Serum Biomarkers to Dynamically Predict the Risk of Cardiovascular Events in Patients under Oncologic Therapy. A Multicenter Observational Study.

Background: Serum biomarkers have been investigated as predictive risk factors for cancer-related cardiovascular (CV) risk, but their analysis is limited to their baseline level rather than their overtime change. Besides historically validated causal factors, inflammatory and oxidative stress (OS) related markers seem to be correlated to CV events but this association needs to be further explored. We conducted an observational study to determine the predictive role of the longitudinal changes of commonly used and OS-related biomarkers during the cancer treatment period. Methods: Patients undergoing anticancer therapies, either aged 75+ years old or younger with an increased CV risk according to European Society of Cardiology guidelines, were enrolled. We assessed the predictive value of biomarkers for the onset of CV events at baseline and during therapy using Cox model, Subpopulation Treatment-Effect Pattern Plot (STEPP) method and repeated measures analysis of longitudinal data. Results: From April 2018 to August 2021, 182 subjects were enrolled, of whom 168 were evaluable. Twenty-eight CV events were recorded after a median follow up of 9.2 months (Interquartile range, IQR: 5.1-14.7). Fibrinogen and troponin levels were independent risk factors for CV events. Specifically, patients with higher than the median levels of fibrinogen and troponin at baseline had higher risk compared with patients with values below the medians, hazard ratio (HR) = 3.95, 95% CI, 1.25-12.45 and HR = 2.48, 0.67-9.25, respectively. STEPP analysis applied to Cox model showed that cumulative event-free survival at 18 and 24 months worsened almost linearly as median values of fibrinogen increased. Repeated measure analysis showed an increase over time of D-Dimer (p-interaction event*time = 0.08), systolic (p = 0.07) and diastolic (p = 0.05) blood pressure and a decrease of left ventricular ejection fraction (p = 0.15) for subjects who experienced a CV event. Conclusions: Higher levels of fibrinogen and troponin at baseline and an increase over time of D-Dimer and blood pressure are associated to a higher risk of CV events in patients undergoing anticancer therapies. The role of OS in fibrinogen increase and the longitudinal monitoring of D-dimer and blood pressure levels should be further assessed.

Effects of COVID-19-targeted non-pharmaceutical interventions on pediatric emergency department use: a quasi-experimental study interrupted time-series analysis in North Italian hospitals, 2017 to 2022.

Background: The use of Non-Pharmaceutical Interventions (NPIs) during the COVID-19 pandemic is debated. Understanding the consequences these measures may have on vulnerable populations including children and adolescents is important. Methods: This is a multicenter, quasi-experimental before-after study involving 12 hospitals of the North Italian Emilia-Romagna Region, with NPI implementation as the intervention event. The 3 years preceding NPI implementation (in March 2020) constituted the pre-pandemic phase. The subsequent 2 years were further subdivided into a school closure phase (SC) and a subsequent mitigation measures phase (MM) with milder restrictions. Interrupted Time Series (ITS) regression analysis was used to calculate PED Standardized Incidence Rate Ratios (SIRR) on the diagnostic categories exhibiting the greatest frequency and/or variation. Results: In the 60 months of the study there were 765,215 PED visits. Compared to the pre-pandemic rate, overall PED presentations dropped by 58 and 39% during SC and MM, respectively. "Symptoms, signs and Ill-defined conditions," "Injury and poisoning" and "Diseases of the Respiratory System" accounted for 74% of the reduction. A different pattern was instead seen for "Mental Disorders," which exhibited the smallest decrease during SC, and is the only category which rose already at the end of SC. ITS analysis confirmed the strong decrease during SC (level change, IRR 0.17, 95%CI 0.12-0.27) and a significant increase in MM (slope change, IRR 1.23, 95%CI 1.13-1.33), with the sharpest decline (-94%) and rise (+36%) observed in the "Diseases of the Respiratory System" category. Mental Disorders showed a significant increasing trend of 1% monthly over the whole study period exceeding pre-pandemic levels at the end of MM. Females and adolescents showed higher increasing rates both in SC and MM. Conclusion: NPIs appear to have influenced PED attendance in different ways according to diagnostic categories, mirroring different mechanisms of action. These effects are beneficial in some cases and harmful in others, and establishing a clear balance between pros and cons is a difficult task for public health decision makers. The role of NPIs on PED use appropriateness deserves investigation. The rise in pediatric mental disorders independent of the pandemic makes interventions addressing these issues urgent.

