Search

Shared strategies and correct information are essential to guide physicians in the management of such an uncommon disease as Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL). A systematic review of the literature was performed to collect the most relevant evidence on BIA-ALCL reported cases. A panel of multidisciplinary experts discussed the scientific evidence on BIA-ALCL, and updated consensus recommendations were developed through the Delphi process. The lastest reported Italian incidence of BIA-ALCL is 3.5 per 100.000 implanted patients (95% CI, 1.36 to 5.78), and the disease counts over 1216 cases worldwide as of June 2022. The most common presentation symptom is a late onset seroma followed by a palpable breast mass. In the event of a suspicious case, ultrasound-guided fine-needle aspiration should be the first step in evaluation, followed by cytologic and immunohistochemical examination. In patients with confirmed diagnosis of BIA-ALCL confined to the capsule, the en-bloc capsulectomy should be performed, followed by immediate autologous reconstruction, while delayed reconstruction applies for disseminate disease or radically unresectable tumor. Nevertheless, a multidisciplinary team approach is essential for the correct management of this pathology.

BACKGROUND: Recently, the first report of lung ultrasound (LUS) guided recruitment during open lung ventilation in neonates has been published. LUS guided recruitment can change the approach to open lung ventilation, which is currently performed without any measure of lung function/lung expansion in the neonatal population. METHODS: We included all the newborn infants that underwent a LUS-guided recruitment maneuver during mechanical ventilation as a rescue attempt for an extremely severe respiratory condition with oxygen saturation/fraction of inspired oxygen (SpO2/FIO2) ratio below 130 or the inability to wean off mechanical ventilation. RESULTS: We report a case series describing 4 LUS guided recruitment maneuvers, underlying crucial aspects of this technique that can improve the effectiveness of the procedure. In particular, we describe a novel pattern (the S-pattern) that allows us to distinguish the recruitable from the unrecruitable lung and guide the pressure titration phase. Additionally, we describe the optimal LUS-guided patient positioning. CONCLUSIONS: We believe that the inclusion of specifications regarding patient positioning and the S-pattern in the LUS-guided protocol may be beneficial for the success of the procedure.

Background Dengue virus (DENV) and Zika virus (ZIKV) have a severe impact on human health worldwide. To understand the dynamics of these viruses in mosquito populations, it is necessary to maintain surveillance during non-epidemic years. Methods We aimed to assess the presence of DENV and ZIKV in Aedes aegypti females in the state of Sergipe, northeastern Brazil, during a non-epidemic year. The Ae. aegypti females collected were sectioned, and the heads and thorax were used to analyze the infection rate. Each female was first analyzed to detect Flavivirus using RT-PCR. Flavivirus-positive samples were further screened to detect ZIKV and DENV types 1, 2, 3 and 4. Results A total of 184 females were collected. ZIKV was identified in 5.4% of the sample and DENV in 7.1%, with the DENV-positive samples belonging to subtypes 2, 3 and 4. The presence of coinfected vectors was also observed. Of the four cities tested, only one was negative for all viruses. Conclusions These results show that the maintenance of vigilance during non-epidemic years can provide data on viruses circulating before the onset of outbreaks. This can enable the planning and implementation of local control measures to prevent the appearance of new outbreaks.

Objectives To assess the prevalence of delirium (DEL) among older patients living at home and periodically visited by their General Practitioners (GPs). Design Observational study. Setting In Italy, programmed home visits by the GPs are regularly scheduled for their vulnerable and frail patients who are often on poly-drug regimens and suffering from dementia. Participants N = 102 patients among those receiving programmed home visits by n = 6 GP based in the Brianza area (Lombardy). Measurements Patients were screened for delirium with the Italian version of the 4AT, with a score ≥ 4 considered as a positive indicator for DEL. The Charlson Comorbidity Index (CCI), the Short Physical Performance Battery (SPPB), the presence of dementia, and benzodiazepine (BZD) use were recorded. Results DEL+ was detected in almost half of the recruited sample (44.1%), and it was clearly associated with increased comorbidity and decreased motor abilities. Pre-existing dementia was documented in most of DEL+ patients (71.1%), while this was the case for only a minority of DEL- (5.2%, p vs. 22.8%, p Conclusions DEL prevalence as detected by GP during programmed home visits is surprisingly high, and related to motor impairment, comorbidities (among which dementia), and BZD use. DEL prompt recognition should be one of the goals of GP-programmed home visits, since this treatable and preventable condition is associated to an elevated burden of frailty and risk of death.

Background: The phase 3 GIMEMA-MMY-3006 trial, which compared bortezomib, thalidomide, and dexamethasone (VTD) combination therapy with thalidomide and dexamethasone (TD) as induction therapy before and consolidation therapy after double autologous haematopoietic stem-cell transplantation (HSCT) for newly diagnosed multiple myeloma, showed the superiority of the triplet regimen over the doublet in terms of increased complete response rate and improved progression-free survival. We report the results from the final analysis of the study. Methods: In this randomised, open-label, phase 3 study, patients aged 18–65 years with previously untreated symptomatic multiple myeloma and a Karnofsky Performance Status of 60% or higher were enrolled at 73 centres in Italy. Patients were randomised (1:1) by a web-based system to receive three 21-day cycles of thalidomide (100 mg daily orally for the first 14 days and 200 mg daily thereafter) plus dexamethasone (total 320 mg per cycle; 40 mg on days 1–2, 4–5, 8–9, and 11–12 in the VTD regimen, and 40 mg on days 1–4 and 9–12 in the TD regimen), either alone (TD group) or with bortezomib (1·3 mg/m2 intravenously on days 1, 4, 8, and 11; VTD group). After double autologous HSCT, patients received two 35-day cycles of either the VTD or TD regimen, according to random assignment, as consolidation therapy. The primary outcome was the rate of complete response and near complete response after induction (already reported). In this updated analysis we assessed long-term progression-free survival and overall survival (secondary endpoints of the study) with an extended 10-year median follow-up, and analysed the variables influencing survival. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, NCT01134484. Findings: Between May 10, 2006, and April 30, 2008, 480 patients were enrolled and randomly assigned to receive VTD (241 patients) or TD (239 patients). Six patients withdrew consent before start of treatment. 236 (99 [42%] women) in the VTD group and 238 (102 [43%] women) in the TD group were included in the intention-to-treat analysis. The data cutoff date for this analysis was May 31, 2018. Median follow-up for surviving patients was 124·1 months (IQR 117·2–131·7). The 10-year progression-free survival estimate for patients in the VTD group was 34% (95% CI 28–41) compared with 17% (13–23) for the TD group (hazard ratio [HR] 0·62 [95% CI 0·50–0·77]; p

Reach&grasp requires highly coordinated activation of different brain areas. We investigated whether reach&grasp kinematics is associated to EEG-based networks changes. We enrolled 10 healthy subjects. We analyzed the reach&grasp kinematics of 15 reach&grasp movements performed with each upper limb. Simultaneously, we obtained a 64-channel EEG, synchronized with the reach&grasp movement time points. We elaborated EEG signals with EEGLAB 12 in order to obtain event related synchronization/desynchronization (ERS/ERD) and lagged linear coherence between Brodmann areas. Finally, we evaluated network topology via sLORETA software, measuring network local and global efficiency (clustering and path length) and the overall balance (small-worldness). We observed a widespread ERD in α and β bands during reach&grasp, especially in the centro-parietal regions of the hemisphere contralateral to the movement. Regarding functional connectivity, we observed an α lagged linear coherence reduction among Brodmann areas contralateral to the arm involved in the reach&grasp movement. Interestingly, left arm movement determined widespread changes of α lagged linear coherence, specifically among right occipital regions, insular cortex and somatosensory cortex, while the right arm movement exerted a restricted contralateral sensory-motor cortex modulation. Finally, no change between rest and movement was found for clustering, path length and small-worldness. Through a synchronized acquisition, we explored the cortical correlates of the reach&grasp movement. Despite EEG perturbations, suggesting that the non-dominant reach&grasp network has a complex architecture probably linked to the necessity of a higher visual control, the pivotal topological measures of network local and global efficiency remained unaffected.

