CI 30.8–37.4) for Luminal A patients, which was significantly higher than that for both Luminal B (28.9 months, 95% CI 26.2–31.2) and TNBC (18.5 months, 95% CI 16–20.1, F-ratio 7.44, p = 0.0006). The GIM 13—AMBRA study is one of the largest collections ever published in Italy and provides useful results in terms of time outcomes for first, second, and further lines of treatment in HER2- MBC patients. [ABSTRACT FROM AUTHOR]

Background: Improvements in perinatal care have substantially decreased mortality rates among preterm infants, yet their neurodevelopmental outcomes and quality of life persist as a pertinent public health concern. Family-centered care has emerged as a holistic philosophy that promotes effective alliances among patients, families, and healthcare providers to improve the quality of care. Aims: This longitudinal prospective study aims to evaluate the neurodevelopmental outcomes and brain MRI findings in a cohort of preterm newborns admitted to a neonatal intensive care unit (NICU) adopting a family-centered care model. Methods: Very low birth weight (VLBW) infants admitted to the NICU of Modena between 2015 and 2020 were enrolled. Infants who underwent conventional brain magnetic resonance imaging (MRI) at term-equivalent age were included. Neurodevelopmental follow-up was performed until the age of 24 months by a multidisciplinary team using the Amiel-Tison neurological assessment and the Griffiths Mental Developmental Scales (GMDS-R). Neurodevelopmental outcomes were classified as major sequelae (cerebral palsy, DQ ≤ 70, severe sensory impairment), minor sequelae (minor neurological signs such as clumsiness or DQ between 71 and 85), and normal outcomes (no neurological signs and DQ > 85). Risk factors for severe outcomes were assessed. Results: In total, 49 of the 356 infants (13.8%) died before hospital discharge, and 2 were excluded because of congenital disorders. Of the remaining 305 infants, 222 (72.8%) completed the 24 month follow-up and were included in the study. Neurodevelopmental outcomes were classified as normal (n = 173, 77.9%), minor (n = 34, 15.3%), and major sequelae (n = 15, 6.8%). Among 221 infants undergoing brain MRI, 76 (34.4%) had major lesions (intraventricular hemorrhage, hemorrhagic parenchymal infarction, periventricular leukomalacia, and large cerebellar hemorrhage). In the multivariate regression model, the retinopathy of prematurity (OR 1.8; p value 0.016) and periventricular–intraventricular hemorrhage (OR 5.6; p value < 0.004) were associated with major sequelae. Conclusions: We reported low rates of severe neurodevelopmental outcomes in VLBW infants born in an Italian NICU with FCC. Identifying the risk factors for severe outcomes can assist in tailoring and optimizing early interventions on an individual basis, both within the NICU and after discharge. [ABSTRACT FROM AUTHOR]

Simple Summary: Inflammatory bowel disease (IBD) increases the risk of cancer, particularly of the gastrointestinal tract. Modern management of IBD including a low threshold for acceptable inflammation (treat-to-target approach) and strict surveillance are believed to have reduced the incidence of malignancies associated with IBD. We conducted a retrospective study in two tertiary referral centers in Italy to evaluate incidence rates of all malignancies and colorectal cancer in patients with IBD and compare them with the general population. We observed incidence rates for all cancers and for colorectal cancer similar to that of the general population, and early-stage detection of malignancies through surveillance. Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), increase the risk of malignancies, particularly colorectal cancer (CRC). We aimed to assess the incidence of malignancies in IBD patients managed using a treat-to-target approach and recommended surveillance. We retrospectively searched the electronic databases of two tertiary IBD centers in Milan from 2010 to 2019 for new diagnoses of malignancy in patients with pre-existing IBD. A total of 5239 patients with a follow-up of 19,820 years were included. In total, 71 malignancies were diagnosed in 70 patients (38 CD, 32 UC) with a mean age of 52.9 years, of whom 64% were former or active smokers. The annual incidence of all malignancies was 358 per 100,000 patient years (95% CI 275–444), and the standardized incidence rate (SIR) was 0.93 (95% CI 0.73–1.16). Gastrointestinal cancers were the most frequent (n = 17, 23.9%), in particular, CRC (n = 9), with an incidence of 45 per 100,000 (95% CI 15–74) and an SIR of 1.18 (95% CI 0.54–2.09). CRC occurred mainly in UC patients (6/8), while small bowel cancer was seen in CD patients (5/9). Melanoma and breast cancer (n = 8 each) were the most common non-GI cancers. No significant difference in incidence was found between CD or UC. Death occurred in nine patients (11%) and was due to cancer in eight of these cases, two of which were IBD-related. Most malignancies included in the surveillance were diagnosed at early (I–II) stages (20 vs. 4, p < 0.05). In patients with IBD, treat-to-target and strict surveillance were associated with a low incidence of cancer, similar to that of the general population, and the detection of malignancies at an early stage. [ABSTRACT FROM AUTHOR]

