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Introduction: Suicide is the outcome of a process starting with the experimentation of an unbearable pain or hopelessness, passing from suicidal ideation/planning, arriving to parasuicidal behaviors/effective attempts. A better understanding of the role of motivation in structuring the suicidal process could represent a better guide to the clinical intervention. Most instruments investigating the suicidal motivation are self-reports, possibly resulting in a lack of valid evaluations: there is a need for assessment involving clinician report interviews. Objectives: The objectives of this study are to validate the Motivational Interview for Suicidality (MIS) and to investigate the associations between the MIS areas and the different aspects of suicidal process. Methods: The sample is composed by 80 adolescents referred to the Mood Disorders Unit of the Bambino Gesù Pediatric Hospital assessed as at risk for suicidal behavior using the Columbia-Suicide Severity Rating Scale. The MIS is a semi-structured clinician-report interview. The interview is composed by 7 areas and 14 sub-areas, evaluated on Likert scale 0-4: illnessmotivated attempts area, chronic presence of internal pessimistic criticism area, sense of defeat and entrapment area, relational area, external motivated crisis area, extreme and unusual cases area, discontrol area. Results: Interpersonal influence, Escape' Fantasy, Impulsivity and Fearless Conducts significatively differ between ideators and attempters, while only the Fearless Conducts significatively differ between low and high potential lethality's attempts. Conclusions: Several motivations were found to be characteristic of the attempters and of the high potential lethality attempters and must therefore be considered in the assessment of suicidal risk. [ABSTRACT FROM AUTHOR]

Despite research efforts being made towards preserving (or even regenerating) heart tissue after an ischemic event, there is a lack of resources in current clinical treatment modalities for patients with acute myocardial infarction that specifically address cardiac tissue impairment. Modified messenger RNA (modRNA) presents compelling properties that could allow new therapeutic strategies to tackle the underlying molecular pathways that ultimately lead to development of chronic heart failure. However, clinical application of modRNA for the heart is challenged by the lack of effective and safe delivery systems. Lipid nanoparticles (LNPs) represent a well characterized class of RNA delivery systems, which were recently approved for clinical usage in mRNA-based COVID-19 vaccines. In this study, we evaluated the potential of LNPs for cardiac delivery of modRNA. We tested how variations in C12-200 modRNA-LNP composition affect transfection levels and biodistribution after intramyocardial administration in both healthy and myocardial-infarcted mice, and determined the targeted cardiac cell types. Our data revealed that LNP-mediated modRNA delivery outperforms the current state of the art (modRNA in citrate buffer) upon intramyocardial administration in mice, with only minor differences among the formulations tested. Furthermore, we determined both in vitro and in vivo that the cardiac cells targeted by modRNA-LNPs include fibroblasts, endothelial cells and epicardial cells, suggesting that these cell types could represent targets for therapeutic interference with these LNP formulations. These outcomes may serve as a starting point for LNP development specifically for therapeutic mRNA cardiac delivery applications., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Few studies on adolescents have investigated intelligence quotient (IQ) in mood disorders. Evidence on Disruptive Mood Dysregulation Disorder (DMDD), a controversial entity among depressive disorders, is more limited., Materials and Methods: We performed an exploratory study on adolescent inpatients with unipolar mood disorders to test specific impairment in cognitive and adaptive profile. We also considered common psychopathological comorbidities. We retrospectively collected data on inpatients with a diagnosis of major depressive disorder (MDD), DMDD or Depressive Disorder - Not Otherwise Specified (DD-NOS) evaluated with Wechsler Scales of Intelligence, Adaptive Behavior Assessment System (ABAS-II), and Children's Global Assessment Scale (C-GAS)., Results: Out of 198 inpatients (85.9% females), 33.3% had MDD, 60.1% DD-NOS and 6.6% DMDD. DMDD patients had higher rates of ADHD (15.4%) and learning disorders (LD, 23.1%), a lower mean IQ (87.8 ± 10.7; p  = 0.001) and ABAS-II scores (general composite 68.8 ± 16.8; p  = 0.002) than other groups. In linear regression analysis, DMDD retained a significant correlation with lower IQ and adaptive abilities when controlling for sex, and comorbidities. Among comorbidities, LD correlated with lower perceptual reasoning and IQ, and ADHD with lower conceptual adaptive abilities. In all diagnosis groups, working memory and processing speed were lower than verbal comprehension and perceptual reasoning., Discussion: While impairment in working memory and processing speed is a non-specific correlate of active mood disorder, DMDD is burdened by lower general intelligence and adaptive abilities and higher rate of neurodevelopmental comorbidities. Lower IQ in the normal range is a correlate of DMDD among variables examined, not explained by the effect of neurodevelopmental comorbidities. These findings are discussed with regards to possible implications for the consideration of DMDD as a bridge condition between neurodevelopmental disorders and mood disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Apicella, Pisa, Averna, Labonia, Pontillo and Vicari.)