The 2017 version of the European LeukemiaNet (ELN) recommendations, by integrating cytogenetics and mutational status of specific genes, divides patients with acute myeloid leukemia into 3 prognostically distinct risk categories: favorable (ELN2017-FR), intermediate (ELN2017-IR), and adverse (ELN2017-AR). We performed a post hoc analysis of the GIMEMA (Gruppo Italiano Malattie EMatologiche dell’Adulto) AML1310 trial to investigate the applicability of the ELN2017 risk stratification to our study population. In this trial, after induction and consolidation, patients in complete remission were to receive an autologous stem cell transplant (auto-SCT) if categorized as favorable risk or an allogeneic stem cell transplant (allo-SCT) if adverse risk. Intermediate-risk patients were to receive auto-SCT or allo-SCT based on the postconsolidation levels of measurable residual disease as measured by using flow cytometry. Risk categorization was originally conducted according to the 2009 National Comprehensive Cancer Network recommendations. Among 500 patients, 445 (89%) were reclassified according to the ELN2017 criteria: ELN2017-FR, 186 (41.8%) of 455; ELN2017-IR, 179 (40.2%) of 445; and ELN2017-AR, 80 (18%) of 455. In 55 patients (11%), ELN2017 was not applicable. Two-year overall survival (OS) was 68.8%, 51.3%, 45.8%, and 42.8% for the ELN2017-FR, ELN2017-IR, ELN2017-not classifiable, and ELN2017-AR groups, respectively (P < .001). When comparing the 2 different transplant strategies in each ELN2017 risk category, a significant benefit of auto-SCT over allo-SCT was observed among ELN2017-FR patients (2-year OS of 83.3% vs 66.7%; P = .0421). The 2 transplant procedures performed almost equally in the ELN2017-IR group (2-year OS of 73.9% vs 70.8%; P = .5552). This post hoc analysis of the GIMEMA AML1310 trial confirms that the ELN2017 classification is able to accurately discriminate patients with different outcomes and who may benefit from different transplant strategies. This trial was registered as EudraCT number 2010-023809-36 and at www.clinicaltrials.gov as #NCT01452646.

The humoral and cellular response to SARS-CoV-2 mRNA full vaccination and booster dose as well as the impact of the spike variants, including Omicron, are still unclear in patients with multiple myeloma (MM) and those with pre-malignant monoclonal gammopathies. In this study, involving 40 patients, we found that MM patients with relapsed-refractory disease (MMR) had reduced spike-specific antibody levels and neutralizing titers after SARS-CoV-2 vaccination. The five analyzed variants, remarkably Omicron, had a significant negative impact on the neutralizing ability of the vaccine-induced antibodies in all patients with MM and smoldering MM. Moreover, lower spike-specific IL-2-producing CD4

Objectives: Evidences from either small series or spontaneous reporting are accumulating that SARS-CoV-2 involves the Nervous Systems. The aim of this study is to provide an extensive overview on the major neurological complications in a large cohort of COVID-19 patients. Methods: Retrospective, observational analysis on all COVID-19 patients admitted from February 23rd to April 30th, 2020 to ASST Papa Giovanni XXIII, Bergamo, Italy for whom a neurological consultation/neurophysiological assessment/neuroradiologic investigation was requested. Each identified neurologic complication was then classified into main neurologic categories. Results: Of 1760 COVID-19 patients, 137 presented neurologic manifestations that manifested after COVID-19 symptoms in 98 pts and was the presenting symptom in 39. Neurological manifestations were classified as: (a) cerebrovascular disease [53 pts (38.7%)] including 37 ischemic and 11 haemorrhagic strokes, 4 transient ischemic attacks, 1 cerebral venous thrombosis; (b) peripheral nervous system diseases [31 (22.6%)] including 17 Guillain–Barrè syndromes; (c) altered mental status [49 (35.8%)] including one necrotizing encephalitis and 2 cases with RT-PCR detection of SARS-Cov-2 RNA in CSF; (d) miscellaneous disorders, among whom 2 patients with myelopathy associated with Ab anti-SARS-CoV-2 in CSF. Patients with peripheral nervous system involvement had more frequently severe ARDS compared to patients with cerebrovascular disease (87.1% vs 42%; difference = 45.1% 95% CI 42.0–48.2; χ2= 14.306; p < 0.0002) and with altered mental status (87.1% vs 55.6%; difference = 31.5% 95% CI 27.5–37.5%; χ2= 7.055; p < 0.01). Conclusion: This study confirms that involvement of nervous system is common in SARS-CoV-2 infection and offers clinicians useful information for prevention and prompt identification in order to set the adequate therapeutic strategies.

Background Alzheimer’s disease (AD) patients often express significant behavioral symptoms: for this reason, accessible related biomarkers could be very useful. Neuroinflammation is a key pathogenic process in both AD and delirium (DEL), a clinical condition with behavioral symptoms resembling those of AD. Methods A total of n = 30 AD patients were recruited together with n = 30 DEL patients and n = 15 healthy controls (CTRL). Serum diazepam binding inhibitor (DBI), IL-17, IL-6, and TNF-α were assessed by ELISA. Results DBI serum levels were increased in AD patients with respect to CTRL (+ 81%), while DEL values were 70% higher than AD. IL-17 was increased in DEL with respect to CTRL (+ 146%), while AD showed dispersed values and failed to reach significant differences. On the other hand, IL-6 showed a more robust increase in DEL with respect to the other two groups (+ 185% and + 205% vs. CTRL and AD, respectively), and TNF-α failed to show any change. Conclusions DBI may be a very promising candidate for AD, perhaps marking psychomotor DEL-like symptoms, in view of developing future helping tool for practicing physicians. Furthermore, DBI rise in DEL offers novel cues for a better comprehension of the pathogenesis of this potentially fatal condition.

