Treatment of Aggressive Behavior and Agitation in an 11-Year-Old Boy with Co-Occurring Autism and ADHD: A Case Report and Literature Review on the Use of Intravenous Valproate in Emergency Psychiatry.

Background: Autism spectrum disorder (ASD) is a persistent neurodevelopmental disorder frequently co-occurring with attention-deficit/hyperactivity disorder (ADHD) and behavior-related disorders. While behavioral therapy is the first-line option to manage the core symptoms of ASD, pharmacological therapy is sometimes needed to treat acute problems, such as agitation and aggressive behaviors. Recent guidelines recommend the use of neuroleptics to reduce psychomotor agitation in patients with ASD. However, as children with ASD are often drug-resistant, alternative treatments are often justified. Reports from the literature have indicated that intravenous valproate (IV-VPA) can be effective in reducing agitation in psychiatric patients, with a lower frequency of adverse events compared to conventional treatments. However, as the related findings are occasionally inconsistent, IV-VPA is not yet an approved option in the context of clinical psychiatry. We aim to improve knowledge of the IV-VPA treatment option for emergency psychiatric treatment in pediatric patients. Methods: We report the case of an 11-year-old boy suffering from a complex neurodevelopmental condition who experienced a psychotic episode with severe aggressive and disruptive behaviors and was successfully treated with IV-VPA. Furthermore, we provide an updated literature review on this topic. Conclusion: In our case, first-line therapies proved to be ineffective. To the contrary, IV-VPA led to safe and prompt clinical success, which is in line with other reports. Based on our literature review, IV-VPA can be highly effective and reduces the risk of adverse events that frequently occur with the use of high-dose standard medications in emergency psychiatry.

Diagnostic Accuracy of DNA-Methylation in Detection of Cervical Dysplasia: Findings from a Population-Based Screening Program.

BACKGROUND: Epigenetic biomarkers in cancer have emerged as promising tools for early detection, prognosis, and treatment response prediction. In cervical cells, hypermethylation of the host and viral HPV-genome increases with the severity of lesions, providing a useful biomarker in the triage of hr-HPV-positive women and during treatment. The present study focuses on evaluating the clinical performance of the FAM19A4/miR124-2 methylation test in a population-based cervical screening program. METHODS: Previously collected cervical samples, after bisulfite-converted DNA, were analyzed by PreCursor-M+ kit (distributed by Fujirebio Europe), for DNA methylation. The sensitivity, specificity, and negative/positive predictive values of DNA methylation were compared to histology, colposcopy, the HPV-DNA test, and cytology results. RESULTS: Among the 61-sample set, the specificity of methylation vs. positive histology (≥CIN2) and colposcopy (≥G2) were 87% and 90%, whereas the sensitivity was 50% and 33.3%, respectively. The combination of methylation analysis with standard methods increases diagnostic accuracy. CONCLUSIONS: Overall, we found a good specificity of DNA methylation in comparison to currently used techniques. Further larger studies could support the use of FAM19A4/miR124-2 as reliable biomarkers in the prevention of cervical cancer as triage in the screening protocol.

The echocardiographic pulmonary to left atrial ratio: A noninvasive variable for the hemodynamic classification of pulmonary hypertension in dogs.

BACKGROUND: Hemodynamic classification of pulmonary hypertension (PH) has important clinical implications. However, only a few echocardiographic variables have been used to hemodynamically classify PH in dogs. OBJECTIVE: To evaluate the echocardiographic pulmonary to left atrial ratio index (ePLAR) in dogs with PH. ANIMALS: Forty-six dogs with intermediate to high probability of PH. METHODS: Cross-sectional study. Variables were compared between dogs with precapillary PH [PrePH (n = 24)] vs postcapillary PH [PostPH (n = 22)], and with combined PH [CombPH (n = 14)] vs isolated PH [IsoPH (n = 8)] using the t-, Mann-Whitney, Pearson's Chi, or Fisher's exact test. The receiver operating characteristic curve and Youden index were used to identify the optimal ePLAR cutoff value to differentiate among the groups, intraclass correlation coefficients (ICC) were used to determine the reliability of measurements. RESULTS: The mean (SD) ePLAR of the PrePH was higher than that of the PostPH group [0.36 (0.13) vs 0.26 (0.09), respectively; P = .005]. The median (interquartile range) ePLAR of the CombPH was higher than that of the IsoPH subgroup [0.29 (0.24-0.38), vs 0.20 (0.16-0.23), respectively; P = .001]. The best cutoff value of ePLAR for identifying IsoPH was <0.245 [AUC at cutoff point = 0.86; sensitivity (95% confidence interval [CI]) = 0.71 (0.47-0.95); specificity (95% CI) = 1 (0.76-1)]. The ICC analysis indicated a high degree of reliability. CONCLUSIONS AND CLINICAL IMPORTANCE: ePLAR can be considered a valid noninvasive variable to hemodynamically classify PH in dogs with an intermediate to high probability of PH. Assessment of ePLAR can be useful in the therapeutic management of PH in dogs.