The evidence shows that the COVID-19 pandemic dramatically increased the number of urgent psychiatric consultations for children and adolescents in hospital emergency departments (EDs). However, what needs to be further investigated are the characteristics of psychiatric hospitalization in children and adolescents admitted to the Child and Adolescent Neuropsychiatry Unit wards in EDs. Specifically, this retrospective study aimed to examine changes in (i) the number of inpatients and (ii) the distribution of psychopathological disorders and self-injurious behaviors in our Child and Adolescent Neuropsychiatry Unit ward during the COVID-19 lockdown in Italy (March-June 2020; October 2020-January 2021) compared with the same months of previous years. We found a significantly lower number of inpatients during the first four quarantine months than the first four reference months and a higher number of inpatients during the second four quarantine months than the second four reference months. Additionally, we found an increased frequency of mood disorders, non-suicidal self-injurious behavior, and suicidal ideation during the COVID-19 lockdown compared to the reference periods. Our findings underline the need to develop psychological healthcare services for future emergency periods in order to identify and treat psychological distress in children and adolescents early, reducing the risk of psychiatric hospitalization.

Background: Sepsis is a time-dependent disease: the early recognition of patients at risk for poor outcome is mandatory. Aim: To identify prognostic predictors of the risk of death or admission to intensive care units in a consecutive sample of septic patients, comparing different statistical models and machine learning algorithms. Methods: Retrospective study including 148 patients discharged from an Italian internal medicine unit with a diagnosis of sepsis/septic shock and microbiological identification. Results: Of the total, 37 (25.0%) patients reached the composite outcome. The sequential organ failure assessment (SOFA) score at admission (odds ratio (OR): 1.83; 95% confidence interval (CI): 1.41-2.39; p < 0.001), delta SOFA (OR: 1.64; 95% CI: 1.28-2.10; p < 0.001), and the alert, verbal, pain, unresponsive (AVPU) status (OR: 5.96; 95% CI: 2.13-16.67; p < 0.001) were identified through the multivariable logistic model as independent predictors of the composite outcome. The area under the receiver operating characteristic curve (AUC) was 0.894; 95% CI: 0.840-0.948. In addition, different statistical models and machine learning algorithms identified further predictive variables: delta quick-SOFA, delta-procalcitonin, mortality in emergency department sepsis, mean arterial pressure, and the Glasgow Coma Scale. The cross-validated multivariable logistic model with the least absolute shrinkage and selection operator (LASSO) penalty identified 5 predictors; and recursive partitioning and regression tree (RPART) identified 4 predictors with higher AUC (0.915 and 0.917, respectively); the random forest (RF) approach, including all evaluated variables, obtained the highest AUC (0.978). All models' results were well calibrated. Conclusions: Although structurally different, each model identified similar predictive covariates. The classical multivariable logistic regression model was the most parsimonious and calibrated one, while RPART was the easiest to interpret clinically. Finally, LASSO and RF were the costliest in terms of number of variables identified.

