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A 40-year-old woman was referred for the assessment of bilateral corneal opacities with gradual visual decline over the course of the past decade. Her past ocular history is significant for bilateral amblyopia and strabismus surgery in both eyes before age 5. The patient's parents were told by her childhood ophthalmologist that she had a hereditary disorder. Her systemic review was significant for anal fissure and human leukocyte antigen-B27 ankylosing spondylitis. Her past ocular record revealed corrected distance visual acuity (CDVA) of 20/80 in both eyes in 2018 with central corneal haze. On presentation, her uncorrected distance visual acuity was 20/150 in both eyes. Her CDVA was 20/100 in both eyes with manifest refraction of +0.50 -2.50 × 075 in the right eye and +5.00 -2.25 × 094 in the left eye. Corneal topography reflected keratometry of 35.75/38.97 × 171 in the right eye and 36.45/38.35 × 32 in the left eye. Central corneal thickness was 669 μm and 652 μm, respectively. External slitlamp examination revealed a central faint stromal opacity inferior to the visual axis in the right eye and a central faint stromal opacity in the left eye, and both were associated with steep posterior curvature of the cornea (Figure 1). Further findings included 0.5 corneal haze with mild guttata, normal irides, and clear lenses in both eyes. Intraocular pressure was 23 mm Hg and 26 mm Hg, respectively (Figure 2, Supplemental Figures 1 and 2, http://links.lww.com/JRS/A543). Gonioscopy was unremarkable. Dilated fundus examination revealed a 0.15 cup-to-disc ratio bilaterally, but otherwise no pertinent vitreoretinal pathologies were noted. What is the most likely diagnosis? What medical or surgical interventions would you recommend for this patient? What is the prognosis for this patient?

Purpose This study investigates the acoustic environment of children with cochlear implants (CIs) and the relationship between exposure to speech, in noise and in quiet, and the children's lexical production up to 1 year after CI activation, while controlling for the effect of early individual differences in receptive vocabulary growth. Method Eighteen children with CIs were observed at 3, 6, and 12 months after CI activation. Children's spontaneous word production during interaction with their mothers (types and tokens) and their expressive and receptive vocabulary size were considered. The characteristics of the acoustic environments in terms of acoustic scenes (speech in noise or in quiet, quiet, noise, music, and other) and of loudness ranges were assessed using data logging of the children's devices. Results Data analysis showed that both the number of tokens and the number of types produced 1 year after CI activation were affected by the children's exposure to speech in quiet with a loudness range between 40 and 69 dB. Expressive vocabulary size and types were affected by the receptive vocabulary knowledge that the children achieved over the first 3 months after CI activation. Conclusions Our data support the role of speech environment and individual differences in early comprehension on lexical production. The importance of exposure to speech with particular characteristics for the lexical development of children with CIs and the implications for clinical practice are discussed.

ObjectiveThe objectives of this study were to evaluate, in the Italian cultural context, breast cancer patients’ main meaning themes related to the experience of the disease, on the one side, and to be part of an existentially oriented group intervention, on the other.MethodA short reorientation-existential (RET) group intervention, structured by using some tools and background from cognitive analytic therapy (CAT) and based on the meaning-centered psychotherapy (MCP) existential framework, was delivered to 29 breast cancer patients. The sessions were audio-recorded and transcribed verbatim, with the narratives from reflective exercises (meaning of the journey cancer, meaning of the journey of intervention) uploaded to computer software NVivo 11. Analysis of the transcripts emerged from reflective exercises on the personal meaning of cancer and the letters of meaning (goodbye letter) written by the patients to express the meaning of their experience in the group was conducted through the interpretative phenomenological analysis (IPA) framework.ResultsFour superordinate themes were identified in the exercise meaning of the experience of cancer, namely “sense of stigma and loneliness (the foreigner),” “guilt (unjust guilt and anticipatory guilt),” “reconsidering one's own life and nostalgia,” and “rebirth (a new life, life after life).” Three superordinate themes were found in the meaning of the group experience in the letters, namely “togetherness and gratitude,” “legacy,” and “acceptance.”Significance of resultsThe study confirmed that a short group intervention, based on the existentially oriented framework and delivered in a public clinical healthcare setting, was enriched by focusing on the personal meaning of cancer. Some themes, such as loneliness, nostalgia, and rebirth, emerged during reflection giving, in written letters to participants, the sense of the group therapeutic experience.

Background The experience of cancer is highly stressful and potentially traumatic. We assessed the presence of Post‐Traumatic Stress Symptoms (PTSS) in long‐term cancer survivors and their caregivers, while examining the association between PTSS and clinical, demographic and psychological variables in the long term. Methods In this cross‐sectional study 212 survivor‐family caregiver dyads completed measures of post‐traumatic stress symptoms (PTSS) (Impact of Event Scale), depression and anxiety (Hospital Anxiety Depression Scale). Coping strategies, fatigue, cognitive decline, stressful life events and psychopathological history were also assessed among survivors. Data were analyzed using mixed models, accounting both for individual and dyadic effects. Results Cancer survivors and their caregivers were assessed after a mean of 6 years after treatment. Twenty per cent of survivors and 35.5% of caregivers had possible posttraumatic stress disorder (PTSD), while 23 patients (11.0%) and 33 caregivers (15.6%) had probable PTSD. Among cancer patients, the severity of post‐traumatic symptoms was associated with an anxious coping style, previous psychopathology and depression (p, High levels of cancer‐related PTSS are still present several years after treatment in both testixular cancer survivors and caregivers. Psychopathology may derive from complex interactions between coping, previous disorders and between‐person dynamics.

Background Uganda accounts for 5% of all malaria cases and deaths reported globally and, in endemic countries, pregnancy is a risk factor for both acquisition of P. falciparum infection and development of severe malaria. In recent years, malaria control has been threatened by COVID-19 pandemic and by the emergence, in Northern Uganda, of both resistance to artemisinin derivatives and to sulfadoxine-pyrimethamine. Methods In this facility-based, prospective, observational study, pregnant women will be recruited at antenatal-care visits and followed-up until delivery. Collected data will explore the incidence of asymptomatic parasitemia and malaria-related outcomes, as well as the attitudes towards malaria prevention, administration of intermittent preventive treatment, healthcare seeking behavior and use of insecticide-treated nets. A subpopulation of women diagnosed with malaria will be recruited and their blood samples will be analyzed for detection of genetic markers of resistance to artemisinin derivatives and sulfadoxine-pyrimethamine. Also, to investigate the impact of COVID-19 on malaria care among pregnant women, a retrospective, interrupted-time series will be conducted on at the study sites for the period January 2018 to December 2021. Discussion The present study will explore the impact of COVID-19 pandemic on incidence of malaria and malaria-related adverse outcomes, along with the prevalence of resistance to artemisinin derivatives and to sulfadoxine-pyrimethamine. To our knowledge, this is the first study aiming to explore the combined effect of these factors on a cohort of pregnant women. Trial registration: This study has been registered on the ClinicalTrials.gov public website on 26th April, 2022. ClinicalTrials.gov Identifier: NCT05348746.

Chronic kidney disease (CKD) represents a public health problem because it is characterized by several comorbidities, including uremic sarcopenia (US), and a poor quality of life. Currently, there are no standardized treatments available to counteract the onset of US but only some possible therapeutic approaches to slow its progression. The aim of this pilot study is to collect descriptive data in order to design a clinical trial based on the power analysis and simple size. The purpose of this pilot study was to evaluate the possible beneficial action induced by the functional anti-inflammatory and antioxidant bars in combination with the adapted physical activity (APA), on the onset and progression of US and other related-CKD comorbidities. We enrolled 21 CKD patients under conservative therapy, divided into four groups: (A) the physical exercise program (PEP), three times a week, in combination with the daily consumption of the two functional bars group; (B) the PEP group; (C) the daily consumption of the two functional bars group; (D) the control group. The duration of the study protocol was 12 weeks. We observed an improvement trend of body composition, blood pressure levels, lipid metabolism, and functional test in A and B groups. These preliminary data would seem to confirm the effectiveness of APA and to demonstrate the additive role of the natural bioactive compound’s assumption in countering US and other CKD comorbidities.

