Luigi Sacco Hospital

Prolonged monitoring with implantable cardiac monitors (ICMs) effectively detects subclinical atrial fibrillation (SCAF) in patients with cryptogenic stroke (CS). Understanding SCAF progression to higher burdens can affect decisions regarding oral anticoagulant (OAC) and antiarrhythmic therapies. This analysis aimed to quantify initial SCAF burden, its progression, and predictors of progression in CS patients. This multicenter project collected demographics, stroke characteristics, and SCAF daily burden in CS patients implanted with ICM. SCAF progression was defined as an increase in daily burden from initial detection, categorized as: 5 min to 1 h, 1-6 h, 6-24 h, 24 h for < 7 days, and 24 h for ≥ 7 days. Of 593 patients (70.0 ± 11.3 years, 42% female, median CHA2DS2-VASc score 4.7 ± 1.4) monitored over a median of 24.6 months, 32.7% had SCAF detected. While initial SCAF daily burden was < 1 h in 38.7% of SCAF patients, 53.3% progressed to a higher SCAF daily burden, with 30.6% reaching the 24 h burden by 36 months. Higher CHA2DS2-VASc scores and stroke severity were associated with SCAF progression. OAC therapy was initiated in 91.2% patients with a maximum SCAF daily burden < 1 h, while in 98.0% of those with a maximum daily burden ≥ 1 h (p = 0.042). Over half of CS patients with SCAF progressed to a higher burden, and about one-third reached a 24 h SCAF daily burden. These findings highlight the importance of continuous monitoring in CS patients for early SCAF detection and personalized therapy, considering SCAF burden progression and the patient's risk profile.

Ventilator-associated pneumonia (VAP) remains a leading complication in mechanically ventilated patients, yet the contribution of the respiratory microbiota remains poorly understood. The PULMIVAP study is a multicenter, longitudinal cohort investigation of respiratory microbiota composition and host immune responses in critically ill adults intubated for non-pulmonary conditions. A total of 146 intubated adult patients were enrolled across eight Italian ICUs, forming matched groups of 73 with VAP and 73 without. Oropharyngeal swabs and endotracheal aspirates were collected at intubation and either at VAP diagnosis or at a matched point in controls for a total of 584 biological samples. Metataxonomic analyses revealed substantial temporal shifts in microbial communities across both upper and lower respiratory compartments, with a trend toward reduced microbial richness in patients who developed VAP. Several genera, such as Corynebacterium, were more abundant in no-VAP patients, whereas Escherichia-Shigella and Peptoniphilus were enriched in VAP samples. Cytokine-microbiota correlation analysis suggested a pro-inflammatory signature in VAP patients, with Citrobacter positively associated with IFN-γ and TNF-α, while several commensal genera were inversely correlated with inflammatory mediators. Additionally, taxa associated with VAP correlated with lower PaO2/FiO2 ratios, implicating them in disease severity. Consistently, several bacteria, such as Corynebacterium, appeared to be linked to better respiratory outcomes, suggesting protective or risk-associated microbial profiles. Overall, these findings highlight the complex interplay between microbial communities and mucosal immunity in the pathogenesis of VAP. The identification of condition-associated microbial and immunological signatures may inform future strategies for risk stratification and targeted prevention.IMPORTANCEVentilator-associated pneumonia (VAP) remains a major complication of mechanical ventilation, yet most microbiome studies have focused on late-stage infection or single airway compartments, limiting insight into early microbial dynamics associated with VAP risk. By longitudinally characterizing upper and lower airway microbiota before and during VAP development, this study provides new insights into microbial and immune patterns associated with susceptibility and disease severity in humans. These findings contribute to the current understanding of VAP pathogenesis by suggesting a role for early airway dysbiosis and local immune responses alongside clinical factors. Remarkably, the identification of taxa associated with risk or protection supports the potential for microbiota-informed monitoring and future risk stratification strategies during mechanical ventilation.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04849039.

