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Background/Objectives: Oral cavity carcinomas (OCCs) represent roughly 50% of all head and neck cancers. The risk of occult neck metastases for early-stage OCCs ranges from 15 to 35%, thus the need to develop tools that can support the diagnosis detecting these neck metastases. Inflammatory biomarkers and perineural and lympho-vascular invasion are emerging as effective in this field. The aim of this study is to demonstrate the effectiveness of these parameters to detect occult neck metastases in early-stage (T1-T2/N0) OCCs. Methods: A retrospective analysis was conducted on 81 patients surgically treated for early-stage OCC. For all patients, data regarding TNM, pN status after the histopathological examination, inflammatory biomarkers, and perineural and lympho-vascular invasion have been obtained. A statistical analysis was performed using the receiver operating characteristic (ROC) curve to calculate the optimal cutoff values for SII, SIRI, PLR, and NLR. Results: Fifty-eight patients confirmed N0 status after surgery, while twenty-three resulted pN+. The best cut-off to detect occult neck metastases were PLR 249.30, NLR 13.10, MLR 0.439, SII 1043.12, and SIRI 1.85. The accuracy to detect occult neck metastases was PLR 75%, NLR 81%, MLR 74%, SII 73%, SIRI 70%, perineural invasion 70%, and lympho-vascular invasion 83%. Conclusions: Our results confirm that inflammatory biomarkers and perineural and lympho-vascular invasion are effective in detecting occult neck metastases in early-stage OCCs. The clinical relevance of this study is that these parameters could be used routinely as preoperative tools to support diagnosis and to help surgeons in the decision-making process, particularly regarding surgical indications for neck lymph nodes treatment.

The application of biparametric magnetic resonance imaging (bpMRI) [T2-weighted (T2W) and diffusion weighted imaging (DWI)/apparent diffusion coefficient (ADC)] using dedicated structured methods, such as Simplified Prostate Imaging Reporting and Data System (S-PI-RADS) for the detection, categorization, and management of prostate cancer (PCa) is reported. Also, Prostate Imaging Reporting for Local Recurrence and Data System (PI-RRADS) for the detection and assessment of the probability of local recurrence after radiotherapy (RT) or radical prostatectomy (RP) in patients with biochemical recurrence (BCR) is proposed. Both S-PI-RADS and PI-RRADS assign to DWI/ADC a main role for the above purpose. S-PI-RADS identifies four categories and, on the basis of the qualitative and quantitative analysis of the restricted diffusion on ADC map and lesion volume, distinguishes two categories of lesions: category 3 (moderately homogeneous hypointense on ADC map) and category 4 (markedly homogeneous or inhomogeneous hypointense on ADC map). Ιn category 3, two subcategories (3a: volume <0.5 cm and 3b: volume ≥0.5 cm ) suggesting clinical management. PI-RRADS distinguishes four assessment categories and suggests the stratification of the probability (ranging from very low for category 1 to very high for category 4) of local disease recurrence. In clinical practice, S-PI-RADS and PI-RRADS, based on bpMRI represent a potential valid approach that may facilitates the detection and management of PCa and for detecting local recurrence after treatment improving communication with other professionals.

PurposeLower respiratory tract infections (LRTI) are the most frequent infectious complication in patients admitted to the intensive care unit (ICU). We aim to report the clinical characteristics of ICU-admitted patients due to nosocomial LRTI and to describe their microbiology and clinical outcomes.MethodsA prospective observational study was conducted in 13 countries over two continents from 9th May 2016 until 16th August 2019. Characteristics and outcomes of ventilator-associated pneumonia (VAP), ventilator-associated tracheobronchitis (VAT), ICU hospital-acquired pneumonia (ICU-HAP), HAP that required invasive ventilation (VHAP), and HAP in patients transferred to the ICU without invasive mechanical ventilation were collected. The clinical diagnosis and treatments were per clinical practice and not per protocol. Descriptive statistics were used to compare the study groups.Results1060 patients with LRTI (72.5% male sex, median age 64 [50–74] years) were included in the study; 160 (15.1%) developed VAT, 556 (52.5%) VAP, 98 (9.2%) ICU-HAP, 152 (14.3%) HAP, and 94 (8.9%) VHAP. Patients with VHAP had higher serum procalcitonin (PCT) and Sequential Organ Failure Assessment (SOFA) scores. Patients with VAP or VHAP developed acute kidney injury, acute respiratory distress syndrome, multiple organ failure, or septic shock more often. One thousand eight patients had microbiological samples, and 711 (70.5%) had etiological microbiology identified. The most common microorganisms were Pseudomonas aeruginosa (18.4%) and Klebsiella spp (14.4%). In 382 patients (36%), the causative pathogen shows some antimicrobial resistance pattern. ICU, hospital and 28-day mortality were 30.8%, 37.5% and 27.5%, respectively. Patients with VHAP had the highest ICU, in-hospital and 28-day mortality rates.ConclusionVHAP patients presented the highest mortality among those admitted to the ICU. Multidrug-resistant pathogens frequently cause nosocomial LRTI in this multinational cohort study.