High prevalence of orofacial pain in juvenile fibromyalgia as detected by a novel tool specifically devised for children and adolescents.

OBJECTIVES: To examine the prevalence of temporomandibular disorders (TMD) in patients with juvenile fibromyalgia syndrome (JFS) and identify TMD characteristics specifically associated to JFS. METHODS: Signs and symptoms of TMD were assessed using a novel clinical tool specifically devised for children that consists of: 1. a self-report multiple-choice questionnaire; 2. a protocol for the clinical examination of the orofacial region. Multivariate logistic regression model was used to identify TMD features associated with JFS. RESULTS: Thirty JFS patients (median age 15.5 years) and 45 healthy controls (median age 15.0 years) were included in this cross-sectional study. Orofacial pain was reported by 26 of 30 JFS patients (86.7%) and by 3 of 45 controls (6.7%; p<0.001). Pain on TMJ palpation was present in 18 of 30 JFS patients (60%) and in 5 of 45 controls (11.1%; p<0.001). Median values of maximum spontaneous mouth opening, voluntary active opening and assisted passive opening were significantly higher in JFS patients than in controls. On multiple regression analysis spontaneous orofacial pain (OR: 21.0; p=0.005), diffuse tenderness on palpation of the masticatory muscles (OR: 14.9; p=0.026) and TMJ hypermobility (OR 1.42; p=0.008) were independently associated with JFS. CONCLUSIONS: The high prevalence of TMD in JFS highlights the need for a broader interdisciplinary evaluation of JFS patients. TMJ hypermobility, in addition to orofacial and masticatory muscle pain, is an important clue for the diagnosis of TMD in adolescents with JFS. Elucidating the link between these disorders will advance individualised management and improve treatment efficacy.

Effects of COVID-19-targeted non-pharmaceutical interventions on pediatric hospital admissions in North Italian hospitals, 2017 to 2022: a quasi-experimental study interrupted time-series analysis.

Background: The use of Non-Pharmaceutical Interventions (NPIs), such as lockdowns, social distancing and school closures, against the COVID-19 epidemic is debated, particularly for the possible negative effects on vulnerable populations, including children and adolescents. This study therefore aimed to quantify the impact of NPIs on the trend of pediatric hospitalizations during 2 years of pandemic compared to the previous 3 years, also considering two pandemic phases according to the type of adopted NPIs. Methods: This is a multicenter, quasi-experimental before-after study conducted in 12 hospitals of the Emilia-Romagna Region, Northern Italy, with NPI implementation as the intervention event. The 3 years preceding the beginning of NPI implementation (in March 2020) constituted the pre-pandemic phase. The subsequent 2 years were further subdivided into a school closure phase (up to September 2020) and a subsequent mitigation measures phase with less stringent restrictions. School closure was chosen as delimitation as it particularly concerns young people. Interrupted Time Series (ITS) regression analysis was applied to calculate Hospitalization Rate Ratios (HRR) on the diagnostic categories exhibiting the greatest variation. ITS allows the estimation of changes attributable to an intervention, both in terms of immediate (level change) and sustained (slope change) effects, while accounting for pre-intervention secular trends. Results: Overall, in the 60 months of the study there were 84,368 cases. Compared to the pre-pandemic years, statistically significant 35 and 19% decreases in hospitalizations were observed during school closure and in the following mitigation measures phase, respectively. The greatest reduction was recorded for "Respiratory Diseases," whereas the "Mental Disorders" category exhibited a significant increase during mitigation measures. ITS analysis confirms a high reduction of level change during school closure for Respiratory Diseases (HRR 0.19, 95%CI 0.08-0.47) and a similar but smaller significant reduction when mitigation measures were enacted. Level change for Mental Disorders significantly decreased during school closure (HRR 0.50, 95%CI 0.30-0.82) but increased during mitigation measures by 28% (HRR 1.28, 95%CI 0.98-1.69). Conclusion: Our findings provide information on the impact of COVID-19 NPIs which may inform public health policies in future health crises, plan effective control and preventative interventions and target resources where needed.

Real-world outcomes of Italian patients with advanced non-squamous lung cancer treated with first-line pembrolizumab plus platinum-pemetrexed.