Background and aims There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death. Methods and results Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6–14.7 for age ≥85 vs 18–44 y); HR = 4.7; 2.9–7.7 for estimated glomerular filtration rate levels, Highlights • Impaired renal function, elevated C-reactive protein and advanced age were major indicators of death in COVID-19 patients. • These associations were substantially homogenous across all sub-groups analysed. • No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. • Death rates were higher in the Northern as opposed to Central-Southern Italian regions.

Disease severity, progression and response to therapy might be worse in obese rheumatoid arthritis (RA) patients, but paradoxically, obesity also might protect from radiographic joint damage. Thus, the intricate relationship between obesity and RA needs urgent clarification. The aim of this study was to assess the influence of obesity on the onset and development of RA and to determine whether arthritis could modify the adipose tissue biology and whether conventional Disease Modifying Anti-Rheumatic Drugs (cDMARDs) can modulate these alterations. Two strategies were followed: (1) clinical profiling of two cohorts of RA: non-obese and obese patients; and (2) mechanistic studies carried out in both a collagen-induced arthritis (CIA) in an obese mouse model and 3T3-L1 adipocytes treated with cDMARDs (leflunomide, methotrexate, and hydroxychloroquine). In our cohort of RA patients with low-moderate disease activity, the presence of obesity was not related to a higher activity of the disease; actually, disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR) was reduced in the obese RA patients. However, the induction of arthritis promoted transcriptomic changes in the adipose tissue under obesity condition in the obese CIA model. Treatment with hydroxychloroquine reduced weight and insulin resistance, accompanied by beneficial metabolic effects in the adipose tissue. These molecular changes in adipose tissue were also observed after methotrexate administration. In sum, arthritis might affect directly the inflammatory burden and metabolic alterations associated with obesity in adipose tissue. Clinicians should be cautious measuring the activity of the disease in obesity and managing the best therapeutic options for the metabolic comorbidities of these patients, where the combination of hydroxychloroquine and methotrexate should be considered to improve adipose tissue dysfunction in obese RA.

COVID-19 pandemic and its related containment measures have been associated with increased levels of stress, anxiety and depression in the general population. While the use of digital media has been greatly promoted by national governments and international authorities to maintain social contacts and healthy lifestyle behaviors, its increased access may also bear the risk of inappropriate or excessive use of internet-related resources. The present study, part of the COVID Mental hEalth Trial (COMET) study, aims at investigating the possible relationship between social isolation, the use of digital resources and the development of their problematic use. A cross sectional survey was carried out to explore the prevalence of internet addiction, excessive use of social media, problematic video gaming and binge watching, during Italian phase II (May–June 2020) and III (June–September 2020) of the pandemic in 1385 individuals (62.5% female, mean age 32.5 ± 12.9) mainly living in Central Italy (52.4%). Data were stratified according to phase II/III and three groups of Italian regions (northern, central and southern). Compared to the larger COMET study, most participants exhibited significant higher levels of severe-to-extremely-severe depressive symptoms (46.3% vs. 12.4%; p < 0.01) and extremely severe anxiety symptoms (77.8% vs. 7.5%; p < 0.01). We also observed a rise in problematic internet use and excessive gaming over time. Mediation analyses revealed that COVID-19-related general psychopathology, stress, anxiety, depression and social isolation play a significant role in the emergence of problematic internet use, social media addiction and problematic video gaming. Professional gamers and younger subjects emerged as sub-populations particularly at risk of developing digital addictions. If confirmed in larger and more homogenous samples, our findings may help in shedding light on possible preventive and treatment strategies for digital addictions.

Summary A low count of CD4+ and CD8+ lymphocytes is a hallmark laboratory finding in the Coronavirus disease 2019 (COVID‐19). Using flow cytometry, we observed significantly higher CD95 (Fas) and PD‐1 expression on both CD4+ T and CD8+ T cells in 42 COVID‐19 patients when compared to controls. Higher CD95 expression in CD4+ cells correlated with lower CD4+ counts. A higher expression of CD95 in CD4+ and CD8+ lymphocytes correlated with a lower percentage of Naive events. Our results might suggest a shift to antigen‐activated T cells, expressing molecules increasing their propensity to apoptosis and exhaustion during COVID‐19 infection.

Background Infective endocarditis (IE) is characterized by high rates of in-hospital death, and Staphylococcus aureus infection predicts a worse prognosis. We aimed to assess if admission inflammatory biomarkers (white blood cell – WBC – count, C-reactive protein — CRP, and procalcitonin) are informative on microbiological etiology and short-term outcomes. Methods Data from 236 patients admitted for IE from January 2013 to June 2018 were retrieved from a multicenter registry. Results Fifty-two patients (22%) were infected by S. aureus. WBC, CRP and procalcitonin had area under the curve (AUC) values for S. aureus infection of 0.595, 0.675, and 0.727, respectively. Adding procalcitonin to WBC improved discrimination over WBC alone (p = 0.045), and procalcitonin predicted S. aureus infection independently from the other inflammatory biomarkers and patient characteristics. Patients with WBC ≥ 12,800/mm3, CRP ≥ 130 mg/L, and procalcitonin ≥ 1.7 ng/mL had an almost 20-fold higher risk of S. aureus infection than patients with all biomarkers Conclusions Among patients with IE, high levels of inflammatory biomarkers on admission, particularly procalcitonin, are associated with a higher likelihood of S. aureus infection, and a higher risk of in-hospital mortality.

Increasing evidence shows an association between high lipoprotein(a) [Lp(a)] levels and atherothrombotic diseases. Lp(a) trait is largely controlled by kringle-IV type 2 (KIV-2) size polymorphism in LPA gene, encoding for apo(a). Environmental factors are considered to determinate minor phenotypic variability in Lp(a) levels. In the present study, we investigated the possible gene-environment interaction between KIV-2 polymorphism and Mediterranean diet adherence or fish weekly intake in determining Lp(a) levels. We evaluated Lp(a), KIV-2 polymorphism, fish intake and Mediterranean diet adherence in 452 subjects [median age (range) 66 (46-80)years] from Montignoso Heart and Lung Project (MEHLP) population. In subjects with high KIV-2 repeats number, influence of Mediterranean diet adherence in reducing Lp(a) levels was observed (p = 0.049). No significant difference in subjects with low KIV-2 repeats according to diet was found. Moreover, in high-KIV-2-repeat subjects, we observed a trend towards influence of fish intake on reducing Lp(a) levels (p = 0.186). At multivariate linear regression analysis, high adherence to Mediterranean diet remains a significant and independent determinant of lower Lp(a) levels (β = - 64.97, standard error = 26.55, p = 0.015). In conclusion, this study showed that only subjects with high KIV-2 repeats can take advantage to lower Lp(a) levels from correct nutritional habits and, in particular, from Mediterranean diet.

The aim of this multicenter study was to investigate the suicide risk in medically ill patients admitted to six Italian hospitals for whom a consultation-liaison intervention was requested.Participants completed socio-demographic and clinical report forms and the Brief Illness Perception Questionnaire. Suicidality was assessed using the P4 screener that investigates the presence of Past suicide attempts, Plans to commit a suicide, Probability of completing suicide, and Preventive factors. Participants were categorized as being at no, low or high suicide risk. Univariate and multivariable associations of categorical and continuous variables with suicide risk were investigated using multinomial logistic regression.Of the 641 inpatients, with mean age 60 years (SD = 16.9) and 49.2 % male, 13.2 % were at high suicidal risk (HR), 7.6 % low risk (LR) and 79.2 % no risk. Contacts with psychiatrists in the previous six months were associated with LR and HR (OR = 2.159 and 2.634, respectively), ongoing benzodiazepine use was associated with a threefold likelihood of LR (OR = 3.005), and the experienced intensity of illness symptoms was associated with LR and HR (OR = 1.257 and OR = 1.248, respectively). CL psychiatrists prescribed appropriate psychotropic drugs and activated liaison interventions and psychological support for the level of suicidal risk.The use of self-report measures bears the risk of recall bias.Our findings based on psychiatric consultations in the general hospital underscore the need to include suicide risk in the routine assessment of inpatients referred to CL psychiatric services and to plan an appropriate management of suicidal risk after discharge.