Simple Summary: Here, we report real-world treatment patterns and the overall survival of 104 patients with relapsing/refractory (R/R) MF who had received first-line therapy between 1984 and 2016. Our study found that second- and third-line therapies for R/RMF were heterogeneous, including systemic therapies, radiotherapy and topical therapies. More than two-thirds of patients at second- and third-line treatment received chemotherapy, and we observed that the median overall survival was longer with non-chemotherapy (not reached) vs. chemotherapy (6.5 years) treatment, suggesting that non-chemotherapy options may be more beneficial to patients. (1) Background: Most patients with mycosis fungoides (MF), a form of cutaneous T-cell lymphoma (CTCL), develop relapsed/refractory (R/R) disease following front-line systemic therapy. This report describes treatment patterns and outcomes from the subpopulation with R/R MF. (2) Methods: This observational, retrospective, cohort study analyzed patient records (1984–2016) from 27 clinical sites in Europe. Outcomes included treatments received, response to first-, second- and third-line treatment, overall survival (OS) and progression-free survival (PFS). (3) Results: Of 104 patients with MF, 100 received second-line and 61 received third-line therapy. The median (range) times from the start of first-line therapy to the first R/R MF and from the first to the second R/R MF were 11.2 (0.3–166.5) and 13.5 (0.0–174.6) months, respectively. Second-and third-line treatment options varied and comprised systemic therapies (85% and 79% of patients, respectively), radiotherapy (32% and 34%, respectively) and topical therapies (48% and 36%, respectively). The median (95% confidence interval [CI]) OS from the diagnosis of the first R/R MF was 11.5 (6.5–not reached [NR]) years and was higher with non-chemotherapy (NR) versus chemotherapy (6.5 years); the estimated median PFS (95% CI) from the time of the first R/R MF was 1.3 (1.0–2.1) years. (4) Conclusions: High rates of R/R disease were observed after second- and third-line treatments in this real-world cohort, with longer median OS in patients receiving non-chemotherapy treatment versus chemotherapy. Following the standard management of MF and using recently approved targeted therapies can help improve patient outcomes in advanced-stage MF. [ABSTRACT FROM AUTHOR]

Simple Summary: Lynch syndrome (LS) is an inherited genetic condition caused by germline mutations in DNA mismatch repair (MMR) genes. It is associated with a predisposition to different types of cancer, including colorectal cancer (CRC). CRC is the fourth most common cancer worldwide. The screening algorithm for the selection of LS patients is based on the identification of CRC specimens that have MMR loss/high microsatellite instability (MSI-H) and are wild-type for BRAFV600. The aim of this retrospective study was to clinically and molecularly characterize CRC patients with these features. We used a comprehensive approach including tumor testing for the assessment of MSI status, clinical evaluation of patients and their families, and genetic analysis to identify variants in MMR and other cancer-related genes. The clinical and molecular characterization of these patients highlights the importance of personalized medicine to provide tailored genetic counseling, management, and surveillance to families with LS and hereditary cancer. Lynch syndrome (LS) is an inherited cancer susceptibility syndrome caused by germline mutations in a DNA mismatch repair (MMR) gene or in the EPCAM gene. LS is associated with an increased lifetime risk of colorectal cancer (CRC) and other malignancies. The screening algorithm for LS patient selection is based on the identification of CRC specimens that have MMR loss/high microsatellite instability (MSI-H) and are wild-type for BRAFV600. Here, we sought to clinically and molecularly characterize patients with these features. From 2017 to 2023, 841 CRC patients were evaluated for MSI and BRAFV600E mutation status, 100 of which showed MSI-H. Of these, 70 were wild-type for BRAFV600. Among these 70 patients, 30 were genetically tested for germline variants in hereditary cancer predisposition syndrome genes. This analysis showed that 19 of these 30 patients (63.3%) harbored a germline pathogenic or likely pathogenic variant in MMR genes, 2 (6.7%) harbored a variant of unknown significance (VUS) in MMR genes, 3 (10%) harbored a VUS in other cancer-related genes, and 6 (20%) were negative to genetic testing. These findings highlight the importance of personalized medicine for tailored genetic counseling, management, and surveillance of families with LS and other hereditary cancer syndromes. [ABSTRACT FROM AUTHOR]