ImportanceData on the association of COVID-19 vaccination with intensive care unit (ICU) admission and outcomes of patients with SARS-CoV-2–related pneumonia are scarce.ObjectiveTo evaluate whether COVID-19 vaccination is associated with preventing ICU admission for COVID-19 pneumonia and to compare baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU.Design, Setting, and ParticipantsThis retrospective cohort study on regional data sets reports: (1) daily number of administered vaccines and (2) data of all consecutive patients admitted to an ICU in Lombardy, Italy, from August 1 to December 15, 2021 (Delta variant predominant). Vaccinated patients received either mRNA vaccines (BNT162b2 or mRNA-1273) or adenoviral vector vaccines (ChAdOx1-S or Ad26.COV2). Incident rate ratios (IRRs) were computed from August 1, 2021, to January 31, 2022; ICU and baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU were analyzed from August 1 to December 15, 2021.ExposuresCOVID-19 vaccination status (no vaccination, mRNA vaccine, adenoviral vector vaccine).Main Outcomes and MeasuresThe incidence IRR of ICU admission was evaluated, comparing vaccinated people with unvaccinated, adjusted for age and sex. The baseline characteristics at ICU admission of vaccinated and unvaccinated patients were investigated. The association between vaccination status at ICU admission and mortality at ICU and hospital discharge were also studied, adjusting for possible confounders.ResultsAmong the 10 107 674 inhabitants of Lombardy, Italy, at the time of this study, the median [IQR] age was 48 [28-64] years and 5 154 914 (51.0%) were female. Of the 7 863 417 individuals who were vaccinated (median [IQR] age: 53 [33-68] years; 4 010 343 [51.4%] female), 6 251 417 (79.5%) received an mRNA vaccine, 550 439 (7.0%) received an adenoviral vector vaccine, and 1 061 561 (13.5%) received a mix of vaccines and 4 497 875 (57.2%) were boosted. Compared with unvaccinated people, IRR of individuals who received an mRNA vaccine within 120 days from the last dose was 0.03 (95% CI, 0.03-0.04; P P P P P o2) and fraction of inspiratory oxygen (FiO2) at ICU admission (median [IQR]: 138 [100-180] vs 120 [90-158] mm Hg; P = .007). Factors associated with ICU and hospital mortality were higher age, premorbid heart disease, lower Pao2/FiO2 at ICU admission, and female sex (this factor only for ICU mortality). ICU and hospital mortality were similar between vaccinated and unvaccinated patients.Conclusions and RelevanceIn this cohort study, mRNA and adenoviral vector vaccines were associated with significantly lower risk of ICU admission for COVID-19 pneumonia. ICU and hospital mortality were not associated with vaccinated status. These findings suggest a substantial reduction of the risk of developing COVID-19–related severe acute respiratory failure requiring ICU admission among vaccinated people.

Hairy cell leukemia (HCL) is a rare lymphoproliferative disease with an excellent prognosis after treatment with cladribine (2CDA), although relapse may occur during follow-up. The aim of the study is to review the efficacy, safety, long-term remission rate, and overall survival (OS) in those patients who received 2CDA as first-line treatment. We retrospectively reviewed data of HCL patients treated with 2CDA between March 1991 and May 2019 at 18 Italian Hematological centers: 513 patients were evaluable for study purpose. The median age was 54 years (range 24–88) and ECOG was 0 in 84.9% of cases. A total of 330 (64.3%) patients received 2CDA intravenously and 183 (35.7%) subcutaneously. ORR was 91.8%: CR was obtained in 335 patients (65.3%), PR in 96 (18.7%), and hematological response in 40 (7.8%) patients; in 42 (8.2%) no response was observed. Hemoglobin value (p = 0.044), frequency of circulating hairy cells (p = 0.039), recovery of absolute neutrophil count (p = 0.006), and normalization of spleen (p ≤ 0.001) were associated with CR compared to PR in univariable analysis. At a median follow-up of 6.83 years (range 0.04–28.52), the median time to relapse was 12.2 years. A significant difference in duration of response was identified between patients that obtained a CR and PR (19.4 years versus 4.8 years, p

Background Postexercise release of cardiac troponin (cTn) is a well-known phenomenon, although the influence of various confounders remains unclear. The aim of this critical review was to analyze the postexercise release of cTn according to age, sex, different types of sport, exercise intensity and duration, and training level. Data sources A literature search was performed within the National Library of Medicine using the following keywords: cTn, peak, release, and exercise. The search was further refined by adding the keywords athletes, children/adolescents, and sport. Main results For final analysis, 52 studies were included: 43 adult studies, 4 pediatric studies, and 5 with a mixed population of adults and children. Several studies have investigated the kinetics of cTn response after exercise with different biomarkers. The current evidence suggests that sport intensity and duration have significant effects on postexercise cTn elevation, whereas the influence of the type of sport, age, and sex have been not completely defined yet. Most data were obtained during endurance races, whereas evidence is limited (or almost absent), particularly for mixed sports. Data on young adults and professional athletes are limited. Finally, studies on women are extremely limited, and those for non-White are absent. Conclusions Postexercise release of cTn can be observed both in young and master athletes and usually represents a physiological phenomenon; however, more rarely, it may unmask a subclinical cardiac disease. The influence of different confounders (age, sex, sport type/intensity/duration, and training level) should be better clarified to establish individualized ranges of normality for postexercise cTn elevation.

The Transplant Centers belonging to Gruppo Italiano per il Trapianto di Midollo Osseo (GITMO) conducted a survey with the aim of evaluating the effect of SARS-CoV2 pandemic on the allogeneic transplant activity in Italy. The pandemic period from 1/3/2020 to 31/7/2020 was compared with the same period in 2019. Overall, in 2020 there was a 2.4% reduction in the number of allo-HCT cases compared to 2019. Interestingly, this deflection did not affect the acute leukemia cases (+5.7% in 2020). The use of peripheral blood-derived stem cells (+10.7%) and cryopreservation (97.4% of the centers) was highly adopted in 2020. Despite the sanitary emergency, almost all of the surveyed centers declared no impact of SARS-CoV2 pandemic on the transplant timing and outcomes, and the sanitary policy was positively evaluated by the majority of centers. The emergency measures ensured that only a minority of the allo-HCT patients had been infected by SARS-CoV2; however, a mortality of 42.1% among the allo-HCT patients hospitalized for COVID-19 was recorded. This survey gives us the information that the GITMO Group reacted positively to the pandemic. Thanks to the emergency strategies, the Italian allo-HCT activity continued safely, showing only a minor deflection and offering the same probability of cure to the transplanted patients.

Background Childhood overweight and obesity are a global concern, with prevalence rising dramatically over the last decades. The condition is caused by an increase in energy intake and reduction of physical activity, leading to excessive fat accumulation, followed by systemic chronic inflammation and altered function of immune cell responses. This study aimed at providing new insights regarding sex-specificity on the inflammatory response to obesity in the young patient. Design Forty-three Brazilian obese adolescents (Female = 22 and Male=21, BMI (body mass index) Z-score average = 2.78 ± 0.51) and forty-nine eutrophic adolescents (Female = 24 and Male = 25, BMI Z-score average = −0.35 ± 0.88) were enrolled in the study. Anthropometrical analyses and blood cell counts were carried out. Using Luminex®xMAP™ technology, circulating serum cytokines, chemokines, and inflammatory biomarkers were analyzed. Two-way ANOVA test, Tukey’s test, and Spearman’s correlation coefficient were employed, with a significance threshold set at p Results We identified increased levels of serum amyloid A (SAA), platelets, and leukocytes solely in male obese patients. We found a noteworthy sex-dependent pattern in regard to inflammatory response: obese boys showed higher TNFβ, IL15, and IL2 and lower IL10 and IL13, while obese girls showed increased TNFα, CCL3, CCL4, and IP10 content in the circulation. BMI Z-score was significantly linearly correlated with neutrophils, leukocytes, platelets, SAA, TNFα, CCL3, CCL4, IP10, and IL13 levels within the entire cohort (non-sex-dependent). Conclusions Our data support a complex relationship between adiposity, blood cell count, and circulating inflammatory cytokine content. High SAA levels suggest that this factor may play a critical role in local and systemic inflammation. In the eutrophic group, females presented a lower status of inflammation, as compared to males. Both obese boys and girls showed an increased inflammatory response in relation to eutrophic counterparts. Taken together, results point out to clear sex dimorphism in the inflammatory profile of obese adolescents.