PURPOSE: The aim of this multi-center, retrospective/prospective cohort observational study was to evaluate outcomes in routine clinical practice of first-line chemo-immunotherapy with cis/carboplatin, pemetrexed and pembrolizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC) in 33 Italian centers. METHODS: The outcome measure was to evaluate overall survival (OS) in a real-world patient population. Secondary endpoints were: progression-free survival (PFS), objective response rate (ORR), duration of response (DoR) and incidence of treatment-related adverse events (AEs). RESULTS: 1068 patients were enrolled at the time of data cut-off (January 31st, 2023), and 812 (76.0%) belonged to the retrospective cohort. Median age was 66 years (27-85), ECOG PS was ≥ 2 in 91 (8.6%) patients; 254 (23.8%) patients had brain metastases at baseline; 38 (3.6%) patients had tumor with PD-L1 expression ≥ 50%. After a median follow-up of 17.0 months (95% CI, 16.1-17.9), median OS was 16.1 months (95% CI, 14.4-18.8) and PFS was 9.9 months (95% CI, 8.8-11.2). Median DoR (n = 493) was 14.7 months (95% CI, 13.6-17.1). ORR was 43.4% (95% CI, 40.4-46.4). Any-grade AEs occurred in 636 (59.6%) patients and grade ≥ 3 in 253 (23.7%) patients. Most common grade ≥ 3 AEs were neutropenia (6.3%) and anemia (6.3%). CONCLUSIONS: First-line chemo-immunotherapy was effective and tolerable in this large, real-world Italian study of patients with advanced non-squamous NSCLC. Our results were in line with the KEYNOTE-189 registration study, also considering the low number of PD-L1 ≥ 50% patients included in our study.

Procalcitonin for the diagnosis of postoperative bacterial infection after adult cardiac surgery: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Patients undergoing cardiac surgery are subject to infectious complications that adversely affect outcomes. Rapid identification is essential for adequate treatment. Procalcitonin (PCT) is a noninvasive blood test that could serve this purpose, however its validity in the cardiac surgery population is still debated. We therefore performed a systematic review and meta-analysis to estimate the accuracy of PCT for the diagnosis of postoperative bacterial infection after cardiac surgery. METHODS: We included studies on adult cardiac surgery patients, providing estimates of test accuracy. Search was performed on PubMed, EmBase and WebOfScience on April 12th, 2023 and rerun on September 15th, 2023, limited to the last 10 years. Study quality was assessed with the QUADAS-2 tool. The pooled measures of performance and diagnostic accuracy, and corresponding 95% Confidence Intervals (CI), were calculated using a bivariate regression model. Due to the variation in reported thresholds, we used a multiple-thresholds within a study random effects model for meta-analysis (diagmeta R-package). RESULTS: Eleven studies were included in the systematic review, and 10 (2984 patients) in the meta-analysis. All studies were single-center with observational design, five of which with retrospective data collection. Quality assessment highlighted various issues, mainly concerning lack of prespecified thresholds for the index test in all studies. Results of bivariate model analysis using multiple thresholds within a study identified the optimal threshold at 3 ng/mL, with a mean sensitivity of 0.67 (0.47-0.82), mean specificity of 0.73 (95% CI 0.65-0.79), and AUC of 0.75 (IC95% 0.29-0.95). Given its importance for practice, we also evaluated PCT's predictive capability. We found that positive predictive value is at most close to 50%, also with a high prevalence (30%), and the negative predictive value was always > 90% when prevalence was < 20%. CONCLUSIONS: These results suggest that PCT may be used to help rule out infection after cardiac surgery. The optimal threshold of 3 ng/mL identified in this work should be confirmed with large, well-designed randomized trials that evaluate the test's impact on health outcomes and on the use of antibiotic therapy. PROSPERO Registration number CRD42023415773. Registered 22 April 2023.

True prevalence of long COVID in children: a narrative review.