Simple Summary: To assess the percentage of early breast cancer (EBC) patients treated with neoadjuvant systemic therapy (NAT) in Italy, criteria of patient selection and types of therapies delivered, 1276 stage I-II-III patients were enrolled and evaluated in the multicenter prospective observational BRIDE study in 2018–2021. NAT was administered to 13.9% of EBC patients. In multivariate analysis, menopausal status, cT, cN, grade, HER2-positive and Triple Negative (TN) subgroups were significantly associated with the decision to administer NAT. According to phenotypic subgroup, NAT was administered to 53.2% of HER2+/HR-negative (pathologic complete response—pCR-74.2%), 27.9% of HER2+/HR+ (pCR 52.3%), 7.1% of HER2-negative/HR+ (pCR 17.2%) and 30.3% of TN (pCR 37.9%) patients. Phenotypic subgroup influenced the type of NAT delivered. Today, the use of NAT in EBC should be always considered, especially in HER2+ and TN, because of the association between pCR and better survival of patients and the current availability of effective therapies for patients with residual disease. To evaluate the rate of early breast cancer (EBC) patients treated with neoadjuvant systemic therapy (NAT) in Italy, criteria of patient selection and types of therapies delivered, an analysis of 1276 patients with stage I-II-III was conducted out of 1633 patients enrolled in the multicenter prospective observational BRIDE study. A total of 177 patients (13.9%) were treated with NAT and 1099 (85.9%) with surgery; in multivariate analysis, menopausal status, cT, cN, grade, HER2-positive and Triple negative (TN) subgroups were significantly associated with the decision to administer NAT. The type of NAT delivered was influenced by EBC subtype. NAT was administered to 53.2% of HER2+/HR-negative, 27.9% of HER2+/HR+, 7.1% of HER2-negative/HR+ and 30.3% of TN EBC patients. The pCR rates were similar to the ones reported in the literature: 74.2% in HER2+/HR-negative, 52.3% in HER2+/HR+, 17.2% in HER2-negative/HR+ and 37.9% in TN. In clinical practice, patient and tumor characteristics influenced oncologists in the decision to administer NAT in EBC and in the choice of the type of systemic therapy, according to ESMO and AIOM Guidelines. Currently, it is recommended always to evaluate the use of NAT in EBC, mainly in HER2+ and TN patients, considering that pCR is associated with significantly better survival of the patient and that effective therapies are now available for residual disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Concurrence of pregnancy and cancer diagnosis is an uncommon but not rare event: about 1 pregnancy-associated cancer (PAC) out of 1000 pregnancies is the estimation currently available. This frequency is growing due to postponing childbearing to age groups more at risk of cancer. Interest in this topic is both epidemiological and clinical: improvement of diagnostic and therapeutic techniques makes management of cancer increasingly compatible with pregnancy. The occurrence of PAC challenges women and clinicians who need to manage the two events, safeguarding fetal outcomes without changing the maternal prognosis. This retrospective study aims to provide estimates for PAC and its time trend in Italy by analyzing cross-referenced data from population-based cancer registries and hospital discharges. The proposed methodology is applicable to other populations with available data from Cancer Registries linkable at an individual level with hospitalizations. The aim of this study is to describe the frequency and trend of pregnancy-associated cancer (PAC) in Italy, an increasingly relevant phenomenon due to postponing age at childbirth. To this purpose, a population-based retrospective longitudinal study design based on cohorts of women aged 15–49 diagnosed with cancer and concomitant pregnancy is proposed. The study uses 19 population-based Cancer Registries, covering about 22% of Italy, and linked at an individual level with Hospital Discharge Records. A total of 2,861,437 pregnancies and 3559 PAC are identified from 74,165 women of the cohort with a rate of 1.24 PAC per 1000 pregnancies. The most frequent cancer site is breast (24.3%), followed by thyroid (23.9%) and melanoma (14.3%). The most frequent outcome is delivery (53.1%), followed by voluntary termination of pregnancy and spontaneous abortion (both 12.0%). The trend of PAC increased from 2003 to 2015, especially when the outcome is delivery, thus confirming a new attitude of clinicians to manage cancer throughout pregnancy. This represents the first attempt in Italy to describe PAC from Cancer Registries data; the methodology is applicable to other areas with the same data availability. Evidence from this study is addressed to clinicians for improving clinical management of women with PAC. [ABSTRACT FROM AUTHOR]

Background: Dental implants have become the standard for replacing missing teeth. However, patients' demands for shorter treatment times and the desire for aesthetics in their results can complicate the rehabilitation process, particularly when poor-quality bone is involved. In order to address these challenges, new methods of treating implant surfaces have been introduced. These methods aim to make the implants superhydrophilic and bioactive, enhancing their functionality and interactions with the surrounding tissues. Aim: The aim of the study was to retrospectively examine the efficacy of a superhydrophilic and bioactive implant for treatment of the edentulous maxillary anterior area. The study also aimed to evaluate whether this improved implant surface, by enhancing the osseointegration processes, could serve as a factor in speeding up the loading protocols. Materials and Methods: For this retrospective study, a total of 13 implants were included: 6 delayed restored implants and 7 immediately loaded implants placed in the anterior maxillary area. Clinical, radiographic, and esthetic outcomes were assessed. Baseline measurements of the insertion torque value (ITV) and stability implant quotient (ISQ) were recorded for all implants. In the early-loaded group, these measurements were also taken 30 days (t30) and 45 days (t45) after the placement of the implant to monitor their changes over time. Marginal bone loss (MBL) was calculated according to the changes in marginal bone level on intraoral X-rays taken at two different time points: at baseline and one year after loading. To evaluate the esthetic results, the pink esthetic score (PES) and the white esthetic score (WES) were assessed. For this evaluation, intraoral photographs were taken one year after implant loading. Results: A total of 7 implants were immediately restored, with a mean ITV of 32.29 ± 9.01 Ncm and a mean ISQ of 72.71 ± 2.81. These implants were placed in a bone environment with a mean density of 410.00 ± 194.42 HU. On the other hand, 6 implants with delayed loading had a mean ITV of 28.50 ± 3.27 Ncm, an ISQ of 67.92 ± 8.43, and a mean bone density of 607.50 ± 140.83 HU. The mean PES and WES after 1 year were, respectively, 8.71 ± 1.89 and 8.57 ± 0.79 for immediate and 8.33 ± 1.36 and 9.17 ± 1.33 for delayed-loaded implants. At 12 months after loading, the immediately loaded group had a MBL of 0.29 ± 0.29 mm, while the delayed-loaded group had a MBL of 0.33 ± 0.25. No statistically significant differences between the two treatment groups were found for any of the evaluated outcomes. Conclusions: Despite the limitations of this study, the obtained results may support the use of a superhydrophilic and bioactive implant surface for implant-prosthetic rehabilitation in critical loading protocols with satisfactory esthetic results. [ABSTRACT FROM AUTHOR]