We described changes caused by the COVID-19 pandemic in the frequency of Emergency Department (ED) visits for mental health disorders (MHDs) in adolescents on a wider temporal range-that is, not just "the waves" of the pandemic-and characterized the profile of the adolescent seeking emergency psychiatric care. We conducted a retrospective longitudinal study by analyzing ED visits for MHDs from 10 March 2019 to 10 March 2021. A total of 1407 ED visits for MHDs were registered: 702 in the pre-COVID-19 and 707 in the COVID-19 period. The cumulative incidence of ED visits for MHDs was 1.22% in the pre-COVID-19 period and 1.77% in the COVID-19 period, with a statistically significant difference ( p < 0.001). The principal characteristics of the adolescent with MHDs during the pandemic period: the odds of comorbidities decreased by 26% ( p = 0.02), and the odds of transfer from other hospitals decreased by 71% ( p < 0.001), while the odds of the ED presentation as first psychiatric episode were twice greater ( p < 0.001). The risk of hospitalization increased by 54% ( p = 0.001). Regarding psychopathology, the likelihood of attempted suicide increased by 74% during the pandemic ( p = 0.02). The rate of mood and eating disorders grew significantly during the COVID-19 pandemic period ( p = 0.005 and p = 0.031, respectively). Monitoring ED visits for MHDs and understanding changes in the profile of adolescents presenting to ED helps to reinforce the role of ED in identifying special clinical needs for these vulnerable patients in case of a future public health crisis.

Remdesivir is a broad-spectrum antiviral agent able to inhibit the RNA polymerase of SARS-CoV-2. At present, studies focusing on the effect of remdesivir on viral load (VL) are few and with contrasting results. Aim of the present study was to evaluate the effect of remdesivir on SARS-CoV-2 VL from nasopharyngeal swabs (cycle threshold criterion) in a sample of patients treated with the drug, compared with patients who did not receive the antiviral treatment. This retrospective analysis evaluated patients with (1) real-time polymerase chain reaction (RT-PCR) confirmed COVID-19 diagnosis and (2) availability of at least two positive nasopharyngeal swabs analysed with the same analytic platform (ORF target gene, Ingenius ELITe, ELITechGroup, Puteaux, France). Upper respiratory specimens from nasopharyngeal swabs were collected at admission (T0) and 7-14 days after treatment, upon clinical decision. A total of 27 patients treated with remdesivir (Group A) met the inclusion criteria and were compared with 18 patients (Group B) treated with standard care, matched for baseline clinical characteristics. At baseline, both remdesivir-treated and nontreated patients showed comparable VLs (21.73 ± 6.81 vs. 19.27 ± 5.24, p = 0.348). At the second swab, remdesivir-treated patients showed a steeper VL reduction with respect to controls (34.28 ± 7.73 vs. 27.22 ± 3.92; p < 0.001). Longitudinal linear model estimated a mean decrease in cycle threshold equal to 0.61 (SE: 0.09) per day in remdesivir-treated versus 0.33 (SE: 0.10) per day in remdesivir nontreated patients (p for heterogeneity = 0.045). The present study shows that the administration of remdesivir in hospitalized COVID-19 patients significantly reduces the VL on nasopharyngeal swabs., (© 2022 Wiley Periodicals LLC.)

Revolving Door (RD) is a frequent phenomenon afflicting children and adolescents with psychiatric diagnoses. Nevertheless, risk factors for RD are still a matter of debate. To better understand RD phenomenon, we conducted a retrospective study on 224 children and adolescents (165 females and 59 males, aged 6-16 years) with a psychiatric hospitalization, taking the multiple risk factors together. At this aim, 108 patients with multiple hospitalizations and 116 patients with only one hospitalization were compared on demographic characteristics, clinical conditions, psychiatric ward stay, and post-discharge management factors. More than half of psychiatric patients were readmitted within three months of discharge. RD patients presented greater severity of illness, needed longer stays, and were more frequently placed in residential facilities than non-RD patients. Non-suicidal self-injurious and adoption were the main predictors of RD. Clinical instruments that detected behavioural and emotional symptoms, suicidal ideation severity, and level of impairment of the person's functioning were useful to identify patients at high risk for RD. In conclusion, our findings pointed out that several risk factors have to be considered to better understand and, in the future, prevent RD phenomenon.