The current practice in the diagnostic work-up of patients with hemoptysis of unknown etiology: an international survey.

BACKGROUND: Hemoptysis is a challenging and potentially life-threatening medical condition. The most appropriate diagnostic work-up is debated and several diagnostic approaches are implemented worldwide. METHODS: An international, online survey was carried out to investigate the current practice of the diagnostic work-up of patients with hemoptysis of unknown etiology. RESULTS: Overall, 604 physicians responded to the survey. At baseline, chest X-ray was suggested as the first diagnostic investigation by 342 (56.6%) participants. Computed tomography (CT) was suggested in each patient with non- and life-threatening hemoptysis by 310 (51.3%) and 526 (87.1%) respondents, respectively. Contrast-enhanced CT is the currently preferred technique (333, 55.1%). In case of patchy ground glass opacities and negative CT, 287 (47.5%) and 222 (36.8%) participants, respectively, would always offer bronchoscopy. Otorhinolaryngological evaluation was mostly suggested in case of suspected upper airways bleeding before other investigations (212, 35.1%). A follow-up was recommended for idiopathic hemoptysis by the majority of the participants (316, 52.3%). A multidisciplinary assessment is deemed crucial for each patient with life-threatening hemoptysis (437, 72.4%). CONCLUSIONS: Chest X-ray and contrast-enhanced CT are currently preferred as the first diagnostic investigations, regardless of hemoptysis severity. Bronchoscopy is suggested in case of negative radiological examination and when CT shows only ground glass opacities. Otorhinolaryngological evaluation is advised before any other investigations when upper airways bleeding is suspected. Patients with idiopathic hemoptysis are suggested to undergo a clinical follow-up and in case of life-threatening bleeding a multidisciplinary assessment is deemed crucial. Due to the heterogeneous approaches a consensus statement would be needed.

Lung (extracorporeal CO2 removal) and renal (continuous renal replacement therapy) support: the role of ultraprotective strategy in Covid 19 and non-Covid 19 ARDS. A case-control study.

BACKGROUND: Preliminary studies suggest that moderate ARDS and acute renal failure might benefit from extracorporeal CO2 removal (ECCO2R) coupled with CRRT. However, evidence is limited and potential for this coupled treatment may need to be explored. The aim of the present study was to evaluate whether a protective driving pressure was obtained applying low-flow ECCO2-R plus CRRT in patients affected by moderate ARDS with COVID-19 compared to an historical group without COVID-19. METHODS: A case-control study has been conducted comparing a group of consecutive moderate ARDS patients presenting AKI and affected by COVID-19, who needed low-flow ECCO2-R plus CRRT to achieve an ultra-protective ventilatory strategy, with historical group without COVID-19 that matched for clinical presentation and underwent the same ultra-protective treatment. VT was set at 6 mL/kg predicted body weight then ECCO2R was assessed to facilitate ultra-protective low VT ventilation to preserve safe Pplat and low driving pressure. RESULTS: ECCO2R+CRRT reduced the driving pressure from 17 (14-18) to 11.5 (10-15) cmH2O (p<0.0004) in the fourteen ARDS patients by decreasing VT from 6.7 ml/kg PBW (6.1-6.9) to 5.1 (4.2-5.6) after 1 hour (p <0.0001). In the ARDS patients with COVID-19, the driving pressure reduction was more effective from baseline 18 (14-24) cmH2O to 11 (10-15) cmH2O (p<0.004), compared to the control group from 15 (13-17) to 12(10-16) cmH2O (p< 0.03), after one hour. ECCO2R+CRRT did not affected 28 days mortality in the two groups, while we observed a shorter duration of mechanical ventilation (19 {7-29} vs 24 {22-38} days; p=0.24) and ICU length of stay (19 {7-29} vs 24 {22-78} days; p=0.25) in moderate ARDS patients with COVID-19 compared to control group. CONCLUSIONS: In moderate ARDS patients with or without COVID-19 disease, ECCO2R+CRRT may be and effective supportive treatment to reach protective values of driving pressure unless severe oxygenation defects arise requiring ECMO therapy initiation.