Testicular adrenal rest tumors (TARTs) are a common complication in male patients with congenital adrenal hyperplasia (CAH). The aim of our cross-sectional cohort study is to estimate the frequency of TARTs with the correlation of genotype and disease control on tumor development. Thirty-five male patients, aged 14–26 years, were included in the study, all followed by the same center of pediatric endocrinology in Bologna. We studied genotypes, hormonal profiles at different time intervals and testicular ultrasound. A logistic regression model with multivariant analysis was developed for the statistical analysis. TARTs were detected in 31.4% of the cases, 90.9% of them had a classic form with salt wasting, while 9.1% had a non-classic form. Additionally, a significant correlation between the incidence of TARTs and severity of genotype was detected. Patients with TARTs had markedly worse metabolic control on average (p = 0.027), reflected by high ACTH, 17OH progesterone, and overall delta4-androstenedione. In conclusion, a screening tool is mandatory, especially (but not exclusively) in patients with the most severe forms of CAH and poor endocrine control of the disease. [ABSTRACT FROM AUTHOR]

Introduction: The COVID-19 pandemic has had a considerable impact on the psychological and psychopathological status of the population and health care workers in terms of insomnia, anxiety, depression, and post-traumatic stress disorder. The primary aim of this study was to describe and evaluate the impact of the pandemic on insomnia levels of a cohort of Italian nurses, particularly those involved in the care of COVID-19 patients. The secondary aim was to identify the interaction between insomnia and hardiness, anxiety, and sleep disturbances. Materials and Methods: A descriptive–exploratory study was conducted using an online survey during the first wave of the COVID-19 pandemic (March to July 2020). The questionnaire consisted of multiple-choice, open-ended, closed, and semi-closed questions. The psychometric tools administered were the Dispositional Resilience Scale (DRS-15), the State–Trait Anxiety Inventory (STAI-Y), and the Insomnia Severity Index (ISI). Results: a cohort of 1167 nurses fully completed the questionnaire (86.2% of total respondents). The insomnia scale survey showed an increase in post-pandemic scores compared to those before the pandemic, implying that insomnia levels increased after the first pandemic wave. Insomnia scores were directly correlated with anxiety levels (r = 0.571; p ≤ 0.05) and inversely correlated with hardiness levels (r = −0.324; p < 0.001). Multivariate analysis revealed the following protective factors: not having worked in COVID-19 wards, high levels of hardiness (commitment), and the presence of high pre-pandemic insomnia disorder. The main risk factor for insomnia reported in the analysis was a high anxiety score. Discussion and Conclusion: Anxiety represented the main risk factor for insomnia severity in our sample, while hardiness was confirmed as a protective factor. Thus, it is necessary to design further studies to identify additional risk factors for poor sleep quality and to develop educational courses and strategies aimed at enhancing rest and sleep quality, especially for frontline nurses. [ABSTRACT FROM AUTHOR]

Children with celiac disease may face challenges in managing a gluten-free diet during their daily interactions and activities. The objective of this study was to compare how children with celiac disease manage their gluten-free diet and participate in food-related activities in Italy and Israel and to assess their quality of life. The previously validated Children's Activities Report (CD-Chart) and the Disease-specific Health-Related Quality of Life Questionnaire for Children with Celiac Disease (CDDUX) were administered in Italy to children aged 8–16 diagnosed with CD (n = 39). The results were compared to data that had been previously gathered from Israeli children with CD (n = 106). The CD-Chart demonstrated satisfactory internal reliability within each cultural group (Italy: α = 0.82; Israel: α = 0.76). Mann–Whitney U-tests indicated significant differences between the two groups. The Italian children exhibited a significantly higher preference for participating in the activities compared to the Israelis (U = 3283.50, p < 0.001). Nonetheless, the Italian children displayed a notable decrease in their level of involvement in the preparation required before engaging in different activities (U = 760.50, p < 0.001). Moreover, they exhibited significantly lower self-determination in this preparatory process compared to the Israeli children (U = 726.00, p < 0.001). Significant group differences were found between the CDDUX children's self-reports and parents' proxy reports in the Israeli group but not in the Italian group. The CD-Chart revealed both shared and distinct participation characteristics in daily food-related activities across different cultural contexts. By incorporating the CD-Chart and the CDDUX, healthcare professionals can emphasize crucial aspects of day-to-day health management and guide them in establishing suitable intervention objectives to enhance effective health self-management. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnea can have a negative impact on children's and adolescents' neurocognitive abilities and hinder their academic and adaptive progress in academic, social, and/or behavioral dimensions. In this retrospective cross-sectional study, we investigated the influence of body weight conditions and allergy status on long-term mental health, cognitive development, and quality of life in children and adolescents who snored. Methods: The study sample included 47 subjects (age range 4.1 to 15.3 years) who exhibited high levels of snoring and underwent home-based polysomnography between 2015 and 2019. Follow-up assessments (3 years on average between baseline and follow-up) entailed phone interviews with the subject's parents/caregivers who completed three validated questionnaires investigating sleep, quality of life, and parental ratings. Results: We found a correlation between age at diagnosis and being retrospectively overweight and high levels of snoring. In addition to a higher risk of developing emotional symptoms (8.2% increase in retrospective overweight status for each unit increase in the emotional score at follow-up) and oppositional behavior (9% increase in retrospective overweight status for each unit of oppositional T points at follow-up), we also noted reduced long-term social symptoms (11% decrease in retrospective overweight status for each unit increase in the social score at follow-up) and cognitive symptoms (10.6% decrease in retrospective overweight status for each unit increase in the cognitive score at follow-up), as well as a 6.1% increase in retrospective allergy status for each unit increase in academic performance at follow-up. Conclusions: Snoring can have negative impacts on mental health and cognitive development in the long term. Early detection and intervention for neuropsychological disorders is important in children and adolescents who score high on snoring. In the long term, the effects of snoring on neuropsychological disorders may vary based on previous body weight and allergy status. [ABSTRACT FROM AUTHOR]

