Diagnostic Delay of Celiac Disease in Childhood.

Importance: The extent and factors associated with risk of diagnostic delay in pediatric celiac disease (CD) are poorly understood. Objectives: To investigate the diagnostic delay of CD in childhood, and to assess factors associated with this delay. Design, Setting, and Participants: Multicenter, retrospective, cross-sectional study (2010-2019) of pediatric (aged 0-18 years) patients with CD from 13 pediatric tertiary referral centers in Italy. Data were analyzed from January to June 2023. Main Outcomes and Measures: The overall diagnostic delay (ie, the time lapse occurring from the first symptoms or clinical data indicative of CD and the definitive diagnosis), further split into preconsultation and postconsultation diagnostic delay, were described. Univariable and multivariable linear regression models for factors associated with diagnostic delay were fitted. Factors associated with extreme diagnostic delay (ie, 1.5 × 75th percentile) and misdiagnosis were assessed. Results: A total of 3171 patients with CD were included. The mean (SD) age was 6.2 (3.9) years; 2010 patients (63.4%) were female; and 10 patients (0.3%) were Asian, 41 (1.3%) were Northern African, and 3115 (98.3%) were White. The median (IQR) overall diagnostic delay was 5 (2-11) months, and preconsultation and postconsultation diagnostic delay were 2 (0-6) months and 1 (0-3) month, respectively. The median (IQR) extreme overall diagnostic delay (586 cases [18.5%]) was 11 (5-131) months, and the preconsultation and postconsultation delays were 6 (2-120) and 3 (1-131) months, respectively. Patients who had a first diagnosis when aged less than 3 years (650 patients [20.5%]) showed a shorter diagnostic delay, both overall (median [IQR], 4 [1-7] months for patients aged less than 3 years vs 5 [2-12] months for others) and postconsultation (median [IQR], 1 [0-2] month for patients aged less than 3 years vs 2 [0-4] months for others). A shorter delay was registered in male patients, both overall (median [IQR], 4 [1-10] months for male patients vs 5 [2-12] months for female patients) and preconsultation (median [IQR], 1 [0-6] month for male patients vs 2 [0-6] months for female patients). Family history of CD was associated with lower preconsultation delay (odds ratio [OR], 0.59; 95% CI, 0.47-0.74) and lower overall extreme diagnostic delay (OR, 0.75; 95% CI, 0.56-0.99). Neurological symptoms (78 patients [21.5%]; OR, 1.35; 95% CI, 1.03-1.78), gastroesophageal reflux (9 patients [28.1%]; OR, 1.87; 95% CI, 1.02-3.42), and failure to thrive (215 patients [22.6%]; OR, 1.62; 95% CI, 1.31-2.00) showed a more frequent extreme diagnostic delay. A previous misdiagnosis (124 patients [4.0%]) was more frequently associated with gastroesophageal reflux disease, diarrhea, bloating, abdominal pain, constipation, fatigue, osteopenia, and villous atrophy (Marsh 3 classification). Conclusions and Relevance: In this cross-sectional study of pediatric CD, the diagnostic delay was rather short. Some factors associated with risk for longer diagnostic delay and misdiagnosis emerged, and these should be addressed in future studies.

Clinical and atopic features of patients with primary eosinophilic colitis: an Italian multicentre study.

Eosinophilic colitis (EC) is the rarest among primary eosinophilic gastrointestinal disorders (EGID). EC is underdiagnosed due to its blurred and proteiform clinical manifestations. To explore the clinical and atopic characteristic of EC adult patients, the diagnostic delay, and relapse-associated factors, by comparison with patients with eosinophilic esophagitis (EoE) and irritable bowel syndrome (IBS). EC patients followed-up at four clinics were included, and clinical, histopathological, and laboratory data were retrieved. As control groups, age-matched patients with EoE and IBS were recruited. Allergy tests included skin prick test and serum specific IgE. Diagnostic delay was assessed. Overall, data from 73 patients were retrieved, including 40 with EC (median age 39 years IQR 22.5-59, F:M 2.1:1), 12 with EoE (F:M ratio: 1:5), and 21 with IBS (F:M ratio: 1:0.9). The most common features in EC patients were female sex (67.5%), atopy (77.5%), abdominal pain/distention (70%), diarrhoea (77.5%), and faecal calprotectin elevation (22.5%). Blood eosinophils were elevated in EoE, but not in EC (p < 0.001), while ECP did not differ across the three groups (p = 0.4). The frequency of allergen sensitization reached 25% of patients. Several frequent pan-allergens for this region were present. The overall diagnostic delay was 10 months (IQR 4-15). Factors contributing to a greater diagnostic delay were atopy, weight loss, and a previous misdiagnosis. EC is mostly a diagnosis of exclusion, burdened by a substantial diagnostic delay. In female patients the presence of allergen sensitization, abdominal symptoms and faecal calprotectin elevation should raise the suspicion of EC.