Contrary to what is true for adults, little is known about pediatric long COVID (LC). Studies enrolling children are relatively few and extremely heterogeneous. This does not allow to draw definitive conclusions on the frequency and pathogenesis of pediatric LC and limits the development of appropriate and effective measures to contain the clinical, social and economic impact of this condition on the pediatric population. Depending on the methods used to collect and analyze data, studies have found that the incidence rate of pediatric LC may vary from about 25% to less than 5%. However, despite true prevalence of pediatric LC cannot be exactly defined, studies comparing children with previous COVID-19 and uninfected controls have shown that most of the clinical manifestations detected in infected children, mainly mood symptoms, mental health disorders and heart abnormalities could be diagnosed with similar frequency and severity in uninfected subjects also. This seems to indicate that SARS-CoV-2 is the cause of pediatric LC only in a part of children and other factors play a relevant role in this regard. Pandemic itself with the persistent disruption of child lives may have caused persistent stress in all the pediatric population causing mood symptoms, mental health disorders or several organ and body system functional alterations, regardless SARS-CoV-2 infection. These suppositions suggest the need for long-term physical control of all the children after COVID-19 especially when they were already suffering from an underlying disease or have had a severe disease. Moreover, attention should be paid to the assessment of change in children's emotional and behavioral functioning in order to assure adequate interventions for the best emotional and behavioral well being. However, whatever its origin, it seems highly likely that the prevalence of the pediatric LC is set to decline in the future. Preliminary observations seem to suggest that recently developed SARS-CoV-2 variants are associated with less severe COVID-19. This suggests that, as already seen in adults, a lower number of pediatric virus-associated LC cases should occur. Furthermore, the use of COVID-19 vaccines, reducing incidence and severity of SARS-CoV-2 infection, may reduce risk of LC development. Finally, elimination of restrictive measures should significantly reduce mood symptoms and mental health disorders.

Impact of Age and Sex Interaction on Post-Acute Sequelae of COVID-19: An Italian Cohort Study on Adults and Children.

Identifying factors predisposing individuals to post-acute sequelae of COVID-19 (PASC) would allow for the timely treatment of those vulnerable. Attention on the role of sex and age is growing, but published studies have shown mixed results. Our objective was to estimate the effect modification of age on sex as a risk factor for PASC. We analyzed data from two longitudinal prospective cohort studies on adult and pediatric subjects positive to SARS-CoV-2 infection that were enrolled between May 2021 and September 2022. Age classes (≤5, 6-11, 12-50, >50 years) were based on the potential role of sex hormones on inflammatory/immune and autoimmune processes. A total of 452 adults and 925 children were analyzed: 46% were female and 42% were adults. After a median follow-up of 7.8 months (IQR: 5.0 to 9.0), 62% of children and 85% of adults reported at least one symptom. Sex and age alone were not significantly associated to PASC, but their interaction was statistically significant (p-value = 0.024): the risk was higher for males aged 0-5 (females vs. males HR: 0.64, 95% CI: 0.45-0.91, p = 0.012) and for females aged 12-50 (HR: 1.39, 95% CI: 1.04-1.86, p = 0.025), especially those in the cardiovascular, neurological, gastrointestinal and sleep categories. Further research on PASC with regard to sex and age is warranted.

Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Recurrence in Breast Noninvasive Neoplasia: A 10-Year Follow-Up of TAM-01 Study.

PURPOSE: Five-year data of the phase III trial TAM-01 showed that low-dose tamoxifen at 5 mg once daily administered for 3 years in women with intraepithelial neoplasia (IEN) reduced by 52% the recurrence of invasive breast cancer or ductal carcinoma in situ (DCIS), without additional adverse events over placebo. Here, we present the 10-year results. METHODS: We randomly assigned 500 women with breast IEN (atypical ductal hyperplasia, lobular carcinoma in situ [LCIS], or hormone-sensitive or unknown DCIS) to low-dose tamoxifen or placebo after surgery with or without irradiation. The primary end point was the incidence of invasive breast cancer or DCIS. RESULTS: The TAM-01 population included 500 women (20% atypical ductal hyperplasia, 11% LCIS, and 69% DCIS). The mean (±SD) age at the start of treatment was 54 ± 9 years, and 58% of participants were postmenopausal. After a median follow-up of 9.7 years (IQR, 8.3-10.9 years), 66 breast cancers (15 in situ; 51 invasive) were diagnosed: 25 in the tamoxifen group and 41 in the placebo group (annual rate per 1,000 person-years, 11.3 with tamoxifen v 19.5 with placebo; hazard ratio [HR], 0.58; 95% CI, 0.35 to 0.95; log-rank P = .03). Most recurrences were invasive (77%) and ipsilateral (59%). Regarding contralateral breast cancer incidence, there were six events in the tamoxifen arm and 16 in the placebo arm (HR, 0.36; 95% CI, 0.14 to 0.92; P = .025). The number needed to be treated to prevent one case of breast event with tamoxifen therapy was 22 in 5 years and 14 in 10 years. The benefit was seen across all patient subgroups. There was a significant 50% reduction of recurrence with tamoxifen in the DCIS cohort, which represents 70% of the overall population (HR, 0.50; 95% CI, 0.28 to 0.91; P = .02). No between-group difference in the incidence of serious adverse events was reported during the prolonged follow-up period. CONCLUSION: Tamoxifen 5 mg once daily for 3 years significantly prevents recurrence from noninvasive breast cancer after 7 years from treatment cessation without long-term adverse events.