Purpose This study aims to provide real-world data about starting-dose of NOACs and dose- adjustment in patients with AF. In fact, even if new oral anticoagulation agents (NOACs) have a predictable effect without need for regular monitoring, dose-adjustments should be performed according to the summary of product information and international guidelines. Methods We employed the Italian Medicines Agency monitoring registries comprising data on a nationwide cohort of patients with AF treated with NOACs from 2013 to 2018. Logistic regression analysis was used to evaluate the determinants of dosage choice. Results During the reference period, treatment was commenced for 866539 patients. Forty-five percent of the first prescriptions were dispensed at a reduced-dose (dabigatran 60.3%, edoxaban 45.2%, apixaban 40.9%, rivaroxaban 37.4%). The prescription of reduced-dose was associated with older age, renal disease, bleeding risk and the concomitant use of drugs predisposing to bleeding, but not with CHA₂DS₂-VASc and HAS-BLED. A relative reduction of the proportion of patients treated with low-dosages was evident overtime for dabigatran and rivaroxaban; whereas prescription of low-dose apixaban and edoxaban increased progressively among elderly patients. Conclusions Evidence based on real-world data shows a high frequency of low-dose prescriptions of NOACs in AF patients. Except for older age, renal disease, bleeding risk and the concomitant use of drugs predisposing to bleeding, other factors that may determine the choice of reduced-dose could not be ascertained. There may be potential under-treatment of AF patients, but further evaluation is warranted.

The COVID-19 pandemic is impressively challenging the healthcare system. Several prognostic models have been validated but few of them are implemented in daily practice. The objective of the study was to validate a machine-learning risk prediction model using easy-to-obtain parameters to help to identify patients with COVID-19 who are at higher risk of death. The training cohort included all patients admitted to Fondazione Policlinico Gemelli with COVID-19 from March 5, 2020, to November 5, 2020. Afterward, the model was tested on all patients admitted to the same hospital with COVID-19 from November 6, 2020, to February 5, 2021. The primary outcome was in-hospital case-fatality risk. The out-of-sample performance of the model was estimated from the training set in terms of Area under the Receiving Operator Curve (AUROC) and classification matrix statistics by averaging the results of fivefold cross validation repeated 3-times and comparing the results with those obtained on the test set. An explanation analysis of the model, based on the SHapley Additive exPlanations (SHAP), is also presented. To assess the subsequent time evolution, the change in paO2/FiO2 (P/F) at 48 h after the baseline measurement was plotted against its baseline value. Among the 921 patients included in the training cohort, 120 died (13%). Variables selected for the model were age, platelet count, SpO2, blood urea nitrogen (BUN), hemoglobin, C-reactive protein, neutrophil count, and sodium. The results of the fivefold cross-validation repeated 3-times gave AUROC of 0.87, and statistics of the classification matrix to the Youden index as follows: sensitivity 0.840, specificity 0.774, negative predictive value 0.971. Then, the model was tested on a new population (n = 1463) in which the case-fatality rate was 22.6%. The test model showed AUROC 0.818, sensitivity 0.813, specificity 0.650, negative predictive value 0.922. Considering the first quartile of the predicted risk score (low-risk score group), the case-fatality rate was 1.6%, 17.8% in the second and third quartile (high-risk score group) and 53.5% in the fourth quartile (very high-risk score group). The three risk score groups showed good discrimination for the P/F value at admission, and a positive correlation was found for the low-risk class to P/F at 48 h after admission (adjusted R-squared = 0.48). We developed a predictive model of death for people with SARS-CoV-2 infection by including only easy-to-obtain variables (abnormal blood count, BUN, C-reactive protein, sodium and lower SpO2). It demonstrated good accuracy and high power of discrimination. The simplicity of the model makes the risk prediction applicable for patients in the Emergency Department, or during hospitalization. Although it is reasonable to assume that the model is also applicable in not-hospitalized persons, only appropriate studies can assess the accuracy of the model also for persons at home.

Objectives NEAT001/ANRS143 demonstrated non-inferiority of once-daily darunavir/ritonavir (800/100 mg) + twice-daily raltegravir (400 mg) versus darunavir/ritonavir + tenofovir disoproxil fumarate/emtricitabine (245/200 mg once daily) in treatment-naive patients. We investigated the population pharmacokinetics of darunavir, ritonavir, tenofovir and emtricitabine and relationships with demographics, genetic polymorphisms and virological failure. Methods Non-linear mixed-effects models (NONMEM v. 7.3) were applied to determine pharmacokinetic parameters and assess demographic covariates and relationships with SNPs (SLCO3A1, SLCO1B1, NR1I2, NR1I3, CYP3A5*3, CYP3A4*22, ABCC2, ABCC10, ABCG2 and SCL47A1). The relationship between model-predicted darunavir AUC0–24 and C24 with time to virological failure was evaluated by Cox regression. Results Of 805 enrolled, 716, 720, 347 and 361 were included in the darunavir, ritonavir, tenofovir and emtricitabine models, respectively (11% female, 83% Caucasian). No significant effect of patient demographics or SNPs was observed for darunavir or tenofovir apparent oral clearance (CL/F); coadministration of raltegravir did not influence darunavir or ritonavir CL/F. Ritonavir CL/F decreased by 23% in NR1I2 63396C>T carriers and emtricitabine CL/F was linearly associated with creatinine clearance (P Conclusions Darunavir concentrations were unaltered in the presence of raltegravir and not associated with virological failure. Polymorphisms investigated had little impact on study-drug pharmacokinetics. Darunavir/ritonavir + raltegravir may be an appropriate option for patients experiencing NRTI-associated toxicity.

Background. Greater levels of insight may be linked with depressive symptoms among patients with schizophrenia, however, it would be useful to characterize this association at symptom-level, in order to inform research on interventions. Methods. Data on depressive symptoms (Calgary Depression Scale for Schizophrenia) and insight (G12 item from the Positive and Negative Syndrome Scale) were obtained from 921 community-dwelling, clinically-stable individuals with a DSM-IV diagnosis of schizophrenia, recruited in a nationwide multicenter study. Network analysis was used to explore the most relevant connections between insight and depressive symptoms, including potential confounders in the model (neurocognitive and social-cognitive functioning, positive, negative and disorganization symptoms, extrapyramidal symptoms, hostility, internalized stigma, and perceived discrimination). Bayesian network analysis was used to estimate a directed acyclic graph (DAG) while investigating the most likely direction of the putative causal association between insight and depression. Results. After adjusting for confounders, better levels of insight were associated with greater self-depreciation, pathological guilt, morning depression and suicidal ideation. No difference in global network structure was detected for socioeconomic status, service engagement or illness severity. The DAG confirmed the presence of an association between greater insight and self-depreciation, suggesting the more probable causal direction was from insight to depressive symptoms. Conclusions. In schizophrenia, better levels of insight may cause self-depreciation and, possibly, other depressive symptoms. Person-centered and narrative psychotherapeutic approaches may be particularly fit to improve patient insight without dampening self-esteem., Highlights Better insight seems associated with depressive symptoms in schizophrenia.Network analyses were used to explore this association in a large sample.Insight was associated with self-depreciation, guilt, and suicidal ideation.Although cross-sectional, data suggest causal direction from insight to depression.