Pulmonary Involvement in Recurrent Respiratory Papillomatosis: A Systematic Review.

Recurrent respiratory papillomatosis (RRP) is a non-malignant disease, characterized by the production of wart-like growths in the respiratory tract, affecting both young people and adults (juvenile-onset recurrent respiratory papillomatosis, JORRP, and adult-onset recurrent respiratory papillomatosis, AORRP, respectively). Infection caused by human papillomavirus (HPV) is known as the main factor involved in RRP development. Complications of RRP may rarely occur, including lung involvement and malignant transformation. The present systematic review aimed to evaluate the prevalence of severe complications, such as lung involvement and lung tumor in JORRP and AORRP patients, and assess the role of HPV genotypes in the progression of disease severity following the guideline for reporting systematic reviews and meta-analysis (PRISMA Statement). A total of 378 studies were found on PubMed and Scopus using the following MESH terms: "recurrent respiratory papillomatosis and lung tumor" and "pulmonary tumor and recurrent respiratory papillomatosis". Basing on inclusion and exclusion criteria, a total of 11 studies were included in the systematic review. We found a pooled prevalence of 8% (95% CI: 4-14%; I2: 87.5%) for lung involvement in RRP patients. In addition, we found a pooled risk difference of 5% in lung involvement between JORRP and AORRP (95% CI: -7-18%; I2: 85.6%, p-value: 0.41). Among patients with lung involvement, we observed a pooled prevalence of lung tumor of 4% (95% CI:1-7%; I2: 67.1%) and a pooled prevalence mortality for this group of 4% (95% CI:2-6%; I2: 0%). Overall, the positivity rate for HPV-6 and -11 in patients with RRP was 91%. Considering only cases with pulmonary involvement, the pooled prevalence for HPV-11 was 21% (95% CI: 5-45%; I2: 77.2%). Our results evidenced a low/middle risk of pulmonary involvement and lung tumor in JORRP and AORRP patients, with an increased risk for HPV-11-positive patients. Further studies should be performed to improve knowledge and adopt preventive measures to contrast the progression to severe diseases in RRP patients.

Epidemiology of seropositive myasthenia gravis in Sardinia: A population-based study in the district of Sassari.

INTRODUCTION/AIMS: The global incidence and prevalence of myasthenia gravis (MG) range between 6-31/million and 10-37/100,000, respectively. Sardinia is a high-risk region for different immune-mediated disorders, but the epidemiology of MG remains unclear. We determined the epidemiology of MG with acetylcholine receptor (AChR)-immunoglobulin G (IgG) and muscle-specific tyrosine kinase (MuSK)-IgG in the district of Sassari (North-Western Sardinia; population, 325,288). METHODS: From the laboratory of the University Hospital of Sassari (reference for AChR/MuSK-IgG testing in Sardinia since 1998) and the main neurology units in Sardinia, we retrospectively identified MG patients with (1) AChR-IgG and/or MuSK-IgG positivity by radioimmunoprecipitation assay; and (2) residency in the district of Sassari. Incidence (January 2010-December 2019) and prevalence (December 31, 2019) were calculated. RESULTS: A total of 202 patients were included (incident, 107; prevalent, 180). Antibody specificities were AChR (n = 187 [93%]) and MuSK (n = 15 [7%]). The crude MG incidence (95% confidence interval) was 32.6 (26.8-39.2)/million, while prevalence was 55.3 (47.7-63.9)/100,000. After age-standardization to the world population, incidence decreased to 18.4 (14.3-22.5)/million, while prevalence decreased to 31.6 (26.1-37.0)/100,000. Among incident cases, age strata (years) at MG onset were: <18 (2%), 18-49 (14%), 50-64 (21%), and ≥65 (63%). DISCUSSION: Sardinia is a high-risk region for MG, with a prevalence that exceeds the European threshold for rare disease. Identification of the environmental and genetic determinants of this risk may improve our understanding of disease pathophysiology.

