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The diabetic foot ulcer is the most important reason for non-traumatic limb amputation. Based on recent data, it has been estimated that up to 34% of type 2 diabetes patients may develop diabetic foot ulcers once in their lifetime. Risk factors for developing foot ulcers are distal sensorimotor peripheral neuropathy, peripheral arterial disease, previous ulcers, and/or amputations. Understanding the factors that place patients with diabetes mellitus at high ulceration risk and the early treatment of risk factors, and continuous education of the patient (and/or caregivers) are essential for the prevention and management of diabetic foot complications. Implementing strategies to prevent these complications is a key aspect of diabetes care, but the most effective strategy in prevention has to be investigated. More evidence from well-designed studies is needed on this topic.

Amyloid diseases are global epidemics with no cure currently available. In the past decade, the use of engineered nanomaterials as inhibitors or probes against the pathogenic aggregation of amyloid peptides and proteins has emerged as a new frontier in nanomedicine. In this Minireview, we summarize for the first time the pivotal role of chemical synthesis in enabling the development of this multidisciplinary field.

Background: Taurolidine lock is known to be effective in preventing catheter-related infections in a variety of venous access devices, including long term venous access devices for chemotherapy. Though, literature about the use of taurolidine for treating catheter colonization or catheter-related blood stream infection is scarce. Method: We have retrospectively reviewed the safety and efficacy of 2% taurolidine lock for treatment of catheter-colonization and of catheter-related bloodstream infection in cancer patients with totally implanted venous access devices. Diagnosis of colonization or catheter-related infection was based on paired peripheral and central blood cultures, according to the method of Delayed Time to Positivity. Results: We recorded 24 cases of catheter-related infection and two cases of colonization. Taurolidine lock—associated with systemic antibiotic therapy—was successful in treating all cases of catheter-related infection, with disappearance of clinical symptoms, normalization of laboratory values, and eventually negative blood cultures. Taurolidine lock was also safe and effective in treating device colonization. No adverse effect was reported. Conclusion: In our retrospective analysis, 2% taurolidine lock was completely safe and highly effective in the treatment of both catheter-colonization and catheter-related bloodstream infection in cancer patients with totally implanted venous access devices.

Background: An adequate stabilization of a vascular device is an important part of insertion bundles and is an effective strategy in reducing complications. Dislodgment has a relevant clinical impact and an increase in healthcare costs. Method: We have retrospectively investigated the safety and efficacy of Subcutaneously Anchored Securement (SAS) for Peripherally Inserted Central Catheters (PICC) in cancer patients. Results: We analyzed 639 patients who had a PICC inserted and secured with SAS, over the past 3 years (2018–2020). No immediate complications during SAS placement were reported. In the first 24–48 h, a slight local ecchymosis was reported in 24 cases with rapid spontaneous resolution. No cases of bleeding or hematoma of the exit site were reported. The total number of catheter days was 93078. Dislodgment occurred only in seven cases (1.1%). In 16 patients, the PICC was removed because of catheter-related bloodstream infection (CRBSI): the overall incidence of CRBSI was 0.17 per 1000 catheter days. Symptomatic venous thrombosis was documented in 12 patients (1.9%) and treated with low molecular weight heparin without PICC removal. We had no cases of irreversible lumen occlusion. In 17 patients, local discomfort—including device-related pressure ulcers and painful inflammation—was reported: these cases were treated without SAS removal or PICC removal. Conclusion: In this retrospective analysis, subcutaneously anchored securement of PICCs was a safe and effective strategy for reducing the risk of dislodgment.

To compare brain magnetic resonance imaging (MRI) using T1 3D Silent and fast T1 3D Gradient-Echo (GRE) BRAin VOlume (known as BRAVO) sequences. The primary aim is to assess the quantitative and qualitative analysis of Silent and BRAVO images by the measurement of the contrast (C), the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR). The second aim is to estimate the subjective sound levels and the specific absorption rate (SAR). Twenty-two subjects had T1 3D Silent and T1 3D BRAVO sequences added to the standard MR examination. The qualitative analysis of the two sequences was performed by two radiologists independently. The quantitative analysis was performed by placing regions of interest on the cerebrospinal fluid, on the white and grey matter. The C, the CNR and the SNR were calculated for each sequence. After each T1-3D sequence, subjects gave a score rating to evaluate the acoustic noise. Finally, the SAR was evaluated by the digital imaging and communications in medicine (DICOM) tags. The image quality scores obtained by the two radiologists were higher for BRAVO compared to the Silent. However, qualitatively, the Silent images were similar to BRAVO for diagnostic use. Quantitatively, CNR for GM-CSF was comparable in the two sequences and SNR in CSF was higher in Silent than BRAVO. The acoustic noise of Silent sequence was statistically lower compared with BRAVO. The maximum SAR measured was 1.4 W/kg. 3D T1 Silent can be a valid alternative technique to conventional BRAVO to reduce the acoustic noise preserving the diagnostic accuracy. However, radiologists preferred the conventional sequence to Silent.