Diagnostic effectiveness of [18F]Fluoroestradiol PET/CT in oestrogen receptor-positive breast cancer: the key role of histopathology. Evidence from an international multicentre prospective study.

INTRODUCTION: [18F]Fluoroestradiol ([18F]FES) PET/CT has been proposed as a tool for detecting the oestrogen receptor density in patients with metastatic breast cancer (BC) non-invasively across all disease localizations. However, its diagnostic potential in terms of the detection rate (DR) of metastases is unclear. In this study, we pitted this method against [18F]FDG PET/CT and tried to identify predictors of the diagnostic superiority of the [18F] FES-based method. MATERIALS AND METHODS: From a multicentre database, we enrolled all patients with metastatic BC who had undergone both [18F]FES PET/CT and [18F]FDG PET/CT. Two readers assessed both images independently and used a patient-based (PBA) and lesion-based analysis (LBA) to calculate the DR. Pathology-related and clinical factors were tested as predictors of [18F]FES PET/CT superiority using a multivariate model. RESULTS: 92 patients, bearing a total of 2678 metastases, were enrolled. On PBA, the DR of [18F]FDG and [18F]FES PET/CT was 97% and 86%, respectively (p = 0.018). On LBA, the [18F]FES method proved more sensitive than [18F]FDG PET/CT in lymph nodes, bone, lung and soft tissue (p < 0.01). This greater sensitivity was associated with lobular histology, both on PBA (Odds Ratio (OR) 3.4, 95%CI 1.0-12.3) and on LBA (OR 4.4, 95%CI 1.2-16.1 for lymph node metastases and OR 3.29, 95%CI 1.1-10.2 for bone localizations). CONCLUSIONS: The overall DR of [18F]FES PET/CT appears to be lower than that of [18F]FDG PET/CT on PBA. However, the [18F]FES method, if positive, can identify more lesions than [18F]FDG at most sites. The higher sensitivity of [18F]FES PET/CT was associated with lobular histology.

The FDG Pattern of Autonomously Functioning Thyroid Nodules Correlates With Thyroid-Stimulating Hormone and Histopathology.

PURPOSE OF THE REPORT: Whereas the 18 F-FDG PET/CT pattern of malignant thyroid neoplasia is known, the glucose uptake of autonomously functioning thyroid nodules (AFTNs) has not been fully investigated. We aimed to analyze the FDG uptake of AFTNs and its correlation with clinical, laboratory, ultrasonography, and histological features. METHODS: We retrospectively analyzed the records of all AFTN patients from 2 centers, in which an 18 F-FDG PET/CT, thyroid function tests, and neck ultrasound were available within a 3-month window from the thyroid scintigraphy. Forty-five patients (35 female patients; median age, 65 years) were retrospectively included. The presence of FDG uptake was compared with the laboratory data and, whenever available, the histology. RESULTS: Over a 36-month follow-up, 20 patients underwent surgery; 4 cancers, 10 follicular adenomas, and 6 follicular hyperplasias were found. Twenty-two AFTNs (48.9%) were FDG-positive, whereas the remaining 23 (51.1%) were not. Thyroid-stimulating hormone (TSH) was significantly lower in FDG-positive AFTNs than in negative ones (0.055 [0.02-0.42] vs 0.65 [0.2-0.96] mIU/L, P = 0.0018). On multivariate analysis, only TSH was independently associated with FDG uptake ( P = 0.008). On receiver operating characteristic curve analysis, TSH <0.08 mIU/L indicated FDG-positive AFTNs, with 64% sensitivity, 87% specificity, 4.88 positive likelihood ratio, and 0.42 negative likelihood ratio. In histologically proven benign lesions, TSH was significantly lower in follicular adenomas than in follicular hyperplasias ( P < 0.001). Patients with cancer had TSH in the low-normal range. CONCLUSIONS: Autonomously functioning thyroid nodules show heterogeneous uptake FDG pattern, which depends on histopathology and thyroid function. Particularly, follicular adenomas tend to display increased glucose uptake and suppressed TSH.

The Effects of Patient-Reported Outcome Screening on the Survival of People with Cancer: A Systematic Review and Meta-Analysis.