To investigate the prognostic role of procalcitonin (PCT) assessment and blood culture (BC) acquisition in the emergency department (ED) in patients with urinary tract infection (UTI) or urosepsis. We enrolled patients admitted for UTI to our ED over a 10-year period. Mortality and in hospital length of stay (LOS) were compared between patients with UTI or urosepsis who had sampling for PCT levels and BC taken in the ED (ePCT group-eBC group) and those who had not (no-ePCT group-no-eBC group). 1029 patients were analyzed, 52.7% of which were female. Median age was 77 [65-83]; 139 patients (13.5%) had complicated UTI. Median LOS was 10 [7-17] days. In the ePCT group, LOS was 10 [7-16] days, vs. 10 [7-17] (p = 0.428) in the no-ePCT group. In the eBC group, LOS was 10 [6-16] days vs. 10 [7-17] days (p = 0.369) in the no-eBC group. The overall mortality rate was 6.6%. The mortality rate was not affected by early PCT determination (6% in the ePCT group vs. 6.9% in the no-ePCT group, p = 0.584). Similarly, the mortality rate was not different in the eBC group as compared to the no-eBC group (5.4% vs. 6.9%, p = 0.415). Performance of ePCT or eBC testing made no significant difference in terms of improvement of mortality rates in septic patients (11.4% vs. 7.2%; p = 0.397 and 8.8% vs. 9.8%; p = 0.845, respectively). The prognostic relevance of early evaluation of PCT and BC in the ED of patients with febrile UTI appears limited. In complicated UTI patients, PCT and BC testing may be more appropriate in the context of improving antibiotic stewardship, or as an integral component of PCT-guided standardized protocols.

Background Late Life Bipolar Disorder (LLBD) is associated with a high prevalence of cognitive impairments, but few studies have examined their risk factors and clinical correlates Methods Participants with bipolar disorder older than 60 ( n = 86) were recruited from psychiatric outpatient and inpatients units. Patients were assessed with various instruments, including the Clinical Dementia Rating scale, the Montreal Cognitive Assessment and the Cumulative Illness Rating Scale. The distribution of disorder-specific and general risk factors was compared between patients with LLBD plus cognitive impairments (mild cognitive impairment or dementia) and those with LLBD but no cognitive impairment. Analyses were first conducted at the bivariate level, then using multiple regression. The association with disability, aggressive behavior and suicidal ideation was also explored. Results Cognitive impairments in LLBD were associated with a diagnosis of type 1 bipolar disorder (OR = 6.40, 95%CI: 1.84 – 22.31, p = 0.004), fewer years of education (OR = 0.79, 95%CI: 0.69 – 0.91, p = 0.001) and higher severity of physical diseases (OR 26.54, 95%CI: 2.07 – 340.37, p = 0.01). Moreover, cognitive impairments were associated with an increased likelihood of disability and recent aggressive behavior, but not suicidal ideation. Limitations retrospective design, conflation of MCI and dementia, not all subjects were in euthymia Conclusions In LLBD, the presence of cognitive impairments was associated with a diagnosis of type I bipolar disorder, lower education and more severe physical comorbidities. In turn, MCI or dementia were associated with increased disability and aggressive behavior. These findings may aid the identification of patients at risk for cognitive deterioration in everyday clinical practice.

Importance: The goal of schizophrenia treatment has shifted from symptom reduction and relapse prevention to functional recovery; however, recovery rates remain low. Prospective identification of variables associated with real-life functioning domains is essential for personalized and integrated treatment programs. Objective: To assess whether baseline illness-related variables, personal resources, and context-related factors are associated with work skills, interpersonal relationships, and everyday life skills at 4-year follow-up. Design, Setting, and Participants: This multicenter prospective cohort study was conducted across 24 Italian university psychiatric clinics or mental health departments in which 921 patients enrolled in a cross-sectional study were contacted after 4 years for reassessment. Recruitment of community-dwelling, clinically stable persons with schizophrenia was conducted from March 2016 to December 2017, and data were analyzed from January to May 2020. Main Outcomes and Measures: Psychopathology, social and nonsocial cognition, functional capacity, personal resources, and context-related factors were assessed, with real-life functioning as the main outcome. Structural equation modeling, multiple regression analyses, and latent change score modeling were used to identify variables that were associated with real-life functioning domains at follow-up and with changes from baseline in these domains. Results: In total, 618 participants (427 male [69.1%]; mean [SD] age, 45.1 [10.5] years) were included. Five baseline variables were directly associated with real-life functioning at follow-up: neurocognition with everyday life (β, 0.274; 95% CI, 0.207-0.341; P

Background and Objectives: Fever is one of the most common presenting complaints in the Emergency Department (ED). The role of serum procalcitonin (PCT) determination in the ED evaluation of adults presenting with fever is still debated. The aim of this study was to evaluate if, in adults presenting to the ED with fever and then hospitalized, the early PCT determination could improve prognosis. Materials and Methods. This is a retrospective, mono-centric study, conducted over a 10-year period (2009–2018). We analyzed consecutive patients ≥18 years admitted to ED with fever and then hospitalized. According to quick sequential organ failure assessment (qSOFA) at admission, we compared patients that had a PCT determination vs. controls. Primary endpoint was overall in-hospital mortality, secondary endpoints were in-hospital length of stay, and mortality in patients with bloodstream infection and acute respiratory infections. Results. The sample included 12,062 patients, median age was 71 years and 55.1% were men. In patients with qSOFA ≥ 2 overall mortality was significantly lower if they had a PCT-guided management in ED, (20.5% vs. 26.5%, p = 0.046). In the qSOFA &lt, 2 group the mortality was not significantly different in PCT patients, except for those with a final diagnosis of bloodstream infection. Conclusions. Among adults hospitalized with fever, the PCT evaluation at ED admission was not associated with better outcomes, with the possible exception of patients affected by bloodstream infections. However, in febrile patients presenting to the ED with qSOFA ≥ 2, the early PCT evaluation could improve the overall in-hospital survival.

Objective Restriction in healthcare services during the COVID-19 pandemic caused delays in the diagnosis and treatment of several diseases. To overcome the risk of missed diagnosis of head and neck cancers, before deleting the scheduled appointments, we have introduced a selection of the patients by examining the clinical presenting issue and previous medical history. The aim of this study is to show the effects of the abovementioned strategy on the diagnosis and management of laryngeal cancer. Methods Data were extracted from the Hospital software regarding the new diagnosis of laryngeal SCC in the periods from March 2020 to December 2020 during the pandemic (study group) and from March 2019 to December 2019 (control group) were collected. Data were compared regarding: TNM stage, time from first medical examination to histological diagnosis (Time-1), and time form histological diagnosis to beginning of treatments (Time-2). Results The final study group was composed by 19 laryngeal cancers, the control group by 25 cases. No significant differences were found in the tumour stage between the groups. In the study group, Time-1 was shorter (24 days versus 43 days, p = 0.012), while Time-2 in surgically-treated patients was longer (20 days versus 9 days, p = 0.012). Conclusion During the pandemic, there was a dramatic lack of medical and nurse staff needed for surgical procedures. As consequence, the time between the diagnosis of malignancy and surgical treatment increased. In our unit, an efficient patient selection strategy to reschedule medical appointments avoided a dangerous shift toward higher laryngeal cancer stages.

Introduction The novel coronavirus SARS-Cov-2 can infect the respiratory tract causing a spectrum of disease varying from mild to fatal pneumonia, and known as COVID-19. Ongoing clinical research is assessing the potential for long-term respiratory sequelae in these patients. We assessed the respiratory function in a cohort of patients after recovering from SARS-Cov-2 infection, stratified according to PaO2/FiO2 (p/F) values. Method Approximately one month after hospital discharge, 86 COVID-19 patients underwent physical examination, arterial blood gas (ABG) analysis, pulmonary function tests (PFTs), and six-minute walk test (6MWT). Patients were also asked to quantify the severity of dyspnoea and cough before, during, and after hospitalization using a visual analogic scale (VAS). Seventy-six subjects with ABG during hospitalization were stratified in three groups according to their worst p/F values: above 300 (n = 38), between 200 and 300 (n = 30) and below 200 (n = 20). Results On PFTs, lung volumes were overall preserved yet, mean percent predicted residual volume was slightly reduced (74.8 ± 18.1%). Percent predicted diffusing capacity for carbon monoxide (DLCO) was also mildly reduced (77.2 ± 16.5%). Patients reported residual breathlessness at the time of the visit (VAS 19.8, p Conclusion Approximately one month after hospital discharge, patients with COVID-19 can have residual respiratory impairment, including lower exercise tolerance. The extent of this impairment seems to correlate with the severity of respiratory failure during hospitalization.