The coronavirus disease 2019 (Covid-19) pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and presents a global health emergency that needs urgent intervention. Viruses constantly change through mutation, and new variants of a virus are expected to occur over time. In the United Kingdom (UK), a new variant called B.1.1.7 has emerged with an unusually large number of mutations. The aim of this study is to evaluate the level of protection of sera from 12 patients infected and later healed in Apulia Region (Italy) with Covid-19 between March and November 2020, when the English variant was not circulating in this territory yet, against the new VOC 202012/01 variant by seroneutralization assay. The sera of patients had already been tested before, using a virus belonging to the lineage B.1 and showed an antibody neutralizing titer ranging between 1:160 and 1:320. All the 12 sera donors confirmed the same titers of neutralizing antibodies obtained with a strain belonging to the lineage B.1.1.7 (VOC 202012/01). These data indicate that antibodies produced in subjects infected with variants of Sars-CoV-2 strain before the appearance of the English one, seem to have a neutralizing power also against this variant.

Catatonia is a rare condition that can occur in developmental disorders, but it is more frequently seen in schizophrenia. Recently, a high prevalence of cerebrospinal fluid abnormalities including the detection of antineuronal autoantibodies has been observed in psychotic patients. Among these autoimmune encephalopathies associated with a psychiatric condition, a great deal of attention has been paid to anti-N-methyl-D-aspartate receptor (NMDAr) encephalitis, which may present, among other things, symptoms such as catatonia, which therefore imposes a differential diagnosis with respect to the early psychosis. The aim of our study was to describe the clinical characteristics of 4 cases with catatonic symptoms to understand the differences between the psychotic symptoms due to a type of encephalitis anti-NMDAr and the psychotic symptoms without anti-NMDAr.

Objective: A careful choice of perioperative care strategies is pivotal to improve survival in cardiac surgery. However, there is no general agreement or particular attention to which nonsurgical interventions can reduce mortality in this setting. The authors sought to address this issue with a consensus-based approach., Design: A systematic review of the literature followed by a consensus-based voting process., Setting: A web-based international consensus conference., Participants: More than 400 physicians from 52 countries participated in this web-based consensus conference., Interventions: The authors identified all studies published in peer-reviewed journals that reported on interventions with a statistically significant effect on mortality in the setting of cardiac surgery through a systematic Medline/PubMed search and contacts with experts. These studies were discussed during a consensus meeting and those considered eligible for inclusion in this study were voted on by clinicians worldwide., Measurements and Main Results: Eleven interventions finally were selected: 10 were shown to reduce mortality (aspirin, glycemic control, high-volume surgeons, prophylactic intra-aortic balloon pump, levosimendan, leuko-depleted red blood cells transfusion, noninvasive ventilation, tranexamic acid, vacuum-assisted closure, and volatile agents), whereas 1 (aprotinin) increased mortality. A significant difference in the percentages of agreement among different countries and a variable gap between agreement and clinical practice were found for most of the interventions., Conclusions: This updated consensus process identified 11 nonsurgical interventions with possible survival implications for patients undergoing cardiac surgery. This list of interventions may help cardiac anesthesiologists and intensivists worldwide in their daily clinical practice and can contribute to direct future research in the field., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The aim of this study was to test efficacy and safety of intravenous (IV) valproate for aggression in children and adolescents with mood or conduct disorder and concomitant substance abuse. Six patients received a 20 mg/kg dose of IV valproic acid as an add-on therapy to their standard therapy with second-generation antipsychotics and benzodiazepines. Agitation and general psychopathology were measured at baseline and after the first injection using the Modified Overt Aggression Scale, the Brief Psychiatric Rating Scale, and the Children's Global Assessment Scale. The findings suggested that in emergency psychiatry clinical settings, IV valproate was effective in reducing agitation and aggressive behaviors with a good tolerability profile and better treatment compliance.