The most recent international guidelines recommend the measurement of cardiac troponin I (cTnI) and cardiac troponin T (cTnT) using high-sensitivity methods (hs-cTn) for the detection of myocardial injury and the differential diagnosis of acute coronary syndromes. Myocardial injury is a prerequisite for the diagnosis of acute myocardial infarction, but also a distinct entity. The 2018 Fourth Universal Definition of Myocardial Infarction states that myocardial injury is detected when at least one value above the 99th percentile upper reference limit is measured in a patient with high-sensitivity methods for cTnI or cTnT. Not infrequently, increased hs-cTnT levels are reported in patients with congenital or chronic neuromuscular diseases, while the hs-cTnI values are often in the normal range. Furthermore, some discrepancies between the results of laboratory tests for the two troponins are occasionally found in individuals apparently free of cardiac diseases, and also in patients with cardiac diseases. In this review article, authors discuss the biochemical, pathophysiological and analytical mechanisms which may cause discrepancies between hs-cTnI and hs-cTnT test results.

Ovarian cancer is one of the deadliest malignancies among women. Approximately 75% of the patients with ovarian cancer are diagnosed with advanced disease that already has metastasis, particularly to the omentum. The omentum constitutes the ideal soil for ovarian cancer metastasis due to a complex intraperitoneal milieu that favors and supports the whole metastatic process. Adipose-derived stem/stromal cells (ADSCs) are part of this microenvironment and foster tumor progression via sustained paracrine secretion, including extracellular vesicles (EVs). Nonetheless, the preferential relationship between ADSCs, ADSC-derived EVs, and ovarian cancer cells could be exploited to use ADSCs and EVs as a vehicle for anti-cancer therapies. This review will analyze the strict relations between tumor progression, metastatic disease, and adipose tissue with its staminal components. In addition, we will describe the crosstalk and biologic relationship between ADSCs and tumor cells, the role of EVs in intercellular communication, the establishment of drug resistance, metastatic capacity, and ovarian cancer progression. We will analyze the new therapeutic opportunities in treating ovarian cancer offered by ADSCs and EVs as a vehicle for therapeutic molecules to target precisely tumor cells and limit the systemic adverse effects. Finally, we will discuss the limitations of these therapeutic approaches.

Background Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome-coronavirus-2. Consensus suggestions can standardise care, thereby improving outcomes and facilitating future research. Methods An International Task Force was composed and agreement regarding courses of action was measured using the Convergence of Opinion on Recommendations and Evidence (CORE) process. 70% agreement was necessary to make a consensus suggestion. Results The Task Force made consensus suggestions to treat patients with acute COVID-19 pneumonia with remdesivir and dexamethasone but suggested against hydroxychloroquine except in the context of a clinical trial; these are revisions of prior suggestions resulting from the interim publication of several randomised trials. It also suggested that COVID-19 patients with a venous thromboembolic event be treated with therapeutic anticoagulant therapy for 3 months. The Task Force was unable to reach sufficient agreement to yield consensus suggestions for the post-hospital care of COVID-19 survivors. The Task Force fell one vote shy of suggesting routine screening for depression, anxiety and post-traumatic stress disorder. Conclusions The Task Force addressed questions related to pharmacotherapy in patients with COVID-19 and the post-hospital care of survivors, yielding several consensus suggestions. Management options for which there is insufficient agreement to formulate a suggestion represent research priorities., For patients with acute COVID-19 pneumonia who require oxygen support, the International Task Force made suggestions for remdesivir and dexamethasone, but against hydroxychloroquine. Post-discharge management of COVID-19 survivors is a research priority. https://bit.ly/32B96uI

This study aimed to improve the quality of cryopreserved beef bull (Piedmontese) semen by incorporation of relaxin in diluted semen before cryopreservation procedures. Semen samples were collected from 4 proven fertile bulls, using artificial vagina, once per week for 8 consecutive weeks and pooled together then diluted with Bullxcell® extender, and supplemented with different concentrations of relaxin (0 (control), 25, 50 and 100 ng/ml) before cooling, equilibration and freezing procedures. Frozen semen was thawed and assessed for motility by Computer-Assisted Sperm Analysis and vitality parameters such as acrosome, plasma membrane and DNA integrities, apoptosis, mitochondrial membrane potential, mucus penetration and SOD activity. The developmental potential of bovine embryos produced in vitro by using relaxin-treated was also investigated. In the present study, 50 and 100 ng/ml relaxin incorporation in extended bull semen before cryopreservation induced a reduction of sperm motility immediately after thawing (0h), whereas, during long incubation periods (1–2 h), relaxin showed a significant positive effect on sperm quality by improving the sperm motility and velocity parameters. Interestingly, sperm vitality was improved by 25 and 100 ng/ml relaxin and the blastocyst developmental rate was significantly increased in the 25 ng/ml relaxin group compared with controls (52/118, 44.0% vs. 32/116, 27.6%, respectively). These findings suggest a potential use of relaxin at the doses tested in the present study as an additive in the cryopreservation media of bull semen to improve sperm quality.

Background The oncolytic viruses have shown promising results for the treatment of multiple myeloma. However, the use of human viruses is limited by the patients’ antiviral immune response. In this study, we investigated an alternative oncolytic strategy using non-human pathogen viruses as the bovine viral diarrhea virus (BVDV) that were able to interact with CD46. Methods We treated several human myeloma cell lines and non-myeloma cell lines with BVDV to evaluate the expression of CD46 and to study the effect on cell viability by flow cytometry. The possible synergistic effect of bortezomib in combination with BVDV was also tested. Moreover, we infected the bone marrow mononuclear cells obtained from myeloma patients and we checked the BVDV effect on different cell populations, defined by CD138, CD14, CD3, CD19, and CD56 expression evaluated by flow cytometry. Finally, the in vivo BVDV effect was tested in NOD-SCID mice injected subcutaneously with myeloma cell lines. Results Human myeloma cells were selectively sensitive to BVDV treatment with an increase of cell death and, consequently, of apoptotic markers. Consistently, bone marrow mononuclear cells isolated from myeloma patients treated with BVDV, showed a significant selective decrease of the percentage of viable CD138+ cells. Interestingly, bortezomib pre-treatment significantly increased the cytotoxic effect of BVDV in myeloma cell lines with a synergistic effect. Finally, the in vitro data were confirmed in an in vivo myeloma mouse model showing that BVDV treatment significantly reduced the tumoral burden compared to the vehicle. Conclusions Overall, our data indicate, for the first time, a direct oncolytic effect of the BVDV in human myeloma cells suggesting its possible use as novel alternative anti-myeloma virotherapy strategy.