First generation antipsychotics (FGAs) are more likely to induce extrapyramidal side-effects (EPS) than second generation antipsychotics (SGAs), and EPS have been shown associated to cognitive deficits in schizophrenia. So far, no study has explored the relationships between EPS and social cognition (SC) in people with schizophrenia. Therefore, we assessed the prevalence of EPS in a large sample of drug-treated community-dwelling persons with schizophrenia and explored their relationships with patients' neurocognitive and SC abilities. 875 patients underwent EPS, psychopathological, neurocognitive and SC assessments by means of standardized measures. Relationships between EPS, psychopathology and neurocognitive and SC measures were investigated by correlation tests. Moreover, a partial correlation network was computed by means of a network analysis. 256 patients were treated with FGAs alone or in combination with SGA and 619 with SGAs. EPS were significantly more frequent in FGA-treated group than in the SGA-treated one. Patients with EPS disclosed a more severe psychopathology and were more impaired in neurocognitive and SC measures compared to those without EPS. Disorganization, expressive deficit, and duration of illness were significantly associated to both neurocognitive and SC measures while EPS were associated to neurocognitive measures only. The network analysis showed that parkinsonism was the sole EPS directly connected to both psychopathological and neurocognitive indices whereas no direct connection emerged between EPS and SC measures. Present findings confirm that EPS are still present in the era of SGAs and contribute, together with other clinical variables, to the neurocognitive but not to the SC impairment of patients with schizophrenia.

AIM To examine the incidence of with first-episode psychosis (FEP) in the Integrated Department of Mental Health and Pathological Addictions in Ferrara, Italy, and to examine the association between the Duration of Untreated Psychosis (DUP) and the clinical course. METHODS Participants recruited in 2013-2019 were assessed with the Health of the Nation Outcome Scale (HoNOS) every 6 months for 24 months. Hierarchical growth models analysed changes of global severity (HoNOS total scores) and symptom dimensions. Regression modelled factors associated with remission (HoNOS

NUT carcinoma (NUT-C) is a relatively new malignancy that was recently listed in the 4th edition of the WHO Classification of Head and Neck Tumors in 2017. NUT carcinoma is a rare, aggressive, poorly differentiated carcinoma genetically defined by chromosomal rearrangement of the nuclear protein in testis (NUTM1) gene. The prognosis is extremely poor, with a mean survival

To develop a deep learning-based decision tree for the primary care setting, to stratify adult patients with confirmed and unconfirmed coronavirus disease 2019 (COVID-19), and to predict the need for hospitalization or home monitoring.We performed a retrospective cohort study on data from patients admitted to a COVID hospital in Rome, Italy, between 5 March 2020 and 5 June 2020. A confirmed case was defined as a patient with a positive nasopharyngeal RT-PCR test result, while an unconfirmed case had negative results on repeated swabs. Patients' medical history and clinical, laboratory and radiological findings were collected, and the dataset was used to train a predictive model for COVID-19 severity.Data of 198 patients were included in the study. Twenty-eight (14.14%) had mild disease, 62 (31.31%) had moderate disease, 64 (32.32%) had severe disease, and 44 (22.22%) had critical disease. The G2 value assessed the contribution of each collected value to decision tree building. On this basis, SpO2 (%) with a cut point at 92 was chosen for the optimal first split. Therefore, the decision tree was built using values maximizing G2 and LogWorth. After the tree was built, the correspondence between inputs and outcomes was validated.We developed a machine learning-based tool that is easy to understand and apply. It provides good discrimination in stratifying confirmed and unconfirmed COVID-19 patients with different prognoses in every context. Our tool might allow general practitioners visiting patients at home to decide whether the patient needs to be hospitalized.

OBJECTIVE To examine knowledge about, perception of and current risk factors for cancer, among patients with severe mental illness (SMI) and to compare these variables with patients without SMI. METHODS A series of patients affected by SMI (i.e., schizophrenia spectrum disorders, bipolar disorders and severe personality disorders) and a matched (gender, age) control group of primary care attenders were assessed, by using an ad hoc semi-structured interview and a short true/false 17-item questionnaire, about family history of cancer, cancer risk-related lifestyles, personal perception and knowledge of risk for cancer. RESULTS Patients with SMI (n = 185, mainly schizophrenia spectrum disorders, 48%, and mood disorders, 33%) significantly differed from primary care attenders (n = 173) for: lower participation to occult stool blood screening test, Pap smear test and mammography; higher prevalence of current and past smoking habits; lower awareness towards their own physical symptoms and their perception of risks for cancer; lower physical exercise practicing; lower knowledge about risk factors for cancer (e.g. familiarity for cancer, smoke-habits, breast and uterine cancer). CONCLUSIONS Patients suffering from SMI had higher at-risk behavior for cancer and showed fewer concerns and less knowledge about risk for cancer than primary care attendees. These findings can guide to implement screening for cancer (e.g., Pap test, blood) and to design evidence-based interventions to reduce cancer risk (e.g., educational and behavioral change for smoking cessation, dietary habits) among patients with SMI.

Background:Late-life depression is often associated with cognitive impairments and disability, which may persist even after adequate antidepressant drug treatment. Physical exercise is increasingly recognized as an effective antidepressant agent, and may exert positive effects on these features too. However, few studies examined this issue, especially by comparing different types of exercises.Methods:We performed secondary analyses on data from the Safety and Efficacy of Exercise for Depression in Seniors study, a trial comparing the antidepressant effectiveness of sertraline (S), sertraline plus thrice-weekly non-progressive exercise (S+NPE), and sertraline plus thrice-weekly progressive aerobic exercise (S+PAE). Exercise was conducted in small groups and monitored by heart rate meters. Patients with late-life depression without severe cognitive impairment were recruited from primary care and assessed at baseline and 24 weeks, using the Montreal Cognitive Assessment (MOCA, total and subdomain scores) and Brief Disability Questionnaire. Analyses were based on Generalized Linear Models.Results:In total, 121 patients (mean age 75, 71% females) were randomized to the study interventions. Compared with the S group, patients in the S+PAE group displayed greater improvements of MOCA total scores (p=0.006, effect size=0.37), visuospatial/executive functions (p=0.001, effect size=0.13), and disability (p=0.02, effect size=−0.31). Participants in the S+NPE group did not display significant differences with the control group.Conclusions:Adding aerobic, progressive exercise to antidepressant drug treatment may offer significant advantages over standard treatment for cognitive abilities and disability. These findings suggest that even among older patients exercise may constitute a valid therapeutic measure to improve patients’ outcomes.

Importance Enhanced understanding of factors associated with symptomatic and functional recovery is instrumental to designing personalized treatment plans for people with schizophrenia. To date, this is the first study using network analysis to investigate the associations among cognitive, psychopathologic, and psychosocial variables in a large sample of community-dwelling individuals with schizophrenia. Objective To assess the interplay among psychopathologic variables, cognitive dysfunctions, functional capacity, personal resources, perceived stigma, and real-life functioning in individuals with schizophrenia, using a data-driven approach. Design, Setting, and Participants This multicenter, cross-sectional study involved 26 university psychiatric clinics and/or mental health departments. A total of 921 community-dwelling individuals with a DSM-IV diagnosis of schizophrenia who were stabilized on antipsychotic treatment were recruited from those consecutively presenting to the outpatient units of the sites between March 1, 2012, and September 30, 2013. Statistical analysis was conducted between July 1 and September 30, 2017. Main Outcomes and Measures Measures covered psychopathologic variables, neurocognition, social cognition, functional capacity, real-life functioning, resilience, perceived stigma, incentives, and service engagement. Results Of 740 patients (221 women and 519 men; mean [SD] age, 40.0 [10.9] years) with complete data on the 27 study measures, 163 (22.0%) were remitted (with a score of mild or better on 8 core symptoms). The network analysis showed that functional capacity and everyday life skills were the most central and highly interconnected nodes in the network. Psychopathologic variables split in 2 domains, with positive symptoms being one of the most peripheral and least connected nodes. Functional capacity bridged cognition with everyday life skills; the everyday life skills node was connected to disorganization and expressive deficits. Interpersonal relationships and work skills were connected to avolition; the interpersonal relationships node was also linked to social competence, and the work skills node was linked to social incentives and engagement with mental health services. A case-dropping bootstrap procedure showed centrality indices correlations of 0.75 or greater between the original and randomly defined samples up to 481 of 740 case-dropping (65.0%). No difference in the network structure was found between men and women. Conclusions and Relevance The high centrality of functional capacity and everyday life skills in the network suggests that improving the ability to perform tasks relevant to everyday life is critical for any therapeutic intervention in schizophrenia. The pattern of network node connections supports the implementation of personalized interventions.