This study examined the effects of the routine assessment of patient-reported outcomes (PROs) on the overall survival of adult patients with cancer. We included clinical trials and observational studies with a control group that compared PRO monitoring interventions in cancer clinical practice to usual care. The Cochrane risk-of-bias tools were used. In total, six studies were included in the systematic review: two randomized trials, one population-based retrospectively matched cohort study, two pre−post with historical control studies and one non-randomized controlled trial. Half were multicenter, two were conducted in Europe, three were conducted in the USA and was conducted in Canada. Two studies considered any type of cancer, two were restricted to lung cancer and two were restricted to advanced forms of cancer. PRO screening was electronic in four of the six studies. The meta-analysis included all six studies (intervention = 130.094; control = 129.903). The pooled mortality outcome at 1 year was RR = 0.77 (95%CI 0.76−0.78) as determined by the common effect model and RR = 0.82 (95%CI 0.60−1.12; p = 0.16) as determined by the random-effects model. Heterogeneity was statistically significant (I2 = 73%; p < 0.01). The overall risk of bias was rated as moderate in five studies and serious in one study. This meta-analysis seemed to indicate the survival benefits of PRO screening. As routine PRO monitoring is often challenging, more robust evidence regarding the effects of PROs on mortality would support systematic applications.

Association between multidimensional prognostic index (MPI) and pre-operative delirium in older patients with hip fracture.

Pre-operative delirium may cause delay in surgical intervention in older patients hospitalized for hip fracture. Also it has been associated with higher risk of post-surgical complications and worst functional outcomes. Aim of this retrospective cohort study was to evaluate whether the multidimensional prognostic index (MPI) at hospital admission was associated with pre-operative delirium in older individuals with hip fracture who are deemed to require surgical intervention. Consecutive older patients (≥ 65 years) with hip fracture underwent a comprehensive geriatric assessment to calculate the MPI at hospital admission. According to previously established cut-offs, MPI was expressed in three grades, i.e. MPI-1 (low-risk), MPI-2 (moderate-risk) and MPI-3 (high risk of mortality). Pre-operative delirium was assessed using the four 'A's Test. Out of 244 older patients who underwent surgery for hip fracture, 104 subjects (43%) received a diagnosis of delirium. Overall, the incidence of delirium before surgery was significantly higher in patients with more severe MPI score at admission. Higher MPI grade (MPI-3) was independently associated with higher risk of pre-operative delirium (OR 2.45, CI 1.21-4.96). Therefore, the MPI at hospital admission might help in early identification of older patients with hip fracture at risk for pre-operative delirium.

Can we get out of the COVID pandemic without adequate vaccination coverage in the pediatric population?

BACKGROUND: During the first and second COVID-19 pandemic waves, children, despite susceptible to SARS-CoV-2 infection, appeared at lower risk of severe disease, hospitalization, and death than adults and the elderly. Moreover, they seemed to play a minor role in the diffusion of the virus. The aim of this manuscript is to show epidemiological surveillance on COVID-19 incidence and hospitalization in the pediatric cohort in order to explain the importance of an adequate COVID-19 vaccination coverage in the pediatric population. METHODS: All subjects with documented SARS-CoV-2 infection diagnosed in Parma, Italy, between February 21st, 2020, and January, 31st, 2022, were recruited in this epidemiological surveillance. Diagnosis of infection was established in presence of at least one respiratory specimen positive for SARS-CoV-2 nucleic acid using a validated real-time reverse-transcriptase polymerase-chain-reaction (RT-PCR) assay. RESULTS: The number of COVID-19 pediatric cases remained very low and lower than that recorded in the general population between early February 2020 and the end of October 2021, despite in the last part of this period the Delta variant emerged. On the contrary, starting from November 2021, a sharp and significant increase in COVID-19 incidence in the pediatric population was evidenced. This was detected in all the age groups, although greater in the populations aged 5-11 and 12-17 years old. Interestingly, the peak in hospitalization rate was observed in children < 5 years old, for whom COVID-19 vaccination is not approved yet. At the beginning of November 2021 among people older than 18 years of age 85.7% had completed the primary series of COVID-19 vaccine. Almost all the infants and pre-school children were susceptible. Until January 31st, 2022, 80.4% of adolescents aged 11-17 years had received at least two doses of COVID-19 vaccine and only 52.4% received the booster. Among children 5-11 years old, on January 31st, 2022, only 28.5% had received at least one vaccine dose. CONCLUSIONS: Compared with adults and the elderly, presently a greater proportion of children and adolescents is susceptible to SARS-CoV-2 and could play a relevant role for the prolongation of the COVID-19 pandemic. Only a rapid increase in vaccination coverage of the pediatric populations can effectively counter this problem.