Cardiac implantable electronic devices and bloodstream infections: management and outcomes.

BACKGROUND AND AIMS: Bloodstream infection (BSI) of any cause may lead to device infection in cardiac implantable electronic device (CIED) patients. Aiming for a better understanding of the diagnostic approach, treatment, and outcome, patients with an implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy and defibrillator (CRT-D) hospitalized with BSI were investigated. METHODS: This is a single-centre, retrospective, cohort analysis including consecutive ICD/CRT-D patients implanted between 2012 and 2021. These patients were screened against a list of all hospitalized patients having positive blood cultures consistent with diagnosed infection in any department of a local public hospital. RESULTS: The total cohort consisted of 515 patients. Over a median follow-up of 59 months (interquartile range 31-87 months), there were 47 BSI episodes in 36 patients. The majority of patients with BSI (92%) was admitted to non-cardiology units, and in 25 episodes (53%), no cardiac imaging was performed. Nearly all patients (85%) were treated with short-term antibiotics, whereas chronic antibiotic suppression therapy (n = 4) and system extraction (n = 3) were less frequent. Patients with BSI had a nearly seven-fold higher rate (hazard ratio 6.7, 95% confidence interval 3.9-11.2; P < .001) of all-cause mortality. CONCLUSIONS: Diagnostic workup of defibrillator patients with BSI admitted to a non-cardiology unit is often insufficient to characterize lead-related endocarditis. The high mortality rate in these patients with BSI may relate to underdiagnosis and consequently late/absence of system removal. Efforts to increase an interdisciplinary approach and greater use of cardiac imaging are necessary for timely diagnosis and adequate treatment.

Effectiveness of Preoperative Immunonutrition in Improving Surgical Outcomes after Radical Cystectomy for Bladder Cancer: Study Protocol for a Multicentre, Open-Label, Randomised Trial (INu-RC).

Radical cystectomy (RC) with pelvic lymph node dissection is the standard treatment for patients with limited-stage muscle-invasive bladder cancer. RC is associated with a complication rate of approximately 50-88%. Immunonutrition (IMN) refers to the administration of substrates, such as omega-3 fatty acids, arginine, glutamine, and nucleotides, that modulate the immune response. IMN has been associated with improved outcomes following surgery for esophagogastric, colorectal and pancreatic cancer. In this paper, we describe a study protocol for a multicentre, randomised, open-label clinical trial to evaluate the effect of IMN in patients undergoing RC for bladder cancer. A 7-day preoperative course of IMN is compared with a standard high-calorie high-protein oral nutritional supplement. The primary outcome of this study is the rate of complications (infectious, wound-related, gastrointestinal, and urinary complications) in the first 30 days after RC. Secondary outcomes include time to recovery of bowel function and postoperative mobilisation, changes in muscle strength and body weight, biochemical modifications, need for blood transfusion, length of stay, readmission rate, and mortality. The results of this study may provide new insights into the impact of IMN on postoperative outcomes after RC and may help improve IMN prescribing based on patient nutritional status parameters.

Continuous Glucose Monitoring System After Coronary Artery Bypass Graft Surgery: A Feasibility Study.