Epidemiology of aquaporin-4-IgG-positive NMOSD in Sardinia.

PURPOSE: The Italian Island of Sardinia (population, 1,578,146) is recognized for the high risk of multiple sclerosis (MS) but the epidemiological burden of other less common demyelinating diseases of the central nervous system (CNS), such as aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+NMOSD), is unknown. In this study, we determined the incidence and prevalence of AQP4-IgG+NMOSD in Sardinia over a ten-year study period (2013-2022). METHODS: Patients with a diagnosis of AQP4-IgG+NMOSD (per 2015 IPND diagnostic criteria) were retrospectively identified using two sources: (1) Archives of the reference and only laboratory for AQP4-IgG testing in Sardinia; and (2) medical records of the four MS units in the island. Incidence (January 2013-December 2022) and prevalence (December 31, 2022) were calculated. RESULTS: A total of 45 cases were included: incident, 31; prevalent, 41. The median age (range) at disease presentation was 51 (6-78) years; female/male ratio was 9:1. The crude (95 % CI) incidence and prevalence were 1.9 (1.3-2.7) per million and 2.6 (1.9-3.5) per 100,000, respectively. Prevalence increased from 2013 (1.1 per 100,000) to 2022 (2.6 per 100,000); p = 0.002. After age-standardization to the world, incidence and prevalence (95 % CI) decreased to 1.3 (0.7-2) per million and 1.8 (1.3-2.3) per 100,000, respectively. Coexisting immune-mediated disorders, mostly autoimmune thyroiditis, were reported in 50 % of patients. CONCLUSIONS: The epidemiology of AQP4-IgG+NMOSD in Sardinia is overall in line with other Caucasian populations. The high MS risk in the island seems disease-specific and not associated with an increased risk of other CNS demyelinating disorders, confirming different pathophysiology.

Electrocardiography in Children Hospitalized for COVID-19 and Not Suffering from Multisystem Inflammatory Syndrome in Children (MIS-C): An Observational Study.

The risk of cardiac involvement with electrophysiological abnormalities during COVID-19 infection has been reported in adults but remains poorly studied in children. Our aim was to determine the frequency of cardiac involvement and the necessity of routine cardiac evaluation in children hospitalized for COVID-19. This observational study included 127 children, with a median (IQR) age of 2 (0.83-6.0) years, who were hospitalized for COVID-19 between 1 January 2021 and 31 August 2022, 62 (48.8%) of whom were males. Each patient underwent an ECG on admission and discharge as well as a laboratory assessment. A comparison between patients with COVID-19 and healthy controls showed significantly higher HR (p < 0.0001) and lower PR values (p = 0.02) in the first group. No arrhythmias or other electrocardiographic abnormalities were detected during hospitalization. The median levels of troponin, NT-proBNP, ferritin, and D-dimer were significantly higher in children aged <2 years, but they fell within the normal range for their age. Our results indicate that a detectable cardiac involvement is very rare in children hospitalized for COVID-19 and not suffering from Multisystem Inflammatory Syndrome in Children (MIS-C) and suggest that routine electrocardiographic assessment is not mandatory in these patients in the absence of cardiac symptoms/signs.

Diagnostic delay in bronchiectasis: an Italian perspective.

It takes ∼3.5 years to reach a diagnosis of bronchiectasis from onset of symptoms: the long patient's journey in Italy https://bit.ly/46XMWAz.

Vitamin D Status in an Italian Pediatric Cohort: Is There a Role for Tobacco Smoking Exposure?

Introduction: Vitamin D deficiency is a common public health issue worldwide. The purpose of this study was to investigate the vitamin D status and its potential determinants in children residing in Sardinia (40°N), Italy. Methods: A total of 182 children (males: 51.7%; median age: 9 years) were enrolled over a 12-month period. Serum 25(OH)D was measured by an immune-chemiluminescence assay. A questionnaire was used to gather information on other variables, including passive smoke exposure. Results: Mean (SD) serum 25(OH)D was 25.2 (8.3) ng/mL for the whole group. The majority (n=123, 67.6%) of children had vitamin D sufficient values >20 ng/mL, while about 1/3 had vitamin D insufficient/deficient values (≤20 ng/mL (n=59, 32.4%). Among the variables investigated, passive smoke exposure was significantly associated with insufficient 25(OH)D levels (p<0.0001). Conclusion: Our results further prove that hypovitaminosis D is common in the Italian children and documented that passive smoke exposure is a significant risk factor for hypovitaminosis D.