Infertility is a global health problem affecting 10-15% of couples in reproductive age. Recent studies have provided growing evidence supporting that lifestyle factors can affect male fertility through alterations in endocrine profiles, spermatogenesis and/or sperm function. One of these critical factors could be the change in the food intake behavior in modern societies that produces metabolic alterations. Regarding this, metabolic syndrome (MetS) prevalence has increased in epidemic in the last 40-50 years. Although MetS is associated with advanced age, changes in lifestyles have accelerated the appearance of symptoms in the reproductive age. We review herein the current understanding of the relationship between MetS and the male reproductive status. For this purpose, in this narrative review a comprehensive literature search was made in both animal models and men, allowing us to evaluate such relationship. This analysis showed a high variability in the reproductive phenotypes observed in patients and mice suffering MetS, including sperm parameters, fertility and offspring health. In view of this, we proposed that the reproductive effects, which are diverse and not robust, observed among MetS-affected males, might depend on additional factors not associated with the metabolic condition and contributed not only by the affected male but also by his partner. With this perspective, this review provides a more accurate insight of this syndrome critical for the identification of specific diagnostic indicators and treatment of MetS-induced fertility disorders.

ObjectiveTo perform a systematic review and meta-analysis to determine whether fluid and imaging astrocyte biomarkers are altered in Alzheimer disease (AD).MethodsPubMed and Web of Science databases were searched for articles reporting fluid or imaging astrocyte biomarkers in AD. Pooled effect sizes were determined with standardized mean differences (SMDs) using the Hedge G method with random effects to determine biomarker performance. Adapted questions from the Quality Assessment of Diagnostic Accuracy Studies were applied for quality assessment. A protocol for this study has been previously registered in PROSPERO (registration number: CRD42020192304).ResultsThe initial search identified 1,425 articles. After exclusion criteria were applied, 33 articles (a total of 3,204 individuals) measuring levels of glial fibrillary acidic protein (GFAP), S100B, chitinase-3-like protein 1 (YKL-40), and aquaporin 4 in the blood and CSF, as well as monoamine oxidase-B indexed by PET 11C-deuterium-l-deprenyl, were included. GFAP (SMD 0.94, 95% confidence interval [CI] 0.71–1.18) and YKL-40 (SMD 0.76, 95% CI 0.63–0.89) levels in the CSF and S100B levels in the blood (SMD 2.91, 95% CI 1.01–4.8) were found to be significantly increased in patients with AD.ConclusionsDespite significant progress, applications of astrocyte biomarkers in AD remain in their early days. This meta-analysis demonstrated that astrocyte biomarkers are consistently altered in AD and supports further investigation for their inclusion in the AD clinical research framework for observational and interventional studies.

Abstract:: In developed countries, the prevalence of persons with diabetes and peripheral arterial disease (PAD) is approximately 50%. The presence of PAD is associated with non-healing ulcers, major amputation, cardiovascular morbidity, and mortality. It is estimated that persons with diabetes, foot ulceration and PAD have 50% of 5-years mortality rate. Therefore, subjects with ischemic diabetic foot ulcers (DFUs) should be considered a special group of patients with specific clinical characteristics, general health status and prognosis. In persons with ischemic DFUs, an early diagnosis and treatment are mandatory to reduce the risk of worse outcomes such as major amputation. Revascularization of occluded lower extremity arteries is the main treatment to restore blood flow in the foot and promote wound healing. Nonetheless, there are several unmet needs in the management of diabetic subjects with PAD and foot ulceration as medical therapy, diagnostic criteria and indications for revascularization, revascularization strategy and technical approach as well as the management of no-option critical limb ischemia patients. It is a common opinion that there is an evolution of PAD features in diabetic persons, which seems to present a more aggressive pattern. This may be related to the frequent presence of concomitant comorbidities such as renal failure which could influence the characteristics of atherosclerotic plaques and their distribution. The aim of this review is to commence a complete overview and state of the art in the treatment of patients with diabetes, PAD, and foot ulceration and to describe the current challenges and future perspectives.

Background Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor approved for the treatment of T790M-positive non-small-cell lung cancer. More recently, osimertinib demonstrated improved disease control compared to other EGFR-TKIs. Multiple mechanisms of resistance have been described in T790M-positive patients who experienced treatment failure with osimertinib. Case report We report the case of a 78-year-old non-smoker woman with stage IV EGFR L858R-positive lung adenocarcinoma presented with T790M mutation after five years of treatment with gefitinib. The patient was started on osimertinib, but after two and a half years of treatment experienced disease progression. The analyses of circulating tumor DNA using next-generation sequencing showed, together with the pre-existing T790M and exon 21 L858R, the presence of the EGFR C797G resistance mutation. Conclusion Our case report revealed a rare EGFR-dependent acquired resistance mutation to osimertinib in circulating tumor DNA. Liquid biopsy appears to be a promising resource to understand the biology of osimertinib resistance by clonal evolution monitoring and the identification of novel resistance mechanisms.