Peri-Operative Prophylaxis in Patients of Neonatal and Pediatric Age Subjected to Cardiac and Thoracic Surgery: A RAND/UCLA Appropriateness Method Consensus Study.

Surgical site infections (SSIs) represent a potential complication of surgical procedures, with a significant impact on mortality, morbidity, and healthcare costs. Patients undergoing cardiac surgery and thoracic surgery are often considered patients at high risk of developing SSIs. This consensus document aims to provide information on the management of peri-operative antibiotic prophylaxis for the pediatric and neonatal population undergoing cardiac and non-cardiac thoracic surgery. The following scenarios were considered: (1) cardiac surgery for the correction of congenital heart disease and/or valve surgery; (2) cardiac catheterization without the placement of prosthetic material; (3) cardiac catheterization with the placement of prosthetic material; (4) implantable cardiac defibrillator or epicardial pacemaker placement; (5) patients undergoing ExtraCorporal Membrane Oxygenation; (6) cardiac tumors and heart transplantation; (7) non-cardiac thoracic surgery with thoracotomy; (8) non-cardiac thoracic surgery using video-assisted thoracoscopy; (9) elective chest drain placement in the pediatric patient; (10) elective chest drain placement in the newborn; (11) thoracic drain placement in the trauma setting. This consensus provides clear and shared indications, representing the most complete and up-to-date collection of practice recommendations in pediatric cardiac and thoracic surgery, in order to guide physicians in the management of the patient, standardizing approaches and avoiding the abuse and misuse of antibiotics.

Surgical Antimicrobial Prophylaxis in Pediatric Patients Undergoing Plastic Surgery: A RAND/UCLA Appropriateness Method Consensus Study.

For many years, it was clearly shown that surgical procedures might be associated with surgical site infection (SSI). Many scientific institutions prepared guidelines to use in surgery to reduce abuse and misuse of antibiotics. However, in the general guidelines for surgical antibiotic prophylaxis, plastic surgical procedures are not addressed or are only marginally discussed, and children were almost systematically excluded. The main aim of this Consensus document is to provide clinicians with recommendations on antimicrobial prophylaxis for pediatric patients undergoing plastic surgery. The following scenarios were considered: clean plastic surgery in elective procedures with an exclusive skin and subcutis involvement; clean-contaminated/contaminated plastic surgery in elective procedures with an exclusive skin and subcutis involvement; elective plastic surgery with use of local flaps; elective plastic surgery with the use of grafts; prolonged elective plastic surgery; acute burns; clean contused lacerated wounds without bone exposure; high-risk contused lacerated wounds or with bone exposure; contused lacerated wound involving the oral mucosa; plastic surgery following human bite; plastic surgery following animal bite; plastic surgery with tissue expander insertion. Our Consensus document shows that antimicrobial perioperative prophylaxis in pediatric patients undergoing plastic surgery is recommended in selected cases. While waiting the results of further pediatric studies, the application of uniform and shared protocols in these procedures will improve surgical practice, with a reduction in SSIs and consequent rationalization of resources and costs, as well as limiting the phenomenon of antimicrobial resistance.

Prognostic Factors for Post-COVID-19 Syndrome: A Systematic Review and Meta-Analysis.

Evidence shows that a substantial proportion of patients with COVID-19 experiences long-term consequences of the disease, but the predisposing factors are poorly understood. We conducted a systematic review and meta-analysis to identify factors present during COVID-19 hospitalization associated with an increased risk of exhibiting new or persisting symptoms (Post-COVID-19 Syndrome, PCS). MedLine and WebOfScience were last searched on 30 September 2021. We included English language clinical trials and observational studies investigating prognostic factors for PCS in adults previously hospitalized for COVID-19, reporting at least one individual prospective follow-up of minimum 12 weeks. Two authors independently assessed risk of bias, which was judged generally moderate. Risk factors were included in the analysis if their association with PCS was investigated by at least two studies. To summarize the prognostic effect of each factor (or group of factors), odds ratios were estimated using raw data. Overall, 20 articles met the inclusion criteria, involving 13,340 patients. Associations were statistically significant for two factors: female sex with any symptoms (OR 1.52; 95% CI 1.27-1.82), with mental health symptoms (OR 1.67, 95% CI 1.21-2.29) and with fatigue (OR 1.54, 95% CI 1.32-1.79); acute disease severity with respiratory symptoms (OR 1.66, 95% CI 1.03-2.68). The I² statistics tests were calculated to quantify the degree of study heterogeneity. This is the first meta-analysis measuring the association between factors present during COVID-19 hospitalization and long-term sequelae. The role of female sex and acute disease severity as independent prognostic factors must be confirmed in robust longitudinal studies with longer follow-up. Identifying populations at greatest risk for PCS can enable the development of targeted prevention and management strategies. Systematic review registration: PROSPERO CRD42021253467.