Background: Congenital cytomegalovirus (cCMV) infection is the leading cause of non-hereditary sensorineural hearing loss in children. While about 10% of children reportedly display symptoms at birth, 85–90% of cCMV infection cases are asymptomatic. However, 10–15% of these asymptomatic infants may later develop hearing, visual, or neurodevelopmental impairments. This study aimed to evaluate the impact of cCMV infection on newborns' hearing function with a particular emphasis on progressive and late-onset cases. Methods: This study is a retrospective chart analysis with longitudinal character and was conducted in two Italian centers: Center 1 (from 1 November 2007 to 31 December 2021) and Center 2 (from 1 January 2012 to 31 December 2021). Data collected included newborn hearing screening results, characterization of hearing loss (unilateral/bilateral, degree of impairment), and audiological follow-up. Results: The cohort consisted of 103 children (42% males, 58% females). In total, 28 children presented with hearing impairment; 71.4% (20 out of 28) of the cases of hearing loss were severe/profound, with 35.7% of the cases due to unilateral hearing loss. Out of twenty-eight, six experienced progression of hearing loss and four had late-onset hearing loss. Conclusions: In the absence of universal cCMV screening, hearing screening at birth for cCMV remains a critical factor for early diagnosis. A significant percentage of children affected by cCMV with normal audiological evaluations at birth is easily lost to follow-up. Close collaboration between neonatologists, pediatricians, and audiological services is fundamental to ensure timely diagnosis and treatment of cCMV-related hearing loss. [ABSTRACT FROM AUTHOR]

Simple Summary: The malignant transformation risk of oral lichen planus (OLP) is still a dilemma in the literature. The first report of oral squamous cell carcinoma with the origin of OLP was in 1910. Initially, the reported risk in the literature was high after this date; then, with the application of restricted criteria for the diagnosis of OLP, the reported risk become too low. Currently, there is a recommendation to conduct further studies in which other variables are considered, such as smoking and drinking habits and the type and localization of the lesion. This is in order to evaluate the exact risk of OLP and, correspondingly, to avoid the clinical underestimation by medical staff of the risk of malignant transformation of OLP. This study aims to retrospectively assess the potential risk of malignant transformation in patients with diagnosed oral lichen planus (OLP) between 2015 and 2022, and to evaluate the influence of different risk factors. The department's database and medical records from 2015 to 2022 were searched for patients with a confirmed diagnosis of OLP based on both clinical and histological parameters. A total of 100 patients (59 females and 41 males) were found with a mean age of 64.03 years. In the considered period, the percentage of diagnosed OLP patients was 1.6%, while the percentage of diagnosed OLP patients with transformation to oral squamous cell carcinoma (OSCC) was 0.18%. A statistically significant difference was found with age (p = 0.038), tobacco status (p = 0.022), and radiotherapy (p = 0.041). The analysis revealed the presence of significant risk in ex-smokers (>20 pack-years), with an odds ratio (OR) of 10.0000 (95% confidence interval (95% CI) 1.5793–63.3186); in alcohol-drinker patients, with an OR of 4.0519 (95% CI 1.0182–16.1253); in ex-smoker and alcohol-drinker patients, with OR of 17.6250 (95% CI 2.2464–138.2808); and in patients who had undergone radiotherapy, with OR of 6.3000 (95% CI 1.2661–31.3484). The malignant transformation of oral lichen planus was slightly higher than thought, and the results revealed a possible association with age, tobacco and alcohol status, and history of radiotherapy. An elevated risk of malignant transformation was observed in heavy ex-smoker patients, alcohol-drinker patients, and alcohol-drinker patients with a history of smoking (ex-smokers). Persuading the patient to quit tobacco and alcohol consumption and periodic follow-ups are recommended in general, but particularly in the presence of these risk factors. [ABSTRACT FROM AUTHOR]