Impact of COVID-19 on patients with beta-thalassemia major: an observational study.

INTRODUCTION:  The prevalence of COVID-19 is slightly lower, and its mortality is higher in beta-thalassemia patients than in the general population. We evaluated the impact of COVID-19 in terms of incidence, clinical course, management, and specific antibody response to vaccination in a cohort of patients with beta-thalassemia major. METHODS:  We retrospectively enrolled all transfusion-dependent beta-thalassemia major patients attending the Thalassemia Day Care Center of the University Hospital of Sassari, Italy, from March 1, 2020, to May 31, 2021. For each patient, demographic, clinical, laboratory, instrumental, and therapy data were collected. Patients aged ≥16 years received two doses of mRNA COVID-19 vaccine. Anti-SARS-CoV-2 serum antibodies were tested before and after the first vaccine dose. RESULTS:  A total of 68 patients (median age: 36.5 years; IQR: 13-42 years) were included. Nasopharyngeal swab (NPS) for SARS-CoV-2 detection by RT-PCR was positive in 5 (7.35%) of 68 patients (4 symptomatic). No COVID-19-related complications, hospitalizations, or deaths were observed. The transfusion regimen and iron chelation therapy were not significantly changed. Prior to COVID-19 vaccination, anti-SARS-CoV-2 antibodies were tested in 61 patients, 51 negative and 10 positive; five of the latter were also positive for SARS-CoV-2 on NPS. The 46 vaccinated subjects had an antibody response, with higher levels in subjects previously infected with SARS-CoV-2. CONCLUSION:   Our findings suggest that patients with beta-thalassemia major are not at a higher risk of contracting SARS-CoV-2 infection and developing a severe form of COVID-19 despite being considered more vulnerable than the general population.

New score to predict COVID-19 progression in vaccine and early treatment era: the COVID-19 Sardinian Progression Score (CSPS).

BACKGROUND: Several scores aimed at predicting COVID-19 progression have been proposed. As the variables vaccination and early SARS-CoV-2 treatment were systematically excluded from the prognostic scores, the present study's objective was to develop a new model adapted to the current epidemiological scenario. METHODS: We included all patients evaluated by the Infectious Disease Unit in Sassari, with SARS-CoV-2 infection and without signs of respiratory failure at the first evaluation (P/F > 300). Disease progression was defined by the prescription of supplemental oxygen. In addition, variables related to demographics, vaccines, comorbidities, symptoms, CT scans, blood tests, and therapies were collected. Multivariate logistic regression modelling was performed to determine factors associated with progression; any variable with significant univariate test or clinical relevance was selected as a candidate for multivariate analysis. Hosmer-Lemeshow (HL) goodness of fit statistic was calculated. Odds ratio values were used to derive an integer score for developing an easy-to-use progression risk score. The discrimination performance of the risk index was determined using the AUC, and the best cut-off point, according to the Youden index, sensitivity, specificity, predictive value, and likelihood ratio, was chosen. RESULTS: 1145 patients [median (IQR) age 74 (62-83) years; 53.5% males] were enrolled; 336 (29.3%) had disease progression. Patients with a clinical progression were older and showed more comorbidities; furthermore, they were less vaccinated and exposed to preventive therapy. In the multivariate logistic regression analysis, age ≥ 60 years, COPD, dementia, haematological tumours, heart failure, exposure to no or one vaccine dose, fever, dyspnoea, GGO, consolidation, ferritin, De Ritis ≥ 1.2, LDH, and no exposure to early anti-SARS-CoV-2 treatment were associated with disease progression. The final risk score ranged from 0 to 45. The ROC curve analysis showed an AUC of 0.92 (95% CI 0.90-0.93) with a 93.7% specificity and 72.9% sensitivity. Low risk was defined when the cut-off value was less than 23. Three risk levels were identified: low (0-23 points), medium (24-35), and high (≥ 36). CONCLUSIONS: The proportion of patients with progression increases with high scores: the assessment of the risk could be helpful for clinicians to plan appropriate therapeutic strategies.