BACKGROUND: Blood glucose level variability has been associated with increased risk of complication in the postoperative setting of cardiovascular surgery. Although interesting for optimization of blood glucose management in this context, continuous blood glucose (CBG) devices can have a limited reliability in this context, in particular because of the use of paracetamol. The aim of this study was to evaluate the reliability of Dexcom G6®, a recently developed continuous glucose monitoring device. METHODS: We performed a prospective, observational, non-randomized, single-centre study comparing Dexcom G6® CBG level monitoring with the standard methods routinely used in this context. The standard blood glucose values were paired to the time corresponding values measured with Dexcom G6®. Agreement between the two methods and potential correlation in case of paracetamol use were calculated. RESULTS: From May 2020 to August 2021, 36 out of 206 patients operated for isolated coronary artery bypass grafting were enrolled; 673 paired blood glucose level were analyzed. Global agreement (ρc) was 0.85 (95% C.I.: 0.84-0.86), intensive care unit agreement was 0.78 (95%C.I.: 0.74-0.82) and ward agreement was 0.91 (95%C.I.: 0.89-0.93). In the diabetic population, it was 0.87 (95%C.I.: 0.85-0.90). When paracetamol was used, the difference was 0.02 mmol/l (95%C.I.: 0.29-0.33). CONCLUSIONS: Dexcom G6® provides good blood glucose level accuracy in the postoperative context of cardiac surgery compared to the standard methods of measurements. The results are particularly reliable in the ward where the need for repeated capillary glucose measurements implies patient discomfort and time-consuming manipulations for the nursing staff.

Does pulmonary endarterectomy improve the clinical conditions of patients with chronic thromboembolic pulmonary disease without pulmonary hypertension?

To verify whether the new hemodynamic definition of pulmonary hypertension (PH) has any implication in treatment of Chronic Thrombo-Embolic Pulmonary Disease (CTEPD) patients without PH, we retrospectively analysed the clinical and functional changes determined by pulmonary endarterectomy (PEA) in 63 CTEPD patients without PH who underwent surgery at our center, comparing those in whom the hemodynamic diagnosis of PH met recent guideline recommendations versus those in whom the diagnosis only met previous hemodynamic thresholds. The results show that the vast majority of CTEPD patients without PH operated at our center would now be defined as chronic thromboembolic pulmonary hypertension (CTEPH) patients. PEA did not result in any improvement in exercise capacity nor in right ventricular function or lung function test in patients with mean pulmonary artery pressure (mPAP) ≤ 20 mm Hg and pulmonary vascular resistance (PVR) ≤ 2 WU; on the contrary, hemodynamic parameters, exercise capacity, right ventricular function and lung function significantly improved in patients with mPAP between 21 and 24 mm Hg.

Follow-up evaluation and management of anemia in inflammatory bowel disease: A study by the Italian Group for Inflammatory Bowel Diseases (IG-IBD).

BACKGROUND: The RIDART I study found a 13.6% prevalence of anemia in Italian patients with inflammatory bowel disease (IBD); most cases were due to iron-deficiency anemia (IDA). AIMS: To evaluate changes in hemoglobin concentration during a 24-week follow-up of anemic patients with IBD. METHODS: Follow-up laboratory and clinical data were obtained from RIDART I study patients with anemia. Factors affecting hemoglobin concentration, the impact of anemia on fatigue and quality of life (QoL), and its relationship with treatment, disease activity and disease complications were investigated. RESULTS: Hemoglobin was 108 g/L at baseline, increased to 121 g/L at follow-up week 12 (p < 0.001) and then stabilized until week 24, but most patients remained anemic, with IDA, throughout the study. Hemoglobin improvement was greater in patients receiving either oral or parenteral iron supplementation. Following hemoglobin normalization, anemia relapse rate during follow-up was 30%. Oral iron did not cause disease reactivation. Lower follow-up hemoglobin was associated with a higher probability of having active disease, clinical complications, increased fatigue and reduced QoL. CONCLUSIONS: In anemic patients with IBD, anemia represents a long-lasting problem, in most cases persisting for up to 24 weeks, with high relapse rate and a negative impact on fatigue and QoL.

A Longitudinal RCT on the Effectiveness of a Psychological Intervention for Hospital Healthcare Workers During the COVID-19 Pandemic: What We Learned to Date.

The COVID-19 pandemic has led to significant psychological distress among frontline healthcare workers (HCWs), with a particular increase in trauma-related symptoms. This study investigated the longitudinal course of trauma-associated symptoms and behaviors in HCWs and the effectiveness of a brief dialectical behavior therapy (DBT)-informed intervention in mitigating these symptoms over 12 months. The trial included 225 HCWs randomly assigned to one of three groups: no intervention (control), in-person DBT-informed intervention, or online DBT-informed intervention. Over time, a natural decrease in PTSD symptoms was observed in all groups. Contrary to expectations, no difference was found between the control and intervention groups. However, for participants with severe PTSD symptoms, the intervention significantly mitigated their distress. No differences emerged between in-person and online interventions, suggesting equal effectiveness. Females reported higher trauma-related symptoms, while no differences emerged among different professional roles. These findings underscore the importance of targeted interventions for HCWs experiencing severe symptoms and highlight the potential of online modalities. Further research is needed to optimize the deployment of mental health resources within the healthcare setting, particularly during crises.