Objective The study aimed to explore premorbid academic and social functioning in patients with schizophrenia, and its associations with the severity of negative symptoms and neurocognitive impairment. Method Premorbid adjustment (PA) in patients with schizophrenia was compared to early adjustment in unaffected first-degree relatives and healthy controls. Its associations with psychopathology, cognition, and real-life functioning were investigated. The associations of PA with primary negative symptoms and their two factors were explored. Results We found an impairment of academic and social PA in patients (P ≤ 0.000001) and an impairment of academic aspects of early adjustment in relatives (P ≤ 0.01). Patients with poor PA showed greater severity of negative symptoms (limited to avolition after excluding the effect of depression/parkinsonism), working memory, social cognition, and real-life functioning (P ≤ 0.01 to ≤0.000001). Worse academic and social PA were associated with greater severity of psychopathology, cognitive impairment, and real-life functioning impairment (P ≤ 0.000001). Regression analyses showed that worse PA in the academic domain was mainly associated to the impairment of working memory, whereas worse PA in the social domain to avolition (P ≤ 0.000001). Conclusion Our findings suggest that poor early adjustment may represent a marker of vulnerability to schizophrenia and highlight the need for preventive/early interventions based on psychosocial and/or cognitive programs.

Assessing the risk to develop a specific disease is the first step towards prevention, both at individual and population levels. The development and validation of risk prediction models (RPMs) is the norm within different fields of medicine but still underused in psychiatry, despite the global impact of mental disorders. In particular, there is a lack of RPMs to assess the risk of developing depression, the first worldwide cause of disability and harbinger of functional decline in old age. We present the depression risk assessment tool DRAT-up, the first prospective RPM to identify late-life depression among community-dwelling subjects aged 60-75. The development of DRAT-up was based on appraisal of relevant literature, extraction of robust risk estimates, and integration into model parameters. A unique feature is the ability to estimate risk even in the presence of missing values. To assess the properties of DRAT-up, a validation study was conducted on three European cohorts, namely, the English Longitudinal Study of Ageing, the Invecchiare nel Chianti, and the Irish Longitudinal Study on Ageing, with 20 206, 1359, and 3124 eligible samples, respectively. The model yielded accurate risk estimation in the three datasets from a small number of predictors. The Brier scores were 0.054, 0.133, and 0.041, respectively, while the values of area under the curve (AUC) were 0.761, 0.736, and 0.768, respectively. Sensitivity analyses suggest robustness to missing values: setting any individual feature to unknown caused the Brier scores to increase by 0.004 and the AUCs to decrease by 0.045 in the worst cases. DRAT-up can be readily used for clinical purposes and to aid policy-making in the field of mental health.

Late-life depression has multiple, heterogeneous clinical presentations. The aim of the study was to identify higher-order homogeneous clinical features (symptom complexes), while accounting for their potential causal interactions within the network approach to psychopathology. We analyzed cross-sectional data from community-dwelling adults aged 65-85 years recruited by the European MentDis_ICF65+ study (n = 2623, mean age 74, 49% females). The severity of 33 depressive symptoms was derived from the age-adapted Composite International Diagnostic Interview. Symptom complexes were identified using multiple detection algorithms for symptom networks, and their fit to data was assessed with latent network models (LNMs) in exploratory and confirmatory analyses. Sensitivity analyses included the Partial Correlation Likelihood Test (PCLT) to investigate the data-generating structure. Depressive symptoms were organized by the Walktrap algorithm into eight symptom complexes, namely sadness/hopelessness, anhedonia/lack of energy, anxiety/irritability, self-reproach, disturbed sleep, agitation/increased appetite, concentration/decision making, and thoughts of death. An LNM adequately fit the distribution of individual symptoms' data in the population. The model suggested the presence of reciprocal interactions between the symptom complexes of sadness and anxiety, concentration and self-reproach and between self-reproach and thoughts of death. Results of the PCLT confirmed that symptom complex data were more likely generated by a network, rather than a latent-variable structure. In conclusion, late-life depressive symptoms are organized into eight interacting symptom complexes. Identification of the symptom complexes of late-life depression may streamline clinical assessment, provide targets for personalization of treatment, and aid the search for biomarkers and for predictors of outcomes of late-life depression.

Objectives Surgical antibiotic prophylaxis (SAP) represents a major indication of antibiotic consumption worldwide. The present study aims to report the results of an enabling, long-term AMS intervention conducted between 2013 and 2019 on an Italian University Hospital performing more than 40.000 surgical interventions per year. Methods SAP inappropriateness was defined according to the ASHP guidelines and divided in four main categories: indication, selection and dosing, duration, timing. Between 2013 and 2019, we conducted a continuative AMS intervention over 14 surgical departments that included enablement, review of selected clinical records and feedback. Results We collected a total of 789 SAP prescribed to 735 patients (mean age 56.7 ± 17.8y). Overall, guideline adherence improved from 36.6% (n = 149) at baseline to 57.9% (n = 221) post-intervention (P P indication (from 58.5 to 93.2%), selection and dosing (from 58.5 to 80.6%), timing (from 92.4 to 97.6%), duration (from 71 to 80.1%). Conclusions Though results cannot be generalized to all hospital populations, enabling AMS interventions may be effective in establishing a sustained improvement in SAP appropriateness rates. Once identified the main causes of SAP inappropriateness, tailored AMS interventions for each department may be beneficial. Further studies are needed to evaluate specific outcomes as incidence of surgical site infections and antimicrobial resistance.

This study aims to analyze the early and late outcomes of our 30-year experience with mycotic aneurysms of the abdominal aorta and iliac arteries.This retrospective cohort study compared the outcomes of all the patients with mycotic aneurysm, by analyzing prospectively collected data between September 1989 and October 2019 from the Unit of Vascular Surgery of Fondazione Policlinico Universitario Gemelli - IRCCS in Rome, Italy.Twenty-three patients with mycotic aneurysm were included. Twenty-two patients underwent surgery; one patient arrived at the emergency room with unstable clinical conditions and died before being treated. Fourteen cases (60.9%) were located at the infrarenal aorta, while three cases (13.0%) were pararenal aortic aneurysms. Six cases (26.1%) had an iliac arteries localization. Seventeen patients (77.3%) underwent open surgical repair aneurysmectomy with in situ reconstruction, while three cases (13.6%) underwent extra-anatomic revascularization. Three patients (13.6%) underwent the placement of an endoprosthesis, of whom two underwent hybrid procedures, and one EVAR. The latter underwent an early conversion to open repair due to a type I endoleak. The mean length of hospital stay was 35 ± 18.7 days. Five patients (22.7%) died in the immediate postoperative period. In the follow-up of 45.5 ± 41.3 months (range 2-156), we documented six deaths (35.3%), of whom two (11.8%) were aortic-related for a 34.8% overall aortic-related mortality. Eleven patients were alive, with an overall survival of 47.8%.Mycotic aneurysm is an extremely rare and varied pathology. Open surgical repair showed to be a safe approach because of a complete and aggressive debridement of local infected tissues, with an acceptable long-term mortality rate.