Prostate specific antigen (PSA) remains the most used test to assess the response after therapies including the radiation therapy (RT). Apparent diffusion coefficient (ADC) derived from the conventional diffusionweighted imaging (DWI), as a part of noncontrast or biparametric MRI (bpMRI) (T2-weighted and DWI), offers diagnostic accuracy and cancer detection rate equivalent to that of multiparametric MRI. Cellular changes induced by RT can be quali-qualitatively demonstrated as early as 3months after RT as an increase in the signal intensity of the tumor on the ADC map. ADC, in association with PSA, represents a potential biomarker imaging for evaluating treatment efficacy in PCa both during and shortly after RT.

BackgroundData on asthma with fixed airway obstruction (FAO) are heterogeneous due to different and misleading definitions. Describing the FAO phenotype has significant implications for severe asthma (SA) comprehension.ObjectiveTo characterise SA patients with FAO in the Severe Asthma Network in Italy (SANI) registry at baseline, and to compare with those with reversible airway obstruction (bronchodilator responsiveness, BDR). The potential for re-evaluating FAO or BDR in the follow-up was explored.MethodsFAO was defined as a forced expiratory volume in the first second (FEV1)/forced vital capacity ratio < Lower Limit of Normal (LNN) after a bronchodilator test with an increase in FEV1 of <12% or 200 mL, compared with BDR and no airway obstruction (no-AO). Clinical reported outcomes, including asthma control (ACT), quality of life (AQLQ) and exacerbations (AEs) were collected. The effect of demographic, clinical and biohumoral variables on FAO, BDR and no-AO groups at baseline and during the follow-up was estimated.ResultsAmong 354 patients, 190 (53.7%) reported AO with 116 (60.1%) resulting in FAO. The overall FAO rate at enrolment was 32.8%. Compared with BDR, FAO patients had better asthma control (34.5% vs 20.3%, p=0.004), a higher ACT (17.4 vs 15.2, p=0.005) and AQLQ (4.6 vs 3.8, p=0.001) score. FAO patients were less likely to visit the emergency room or be hospitalised than BDR (p=0.050), with no difference in AEs. The effect of airway calibre on fractional exhaled nitric oxide is more likely to cause its lower level within FAO compared with BDR (29.5 vs 46.0 ppb, p=0.04) than a lower T2 burden. A variation from FAO to BDR or no-AO was associated with the Global Initiative for Asthma classification (step 4 vs 5: HR 3.58 (95% CI 1.16 to 11.03)) and the age of asthma onset (30–39 vs <20 years: HR 3.94 (95% CI 1.09 to 14.30))ConclusionStratifying SA patients from the SANI registry reveals an FAO phenotype that expresses different clinical outcomes and biological markers compared to BDR. Over time, FAO may be reversible in late-onset SA with less inhaled corticosteroid treatment.

Introduction We report the experiences of 25 Italian centers, analyzing intra- and periprocedural complications of endovascular treatment of intracranial aneurysms using Silk (Balt Extrusion, Montmorency, France) and pipeline embolization devices (EV3 Inc, Irvine California). Methods Two hundred seventy-three patients with 295 cerebral aneurysms, enrolled in 25 centers in Italy and treated with the new flow-diverter devices, were evaluated; 142 patients were treated with Silk and 130 with pipeline (in one case, both devices were used). In 14 (5.2 %) cases devices were used with coils. Aneurysm size was >15 mm in 46.9 %, 5–15 mm in 42.2 %, and <5 mm in 10.8 %. Aneurysm locations were supraclinoid internal carotid artery (ICA) in 163 cases (55.2 %), cavernous ICA in 76 (25.7 %), middle cerebral artery in 11 (3.7 %), PCoA in 6 (2 %), and ACoA in 2 (0.7 %); the vertebrobasilar system accounted for 32 cases (10.8 %) and PCA in 5 (1.7 %). Results Technical adverse events occurred with 59 patients (21.6 %); 5 patients died after ischemic events, 10 to hemorrhagic complications, and 1 from external ventricular drain positioning. At 1 month, morbidity and mortality rates were 3.7 % and 5.9 %, respectively Conclusion Our retrospective study confirms that morbidity and mortality rates in treatment with FDD of unruptured wide-neck or untreatable cerebral aneurysms do not differ from those reported in the largest series.