Validation of Utstein-Based score to predict return of spontaneous circulation (UB-ROSC) in patients with out-of-hospital cardiac arrest.

BACKGROUND AND AIMS: The Utstein Based-ROSC (UB-ROSC) score has been developed to predict ROSC in OHCA victims. Aim of the study was to validate the UB-ROSC score using two Utstein-based OHCA registries: the SWiss REgistry of Cardiac Arrest (SWISSRECA) and the Lombardia Cardiac Arrest Registry (Lombardia CARe), northern Italy. METHODS: Consecutive patients with OHCA of any etiology occurring between January 1st, 2019 and December 31st 2021 were included in this retrospective validation study. UB-ROSC score was computed for each patient and categorized in one of three subgroups: low, medium or high likelihood of ROSC according to the UB-ROSC cut-offs (≤-19; -18 to 12; ≥13). To assess the performance of the UB-ROSC score in this new cohort, we assessed both discrimination and calibration. The score was plotted against the survival to hospital admission. RESULTS: A total of 12.577 patients were included in the study. A sustained ROSC was obtained in 2.719 patients (22%). The UB-ROSC model resulted well calibrated and showed a good discrimination (AUC 0.71, 95% CI 0.70-0.72). In the low likelihood subgroup of UB-ROSC, only 10% of patients achieved ROSC, whereas the proportion raised to 36% for a score between -18 and 12 (OR 5.0, 95% CI 2.9-8.6, p < 0.001) and to 85% for a score ≥13 (OR 49.4, 95% CI 14.3-170.6, p < 0.001). CONCLUSIONS: UB-ROSC score represents a reliable tool to predict ROSC probability in OHCA patients. Its application may help the medical decision-making process, providing a realistic stratification of the probability for ROSC.

Long-Term Natural History of Autoimmune Gastritis: Results From a Prospective Monocentric Series.

INTRODUCTION: The natural history of autoimmune gastritis (AIG) has been poorly described. In this study, we report the long-term natural history and clinical clustering of the full spectrum of AIG, from the potential to the complicated stage. METHODS: Prospective single-center study conducted in a tertiary referral center. Patients with AIG at any stage (0 = potential; 1 = early; 2 = florid; 3 = severe; and 4 = complicated) were enrolled (January 2000-December 2022). The histopathological evolution, the clinical presentation, and the correlates of evolution of potential AIG were assessed. RESULTS: Four hundred ninety-eight patients with AIG (mean age 56.7 ± 15.2 years, F:M ratio 2.5:1) were included, of whom 93 experienced potential AIG. The maximum disease duration was 27 years (median 18, interquartile range 14-23), while the overall median follow-up was 52 months (interquartile range 12-95). Age was significantly lower in stage 0 compared with that in the other stages. Accidental histologic evidence and hematologic findings were the most common clusters of diagnosis. The overall median rate of progression was 7.29 per 100 persons/yr (95% confidence interval [CI] 6.19-8.59), while the stage-specific rates of progression were 10.85 (stage 0; 95% CI 7.75-15.18), 14.83 (stages 1-2; 95% CI 11.89-18.49), and 2.68 (stage 3; 95% CI 1.88-3.84). Newly onset neoplastic complications at follow-up occurred in 41/483 patients (8.5%; 23 neuroendocrine tumors and 18 epithelial dysplasia). No cases of adenocarcinoma were noticed. Male sex was associated with a greater likelihood of evolving from potential AIG to overt AIG. DISCUSSION: AIG is a progressive disorder, with a virtually absent risk of gastric adenocarcinoma. Patients with potential AIG should be monitored because they carry a high risk of evolving into overt AIG.

The impact of COVID-19 pandemic on out-of-hospital cardiac arrest: An individual patient data meta-analysis.