Vaccination and Antiviral Treatment Reduce the Time to Negative SARS-CoV-2 Swab: A Real-Life Study.

Clinical trials demonstrated the role of vaccines and antiviral treatments against SARS-CoV-2 in reducing the likelihood of disease progression and death. However, there are limited data available regarding the time to negativity of people who received these treatments. Further, several comorbidities and risk factors might affect the impact of vaccines and antiviral treatments. To this end, we aimed to evaluate and disentangle the impact of anti-SARS-CoV-2 treatments and that of underlying clinical factors associated with a shortened length of SARS-CoV-2 infection. Hence, we recorded the timeframe of positive nasopharyngeal swab in people infected while being hospitalized for reasons other than SARS-CoV-2 infection. All patients who died or were discharged with a positive swab were excluded from the study. A total of 175 patients were included in this study. Clinical conditions encompass malignancies, immunological disorders, cardiovascular, metabolic, neurodegenerative, and chronic kidney disease. Most of the participants (91.4%) were vaccinated before admission to the hospital, and 65.1% received antiviral treatment within three days after the symptom's onset. Unvaccinated patients had a longer median time to negativity than people who received at least two doses of vaccine (18 vs. 10 days). Concerning the clinical conditions of all patients, multivariate analysis highlighted a lower probability of 14-day conversion of antigenic test positivity in patients with hematological malignancy, including those vaccinated and those exposed to antiviral therapies. In conclusion, our data showed that prompt administration of antiviral treatments accelerates the clearance of SARS-CoV-2. Further, in the elderly patients under study, previous vaccination and antiviral treatment synergize to reduce time to negativity. This translates into a shorter hospitalization time and a lower risk of transmission through patients and connected healthcare workers in a hospital ward setting, with considerable improvement in cost-effective care management.

Comparison of genotypic and phenotypic antimicrobial profile in carbapenemases producing Klebsiella pneumoniae.

BACKGROUND AND AIM: Prompt administration of appropriate antibiotic therapy is crucial in improving outcomes, particularly in cases sustained by multi-drug resistant strains. Although phenotypic antimicrobial susceptibility testing (AST) represents the gold standard to address antibiotics treatment, the long time required to obtained affordable results could negatively affect the prognosis. In contrast, rapid genotypic AST provide essential information for treatment and surveillance program. In order to evaluate the potential adoption of rapid AST in clinical routine, we compared the genotypic and phenotypic antimicrobial profiles of different K.pneumoniae strains, characterized by different expression of carbapenemases-encoding genes. METHODS: A set of 109 strains of Cr-Kp were tested for the antimicrobial drugs by the automatized Vitek II system and, in parallel, to the new combination of ß-lactams/ß-lactamases inhibitors (BL/BLI) by Etest. An antimicrobial resistance index (ARI) was calculated for each strain, assigning each 1 or 0 points based on observed resistance/susceptibility, and dividing the total by the number of antibiotics tested. Kruskal-Wallis test, followed by Dunn's post hoc test (Bonferroni correction), were used to compare quantitative variables among resistance gene subgroups. RESULTS: We observed a higher ARI score in KPC/OXA-48 strains, similar profile in KPC alone and KPC/CTX-M groups and a significant lower resistance in no-carbapenemases-producing group. Same trend was observed in AST for BL/BLI. CONCLUSIONS: These preliminary results showed a close link between genotypic and phenotypic AST, supporting the adoption of rapid AST in cases of severe infections, ensuring to saving time and providing, the surveillance of MDR strains and improving stewardship programs.

Stratification of Amniotic Fluid Cells and Amniotic Fluid by Sex Opens Up New Perspectives on Fetal Health.