Major depressive disorder (MDD) is a leading cause of disability worldwide and contributes significantly to the global burden of disease. Recent data show an increasing prevalence of treatment-resistant depression (TRD). Patients with autism spectrum disorder (ASD) often exhibit MDD as a comorbidity and it is often resistant to conventional treatments. ASD determines emotional dysregulation and a reduced ability to understand mental states (mentalization). These features can lead to suicidal ideation and/or behavior. Intranasal esketamine may offer a novel therapeutic option for this population. This case series focuses on the clinical response to intranasal esketamine in patients with autism and TRD; esketamine is approved in Italy as an add-on therapy in TRD, so our case study is based on an in-label treatment. Three young patients (n = 3, F/M 2:1, age range 20-25 y) with light to moderate autism (Level 1 or 2) were treated. Esketamine was administered in augmentation with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in accordance with EMA/AIFA guidelines. A structured follow-up protocol was set to monitor depressive symptoms, social cognition, and mentalization. Follow-up during treatment was maintained for six months, and psychometric evaluations were performed at six time points: baseline (T0), 1 week (T1), 1 month (T2), 2 months (T3), 3 months (T4), and 6 months (T5). Also, subjective quality of life was investigated before and after the observation period. Despite differences in clinical profile, all patients showed good efficacy of esketamine in reducing depressive symptoms: two patients experienced clinical remission at T5 (MADRS < 10), one patient showed partial response (dMADRS = 43.24%). No major side effects were reported. Significant improvements were observed after the first week of treatment (P1: MADRS_T0 = 37, MADRS_T1 = 12; P2: MADRS_T0 = 32, MADRS_T1 = 21; P3: MADRS_T0 = 25, MADRS_T1 = 12). Depressive relapses occurred (e.g., P1, T3-T4), but they were not associated with hospitalizations and/or suicidal attempts. Suicidal ideation, when present, decreased by the end of the follow-up period. Lack of mentalization and in social cognition was noted, with just mild improvements during therapy. Subjective quality of life improved significantly for all patients (P1: 28% at T0, 73% at T5. P2: 25% at T0, 71% at T5. P3: 35% at T0, 80% at T5). Intranasal esketamine showed a favorable efficacy and safety in these three cases of TRD in comorbidity with ASD (at six months: total remission = 66.66%, partial remission = 33.33%, inefficacy = 0%, drop-out = 0, severe adverse events = 0). Besides improvements in depressive symptoms, esketamine was associated with a constant decrease in suicidal thoughts. A case series is unfit to form statistical conclusions; preliminary data warrant further investigation in randomized controlled studies to validate the therapeutic potential of esketamine in this population.

Background: Intravenous fluids modify acid-base balance by changing plasma strong ion difference (SIDPL) and total non-volatile weak acids. Experimental data suggest that pre-infusion plasma bicarbonate (HCO3-) may further modulate these effects. We tested this hypothesis in a large cohort of postoperative ICU patients receiving intravenous fluids. Methods: We retrospectively analyzed all-consecutive post-operative ICU admissions over a 21-month period who received fluid therapy. Fluid inputs/outputs, plasma electrolytes, and arterial blood gases were collected from admission to 9:00 A.M. of postoperative day one. Average SID of infused fluids (SIDINF) was calculated, and SIDPL and standard base excess variations (ΔSBE) were assessed. Patients were stratified by SIDINF tertiles (low, <41.0 mEq/L; medium, 41.2-54.6 mEq/L; high, ≥55.0 mEq/L), median pre-infusion HCO3- (24.3 [22.4-26.3] mmol/L), and tertiles of SIDINF-HCO3- difference. Results: Among 650 admissions, 641 were included (83% elective surgery). Pre-infusion acid-base was, as average, within normal ranges. Total infused volume averaged 2327 ± 1111 mL. Across SIDINF tertiles, ΔSBE increased from 1.2 ± 3.4 to 3.0 ± 3.0 and 3.4 ± 3.0 mmol/L (p < 0.001), paralleled by ΔSIDPL rise (0.6 ± 2.3, 1.3 ± 2.4 and 1.4 ± 2.3 mEq/L, respectively; p = 0.004). For any given SIDINF, patients with lower pre-infusion HCO3- showed greater ΔSBE and ΔSIDPL (p < 0.001). When analyzed by tertiles of SIDINF-HCO3- difference, ΔSBE rose from 1.0 ± 3.2 to 2.7 ± 2.9 and 4.0 ± 3.0 mmol/L (p < 0.001), with amplified effects at higher infused volume (>2500 mL). Conclusions: In postoperative ICU patients, fluid-induced acid-base changes are largely driven by SIDINF-HCO3- difference, supporting individualized fluid selection based on baseline HCO3-.