Simple Summary: Pheochromocytoma and sympathetic paraganglioma (PHEO/sPGL) are rare and mainly sporadic tumors arising from chromaffin cells, for which hereditary variants occur in about one-third of cases. The discrimination between benign and malignant lesions is extremely challenging in PHEO/sPGL and the prognosis is indeterminate. The study aimed to analyze the long-term outcomes of PHEO/sPGL in a cohort of 170 patients. The results demonstrated that new tumor recurrence occurred more frequently with hereditary variants, even though new tumors also reoccurred with sporadic variants. Moreover, even if the risk of metastatic recurrence was higher with malignant variants at diagnosis, the risk also occurred with apparently benign cases. This suggests that lifelong follow-up is required for PHEO/sPGL, even in sporadic and apparently benign cases. Background: The prognosis of pheochromocytoma and sympathetic paraganglioma (PHEO/sPGL) is difficult to predict at the time of diagnosis and long-term follow-up data are scarce, especially for apparently benign and sporadic variants. The aim of the study was to analyze the long-term outcomes in PHEO/sPGL patients. Methods: A monocentric series of 170 patients who underwent surgery for PHEO/sPGL was analyzed. Results: The study cohort included 91 female and 79 males with a median age of 48 years (range 6–83). The majority of PHEO/sPGL cases were considered apparently benign at the time of diagnosis; evident malignant behavior was found in 5% of cases. The overall 10-year risk of recurrence was 13%, but it rose up to 33% at 30 years. The risk of new tumor recurrence was higher in patients with hereditary tumors, but the risk was still significant in patients with apparently sporadic variants (20-year risk: 38% vs. 6.5%, respectively; p < 0.0001). The risk of metastatic recurrence was higher in patients with locally aggressive tumors at diagnosis, but the risk was present also in apparently benign variants (5-year risk: 100% vs. 1%, respectively; p < 0.0001). Conclusions: Lifelong follow-up is required not only for hereditary PHEO/sPGL but also for apparently benign and sporadic tumors at diagnosis because of the risk of long-term recurrent disease. [ABSTRACT FROM AUTHOR]

Background: For children with inflammatory bowel disease (IBD), understanding their condition may lead to better outcomes. Knowledge assessment is imperative to identify where education may be required. An IBD knowledge assessment tool (IBD-KID2) is available in English; the aim of this study was to translate IBD-KID2 in to Italian and assess its validity/reliability among children with IBD. Methods: IBD-KID2 has fifteen items, scoring one point per correct answer. IBD-KID2 items were assessed for cultural comprehension/relevance by Italian gastroenterologists using a content validity index; those items with a maximum score proportion <0.78 were reviewed. IBD-KID2 was then translated using 'forward–backward' process and reviewed for content/meaning. A prospective study among Italian children with IBD enabled score comparisons with established populations (z test), and reliability was assessed using test–retest completion (Pearson correlation (r), paired t-test). Results: Twenty-five children participated: 16 (64%) male, mean age 14.9 years (SD2.4), Crohn's disease 13 (52%). The mean IBD-KID2 score was 8.8 (SD2.8), with no association with independent variables. Test–retest showed strong correlation between scores (r = 0.78, p < 0.001), with no mean difference (p = 0.39). Comparison with other pediatric IBD populations (NZ/Australia/Canada) showed no score difference (p = 0.62, CI −0.9 to 1.5). Conclusions: The translation of IBD-KID2 to Italian used a rigorous methodology. Scores showed the translated tool has equivalence and generalizability to Italian children with IBD. [ABSTRACT FROM AUTHOR]

Within the EASY-NET network program (NET-2016-02364191), Work Package 1 Lazio evaluates the effectiveness of a structured audit and feedback (A&F) intervention compared with the web-based regional periodic publication of indicators in improving the appropriateness and timeliness of emergency healthcare for acute myocardial infarction (AMI). This work describes the A&F methodology and presents the results of the first feedback delivered. The intervention involves sending periodic reports via e-mail to participating hospitals. The feedback reports include a set of volume and quality (process and outcome) indicators, calculated by facility through the health information system of the Lazio Region and compared with regional mean, target values and values calculated for hospitals with similar volumes of activity. Health managers and clinicians of each participating hospital represent the "feedback recipients". They are invited to organize clinical and organizational audit meetings to identify possible critical issues in the care pathway and define, where necessary, improvement actions. A total of 16 facilities are involved. Twelve facilities present high volumes in all volume indicators, while three facilities present low volumes for each indicator. Concerning the quality indicators, four facilities do not present critical indicators or had average results, three facilities do not present critical indicators but show average results in at least one of the indicators and six facilities present a critical value for at least one of the indicators. The first report highlighted some critical issues in some facilities on several indicators. During the audit meetings, each facility analyzes these issues, defining appropriate improvement actions. The outcome of these actions will be monitored through subsequent reporting to support the continuous care quality improvement process. [ABSTRACT FROM AUTHOR]

During the clinical examination of subjects with temporomandibular disorders (TMDs), the dentist sometimes must evaluate the cervical spine, due to the anatomical and functional connections between the cervical portion of the spine and the stomatognathic apparatus. The accelerometer is a device that evaluates the Range of Motion (ROM) of the main movements of the head on the neck. To date, only a few studies have investigated the repeatability of the use of the accelerometer in the assessment of cervical ROM. Therefore, the present longitudinal observational study analyzed the repeatability of acquired cervical movements on a sample of volunteer subjects who underwent accelerometer testing. A sample of 32 subjects was tested twice within 14 days to assess cervical ROM using a standardized protocol based on a review of existing literature. The results show that the examination is reliable for all the positions of the jaw, except for the parameters regarding the asymmetries of rotation and bending. In conclusion, the accelerometer can be considered a reliable tool for evaluating the active cervical ROM. However, further studies will be necessary to make better evaluations. [ABSTRACT FROM AUTHOR]