Amniotic fluid is essential for fetus wellbeing and is used to monitor pregnancy and predict fetal outcomes. Sex affects health and medicine from the beginning of life, but knowledge of its influence on cell-depleted amniotic fluid (AF) and amniotic fluid cells (AFCs) is still neglected. We evaluated sex-related differences in AF and in AFCs to extend personalized medicine to prenatal life. AFCs and AF were obtained from healthy Caucasian pregnant women who underwent amniocentesis at the 16th-18th week of gestation for advanced maternal age. In the AF, inflammation biomarkers (TNFα, IL6, IL8, and IL4), malondialdehyde, nitrites, amino acids, and acylcarnitines were measured. Estrogen receptors and cell fate (autophagy, apoptosis, senescence) were measured in AFCs. TNFα, IL8, and IL4 were higher in female AF, whereas IL6, nitrites, and MDA were similar. Valine was higher in male AF, whereas several acylcarnitines were sexually different, suggesting a mitochondrial involvement in establishing sex differences. Female AFCs displayed higher expression of ERα protein and a higher ERα/ERß ratio. The ratio of LC3II/I, an index of autophagy, was higher in female AFCs, while LC3 gene was similar in both sexes. No significant sex differences were found in the expression of the lysosomal protein LAMP1, while p62 was higher in male AFCs. LAMP1 gene was upregulated in male AFCs, while p62 gene was upregulated in female ones. Finally, caspase 9 activity and senescence linked to telomeres were higher in female AFCs, while caspase 3 and ß-galactosidase activities were similar. This study supports the idea that sex differences start very early in prenatal life and influence specific parameters, suggesting that it may be relevant to appreciate sex differences to cover knowledge gaps. This might lead to improving the diagnosis of risk prediction for pregnancy complications and achieving a more satisfactory monitoring of fetus health, even preventing future diseases in adulthood.

Thirty-Day Complications, Unplanned Hospital Encounters, and Mortality after Endosonography and/or Guided Bronchoscopy: A Prospective Study.

BACKGROUND AND OBJECTIVE: Limited data exist regarding the adverse events of advanced diagnostic bronchoscopy, with most of the available information derived from retrospective datasets that primarily focus on early complications. METHODS: We conducted a 15-month prospective cohort study among consecutive patients undergoing endosonography and/or guided bronchoscopy under general anesthesia. We evaluated the 30-day incidence of severe complications, any complication, unplanned hospital encounters, and deaths. Additionally, we analyzed the time of onset (immediate, within 1 h of the procedure; early, 1 h-24 h; late, 24 h-30 days) and identified risk factors associated with these events. RESULTS: Thirty-day data were available for 697 out of 701 (99.4%) enrolled patients, with 85.6% having suspected malignancy and multiple comorbidities (median Charlson Comorbidity Index (IQR): 4 (2-5)). Severe complications occurred in only 17 (2.4%) patients, but among them, 10 (58.8%) had unplanned hospital encounters and 2 (11.7%) died within 30 days. A significant proportion of procedure-related severe complications (8/17, 47.1%); unplanned hospital encounters (8/11, 72.7%); and the two deaths occurred days or weeks after the procedure. Low-dose attenuation in the biopsy site on computed tomography was independently associated with any complication (OR: 1.87; 95% CI 1.13-3.09); unplanned hospital encounters (OR: 2.17; 95% CI 1.10-4.30); and mortality (OR: 4.19; 95% CI 1.74-10.11). CONCLUSIONS: Severe complications arising from endosonography and guided bronchoscopy, although uncommon, have significant clinical consequences. A substantial proportion of adverse events occur days after the procedure, potentially going unnoticed and exerting a negative clinical impact if a proactive surveillance program is not implemented.

Adenotonsillectomy in Children with Obstructive Sleep Apnea Syndrome: Clinical and Functional Outcomes.

Adenotonsillectomy (AT) is the first-line treatment for pediatric obstructive sleep apnea syndrome (OSAS). Relatively few studies have evaluated the clinical and functional outcomes of AT in children with OSAS, but these studies show that surgery improves behavior and quality of life (QOL). However, residual OSAS after AT is reported in severe cases. This study aimed to retrospectively evaluate the clinical and functional outcomes of AT in a cohort of children with OSAS. We consecutively enrolled children with OSAS who underwent AT and were admitted to our clinic from 1 July 2020 to 31 December 2022. For each participant, medical history and physical examinations were performed. Before and after surgery, all patients underwent a standard polygraphic evaluation, and caregivers completed the OSA-18 questionnaire. A total of 65 children with OSAS, aged 2-9 years, were included. After AT, 64 (98.4%) children showed a reduction in AHI, with median (IQR) values decreasing from 13.4/h (8.3-18.5/h) to 2.4/h (1.8-3.1/h) (p-value < 0.0001). Conversely, median (IQR) SpO2 nadir increased after surgery from 89% (84-92%) to 94% (93-95%) (p-value < 0.0001). Moreover, 27 children (18%) showed residual OSAS. The OSA-18 score decreased after AT from median (IQR) values of 84 (76-91) to values of 33 (26-44) (p-value < 0.0001). A positive significant correlation was found between OSA-18 post-operative scores and AHI post-operative scores (rho 0.31; p-value = 0.01). Our findings indicate that, in children with OSAS, AT is associated with significant improvements in behavior, QOL, and polygraphic parameters. However, long-term post-surgical follow-up to monitor for residual OSAS is highly recommended, especially in more severe cases.