Aims An increase in out-of-hospital cardiac arrest (OHCA) incidence has been reported in the very early phase of the COVID-19 epidemic, but a clear demonstration of a correlation between the increased incidence of OHCA and COVID-19 is missing so far. We aimed to verify whether there is an association between the OHCA difference compared with 2019 and the COVID-19 epidemic curve. Methods and results We included all the consecutive OHCAs which occurred in the Provinces of Lodi, Cremona, Pavia, and Mantova in the 2 months following the first documented case of COVID-19 in the Lombardia Region and compared them with those which occurred in the same time frame in 2019. The cumulative incidence of COVID-19 from 21 February to 20 April 2020 in the study territory was 956 COVID-19/100 000 inhabitants and the cumulative incidence of OHCA was 21 cases/100 000 inhabitants, with a 52% increase as compared with 2019 (490 OHCAs in 2020 vs. 321 in 2019). A strong and statistically significant correlation was found between the difference in cumulative incidence of OHCA between 2020 and 2019 per 100 000 inhabitants and the COVID-19 cumulative incidence per 100 000 inhabitants both for the overall territory (ρ 0.87, P < 0.001) and for each province separately (Lodi: ρ 0.98, P < 0.001; Cremona: ρ 0.98, P < 0.001; Pavia: ρ 0.87, P < 0.001; Mantova: ρ 0.81, P < 0.001). Conclusion The increase in OHCAs in 2020 is significantly correlated to the COVID-19 pandemic and is coupled with a reduction in short-term outcome. Government and local health authorities should seriously consider our results when planning healthcare strategies to face the epidemic, especially considering the expected recurrent outbreaks., Graphical Abstract Graphical Abstract

This study evaluated the metabolic cost and stride frequency during exercise while wearing an evenly distributed weight vest in recreationally fit women. Nine healthy women performed a modified Balke treadmill test until volitional fatigue in one of three conditions; (1) unloaded (2) rucksack and (3) weighted vest. Wearing a weighted vest did not show improvement of V̇

The epidemic curve of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is silently rising again. Worldwide, the dominant SARS-CoV-2 variant of concern (VOC) is Omicron, and its virological characteristics, such as transmissibility, pathogenicity, and resistance to both vaccine- and infection-induced immunity as well as antiviral drugs, are an urgent public health concern. The Omicron variant has five major sub-lineages; as of February 2022, the BA.2 lineage has been detected in several European and Asian countries, becoming the predominant variant and the real antagonist of the ongoing surge. Hence, although global attention is currently focused on dramatic, historically significant events and the multi-country monkeypox outbreak, this new epidemic is unlikely to fade away in silence. Many aspects of this lineage are still unclear and controversial, but its apparent replication advantage and higher transmissibility, as well as its ability to escape neutralizing antibodies induced by vaccination and previous infection, are rising global concerns. Herein, we review the latest publications and the most recent available literature on the BA.2 lineage of the Omicron variant.

The negative association between obstructive sleep apnea (OSA) and adverse cardiovascular outcomes in patients undergoing percutaneous coronary intervention (PCI) is well documented. However, little is known about the influence of OSA on fibrinolytic therapy. The aim of this study was to evaluate the impact of severe OSA on pharmacoinvasive treatment in ST elevation myocardial infarction (STEMI) patients. We enrolled consecutive STEMI patients without previous vascular disease, heart failure, or OSA diagnosis. All patients underwent either a pharmacoinvasive therapy or primary PCI. Syntax score (SS) was calculated for all patients, and a full bedside polysomnography was performed in the first 72 h of admission. In-hospital events and 30 days readmissions were analyzed. The sample included 116 patients, 87 men. Patients with severe OSA were older (p = 0.01), had higher neck and abdominal circumferences (p

Objective: to identify scientific evidences available on the literature on nursing interventions on advanced mobile prehospital care for elderly people post-trauma. Method: an integrative review of literature on the databases PubMed, CINAHL, and LILACS, from 2012 to 2017. Results: a sample composed by 26 studies, grouped into six thematic categories: circulation with hemorrhage control (n=11); dysfunction, neurological state (n=7); airway with protection of the cervical spine (n=3); secondary evaluation (n=3); ventilation and breathing (n=1), and environment exposition/control (n=1). Conclusion: Despite having identified nursing interventions, there was no description of specific nursing interventions related to advanced mobile prehospital care for elderly people post-trauma. RESUMEN Objetivo: identificar las evidencias científicas disponibles en la literatura acerca de las intervenciones de enfermería durante la atención prehospitalaria móvil avanzada a ancianos postrauma. Método: revisión integrativa de la literatura en las bases de datos PubMed, CINAHL y LILACS, realizada en el período entre 2012 y 2017. Resultados: la muestra constó de 26 estudios, que fueron agrupados en seis ejes temáticos: Circulación con control de la hemorragia (n=11); Disfunción, estado neurológico (n=7); Vía aérea con protección de la columna cervical (n=3); Evaluación secundaria (n = 3); Ventilación y respiración (n=1); y Exposición/control del ambiente (n=1). Conclusión: en las intervenciones de enfermería identificadas, no se describían intervenciones específicas de enfermería relacionadas a la atención prehospitalaria móvil avanzada a ancianos postrauma. RESUMO Objetivo: identificar as evidências científicas disponíveis na literatura acerca das intervenções de enfermagem no atendimento pré-hospitalar móvel avançado para idosos pós-trauma. Método: revisão integrativa da literatura nas bases de dados PubMed, CINAHL e LILACS, no período de 2012 a 2017. Resultados: amostra composta por 26 estudos, agrupados em seis categorias temáticas: circulação com controle da hemorragia (n=11); disfunção, estado neurológico (n=7); via aérea com proteção da coluna cervical (n=3); avaliação secundária (n=3); ventilação e respiração (n=1) e exposição/controle do ambiente (n=1). Conclusão: apesar de terem sido identificadas intervenções de enfermagem, não houve descrição de intervenções específicas de enfermagem relacionadas ao atendimento pré-hospitalar móvel avançado de idosos pós-trauma.

Malaria is a major health issue with more than 200 million cases occurring annually. Moreover, in Malaria endemic area are frequently observed Malaria-enteroparasite co-infections associated with the modulation of inflammatory response. In this aspect, biomarkers play an important role in the disease prognosis. This study aimed to evaluate inflammatory mediators in malaria during coinfection with enteroparasites. A subset of serum samples already collected was analyzed and divided into four groups: Malaria (n = 34), Co-infected (n = 116), Enteroparasite (n = 120) and Control (n = 95). The serum levels of sTREM-1 and IL-6 were measured by ELISA. TNF-α, and IL-10 levels were previously carried out by flow cytometry. Higher serum levels of sTREM-1 and IL-6 were showed in malaria patients compared to healthy controls. In co-infected malarial patients sTREM-1 serum levels were similar to control group. Interestingly, co-infected malaria patients showed IL-6 serum levels decreased compared to individuals only infected with P. vivax. However, in Malaria patients and co-infected there was a positive correlation between the IL-6 and IL-10 levels (P < 0.0001). This is the first report of sTREM-1 levels in P. vivax infected. Moreover, the results revealing a divergent effect of co-infection with the increased balance between pro-and anti-inflammatory cytokines and reduced IL-6 levels but increases the anemia occurrence. The results also highlight the potential use of IL-6 as a biomarker for P. vivax and enteroparasites coinfection.