Background An ageing population worldwide needs to investigate quality of life (QoL) and level of functioning (LoF) in the elderly and its associated variables. We aimed to study the relationship between Quality of Life (QoL) and Level of Functioning (LoF) in an elderly population in Europe. Method As part of the Ment_Dis65+ European Project, 3142 community-dwelling adults aged 65–84 years in six countries were assessed by using the adaptation for the elderly of the Composite International Diagnostic Interview (CIDI65+) to provide psychiatric diagnosis according to the International Classification of Diseases (10th edition) (ICD-10 Classification of Mental and Behavioural Disorders). Socio-demographic and clinical interviews, and two self-report tools, the World Health Organization QoL assessment (WHO QoL BREF), to assess QoL, and the WHO Disability Assessment Schedule -II (WHODAS-II), to assess LoF, were also administered. Results Most subjects reported good levels of QoL (56.6%) and self-rated health (62%), with no or mild disability (58.8%). There was a linear decrease of the QoL and the LoF by increase of age. Elderly with ICD-10 mental disorder (e.g. somatoform, affective and anxiety disorders) had poorer QoL and lower LoF. There were a number of predictors of lower levels of QoL and disability, including both socio-demographic variables (e.g. male gender, increase in age, poor financial situation, retirement, reduced number of close significant others), ICD-10 psychiatric diagnosis (mainly anxiety, somatoform disorders) and presence of medical disorders (mainly heart and respiratory diseases). Conclusions The study indicates that QoL and LoF were quite acceptable in European elderly people. A series of variables, including psychiatric and somatic disorders, as well as socio-demographic factor influenced in a negative way both QoL and LoF. More specific links between mental health, social and health services dedicated to this segment of the population, should be implemented in order to provide better care for elderly people with conditions impacting their QoL and functioning.

Urinary tract infections (UTIs) are among the most common causes of sepsis presenting to hospitals. Treating complicated UTIs is extremely important due to their potential mortality. Levofloxacin is a fluoroquinolone antibacterial that has become one of the cornerstones of antibiotic therapy of complicated UTIs and pyelonephritis since its introduction in the 1990s because of its exceptional pharmacokinetic (PK) and pharmacodynamic (PD) profile. However, the emergence of widespread fluoroquinolone resistance over the past decade has prompted investigators to reexamine its place in the treatment of UTI.This literature review summarizes data about the efficacy and the tolerability of levofloxacin in treating complicated UTIs and pyelonephritis.In the early 2000s, fluoroquinolones became the most commonly prescribed antibiotic in the US. Since then, the resistance rate of

In the face of the rapid evolution of the COVID-19 pandemic, healthcare professionals on the frontline are in urgent need of frequent updates in the accomplishment of their practice. Hence, clinicians started to search for prompt, valid information on sources that are parallel to academic journals. Aim of this work is to investigate the extent of this phenomenon. We administered an anonymous online cross-sectional survey to 645 Italian clinicians. Target of the survey were all medical figures potentially involved in the management of COVID-19 cases. 369 questionnaires were returned. 19.5% (n = 72) of respondents were younger than 30 years-old; 49,3% (n = 182) worked in Infectious Diseases, Internal Medicine or Respiratory Medicine departments, 11.5% (n = 42) in Intensive Care Unit and 7.4% (n = 27) were general practitioner. 70% (n = 261) of respondents reported that their use of social media to seek medical information increased during the pandemic. 39.3% (n = 145) consistently consulted Facebook groups and 53.1% (n = 196) Whatsapp chats. 47% (n = 174) of respondents reported that information shared on social media had a consistent impact on their daily practice. In the present study, we found no difference in social media usage between age groups or medical specialties. Given the urgent need for scientific update during the present pandemic, these findings may help understanding how clinicians access new evidences and implement them in their daily practice.

Background and purpose The objective of this study was to assess the neurological manifestations in a series of consecutive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients, comparing their frequency with a population hospitalized in the same period for flu/respiratory symptoms, finally not related to SARS-CoV-2. Methods Patients with flu/respiratory symptoms admitted to Fondazione Policlinico Gemelli hospital from 14 March 2020 to 20 April 2020 were retrospectively enrolled. The frequency of neurological manifestations of patients with SARS-CoV-2 infection was compared with a control group. Results In all, 213 patients were found to be positive for SARS-CoV-2, after reverse transcriptase polymerase chain reaction on nasal or throat swabs, whilst 218 patients were found to be negative and were used as a control group. Regarding central nervous system manifestations, in SARS-CoV-2-positive patients a higher frequency of headache, hyposmia and encephalopathy always related to systemic conditions (fever or hypoxia) was observed. Furthermore, muscular involvement was more frequent in SARS-CoV-2 infection. Conclusions Patients with COVID-19 commonly have neurological manifestations but only hyposmia and muscle involvement seem more frequent compared with other flu diseases.

Purpose Circulating micro-ribonucleic acids (miRNAs) are small noncoding RNA molecules that influence gene transcription. We conducted the present profiling study to characterize the expression of circulating miRNAs in lean and obese patients with polycystic ovary syndrome (PCOS), the most common endocrine and metabolic disorder in premenopausal women. Basic Procedures We selected 11 control women, 12 patients with PCOS and 12 men so that they were similar in terms of body mass index. Five control women, 6 men and 6 patients with PCOS had normal weight whereas 6 subjects per group were obese. We used miRCURY LNA™ Universal RT microRNA PCR for miRNA profiling. Main Findings The expression of 38 miRNAs and was different between subjects with PCOS and male and female controls. The differences in 15 miRNAs followed a pattern suggestive of androgenization characterized by expression levels that were similar in patients with PCOS and men but were different compared with those of control women. The expression of 13 miRNAs in women with PCOS was similar to that of control women and different compared with the expression observed in men, suggesting sexual dimorphism and, lastly, we observed 5 miRNAs that were expressed differently in women with PCOS compared with both men and control women, suggesting a specific abnormality in expression associated with the syndrome. Obesity interacted with the differences in several of these miRNAs, and the expression levels of many of them correlated with the hirsutism score, sex hormones and/or indexes of obesity, adiposity and metabolic dysfunction. Principal Conclusions The present results suggest that several serum miRNAs are influenced by PCOS, sex hormones and obesity. Our findings may guide the targeted search of miRNAs as clinically relevant markers for PCOS and its association with obesity and metabolic dysfunction in future studies.

The Fungitell assay (FA) and the Wako β-glucan test (GT) are employed to measure the serum/plasma 1,3-β-D-glucan (BDG), a well-known invasive fungal disease biomarker. Data to convincingly and/or sufficiently support the GT as a valuable alternative to the FA are yet limited. In this study, we evaluated the FA and the GT to diagnose invasive aspergillosis (IA), invasive candidiasis (IC), and Pneumocystis jirovecii pneumonia (PJP). The FA and GT performances were compared in sera of patients with IA (n = 40), IC (n = 78), and PJP (n = 17) with respect to sera of control patients (n = 187). Using the manufacturer's cutoff values of 80 pg/mL and 11 pg/mL, the sensitivity and specificity for IA diagnosis were 92.5% and 99.5% for the FA and 60.0% and 99.5% for the GT, respectively; for IC diagnosis were 100.0% and 97.3% for the FA and 91.0% and 99.5% for the GT, respectively; for PJP diagnosis were 100.0% and 97.3% for the FA and 88.2% and 99.5% for the GT, respectively. When an optimized cutoff value of 7.0 pg/mL for the GT was used, the sensitivity and specificity were 80.0% and 97.3% for IA diagnosis, 98.7% and 97.3% for IC diagnosis, and 94.1% and 97.3% for PJP diagnosis, respectively. At the 7.0-pg/mL GT cutoff, the agreement between the assays remained and/or became excellent for IA (95.1%), IC (97.3%), and PJP (96.5%), respectively. In conclusion, we show that the GT performed as well as the FA only with a lowered cutoff value for positivity. Further studies are expected to establish the equivalence of the two BDG assays.