Chronic venous disease (CVD) and its most frightening complication, chronic venous ulceration (CVU), represent an important socioeconomic burden in the western world. Metalloproteinases have been identified in the pathogenesis of several vascular diseases such as venous problems. The aim of this study was to evaluate a broad range of metalloproteinases, such as matrix metalloproteinases (MMPs), ADAMs (a disintegrin and metalloproteinases) and ADAMTSs (a disintegrin and metalloproteinases with thrombospondin motifs) and their inhibitors, tissue inhibitor of metalloproteinases (TIMPs) and a related protein, neutrophil gelatinase-associated lipocalin (NGAL), in patients with CVD in order to correlate their serum levels with each stage of the disease. We performed a multicenter open-label study that comprised the enrolment of 541 patients with CVD of clinical stages C1-C6, (178 males, 363 females; mean age 57·29, median age 53·72, age range 29-81); 29 subjects without CVD were included in this study (9 males and 20 females; mean age 54·44, median age 50, age range 28-84) as the control group. Enzyme-linked immunosorbent assay (ELISA) was performed for measuring serum levels of proteases and related proteins. The study found that the serum elevation of MMP-2, ADAMTS-1 and ADAMTS-7 appeared to be correlated with the initial stages of CVD, whereas the serum elevation of MMP-1, MMP-8, MMP-9, NGAL, ADAM-10, ADAM-17 and ADAMTS-4 was particularly involved in skin change complications. This study showed that each stage of CVD may be described by particular patterns of metalloproteinases, and this may have therapeutic implications in discovering new targets and new drugs for the treatment of CVD., (© 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Klebsiella pneumoniae is at the forefront of antimicrobial resistance for Gram-negative pathogenic bacteria, as strains resistant to third-generation cephalosporins and carbapenems are widely reported. The worldwide diffusion of these strains is of great concern due to the high morbidity and mortality often associated with K. pneumoniae infections in nosocomial environments. We sequenced the genomes of 89 K. pneumoniae strains isolated in six Italian hospitals. Strains were selected based on antibiotypes, regardless of multilocus sequence type, to obtain a picture of the epidemiology of K. pneumoniae in Italy. Thirty-one strains were carbapenem-resistant K. pneumoniae carbapenemase producers, 29 were resistant to third-generation cephalosporins, and 29 were susceptible to the aforementioned antibiotics. The genomes were compared to all of the sequences available in the databases, obtaining a data set of 319 genomes spanning the known diversity of K. pneumoniae worldwide. Bioinformatic analyses of this global data set allowed us to construct a whole-species phylogeny, to detect patterns of antibiotic resistance distribution, and to date the differentiation between specific clades of interest. Finally, we detected an ∼ 1.3-Mb recombination that characterizes all of the isolates of clonal complex 258, the most widespread carbapenem-resistant group of K. pneumoniae. The evolution of this complex was modeled, dating the newly detected and the previously reported recombination events. The present study contributes to the understanding of K. pneumoniae evolution, providing novel insights into its global genomic characteristics and drawing a dated epidemiological scenario for this pathogen in Italy., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Introduction: The study aims to investigate the change in the burden of disease and the microbiological characteristics of Invasive Meningococcal Disease (IMD) in Puglia in comparison with overall incidence from 1994 through 2014., Methods: Data are gathered in the frame of the National Surveillance System coordinated by the National Reference Laboratory (NRL) of the Istituto Superiore di Sanità., Results: In Puglia, from 1994 through 2014, the average incidence of IMD was 0.2 per 100 000 inhabitants, below the national average value (0.33). IMD cases tended to be older than the other cases reported in Italy (median age 19 vs 16). The case-fatality rate was 20.4% in Puglia vs 13.3% in Italy. Serogroups B and C were most frequently identified. Serogroups C and Y presented a fairly clonal pattern, whereas serogroup B was genetically rather heterogeneous., Conclusion: Surveillance systems are critical in monitoring any change in the epidemiology of IMD.