AIM: Prior studies have reported increased out-of-hospital cardiac arrests (OHCA) incidence and lower survival during the COVID-19 pandemic. We evaluated how the COVID-19 pandemic affected OHCA incidence, bystander CPR rate and patients' outcomes, accounting for regional COVID-19 incidence and OHCA characteristics. METHODS: Individual patient data meta-analysis of studies which provided a comparison of OHCA incidence during the first pandemic wave (COVID-period) with a reference period of the previous year(s) (pre-COVID period). We computed COVID-19 incidence per 100,000 inhabitants in each of 97 regions per each week and divided it into its quartiles. RESULTS: We considered a total of 49,882 patients in 10 studies. OHCA incidence increased significantly compared to previous years in regions where weekly COVID-19 incidence was in the fourth quartile (>136/100,000/week), and patients in these regions had a lower odds of bystander CPR (OR 0.49, 95%CI 0.29-0.81, p = 0.005). Overall, the COVID-period was associated with an increase in medical etiology (89.2% vs 87.5%, p < 0.001) and OHCAs at home (74.7% vs 67.4%, p < 0.001), and a decrease in shockable initial rhythm (16.5% vs 20.3%, p < 0.001). The COVID-period was independently associated with pre-hospital death (OR 1.73, 95%CI 1.55-1.93, p < 0.001) and negatively associated with survival to hospital admission (OR 0.68, 95%CI 0.64-0.72, p < 0.001) and survival to discharge (OR 0.50, 95%CI 0.46-0.54, p < 0.001). CONCLUSIONS: During the first COVID-19 pandemic wave, there was higher OHCA incidence and lower bystander CPR rate in regions with a high-burden of COVID-19. COVID-19 was also associated with a change in patient characteristics and lower survival independently of COVID-19 incidence in the region where OHCA occurred.

IDH1-mutated Crohn's disease-associated small bowel adenocarcinomas: Distinctive pathological features and association with MGMT methylation and serrated-type dysplasia.

AIMS: Patients with Crohn's disease (CrD) have an elevated risk for the development of small bowel adenocarcinomas (SBAs). Actionable isocitrate dehydrogenase 1 (IDH1) mutations have been reported to be more frequent in CrD-SBAs than in sporadic SBAs. The present study aimed to investigate the clinicopathological and immunophenotypical features, as well as methylation profiles, of IDH1-mutated CrD-SBAs. METHODS AND RESULTS: An international multicentre series of surgically resected CrD-SBAs was tested for IDH1 mutation. Clinicopathological features, immunophenotypical marker expression and O6-methylguanine-DNA methyltransferase (MGMT) and long interspersed nuclear element-1 (LINE-1) methylation were compared between IDH1-mutated and IDH1 wild-type CrD-SBAs. Ten (20%) of the 49 CrD-SBAs examined harboured an IDH1 mutation and all the mutated cancers harboured the R132C variant. Compared to IDH1 wild-type cases, IDH1-mutated CrD-SBAs showed significantly lower rates of cytokeratin 7 expression (P = 0.005) and higher rates of p53 overexpression (P = 0.012) and MGMT methylation (P = 0.012). All three dysplastic growths associated with IDH1-mutated SBAs harboured the same IDH1 variant (R132C) of the corresponding invasive cancer, and all were of non-conventional subtype (two serrated dysplastic lesions and one goblet cell-deficient dysplasia). In particular, non-conventional serrated dysplasia was significantly associated with IDH1-mutated CrD-SBAs (P = 0.029). No significant cancer-specific survival difference between IDH1-mutated CrD-SBA patients and IDH1 wild-type CrD-SBA patients was found (hazard ratio = 0.55, 95% confidence interval = 0.16-1.89; P = 0.313). CONCLUSIONS: IDH1-mutated CrD-SBAs, which represent approximately one-fifth of total cases, are characterised by distinctive immunophenotypical features and methylation profiles, with potential therapeutic implications. Moreover, IDH1-mutated non-conventional, serrated dysplasia is likely to represent a precursor lesion to such CrD-SBAs.

Impact of proton pump inhibitors on the onset of gastrointestinal immune-related adverse events during immunotherapy.