Purpose To determine the risk factors, intraoperative and postoperative complications, therapeutic interventions, and visual outcomes for persistent postoperative inflammation in primary resident-performed cataract surgeries. Setting Ben Taub General Hospital, Houston, Texas, USA. Design Retrospective case series. Methods Primary resident-performed cataract surgeries from January 2012 to June 2015 were analyzed for persistent postoperative inflammation, defined as persistent anterior chamber inflammatory reaction after a standard 1-month topical corticosteroid and nonsteroidal antiinflammatory drug (NSAID) drops taper. Preoperative characteristics, operative complications, therapeutic modalities, and duration of therapy were analyzed. The primary outcome measures were duration of corticosteroid and NSAID therapy, treatment modalities, and postoperative visual outcomes at the 1-month postoperative visit. Results The study assessed 1290 primary resident-performed cataract surgeries. Persistent postoperative inflammation occurred in 82 eyes (6.6%). The presumed etiology was classified as idiopathic persistent postoperative inflammation, nonadherence to topical therapy, and complicated cataract surgery. Patients with persistent postoperative inflammation were more likely of African American descent, had hypertension, or used aspirin, anticoagulants, or prostaglandins (P = .019, P = .027, P = .028, P = .020, respectively). The complicated cataract subgroup required a longer duration of therapy (P = .021) and was the only subgroup to require injections or systemic corticosteroids. There was no significant difference in postoperative corrected distance visual acuity (CDVA) when comparing patients with persistent postoperative inflammation with those without inflammation or between the subgroups. Conclusions The idiopathic and nonadherent subgroups were successfully treated with topical antiinflammatory therapy; the complicated subgroup required longer duration and multiple modalities of treatment. Visual outcomes were comparable to the general cataract population with no differences in postoperative CDVA.

Context Gut microbiota play a major role in health and disease by influencing physiology, metabolism, nutrition, and immune function. Objective To evaluate the composition of gut microbiota in women with polycystic ovary syndrome (PCOS), focusing on the influence of sex, sex hormones and obesity on the associations found. Design Cross-sectional study. Setting Academic hospital. Participants We recruited 15 women with PCOS, 16 nonhyperandrogenic control women, and 15 control men. Participants were classified as nonobese ( Interventions Standardization of diet for 3 consecutive days (at least 300 g of carbohydrates per day) followed by fecal sampling and a standard 75-g oral glucose tolerance test. Main Outcome Measures Analysis of bacterial abundance and composition of gut microbiota by massive sequencing of 16S ribosomal DNA amplicons in a MiSeq platform (Illumina). Results α Bacterial diversity was reduced in women compared with men, and β diversity was reduced particularly in obese patients with PCOS. Women with PCOS presented with specific abnormalities in gut microbiota consisting of an increased abundance of the Catenibacterium and Kandleria genera. When all participants as a whole were considered, indexes of bacterial diversity and the abundance of several bacterial genera correlated positively with serum androgen concentrations and negatively with estradiol levels. Conclusions The diversity and composition of the gut microbiota of young adults are influenced by the combined effects of sex, sex hormone concentrations, and obesity, presenting with specific abnormalities in women with PCOS.

Recent studies have reported contrasting results in the socio-emotional adjustment of Italian adolescents with cochlear implants (CIs). The aim of the present study is to explore the relationship between the socio-emotional adjustment of adolescents with CIs, the quality of their hospital stay, and their age at CI activation. The participants were 29 adolescents with CIs (CI group) and 29 typically developing adolescents (TD group). The Emotional Autonomy Scale, the Loneliness and Aloneness Scale for Children and Adolescents, and the Multidimensional Self-Concept Scale were administered to each participant. The emotional experience reported during the hospital stay was considered for each participant in the CI group. The adolescents with CIs displayed significantly higher levels of loneliness and lower levels of aversion toward aloneness than the TD group participants. Adolescents who had received the CI in preschool displayed a higher level of physical self-concept than adolescents who had received it later. The adolescents’ emotional experiences at the hospital were reported to be quite complex and related to their relationships with parents. In summary, the findings point to a specific type of fragility in socio-emotional adjustment—focused on loneliness/aloneness—rather than a general one.

Objectives Late-life major depression is associated with increased cardiovascular risk and impaired autonomic control of the heart, as evident from reduced heart rate variability (HRV). Moreover, antidepressant drug therapy also might be associated with further reductions of HRV. In the SEEDS study, we investigated whether sertraline associated with physical exercise protocols led to improvements of HRV, compared with antidepressant drug therapy alone. Design Single-blind randomized controlled trial. Setting Psychiatric consultation-liaison program for primary care. Participants Patients aged 65–85 years with major depression, recruited from primary care. Interventions Sertraline plus structured, tailored group physical exercise (S + EX) versus sertraline alone (S) for 24 weeks. Measurements HRV indices (RR, percentage of NN intervals greater than 50 msec [pNN50], square root of the mean squared differences of successive NN intervals [RMSSD], standard deviation of heart rate [SDHR], standard deviation of the NN interval [SDNN], high-frequency band [HF], low-frequency band [LF], and their ratio [LF/HF]) were measured at baseline, week 12, and week 24. Psychiatric and medical assessments. Results Participants displayed significant improvements of most HRV indices over time, irrespective of the group assignment (pNN50, RMSSD, SDHR, SDNN, HF, LF, and LF/HF). Moreover, patients in the S + EX group displayed greater increases of different HRV indices(RR, pNN50, RMSSD, SDHR, SDNN, HF, and LF) compared with those in the S group. Conclusions The combination of structured physical exercise and sertraline might exert positive effects on the autonomic control of the heart among older patients with major depression.

Depression in schizophrenia represents a challenge from a diagnostic, psychopathological and therapeutic perspective. The objective of this study is to test the hypothesis that resilience and self-stigma affect depression severity and to evaluate the strength of their relations in 921 patients with schizophrenia. A structural equation model was tested where depression is hypothesized as affected by resilience, internalized stigma, gender and negative symptoms, with the latter two variables used as exogenous covariates and the former two as mediators. The analysis reveals that low resilience, high negative symptoms, female gender were directly associated with depression severity, and internalized stigma acted only as a mediator between avolition and resilience, with similar magnitude. The cross-sectional study design and the variable selection limit the generalizability of the study results. The model supports a complex interaction between personal resources and negative symptoms in predicting depression in schizophrenia. The clinical implication of these findings is that personal resources could be a significant target of psychosocial treatments.

Background The current global and national indications for antiretroviral treatment (ART, usually triple combination therapy) in adolescent and adults, including pregnant women, recommend early ART before immunologic decline, pre-exposure chemoprophylaxis (PrEP), and treatment of HIV-negative partners in serodiscordant couples. There is limited information on the implementation of these recommendations among pregnant women with HIV and their partners. Methods The present analysis was performed in 2016, using data from clinical records of pregnant women with HIV, followed between 2001 and 2015 at hospital or university clinics within a large, nationally representative Italian cohort study. The study period was divided in three intervals of five years each (2001-2005, 2006-2010, 2011-2015), and the analysis evaluated temporal trends in rates of HIV diagnosis in pregnancy, maternal antiretroviral treatment at conception, prevalence of HIV infection among partners of pregnant women with HIV, and proportion of seronegative and seropositive male partners receiving antiretroviral treatment. Results The analysis included 2755 pregnancies in women with HIV. During the three time intervals considered the rate of HIV diagnosis in pregnancy (overall 23.3%), and the distribution of HIV status among male partners (overall 48.7% HIV- negative, 28.6% HIV-positive and 22.8% unknown) remained substantially unchanged. Significant increases were observed in the proportion of women with HIV diagnosed before pregnancy who were on antiretroviral treatment at conception (from 62.0% in 2001-2005 to 81.3% in 2011-2015, P < 0.001), and in the proportion of HIV-positive partners on antiretroviral treatment (from 73.3% in 2001-2005 to 95.8% in 2011-2015, P = 0.002). Antiretroviral treatment was administered in 99.1% of the pregnancies that did not end early because of miscarriage, termination, or intrauterine death, and in 75.3% of those not ending in a live birth. No implementation of antiretroviral treatment was introduced among male HIV-negative partners. Conclusions The results suggest good implementation of antiretroviral treatment among HIV-positive women and their HIV-positive partners, but no implementation, even in recent years, of Pre-Exposure Prophylaxis (PrEP) among uninfected male partners. Further studies should assess the determinants of this occurrence and clarify the attitudes and the potential barriers to PrEP use.