Role of Dynamic Parameters of 18F-DOPA PET/CT in Pediatric Gliomas.

PURPOSE OF THE REPORT: PET with 18F-DOPA can be used to evaluate grading and aggressiveness of pediatric cerebral gliomas. However, standard uptake parameters may underperform in circumscribed lesions and in diffuse pontine gliomas. In this study, we tested whether dynamic 18F-DOPA PET could overcome these limitations. PATIENTS AND METHODS: Patients with available dynamic 18F-DOPA PET were included retrospectively. Static parameters (tumor/striatum ratio [T/S] and tumor/cortex ratio [T/N]) and dynamic ones, calculated on the tumor time activity curve (TAC), including time-to-peak (TTP), slope steepness, the ratio between tumor and striatum TAC steepness (dynamic slope ratio [DSR]), and TAC shape (accumulation vs plateau), were evaluated as predictors of high/low grading (HG and LG) and of progression-free survival and overall survival. RESULTS: Fifteen patients were included; T/S, T/N, TTP, TAC slope steepness, and DSR were not significantly different between HG and LG. The accumulation TAC shape was more prevalent in the LG than in the HG group (75% vs 27%). On progression-free survival univariate analysis, TAC accumulation shape predicted longer survival (P < 0.001), whereas T/N and DSR showed borderline significance; on multivariate analyses, only TAC shape was retained (P < 0.01, Harrell C index, 0.93-0.95). On overall survival univariate analysis, T/N (P < 0.05), DSR (P < 0.05), and TAC "accumulating" shape predicted survival (P < 0.001); once more, only this last parameter was retained in the multivariate models (P < 0.05, Harrell C index, 0.86-0.89). CONCLUSIONS: Dynamic 18F-DOPA PET analysis outperforms the static parameter evaluation in grading assessment and survival prediction. Evaluation of the curve shape is a simple-to-use parameter with strong predictive power.

Patient- versus physician-reported outcomes in a low-dose tamoxifen trial in noninvasive breast cancer.

BACKGROUND: We recently conducted a de-escalation trial of low-dose tamoxifen 5 mg/day ("babytam", BT) or placebo given for 3 years in 500 women with noninvasive breast cancer. Women on babytam had a 52% reduction of recurrence (invasive breast cancer or DCIS) after 5 years. Since menopausal symptoms are major reasons for treatment withdrawal during tamoxifen preventive therapy, we compared and analyzed the patient-reported outcomes (PROs) with the physician-reported adverse events and studied their association with recurrence. METHODS: Menopausal symptoms recorded by physicians using the Common Terminology Criteria (CTCAEs) were compared with a patient self-reported validated questionnaire reviewed by a research nurse at baseline and every 6 months up to 36 months. Hot flashes (HF), the main outcome measure, were detected through a self-report 7-day diary for frequency and intensity. Treatment adherence and efficacy were assessed by the Kaplan-Meier curves and the Cox model. RESULTS: The number of HF events at 12, 24, and 36 months for PROs versus CTCAEs was 246 versus 12, 238 versus 8, and 210 versus 4, respectively. The majority of events were grade 1. There was no difference in PROs between babytam and placebo except for HF daily frequency, which increased by 1.5 events (95% CI, 1.1-1.8) on placebo to 2.1 on babytam (95% CI, 1.7-2.5, p = 0.05). The presence of HF at baseline was a favorable prognostic factor for recurrence and a predictive factor for response to babytam. Adherence was similar between babytam and placebo. CONCLUSIONS: The use of PROs is effective for identifying frequent mild grade menopausal symptoms which are underestimated by physicians but important prognostic and predictive factors. Research nurse can use these results as a tool to reassure patients about symptoms, improve adherence to treatment, and limit dropouts.