Multiple myeloma (MM) is a monoclonal gammopathy characterized by biological heterogeneity and unregulated proliferation of plasma cells (PCs) in bone marrow (BM). MM is a multistep process based on genomic instability, epigenetic dysregulation and a tight cross-talk with the BM microenvironment that plays a pivotal role supporting the proliferation, survival, drug-resistance and homing of PCs. The BM microenvironment consists of a hematopoietic and a non-hematopoietic compartment, which cooperate to create a tumor environment. Among the non-hematopoietic component, mesenchymal stromal cells (MSCs) and osteoblasts (OBs) appear transcriptionally and functionally different in MM patients compared to healthy donors (HDs) and to patients with pre-malignant monoclonal gammopathies. Alterations of both MSCs and OBs underly the osteolytic lesions that characterize myeloma-associated bone disease. In this review, we will discuss the different characteristics of MSCs and OBs in MM patients, analyzing the transcriptome, the deregulated molecular pathways and the role performed by miRNAs and exosome in the pathophysiology of MM.

Prostate cancer is the most frequent malignancy in the worldwide male population; it is also one of the most common among all the leading cancer-related death causes. In the last two decades, the therapeutic scenario of metastatic castration-resistant prostate cancer has been enriched by the use of chemotherapy and androgen receptor signaling inhibitors (ARSI) and, more recently, by immunotherapy and poly(ADP–ribose) polymerase (PARP) inhibitors. At the same time, several trials have shown the survival benefits related to the administration of novel ARSIs among patients with non-castration-resistant metastatic disease along with nonmetastatic castration-resistant cancer too. Consequently, the therapeutic course of this malignancy has been radically expanded, ensuring survival benefits never seen before. Among the more recently emerging agents, the so-called “antibody–drug conjugates” (ADCs) are noteworthy because of their clinical practice changing outcomes obtained in the management of other malignancies (including breast cancer). The ADCs are novel compounds consisting of cytotoxic agents (also known as the payload) linked to specific antibodies able to recognize antigens expressed over cancer cells’ surfaces. As for prostate cancer, researchers are focusing on STEAP1, TROP2, PSMA, CD46 and B7-H3 as optimal antigens which may be targeted by ADCs. In this paper, we review the pivotal trials that have currently changed the therapeutic approach to prostate cancer, both in the nonmetastatic castration-resistant and metastatic settings. Therefore, we focus on recently published and ongoing trials designed to investigate the clinical activity of ADCs against prostate malignancy, characterizing these agents. Lastly, we briefly discuss some ADCs-related issues with corresponding strategies to overwhelm them, along with future perspectives for these promising novel compounds.

Background Selective bilateral lesions of the parietal–occipital lobes can lead to an uncommon and incompletely understood clinical entity, Balint’ syndrome, which consists of simultanagnosia, oculomotor apraxia, optic ataxia and difficulty in perceiving distances between objects. Case presentation We herein report a rare presentation of Balint’s syndrome in a 65-year-old woman suffering from stroke and SARS-CoV2 infection. Conclusion During SARS-CoV2 pandemic, Italian physicians were forced to work with less instrumental diagnostic resources, relying on their clinical knowledge mostly. The aim of this case report is to highlight the importance of performing a precise neurological evaluation, particularly during these challenging times: it might avoid incorrect diagnosis and favour the discovery of rare clinical diseases.

Inflammation and endothelial activation play a pivotal role in development and progression of diabetic retinopathy (DR), a vision-threatening complication of diabetes mellitus (DM) and the leading cause of blindness in the working age population. Easily accessible and validated biomarkers for DR early diagnosis and progression are required for use in clinical trials: here, we reviewed the available literature to understand the association of circulating levels of selected markers of inflammation and endothelial activation with the presence of nonproliferative and proliferative DR (NPDR and PDR) and investigate the relationship between their systemic and ocular levels. We additionally provide data synthesis and perform statistical analysis for interpretation of the collected evidence. CRP, IL-1β, IL-6, TNFα, sICAM1, and sVCAM1 circulating levels were increased in subjects with DM compared to healthy individuals. Moreover, TNFα and sVCAM1 showed increasing systemic levels with DR presence and severity; circulating CRP increased with the transition from no DR to NPDR, whereas IL-6 was increased in PDR compared to NDPR stages. The relationship between ocular and systemic concentrations of these proteins remained unclear due to the low number of studies with matched sampling. In conclusion, the available data supports the use of systemic biomarkers of inflammation and endothelial activation to identify DM status and DR severity. These systemic biomarkers are likely reflecting an overall state of inflammation and vascular activation in different tissues of the body, including the eyes. Prospective, longitudinal datasets are required to validate these biomarkers as predictors of early DR presence, of DR progression, or for disease monitoring.

There are scarce data regarding influenza vaccination among people with HIV infection (PWHIV). The goal of this explorative study is to assess hesitancy toward influenza vaccination in a group of PWHIV during the COVID-19 pandemic. A questionnaire was administered to 219 patients vaccinated at our clinic during the 2020-2021 campaign. It evaluated subjects' adherence to influenza vaccine over the last three seasonal vaccination campaigns, vaccine confidence, complacency and convenience, and the effect of the pandemic on the choice to become vaccinated. The population was divided into two groups: fully adherent to influenza vaccine (all three campaigns, 117 patients) and non-fully adherent (one or two campaigns, 102 patients). Adherence increased in the non-fully adherent group in 2020-2021, but the pandemic did not affect the choice. Misbeliefs emerged: the influenza vaccine was considered protective against SARS-CoV-2 (22.8% of the total population); almost half of all patients thought the influenza vaccine could improve their CD4 T cell level (57.3% in fully adherent, 40.2% in non-fully adherent, p .05). In 2020-2021 campaign, three quarters of the non-fully adherent group would not have been vaccinated in a location other than our clinic (75.5% vs. 88.9% in the fully adherent group, p .05). Conclusively, offering a secure and private space for vaccination against influenza seems to encourage vaccination; healthcare professionals should improve counseling to increase adherence and correct misbeliefs.

Erector spinae plane block (ESP Block) was introduced in 2016 as a surgical post-operative analgesia procedure. The present prospective, randomized trial aimed to compare ESP Block with serratus plane block (SPB) plus pectoral nerve blocks (PECS I) during breast conserving surgery (BCS).Between February 2019 and March 2021, 104 patients undergoing BCS were randomized to receive either ESP block (ESP group n=54) or SPB+PECS I (SPB group=49). Assessment of postoperative pain was recorded by the dynamic and static visual analog scale (VAS) and was compared between groups.Between-group two-way ANOVA did not reach a statistically significant difference in static and dynamic VAS (p=0.879; p=0.917, respectively). Despite ESP group requiring for higher value of patient-controlled analgesia (PCA) bolus, no statistically significant difference was found in PCA activation pattern between groups (p=0.109). ESP block was a faster technique when compared to SPB+PECS I (p=0.007) and no complications or opioid side-effects were recorded in all groups examined.ESP Block could represent a safe, faster alternative with a single injection to SPB+PECS I in BCS.