INTRODUCTION: The gut microbiota (GM) can influence the pathogenesis of immune-mediated adverse events (irAEs). Proton pump inhibitors (PPIs) can affect the integrity of GM, but their role in promoting irAEs is still poorly understood. METHODS: In this retrospective single-center cohort study, the primary endpoint was the evaluation of the incidence of gastrointestinal (GI) irAEs in cancer patients on PPIs (exposed) versus cancer patients who were not on PPIs (unexposed). RESULTS: Three hundred and sixty three patients' records (248 M/115F, median age 69) were reviewed. Twenty-three exposed patients (92%) developed GI irAEs while only two unexposed patients (8%) developed GI irAEs (hazard ratio [HR] 13.22, 95% confidence interval [CI] 3.11-56.10, p < 0.000). This HR was confirmed after weighting for the propensity score (HR15.13 95% CI 3.22-71.03, p < 0.000). CONCLUSION: Chronic PPI use is associated with an increased risk of GI irAES.

Transvenous Lead Extraction during Cardiac Implantable Device Upgrade: Results from the Multicenter Swiss Lead Extraction Registry.

BACKGROUND: Device patients may require upgrade interventions from simpler to more complex cardiac implantable electronic devices. Prior to upgrading interventions, clinicians need to balance the risks and benefits of transvenous lead extraction (TLE), additional lead implantation or lead abandonment. However, evidence on procedural outcomes of TLE at the time of device upgrade is scarce. METHODS: This is a post hoc analysis of the investigator-initiated multicenter Swiss TLE registry. The objectives were to assess patient and procedural factors influencing TLE outcomes at the time of device upgrades. RESULTS: 941 patients were included, whereof 83 (8.8%) had TLE due to a device upgrade. Rotational mechanical sheaths were more often used in upgraded patients (59% vs. 42.7%, p = 0.015) and total median procedure time was longer in these patients (160 min vs. 105 min, p < 0.001). Clinical success rates of upgraded patients compared to those who received TLE due to other reasons were not different (97.6% vs. 93.0%, p = 0.569). Moreover, multivariable analysis showed that upgrade procedures were not associated with a greater risk for complications (HR 0.48, 95% confidence interval 0.14-1.57, p = 0.224; intraprocedural complication rate of upgraded patients 7.2% vs. 5.5%). Intraprocedural complications of upgraded patients were mostly associated with the implantation and not the extraction procedure (67% vs. 33% of complications). CONCLUSIONS: TLE during device upgrade is effective and does not attribute a disproportionate risk to the upgrade procedure.

Restoration of Life Expectancy After Transcatheter Edge-to-Edge Mitral Valve Repair.

BACKGROUND: Survival data after mitral transcatheter edge-to-edge repair (TEER) are scarce, and its impact on predicted life expectancy is unknown. OBJECTIVES: The aim of this study was to estimate the impact of TEER on postprocedural life expectancy among patients enrolled in the MitraSwiss registry through a relative survival (RS) analysis. METHODS: Consecutive TEER patients 60 to 89 years of age enrolled between 2011 and 2018 (N = 1140) were evaluated. RS was defined as the ratio between post-TEER survival and expected survival in an age-, sex- and calendar period-matched group derived from the Swiss national 2011 to 2019 mortality tables. The primary aim was to assess 5-year survival and RS after TEER. The secondary aim was to assess RS according to the etiology of mitral regurgitation, age class and sustained procedural success over time. RESULTS: Overall, 5-year survival after TEER was 59.3% (95% CI: 54.9%-63.4%), whereas RS reached 80.5% (95% CI: 74.6%-86.0%). RS was 91.1% (95% CI: 82.5%-98.6%) in primary mitral regurgitation (PMR) and 71.5% (95% CI: 63.0%-79.3%) in secondary mitral regurgitation (SMR). Patients 80 to 89 years of age (n = 579) showed high 5-year RS (93.0%; 95% CI: 83.3%-101.9%). In this group, restoration of predicted life expectancy was achieved in PMR with a 5-year RS of 100% (95% CI: 87.9%-110.7%), whereas sustained procedural success increased the RS rate to 90.6% (95% CI: 71.3%-107.3%) in SMR. CONCLUSIONS: Mitral TEER in patients 80 to 89 years of age is able to restore predicted life expectancy in PMR, whereas in SMR with sustained procedural success, high RS estimates were observed. Our analysis suggests that successful, sustained mitral regurgitation reduction is key to survival improvement, particularly in patients 80 to 89 years of age.

Role of luteinizing hormone urinary levels in the diagnostic and therapeutic management of female central precocious puberty.