Earlier studies have shown widespread alterations of functional connectivity of various brain networks in schizophrenia, including the default mode network (DMN). The DMN has also an important role in the performance of cognitive tasks. Furthermore, treatment with second-generation antipsychotic drugs may ameliorate to some degree working memory (WM) deficits and related brain activity. The aim of this study was to evaluate the effects of treatment with olanzapine monotherapy on functional connectivity among brain regions of the DMN during WM. Seventeen patients underwent an 8-week prospective study and completed two functional magnetic resonance imaging (fMRI) scans at 4 and 8 weeks of treatment during the performance of the N-back WM task. To control for potential repetition effects, 19 healthy controls also underwent two fMRI scans at a similar time interval. We used spatial group-independent component analysis (ICA) to analyze fMRI data. Relative to controls, patients with schizophrenia had reduced connectivity strength within the DMN in posterior cingulate, whereas it was greater in precuneus and inferior parietal lobule. Treatment with olanzapine was associated with increases in DMN connectivity with ventromedial prefrontal cortex, but not in posterior regions of DMN. These results suggest that treatment with olanzapine is associated with the modulation of DMN connectivity in schizophrenia. In addition, our findings suggest critical functional differences in the regions of DMN.

Variation of the gene coding for D2 receptors (DRD2) has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560) predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic) and D2L (mainly post-synaptic). However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known. Thirty-seven healthy subjects were genotyped for rs1076560 (G>T) and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors) and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors), as well as BOLD fMRI during N-Back working memory. Subjects carrying the T allele (previously associated with reduced D2S expression) had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers) and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT. Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway.

BackgroundEpidemiological data obtained during the initial wave of the COVID-19 epidemic showed that persons dying with COVID-19 were typically older men with multiple chronic conditions. No studies have assessed if the characteristics of patients dying with COVID-19 have changed in the second phase of the epidemic, when the initial wave subsided. The aim of the present study was to compare characteristics of patients dying with COVID-19 in Italy in the first ‘peak’ phase of the epidemic and in its second phase.MethodsMedical charts of patients with COVID-19 who died while in hospital in Italy were reviewed to extract information on pre-existing comorbidities, in-hospital complications, and disease trajectories. The course of the epidemic was classified in two 3-month periods: March–May 2020 and June–August 2020.FindingsOverall, in the Italian population, 34,191 COVID-19 deaths occurred in March–May 2020 and 1,404 in June–August 2020. Patients dying in March–May were significantly younger (80.1 ± 10.6 vs. 82.8 ± 11.1 years, p < 0.001) and less frequently female (41.9% vs. 61.8%, p < 0.001) than those dying in June–August. The medical charts of 3533 patients who died with PCR-confirmed SARS-CoV-2 infection in March–May 2020 (10.3% of all deaths occurring in this period) and 203 patients who died in June–August 2020 (14.5% of all deaths occurring in this period) were analysed. Patients who died in March–May 2020, compared to those who died in June–August 2020, had significantly lower rates of multiple comorbidities (3 or more comorbidities: 61.8% vs 74.5%, p = 0.001) and superinfections (15.2% vs. 52.5%, p < 0.001). Treatment patterns also substantially differed in the two study periods, with patients dying in March–May 2020 being less likely to be treated with steroids (41.7% vs. 69.3%, p < 0.001) and more likely to receive antivirals (59.3% vs. 41.4%, p < 0.001). Survival time also largely differed, with patients dying in March–May 2020 showing a shorter time from symptoms onset to death (mean interval: 15.0 vs. 46.6 days, p < 0.001). The differences observed between the two periods remained significant in a multivariate analysis.InterpretationThe clinical characteristics of patients dying with COVID-19 in Italy, their treatment and symptom-to-death survival time have significantly changed overtime. This is probably due to an improved organization and delivery of care and to a better knowledge of disease treatment.