Despite evidence supporting the effectiveness of best practices in infection prevention and management, many healthcare workers fail to implement them and evidence-based practices tend to be underused in routine practice. Prevention and management of infections across the surgical pathway should always focus on collaboration among all healthcare workers sharing knowledge of best practices. To clarify key issues in the prevention and management of infections across the surgical pathway, a multidisciplinary task force of experts convened in Ancona, Italy, on May 31, 2019, for a national meeting. This document represents the executive summary of the final statements approved by the expert panel.

Background: Subcortical vascular dementia (sVAD) is considered the most frequent dementia in old population, and it is due to a small vessel disease. It has a very specific nosography, where the dominant factors are dysexecutive functions, depression, and apathy. Very few studies described visual hallucinations in sVAD, apart from in the final stages of it. Methods: This study recruited 577 patients with a diagnosis of sVAD associated with major ocular pathologies and 1118 patients with sVAD without any significant ocular pathology: Patients were followed up for 24 months. We studied the influence of ocular pathologies in precocious visual hallucinations, on behavior disorder (aggressiveness), and gait disorders (instability, fells). We registered the necessity of neuropsychiatric therapies, incidence of hospitalization, and institutionalization. Results: What emerges from our study is that the ocular comorbidities might change the behavior profile of dementia, provoking behavioral alterations, and the need for therapies with adverse effects. As far as old age is a complicated status of life, many factors can modify its development. The possible contribution of multiple biological events cannot be neglected, particularly the underlying influence of chronic diseases as well as the geriatric conditions, per se, might compromise the cognitive functions and the pathological conditions. Ocular pathology as a superimposing event in sVAD might worse the outcome. A correct and rapid identification of critical patients might be relevant for the dynamic life events in these patients and their caregiver

The pathophysiology of essential tremor (ET) is controversial and might be further elucidated by advanced neuroimaging. Focusing on homogenous ET patients diagnosed according to the 2018 consensus criteria, this study aimed to: (1) investigate whether task functional MRI (fMRI) can identify networks of activated and deactivated brain areas, (2) characterize morphometric and functional modulations, relative to healthy controls (HC). Ten ET patients and ten HC underwent fMRI while performing two motor tasks with their upper limb: (1) maintaining a posture (both groups); (2) simulating tremor (HC only). Activations/deactivations were obtained from General Linear Model and compared across groups/tasks. Voxel-based morphometry and linear regressions between clinical and fMRI data were also performed. Few cerebellar clusters of gray matter loss were found in ET. Conversely, widespread fMRI alterations were shown. Tremor in ET (task 1) was associated with extensive deactivations mainly involving the cerebellum, sensory-motor cortex, and basal ganglia compared to both tasks in HC, and was negatively correlated with clinical tremor scales. Homogeneous ET patients demonstrated deactivation patterns during tasks triggering tremor, encompassing a network of cortical and subcortical regions. Our results point towards a marked cerebellar involvement in ET pathophysiology and the presence of an impaired cerebello-thalamo-cortical tremor network.

Assessment of consciousness following severe brain-injury is challenging. Our hypothesis is that electroencephalography (EEG) can provide information on awareness, in terms of oscillatory activity and network task–related modifications, in people with disorders of consciousness. Similar results were obtained with neuroimaging techniques; we aim at demonstrating the use of EEG, which is low cost and routinely implemented, to the same goal. Nineteen-channel EEG was recorded in 7 persons with unresponsive wakefulness syndrome (UWS) and in 10 healthy subjects during the execution of active (attempted movement) and passive motor tasks as well as 2 mental imagery tasks. Event-related synchronization/desynchronization (ERS/ERD), coherence and network parameters were calculated in delta (1-4 Hz), theta (4-8 Hz), alpha1 (8-10 Hz), alpha2 (10-12 Hz), and beta (13-30 Hz) ranges. In UWS subjects, passive movement induced a weak alpha2 ERD over contralateral sensorimotor area. During motor imagery, ERD was detected over the frontal and motor contralateral brain areas; during spatial imagery, ERS in lower alpha band over the right temporo-parietal regions was missing. In UWS, functional connectivity provided evidence of network disruption and isolation of the motor areas, which cannot dialog with adjacent network nodes, likely suggesting a diffuse structural alteration. Our findings suggest that people with a clinical diagnosis of UWS were able to modulate their brain activity when prompted to perform movement tasks and thus suggest EEG as a potential tool to support diagnosis of disorders of consciousness.

Tumor burden is a complex microenvironment where different cell populations coexist and have intense cross-talk. Among them, a heterogeneous population of tumor cells with staminal features are grouped under the definition of cancer stem cells (CSCs). CSCs are also considered responsible for tumor progression, drug resistance, and disease relapse. Furthermore, CSCs secrete a wide variety of extracellular vesicles (EVs) with different cargos, including proteins, lipids, ssDNA, dsDNA, mRNA, siRNA, or miRNA. EVs are internalized by other cells, orienting the microenvironment toward a protumorigenic and prometastatic one. Given their importance in tumor growth and metastasis, EVs could be exploited as a new therapeutic target. The inhibition of biogenesis, release, or uptake of EVs could represent an efficacious strategy to impair the cross-talk between CSCs and other cells present in the tumor microenvironment. Moreover, natural or synthetic EVs could represent suitable carriers for drugs or bioactive molecules to target specific cell populations, including CSCs. This review will discuss the role of CSCs and EVs in tumor growth, progression, and metastasis and how they affect drug resistance and disease relapse. Furthermore, we will analyze the potential role of EVs as a target or vehicle of new therapies.

Our previous work using a melanoma progression model composed of melanocytic cells (melanocytes, primary and metastatic melanoma samples) demonstrated various deregulated genes, including a few known lncRNAs. Further analysis was conducted to discover novel lncRNAs associated with melanoma, and candidates were prioritized for their potential association with invasiveness or other metastasis-related processes. In this sense, we found the intergenic lncRNA U73166 (ENSG00000230454) and decided to explore its effects in melanoma. For that, we silenced the lncRNA U73166 expression using shRNAs in a melanoma cell line. Next, we experimentally investigated its functions and found that migration and invasion had significantly decreased in knockdown cells, indicating an essential association of lncRNA U73166 for cancer processes. Additionally, using naïve and vemurafenib-resistant cell lines and data from a patient before and after resistance, we found that vemurafenib-resistant samples had a higher expression of lncRNA U73166. Also, we retrieved data from the literature that indicates lncRNA U73166 may act as a mediator of RNA processing and cell invasion, probably inducing a more aggressive phenotype. Therefore, our results suggest a relevant role of lncRNA U73166 in metastasis development. We also pointed herein the lncRNA U73166 as a new possible biomarker or target to help overcome clinical vemurafenib resistance.