BackgroundThe increased frequency of spinal surgeries has led to a rise in postoperative spine infections (PSIs), now recognized as the third most common surgical complication. Currently, there is no standardized definition of PSI, complicating clinical management and research. This meta-epidemiological study aimed to develop clear diagnostic criteria to assist clinicians and researchers in identifying and reporting PSIs consistently.2020 PRISMA flow diagramSankey diagram showing the distribution of combination of criteria or definitions used by the authors. This refers to 21 articles that used a definition derived by the authors.MethodsFollowing PRISMA guidelines, a comprehensive literature search was conducted by a medical librarian using Ovid MEDLINE (March 14, 2024). Studies were included if they reported on at least ten adult patients diagnosed with PSI and provided clear diagnostic definitions. The primary objective was to evaluate existing PSI diagnostic criteria and categorize them into thematic clusters. We constructed standardized diagnostic combinations using 13 predefined criteria derived from clinical practice guidelines and prior research (Table 1).Characteristics of the included studies*Total can be more than 100% since some variables can be present in multiple categories.This refers to 21 articles that used a definition derived by the authors. For articles #411 and #630 categorization was not possible as the definition provided only information about the depth of infection and not the criteria for diagnosis. Article #1148 was included as, defining “presumed aspetic” cases meant, by definition, also defining infectious cases.Abbreviations. The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP), Centers for Disease Control and Prevention (CDC), The National Healthcare Safety Network (NHSN), Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA), Magnetic Resonance Imaging (MRI)ResultsFrom an initial 1,466 studies screened, 101 were included (Figure 1). Most studies were retrospective (91/101, 92.1%), and a majority (77/101, 76.2%) relied on established criteria such as those from the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) or the CDC. Seven studies combined predefined criteria with additional detailed explanations. Among the remaining studies using independent definitions, clinical signs and symptoms were the most common criteria (13/24, 54.2%) (Table 1). Criteria were grouped into clinical, microbiological, and radiological categories, with most studies primarily using clinical criteria alone or in combination with microbiological or imaging findings (Figure 2).ConclusionThere was no clear consensus in the literature on what defines a PSI. Our findings emphasize the necessity of establishing a standardized PSI definition that integrates clinical, microbiological, and radiological criteria. Implementing such a unified framework could enhance diagnostic accuracy, address existing limitations associated with hardware complications, wound drainage interpretations, and imaging ambiguities, and improve upon the current shortcomings of surveillance systems.DisclosuresJeremy D. Shaw, MD, Globus: Grant/Research Support|Purgo Scientific: Advisor/Consultant|Purgo Scientific: Stocks/Bonds (Private Company)

Background/Objectives: Suicide is the second leading cause of death among adolescents and young adults. Those suffering from psychiatric illnesses are at particular risk. Our study, conducted at an outpatient mental health facility in Northern Italy, aimed at delineating demographic and psychopathological features of youths aged 16–29 who attempted suicide and were referred to our community-based outpatient service. Methods: We identified 63 subjects, most of whom suffered from personality disorders, mood disorders, and schizophrenia spectrum disorders. Analysis of variance and post hoc pairwise comparisons were performed. Results: Inferential analysis yielded significant results in terms of age at index suicide attempt across diagnostic groups. Patients with personality disorders attempted suicide at a younger age (M = 18.70) compared to those with schizophrenia spectrum disorders (M = 23.64; η2 = 0.32). Conclusions: Our findings highlighted the period of transition from adolescence to adulthood as a stress on the need of preventive approaches towards suicidality in young people in both clinical and non-clinical settings. Moreover, the difference of age at index suicide attempt across different diagnostic groups stresses the need for tailored clinical interventions based on the specific psychopathological trajectories and natural histories of the diseases.

Over the past few decades, demand for sea urchin roe has risen, while wild sea urchin populations have declined. This trend has increased interest in aquaculture techniques and the development of formulated feeds to support ecological restoration and research. Here, we examined the effects of a high-protein formulated feed on gonad development in Paracentrotus lividus, compared to fresh feeds (maize and spinach), across three replicated tanks. We assessed gonad maturation, gamete viability, and larval development, and developed a new histopathological index applicable to both sexes. Formulated feed significantly enhanced gonad maturation, increased gamete production, and led to heavier gonads with higher gonadosomatic indices compared to fresh feeds, which were insufficient to promote maturation within four weeks. Notably, no histological alterations were observed in the gonads. Fertilization trials showed that embryos were produced, but none reached the pluteus stage, indicating decreased embryo viability. Although the formulated feed improved gonad development, it adversely affected water quality, increasing nutrient concentrations and lowering pH. Overall, these findings suggest that high-protein formulated feeds could potentially improve aquaculture production by enhancing gonad maturation and gamete output, but additional measures may be needed to support complete larval development.

Accurate placement of central venous catheter tips is crucial for preventing complications, such as arrhythmias and vascular injuries. Intracavitary electrocardiography (I-EKG) has emerged as a reliable alternative to chest X-rays for catheter tip positioning, offering real-time results without radiation exposure. This study evaluates the quality of I-EKG tracings using two methods: the saline column method with the alligator clip and spindle system (Deltamed, Viadana, Italy) and the pure saline column method using the "red" connector cable (Vygon Card® Vygon, Ecouen, France) and the "yellow" connector cable (Fast Tip® ATL Milano, Assago, Italy). Twelve patients undergoing a peripherally inserted central catheter (PICC) placement were enrolled in this prospective study at Luigi Sacco Hospital, Milan. I-EKG tracings were recorded using all three devices, yielding a total of 36 tracings. Objective measurements of P, QR, and RS wave amplitudes were taken over five heartbeats per tracing, while twelve experienced operators performed subjective evaluations using a 5-point scale. Statistical analyses compared the three techniques. There were no significant differences in tracing quality among the methods. Objective analyses of wave amplitude ratios confirmed equivalent performance across approaches. Subjective evaluations yielded comparable scores for the "alligator-spindle," "red," and "yellow" connector techniques, with no statistically significant variation. With the limits of the small sample size, the pure saline column methods ("red" and "yellow" connectors) present similar EKG trace quality while offering procedural simplicity and enhanced safety. By eliminating the need for a spindle, these may reduce the risk of arrhythmia and avoid possible effects of guidewire contamination. These findings support the broader adoption of pure saline column techniques to optimize catheter placement procedures.