BACKGROUND: Diagnosing central precocious puberty (CPP) requires an integrated approach based on clinical, biochemical and instrumental data. The diagnostic gold standard is represented by GnRH (gonadotropin-releasing hormone) stimulation test. Some undoubted limitations of this procedure led the international scientific community to look for cheaper and less invasive alternative diagnostic methods, such as luteinizing hormone urinary levels (uLH) measurement. This study aims to define the reliability of urinary LH levels as a biomarker of pubertal development, both concerning the initial diagnostic management and the monitoring of patients with central precocious puberty undergoing therapy with GnRH analogues. Furthermore, the study plans to detect the potential association between LH peak serum (pLH) and urinary LH in patients undergoing diagnostic tests with GnRH and to identify a possible cut-off of uLH that may be suggestive of ensued successful hormonal stimulation. METHODS: The study includes 130 female patients with suspected precocious puberty or in follow-up during suppressive therapy. After the collection of the informed consent, the patients underwent clinical evaluation, auxological assessment, and hormone assays (basal levels of LH, FSH, and oestradiol; GnRH stimulating test in patients with suspected precocious puberty; urinary LH assay on the first-morning urine sample, collected after waking up). RESULTS: Two uLH cut-off values have been identified: the first of 0.25 UI/L [C.I. 95% 0.23-0.27], able to distinguish between pubertal and pre-pubertal patients, the second of 0.45 UI/L [C.I. 95% 0,20 - 0,70] suggestive of occurred hormonal stimulation in patients with diagnosis of CPP at GnRH test. All 30 patients with CPP in follow-up during suppressive therapy presented uLH values ≤ 0.45 IU/L (pU < 0.05), and uLH collected in prepubertal group control. CONCLUSIONS: uLH assays on the first morning urine specimen could be considered a low-cost and minimally invasive tool for precocious puberty diagnosing and monitoring, making possible to be easily performed even by a general pediatrician. Thus, this could help referring only selected patients to pediatric endocrinologists. After an appropriate validation, this approach could reasonably reduce hospital attendance and costs of performing more invasive procedures, with a more significant emotional impact on the pediatric patient.

The mental health toll of COVID-19: significant increase in admissions to ICU for voluntary self-inflicted injuries after the beginning of the pandemic.

BACKGROUND: COVID-19 outbreak deeply impacted on mental health, with high rate of psychological distress in healthcare professionals, patients and general population. Current literature on trauma showed no increase in ICU admissions for deliberate self-inflicted injuries in the first weeks after the beginning of COVID-19. OBJECTIVES: We tested the hypothesis that self-inflicted injuries/harms of any method requiring ICU admission increased in the year following COVID-19 outbreak. METHODS: Retrospective cohort single-center study comparing admissions to ICU the year before and the year after the pandemic start. All patients admitted to polyvalent ICUs-Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy from February 21st, 2019 to February 21st, 2020 (pre-COVID) and from February 22nd, 2020 to February 22nd, 2021 (post-COVID) were enrolled. RESULTS: We enrolled 1038 pre-COVID and 854 post-COVID patients. In post-COVID, the incidence of self-inflicted injuries was 32/854 (3.8% [2.5-5.1]), higher than in pre-COVID (23/1038, 2.2%-p = 0.0014-relative increase 72.7%). The increase was more relevant when excluding COVID-19 patients (suicide attempts 32/697 (4.6% [3.0-6.2])-relative increase 109.1%; p < 0.0001). Both in pre-COVID and post-COVID, the most frequent harm mean was poisoning [15 (65.2%) vs. 25 (78.1%), p = 0.182] and the analysed population was younger than general ICU population (p = 0.0015 and < 0.0001, respectively). The distribution of admissions for self-inflicted injuries was homogeneous in pre-COVID along the year. In post-COVID, no admissions were registered during the lockdown; an increase was observed in summer with pandemic curve at minimal levels. CONCLUSIONS: An increase in ICU admissions for self-inflicted injuries/harms was observed in the year following COVID-19 outbreak.

Rationale and design of the CV-PREVITAL study: an Italian multiple cohort randomised controlled trial investigating innovative digital strategies in primary cardiovascular prevention.

INTRODUCTION: Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking. METHODS AND ANALYSIS: The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners' offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed. ETHICS AND DISSEMINATION: This study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study's course and findings through regular meetings. TRIAL REGISTRATION NUMBER: NCT05339841.