Evolving bronchopulmonary dysplasia (BPD) is characterized by impaired alveolarization leading to lung aeration inhomogeneities. Hyperoxia-exposed preterm rabbits have been proposed to mimic evolving BPD; therefore, we aimed to verify if this model has the same lung ultrasound and mechanical features of evolving BPD in human neonates. Semiquantitative lung ultrasound and lung mechanics measurement was performed in 25 preterm rabbits (28 days of gestation) and 25 neonates (mean gestational age ≈ 26 wk) with evolving BPD. A modified rabbit lung ultrasound score (rLUS) and a validated neonatal lung ultrasound score (LUS) were used. Lung ultrasound images were recorded and evaluated by two independent observers blinded to each other's evaluation. Lung ultrasound findings were equally heterogeneous both in rabbits as in human neonates and encompassed all the classical lung ultrasound semiology. Lung ultrasound and histology examination were also performed in 13 term rabbits kept under normoxia as further control and showed the absence of ultrasound and histology abnormalities compared with hyperoxia-exposed preterm rabbits. The interrater absolute agreement for the evaluation of lung ultrasound images in rabbits was very high [ICC: 0.989 (95%CI: 0.975-0.995)

Tissue engineering aims to develop innovative approaches to repair tissue defects. The use of adipose-derived stem cells (ASCs) in tissue regeneration was extensively investigated for osteochondrogenesis. Among the ASC population, ASCs expressing the CD146 were demonstrated to be multipotent and considered as perivascular stem cells, although the functional role of CD146 expression in these cells remains unclear. Herein, we investigated the influence of CD146 expression on osteochondrogenic differentiation of ASCs. Our results showed that, in two-dimensional culture systems, sorted CD146+ ASCs proliferated less and displayed higher adipogenic and chondrogenic potential than CD146- ASCs. The latter demonstrated a higher osteogenic capacity. Besides this, CD146+ ASCs in three-dimensional Matrigel/endothelial growth medium (EGM) cultures showed the highest angiogenic capability. When cultured in three-dimensional collagen scaffolds, CD146+ ASCs showed a spontaneous chondrogenic differentiation, further enhanced by the EGM medium's addition. Finally, CD146- ASCs seeded on hexafluoroisopropanol silk scaffolds displayed a greater spontaneous osteogenetic capacity. Altogether, these findings demonstrated a functional and relevant influence of CD146 expression in ASC properties and osteochondrogenic commitment. Exploiting the combination of specific differentiation properties of ASC subpopulations and appropriate culture systems could represent a promising strategy to improve the efficacy of new regenerative therapies.

The ongoing COVID-19 pandemic is likely to have a profound impact on the lives of high-risk drug users and on the services responding to their needs in at least two important ways: first, through the restrictive measures introduced to mitigate the spread of the virus and, second, as a result of extensive economic downturn. Currently there is great uncertainty as to the future intensity and duration of the pandemic. In addition, the lessons we have been able to learn from previous economic downturns may be of limited applicability to the current situation, which differs in a number of significant respects. Experience nevertheless suggests that the potential consequences for drug users’ health and well-being may be severe. The ongoing uncertainty serves to underline the importance of close monitoring of the drug situation and preparing flexible and innovative solutions to be able to meet new challenges which may arise.

Introduction: Multiple myeloma (MM) is characterized by the high tendency to relapse and develop drug resistance. Areas covered: This review focused on the main novel targets identified to design drugs for the treatment of relapsing MM patients. CD38 and SLAMF7 are the main surface molecules leading to the development of monoclonal antibodies (mAbs) recently approved for the treatment of relapsing MM patients. B cell maturation antigen (BCMA) is a suitable target for antibody-drug conjugates, bispecific T cell engager mAbs and Chimeric Antigen Receptor (CAR)-T cells. Moreover, the programmed cell death protein 1 (PD)-1/PD-Ligand (PD-L1) expression profile by MM cells and their microenvironment and the use of immune checkpoints inhibitors in MM patients are reported. Finally, the role of histone deacetylase (HDAC), B cell lymphoma (BCL)-2 family proteins and the nuclear transport protein exportin 1 (XPO1) as novel targets are also underlined. The clinical results of the new inhibitors in relapsing MM patients are discussed. Expert opinion: CD38, SLAMF7, and BCMA are the main targets for different immunotherapeutic approaches. Selective inhibitors of HDAC6, BCL-2, and XPO1 are new promising compounds under clinical investigation in relapsing MM patients.

Multiple myeloma is the second most frequent hematological cancer after lymphoma and remains an incurable disease. The pervasive support provided by the bone marrow microenvironment to myeloma cells is crucial for their survival. Here, an unbiased assessment of receptor tyrosine kinases overexpressed in myeloma identified ROR2, a receptor for the WNT noncanonical pathway, as highly expressed in myeloma cells. Its ligand, WNT5A is the most abundant growth factor in the bone marrow of myeloma patients. ROR2 mediates myeloma cells interactions with the surrounding bone marrow and its depletion resulted in detachment of myeloma cells from their niche in an in vivo model, triggering apoptosis and thus markedly delaying disease progression. Using in vitro and ex vivo 3D-culture systems, ROR2 was shown to exert a pivotal role in the adhesion of cancer cells to the microenvironment. Genomic studies revealed that the pathways mostly deregulated by ROR2 overexpression were PI3K/AKT and mTOR. Treatment of cells with specific PI3K inhibitors already used in the clinic reduced myeloma cell adhesion to the bone marrow. Together, our findings support the view that ROR2 and its downstream targets represent a novel therapeutic strategy for the large subgroup of MM patients whose cancer cells show ROR2 overexpression.

Although the recent years have witnessed a growing interest in functional connectivity (FC) through brain sources, the FC in extreme situations has not been completely elucidated. This paper is aimed at investigating whether the expertise acquired during the deep-sea diving is reflected in FC in a group of professional divers (PDs) compared to a group of new divers (NDs), and how it could affect the concentration and stress levels. The sources of brain frequency rhythms, derived by the electroencephalography acquisition in a hyperbaric chamber, were extracted in different frequency bands and the corresponding FC was estimated in order to compare the two groups. The results highlighted a significant decrease of the alpha source in PDs during air breathing and a significant increase of the upper beta source over central areas at the beginning of post-oxygen air, as well as an increase of beta FC between fronto-temporal regions in the last minutes of oxygen breathing and in the early minutes of post-oxygen air. This provides evidence in support of the hypothesis that experience and expertise differences would modulate brain networks. These experiments provided the unique opportunity of investigating the impact of the neurophysiological activity in simulated critical scenarios in view of the investigation in real sea-water experiments.

The plasma membrane of cells has a complex architecture based on the bidimensional liquid-crystalline bilayer arrangement of phospho- and sphingolipids, which in turn embeds several proteins and is connected to the cytoskeleton. Several studies highlight the spatial membrane organization into more ordered (L o or lipid raft) and more disordered (L d ) domains. We here report on a fluorescent analog of the green fluorescent protein chromophore that, when conjugated to a phospholipid, enables the quantification of the L o and L d domains in living cells on account of its large fluorescence lifetime variation in the two phases. The domain composition is straightforwardly obtained by the phasor approach to confocal fluorescence lifetime imaging, a graphical method that does not require global fitting of the fluorescence decay in every spatial position of the sample. Our imaging strategy was applied to recover the domain composition in human oligodendrocytes at rest and under treatment with galactosylsphingosine (psychosine). Exogenous psychosine administration recapitulates many of the molecular fingerprints of a severe neurological disease, globoid cell leukodystrophy, better known as Krabbe disease. We found out that psychosine progressively destabilizes plasma membrane, as witnessed by a shrinking of the L o fraction. The unchanged levels of galactosyl ceramidase, i.e., the enzyme lacking in Krabbe disease, upon psychosine treatment suggest that psychosine alters the plasma membrane structure by direct physical effect, as also recently demonstrated in model membranes.