The investigation of this observational case–control study aimed at determining the effectiveness of a combined treatment of extremely low-frequency electromagnetic fields (ELF) with a soft elastic knee brace versus ELF alone in knee osteoarthritis (KOA) with respect to a reduction in pain and functional recovery. We hypothesized that the combined use of ELF and a soft elastic knee brace may provide better results. Thirty-five patients (N = 35, divided into Group 1 = ELF and Group 2 = ELF with the soft elastic knee brace) were analyzed. The rehabilitative protocol consisted of 10 sessions of antiphlogistic and antiedema programs (first cycle) for 2 weeks, followed by twelve sessions of bone repair and connective tissue repair programs (second cycle) in patients with knee osteoarthritis (KOA) for 4 weeks. Patient evaluations were conducted at baseline (T0) and after 2 (T1) and 4 (T2) weeks of treatment. A follow-up evaluation was conducted 6 weeks after treatment (T3). The LIMFA© Therapy System was used to create multifrequency magnetoelectric fields with an intensity of 100 µT and a low-frequency field. The Incrediwear Cred 40 knee sleeve (Incred) was used for alleviating knee pain. The Visual Analogue Scale (VAS), the Knee Injury and Osteoarthritis Outcome Score (KOOS), and the Lysholm score (Ls) were used as outcome measures. The results showed that pain at rest (Vr), pain in motion (Vm), KOOS, and Ls were significantly affected by ELF over time. In conclusion, Group 2 had a better response in terms of pain resolution at rest (p < 0.05) and a concurrent better response at T3 in terms of functional recovery (p < 0.05). [ABSTRACT FROM AUTHOR]

Simple Summary: This study collected data from patients with cutaneous melanoma with mutation in the B-RAF gene who were treated with the combination of dabrafenib and trametinib in 34 Italian hospitals in every-day clinical practice. The aim was to understand how these drugs modify the progression pattern of the tumor in a heterogeneous population of patients who had either a limited (104 patients) or a bulky disease (97 patients). The results showed that fewer patients had lesions at the skin and more patients had lesions in other sites rather than the skin and lymph nodes when the disease progressed compared to baseline, and the proportion of patients with at least three involved organs at the progression increased in both cohorts. The survival and the time without progression were similar to previously published data and no new adverse reactions were reported. Therefore, dabrafenib and trametinib demonstrated to be effective and safe in heterogenous patients. In patients with B-RAF-mutated cutaneous melanoma, targeted therapies are the treatment of choice to achieve a rapid response. In this multicentric, prospective, observational study, patients with B-RAF-mutated cutaneous melanoma who were treated with dabrafenib and trametinib were categorized in two cohorts (cohort A: limited disease (n = 104) and cohort B: bulky disease (n = 97)) according to lactate dehydrogenase levels. The primary endpoint was the progression pattern; the secondary endpoints were overall survival (OS), progression-free survival (PFS), and safety data. From baseline to time of progression, there was a progression from nodal to other sites of disease in cohort A and from skin and nodal to other sites in cohort B. In both the cohorts, the number of involved organs and metastases at each location decreased. The median OS was 32.4 months (95% CI: 20.1 months (not estimable)) for cohort A, and 10.5 months (95% CI: 8.3–14.4 months) for cohort B; median PFS was 12.4 months (95% CI: 10.9–17.0 months) for cohort A, and 8.1 months (95% CI: 6.3–9.4 months) for cohort B. No new safety signals were reported. This study describes the patterns of first-line treatment progression with dabrafenib and trametinib in Italian clinical practice. The effectiveness and safety data were consistent with previous trials and extended to a real-world heterogeneous population. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune check point inhibitors (ICPIs) are one of the treatment options for advanced hepatocellular carcinoma (HCC). No biomarker is currently available to upfront select patients to be addressed to one or another drug. We have tested a prospective series of patients with advanced HCC treated with atezolizumab–bevacizumab combination with the aim of identifying biomarkers of response by using a simple cytofluorimetric test on peripheral blood. Due to the relevant role of granulocyte in the immune response, here we have focused on granulocyte immunophenotype by investigating PD1 and PD-L1 expression on their surface by using a simple cytofluorimetric test on peripheral blood. A low baseline PD1+ granulocyte percentage identified patients likely to benefit from atezolizumab–bevacizumab. Our findings warrant to validate this cheap and immediate cytofluorimetric test in larger cohorts, to verify whether the individual accuracy could be informative for the clinical practice. Introduction: Immune check point inhibitors have recently entered the armamentarium of advanced hepatocellular carcinoma (HCC) treatment. Among them, the combination of atezolizumab plus bevacizumab has pushed it a step forward; however, a number of patients still present primary non-responses without any biomarker to predict responses to different options. Here, we aimed to identify a putative baseline biomarker to predict the response to atezolizumab–bevacizumab, by investigating whether baseline PD1+ and PD-L1+ peripheral granulocyte percentages might offer a non-invasive, cheap, and easily feasible assay. Methods: A prospective Italian cohort of 34 patients treated by atezolizumab–bevacizumab was tested to assay the baseline percentage of peripheral granulocytes and their PD1 and PD-L1 expression. The neutrophil to lymphocyte ratio (NLR) was also considered, and all data were compared with the clinical course of patients. Results: A low-baseline PD1+ peripheral granulocyte percentage turned out to predict responder patients (mean ±SD of PD1+ granulocyte percentage in responders versus non-responders: 9.9 ± 9.1 vs. 29.2 ± 17.6; student's t-test, p < 0.01). In line, patients identified by a low PD1+ granulocyte percentage displayed a longer TTP (log-rank test, p < 0.0001). A lower granulocyte percentage on total white blood cells, irrespective of PD1 or PD-L1 expression, is also associated with responses to atezolizumab–bevacizumab (log-rank test, p < 0.05). No predictive value was observed for either the PD-L1+ granulocyte percentage or NLR. Conclusions: A low-baseline PD1+ peripheral granulocyte percentage is associated with responses to atezolizumab–bevacizumab treatment in advanced HCC. These findings encourage evaluating this minimally invasive, cheap, and easy test in further independent cohorts and outlining the relevance of innate immunity in the response to immune-checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Infant-directed speech (IDS) is an essential factor of mother–infant interaction and facilitates early language processing and word learning during dyadic interactions. This study aimed to longitudinally investigate emotional and prosodic components of IDS in the first year of life by analyzing children's responses to the different prosodic trends that mothers use during the observation of mother–child interactions. Seventeen mothers and infants were recruited for this study during their first hospitalization. The study involved observing communication changes in face-to-face interactions between the mother and child at three, six, and nine months after the child's birth. We analyzed the relationship between gaze direction, smiling, speech speed, and clarity. The results showed that the IDS differs in production when compared to the age of the child; at only nine months, there is high intensity. The same is evident from the results related to the elocution velocity. The verbal sensitivity of the mother and the ability to tune in to the affective states of the child, especially at nine months, can predict the child's understanding of future language. [ABSTRACT FROM AUTHOR]