We report the emergence of VIM-1 MBL and CTX-M-15-producing K. pneumoniae isolates collected from patients at two acute care hospitals (I.R.C.C.S. "S. Matteo" and "Casa Sollievo della Sofferenza" Hospital) and a long-term rehabilitation facility in Northern Italy (I.R.C.C.S. "S. Maugeri"). Between February 2007 and October 2008, 30 K. pneumoniae strains showing decreased susceptibility to carbapenems were collected. PCR and sequencing experiments revealed the presence of blaVIM-1 gene in 14/30 isolates. All the above isolates carried the blaSHV-5 determinant as well; interestingly, 8/14 VIM positive isolates were also CTX-M-1- like producers. VIM-1 positive strains were present in all hospitals. PFGE genomic profiles of the 14/30 isolates showed that 2 different clones, A and B, were responsible for outbreaks. The coexistence in the same bacterial cell of compatible plasmids carrying epidemiologically important emerging resistance genes, such as MBLs and CTX-Ms, is worrisome since it could predict the generation and spread of pan-resistant bacteria and the consequent treatment option limitations that can lead to significant morbidity and mortality. Control measures should be applied to detect MBL-producing strains and to contrast the vertical and plasmidic diffusion of carbapenem-resistant K. pneumoniae in acute care and rehabilitation facilities.

Subdural empyema represents a loculated suppuration between the dura and the arachnoid. It has been described either intracranially or in the spinal canal, the latter localization being quite rare. It is a rare but serious illness with a declining mortality rate but rather frequent neurological sequelae. Morbidity and mortality in intracranial and spinal subdural empyema directly relate to the delay in diagnosis and therapy. The epidemiology, etiology, pathophysiology and symptoms of spinal subdural empyema and cranial subdural empyema are somewhat different, but brain and spinal subdural empyema are not always two different entities. An adequate treatment strategy should be selected on a case-by-case basis, especially for patients with a massive CNS involvement, where management represents a challenge.

An outbreak of Pseudomonas aeruginosa showing a multidrug-resistant (MDR) phenotype (including carbapenems, ceftazidime, cefepime, gentamicin, tobramycin, and fluoroquinolones) was observed, during a 5-month period, in a general intensive care unit of a large tertiary care and clinical research hospital in southern Italy. The outbreak involved 15 patients, with a total of 87 isolates, mostly from lower respiratory tract specimens. Analysis of isolates involved in the outbreak revealed production of metallo-beta-lactamase (MBL) activity, and genotyping by pulsed-field gel electrophoresis of genomic DNA digested by SpeI revealed clonal relatedness among isolates. Molecular analysis of the MBL determinant showed the presence of a bla(IMP-13) gene carried on a gene cassette inserted in a class 1 integron which also contained an aacA4 aminoglycoside resistance cassette encoding an AAC(6')-Ib enzyme. The bla(IMP-13)-containing integron and its genetic environment appeared to be similar to those found in P. aeruginosa isolates producing IMP-13 from a hospital in Rome. The bla(IMP-13) gene was not transferable by conjugation and was apparently carried on the chromosome. The outbreak was coincidental with a shortage of nursing personnel, and resolution was apparently associated with reinstatement of nursing personnel and reinforcement of general infection control practices within the intensive care unit. To our best knowledge this is the first description of a nosocomial outbreak of relatively large size caused by an IMP-producing gram-negative pathogen in Europe.