Preliminary Results of Feasibility and Acceptability of Self-Collection for Cervical Screening in Italian Women.

BACKGROUND: Given the diagnostic accuracy of HPV-DNA tests in terms of self-collected samples, in order to implement self-sampling in cervical screening programs, the standardization of the pre-analytical phase, including decisions concerning the choice of medium, the volume of elution, and storage conditions, are necessary, in addition to understanding the potential factors involved in acceptability by women. On this basis, we carried out a cross-sectional study to assess (i) the stability of dry vaginal self-collected samples stored at room temperature for up to 4 weeks after elution in 2 mL of eNat® (Copan) medium, and (ii) the acceptability of self-collection in enrolled women. METHODS: 185 women were enrolled in the LILT (Italian League Against Tumors) regional project. A self-sampling kit, including a dry FLOQSwab® (Copan), instructions for use, and a satisfaction questionnaire, were supplied for each woman and sent by mail to the laboratory. The HPV-DNA test was carried out using the Anyplex™ II HPV HR (Seegene) kit. To evaluate the specimen's stability, 185 dry vaginal swabs were eluted in eNat®, a lyses-based molecular medium and tested for HPV detection at two different time points (<6 days and 1 month after elution). The Cohen's Kappa coefficients and McNemar test were used to assess the agreement of HPV-DNA at different times. RESULTS: We found high agreement in terms of HPV-DNA results among the samples tested at two different time points (Cohen K = 0.98; p < 0.0001). Moreover, most of the women found it easy to use self-collection devices and the pictorial instructions clear to understand. Approximately half of the enrolled women declared preferring self-sampling to clinician-collected methods. CONCLUSION: Our results display the high reliability and accuracy of HPV-DNA tests using dry vaginal self-collection FLOQSwabs® devices eluted in 2 mL of molecular medium. The analysis of the questionnaire showed a high acceptability of self-collection among women, although a high percentage preferred standard collection devices. Overall, our preliminary results support the adoption of self-collection in screening programs, even though further analyses should be performed to optimize and standardize protocols for HPV tests on self-samples, and educational campaigns are needed to adequately inform and increase responsiveness in a target population.

International fitness scale (IFIS): association with motor performance in children with obesity.

Background: Overweight and obesity are defined as abnormal or excessive fat accumulation that presents a risk to health; and compared with their normal-weight peers, these individuals tend to have a lower level of self-confidence, and consequently lower physical activity adherence. Due to these self-perceived barriers, the aim of our study was to evaluate the efficacy of an online training program on self-reported physical fitness (SRPF) in children with obesity (OB). Methods: A total of 32 children with OB carried out physical fitness (PF) tests and were asked to complete the International Fitness Enjoyment Scale (IFIS) questionnaire. The physical fitness tests were the Standing Broad Jump (SBJ), the 6-Min Walking Test (6MWT) and the 4 × 10 m sprint test. Children participated in a 3-weekly 60-min training session through Zoom platform. Before the beginning of the training protocol, OB children were compared with normal weight (NW) ones for PF batteries and the IFIS questionnaire. Changes in performances after the training were assessed by paired Student t and Wilcoxon tests. Results: After the online training program children increased their performance in 6MWT (mean difference (MD) = 54.93; p < 0.0001) in SBJ (MD = 10.00; p = 0.0001) and in 4 × 10 m sprint test (MD = -0.78; p < 0.0001). No differences were found in children's physical fitness perception. Discussion: Our study highlighted how a structured online training program can lead to improvements in PF of children with OB. Instead, the lack of differences in SRPF after the training suggests interesting questions to be explored on the aspects linked to self-perception. Therefore, even if our training protocol could not directly improve SRPF in children with obesity, the enhancement of their PF could be a starting point for achieving this result with a longer training period and consequently improve PA participation for children with OB.