Simple Summary: Solid-organ transplant recipients are known to be at higher risk of developing several cancer types, mainly virus-related malignancies. Monitoring trends in the incidence of post-transplant cancers among individuals who received solid organ transplantation helps to improve preventive measures and outcomes. This cohort study aimed to examine, over a 25-year period in Italy, variations in the occurrence of post-transplant cancers among 11,418 recipients of kidney transplantation (KT). Cancer incidence over three periods (1997–2004; 2005–2012; and 2013–2021) was analyzed within the cohort and in comparison with the general population. After multivariate adjustment, both approaches highlighted reduced risks of Kaposi's sarcoma, whereas no statistically significant changes over time in the incidence of other cancers were noted. Accordingly, the results of this study highlighted the need to sustain and strengthen cancer-preventive actions in KT recipients. This cohort study examined 25-year variations in cancer incidence among 11,418 Italian recipients of kidney transplantation (KT) from 17 Italian centers. Cancer incidence was examined over three periods (1997–2004; 2005–2012; and 2013–2021) by internal (Incidence rate ratio-IRR) and external (standardized incidence ratios-SIR) comparisons. Poisson regression was used to assess trends. Overall, 1646 post-transplant cancers were diagnosed, with incidence rates/1000 person-years ranging from 15.5 in 1997–2004 to 21.0 in 2013–2021. Adjusted IRRs showed a significant reduction in incidence rates across periods for all cancers combined after exclusion of nonmelanoma skin cancers (IRR = 0.90, 95% confidence interval-CI: 0.76–1.07 in 2005–2012; IRR = 0.72, 95% CI: 0.60–0.87 in 2013–2021 vs. 1997–2004; Ptrend < 0.01). In site-specific analyses, however, significant changes in incidence rates were observed only for Kaposi's sarcoma (KS; IRR = 0.37, 95% CI: 0.24–0.57 in 2005–2012; IRR = 0.09, 95% CI: 0.04–0.18 in 2013–2021; Ptrend < 0.01). As compared to the general population, the overall post-transplant cancer risk in KT recipients was elevated, with a decreasing magnitude over time (SIR = 2.54, 95% CI: 2.26–2.85 in 1997–2004; SIR = 1.99, 95% CI: 1.83–2.16 in 2013–2021; Ptrend < 0.01). A decline in SIRs was observed specifically for non-Hodgkin lymphoma and KS, though only the KS trend retained statistical significance after adjustment. In conclusion, apart from KS, no changes in the incidence of other cancers over time were observed among Italian KT recipients. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer has the third highest cancer incidence in the world. The purpose of our population-based study was to evaluate how non-modifiable factors (sex and age) influence the biological and clinical characteristics of the disease, especially in patients with metastases at diagnosis. Our results indicate that sex and age influence the site of onset, morphology, and metastatic pattern of colorectal cancer, thereby affecting patient survival. Understanding the biological mechanisms that are regulated by sex and age, such as the hormonal profile, may contribute to the earlier diagnosis and better prognosis of this disease. As colorectal cancer is subject to screening, the influence of sex and age should be taken into account to implement a targeted strategy that considers these two factors in the general population. The prognosis of colorectal cancer is affected by factors such as site of origin, tumor morphology, and metastasis at diagnosis, but also age and sex seem to play a role. This study aimed to investigate within the Italian population how sex and age interact in influencing certain aspects of the disease and how they affect patient survival, particularly in the metastatic cohort. Data from four cancer registries were collected, and patients were classified by sex and age (<50, 50–69, and >69 years). Two separate analyses were conducted: one for patients having right or left colon cancer with adenocarcinoma or mucinous morphology, and one for patients having metastases at diagnosis. Women showed significant differences in right colon cases from the youngest to oldest age group (36% vs. 45% vs. 60%). Men <50 years had a significantly higher mucinous carcinoma percentage than their female counterparts (22% vs. 11%), while in the oldest age group women had the highest percentage (15% vs. 11%). The metastatic pattern differed between men and women and by age. The three-year relative survival in the <50 age group was better for women than men, but this survival advantage was reversed in the oldest group. In conclusion, sex and age are factors that influence the biological and clinical characteristics of colorectal cancer, affecting the metastatic pattern as well as patient survival. [ABSTRACT FROM AUTHOR]