PurposeTo quantitatively compare choriocapillaris flow deficit percentages (CCFD%) between eyes with extensive macular atrophy with pseudodrusen-like appearance (EMAP) and geographic atrophy (GA) secondary to age-related macular degeneration (AMD), and to identify predictive factors for CCFD% at the atrophy margin.MethodsThis retrospective cross-sectional study included 53 eyes (27 with GA and 26 with EMAP). CCFD% were computed within a 500-µm-wide marginal zone (CCFD%_M) and beyond the margin (CCFD%_BM) using compensated en face optical coherence tomography angiography (OCTA) images. Atrophy-to-fovea distance (AFD) was quantified by pixel-wise Euclidean analysis.ResultsEyes with EMAP demonstrated significantly higher CCFD% compared to GA both at the atrophy margin (CCFD%_M, P < 0.05) and beyond (CCFD%_BM, P < 0.01). In univariable analysis, belonging to the GA group was associated with a 5.9-unit reduction in CCFD%_M, reflecting a substantial preservation of choriocapillaris (CC) perfusion in GA relative to EMAP. AFD was greater in EMAP (2.35 ± 0.56 mm) than GA (1.74 ± 0.55 mm; P = 0.014) suggesting more eccentric positioning of the lesions in the former. A multivariable mixed-effects model confirmed disease subtype (EMAP vs. GA) as an independent determinant of CC impairment with EMAP associated with a significantly higher CCFD%_M (P < 0.01).ConclusionsCC impairment is more pronounced in EMAP than in GA, with EMAP exhibiting more extensive and diffuse CCFD, particularly at the atrophy margins. This pattern may reflect a more aggressive vascular compromise in EMAP. These findings underscore a distinct CC pathoanatomy between the two conditions, with implications for disease progression and therapeutic targeting.

Abstract Background Patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) have frequently severe mitral annulus calcification (MAC) that can cause mitral stenosis. However, the left ventricular (LV) pressure overload caused by the aortic stenosis may reduce the transmitral pressure gradient and the severity of mitral stenosis may be underestimated. Purpose To evaluate the frequency of severe MAC in patients undergoing TAVI and describe the changes in transmitral pressure gradient after TAVI according to the severity of the MAC. Methods Patients with severe aortic stenosis undergoing TAVI who had cardiac computed tomography data to analyse the severity of MAC and a transthoracic echocardiogram prior to the intervention and at hospital discharge were included. The severity of MAC was defined as mild MAC (3 points or less), moderate MAC (4 to 6 points), and severe MAC (7 points or more) based on the distribution of the calcification of the mitral valve (thickness, circumferential distribution, involvement of the trigones and leaflets). The changes in transmitral pressure gradient were evaluated with linear multivariate regression adjusting for age and sex. Results A total of 203 patients (median age 81 years, 40% male) with severe AS who successfully underwent TAVI were included. According to the classification of MAC severity by cardiac CT, 55 (27%) patients had no MAC, 57 (28%) mild MAC, 55 (27%) moderate MAC, and 36 (18%) severe MAC. The groups were comparable in terms of demographics and clinical characteristic. The NT-proBNP increased progressively with the severity of MAC. Transthoracic echocardiography was performed at a median of 43 days before TAVI and 3 days after TAVI. In terms of echocardiographic characteristics at baseline, there were no statistically significant differences across theg roups except from transmitral pressure gradient, which was significantly higher as the severity of MAC increased on CT . After TAVI, there was no significant change in mean transmitral pressure gradient in patients without MAC. In contrast, patients with mild, moderate and severe MAC had significant increases in trasmitral pressure gradient following TAVI, with greater changes associated with increasing severity of MAC (mild p&amp;lt;0.0001, moderate p&amp;lt; 0.0007, severe p&amp;lt;0.0060) Conclusions In patients with severe aortic stenosis and severe MAC, the transmitral pressure gradient increases significantly after TAVI. Therefore, TAVI may unmask significant mitral stenosis that may impact the results of TAVI at mid term follow-up.