BackgroundCurrently, no data are available on the burden of morbidity and mortality in people with HIV-1 (PWH) harboring a 4-class drug-resistant (4DR) virus (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase strand transfer inhibitors). The study aimed to assess the incidence of clinical events and death in this population.MethodsThis was a cohort study on PWH from the PRESTIGIO Registry with a documented 4DR virus. Burden of disease was defined as the occurrence of any new event including an AIDS-defining event (ADE) or non-AIDS-defining event (NADE) or death from any cause after 4DR evidence (baseline). Cox regression models evaluated factors associated with the risk of new clinical events/death.ResultsAmong 148 PWH followed for a median (interquartile range) of 47 (32–84) months after 4DR evidence, 38 PWH had 62 new events or died from any cause (incidence rate, 9.12/100 person-years of follow-up; 95% CI = 6.85–11.39): 12 deaths (6 AIDS-related and 6 non-AIDS-related), 18 ADEs, 32 NADEs; 20 of the 38 NADEs (45%) of the incident clinical events were malignancies. The 4-year cumulative incidence of death was 6% (95% CI, 3%–13%), and that of ≥1 event or death was 22% (95% CI, 16%–31%). A higher risk of new clinical events/death was more likely in PWH with previous clinical events (adjusted hazard ratio [aHR], 2.67; 95% CI, 1.07–6.67) and marginally associated with lower baseline CD4+/CD8+ ratio (aHR, 0.82; 95% CI, 0.65–1.02).ConclusionsPWH harboring 4DR have a high burden of disease with a worrying incidence of malignancies, strongly advising for close prevention and monitoring interventions as well as access to innovative therapeutic strategies, especially in people with a history of clinical events and low CD4+/CD8+ ratio.

In pediatric acute myeloid leukemia (AML), intensive chemotherapy and allogeneic hematopoietic stem cell transplantation are the cornerstones of treatment in high-risk cases, with severe late effects and a still high risk of disease recurrence as the main drawbacks. The identification of targeted, more effective, safer drugs is thus desirable. We performed a high-throughput drug-screening assay of 1280 compounds and identified thioridazine (TDZ), a drug that was highly selective for the t(6;11)(q27;q23) MLL-AF6 (6;11)AML rearrangement, which mediates a dramatically poor (below 20%) survival rate. TDZ induced cell death and irreversible progress toward the loss of leukemia cell clonogenic capacity in vitro. Thus, we explored its mechanism of action and found a profound cytoskeletal remodeling of blast cells that led to Ca2+ influx, triggering apoptosis through mitochondrial depolarization, confirming that this latter phenomenon occurs selectively in t(6;11)AML, for which AF6 does not work as a cytoskeletal regulator, because it is sequestered into the nucleus by the fusion gene. We confirmed TDZ-mediated t(6;11)AML toxicity in vivo and enhanced the drug’s safety by developing novel TDZ analogues that exerted the same effect on leukemia reduction, but with lowered neuroleptic effects in vivo. Overall, these results refine the MLL-AF6 AML leukemogenic mechanism and suggest that the benefits of targeting it be corroborated in further clinical trials.

Intravenous thrombolysis (IVT)-ineligible patients undergoing direct thrombectomy tended to have poorer functional outcome as compared with IVT-eligible patients undergoing bridging therapy. We aimed to assess radiological and functional outcomes in large vessel occlusion-related stroke patients receiving direct thrombectomy in the presence of absolute exclusion criteria for IVT vs relative exclusion criteria for IVT and vs non-exclusion criteria for IVT. A cohort study on prospectively collected data from 2282 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke cohort for treatment with direct thrombectomy (n = 486, absolute exclusion criteria for IVT alone; n = 384, absolute in combination with relative exclusion criteria for IVT; n = 777, relative exclusion criteria for IVT alone; n = 635, non-exclusion criteria for IVT). After adjustment for unbalanced variables (model 1), ORs for 3-month death was higher in the presence of absolute exclusion criteria for IVT alone (vs relative exclusion criteria for IVT alone) (1.595, 95% CI 1.042–2.440) and in the presence of absolute exclusion criteria for IVT alone (vs non-exclusion criteria for IVT) (1.235, 95% CI 1.014–1.504). After adjustment for predefined variables (model 2: age, sex, pre-stroke mRS ≤ 1, NIHSS, occlusion in the anterior circulation, onset-to-groin time, and procedure time), ORs for 3-month death was higher in the presence of absolute exclusion criteria for IVT alone (vs relative exclusion criteria for IVT alone) (1.235, 95% CI 1.014–1.504) and in the presence of absolute exclusion criteria for IVT alone (vs non-exclusion criteria for IVT) (1.246, 95% CI 1.039–1.495). No significant difference was found between the groups as regards any type of intracerebral hemorrhage and parenchymal hematoma within 24 h, successful and complete recanalization after procedure, and modified Rankin Scale score 0–2 at 3 months. After adjustment for predefined variables of model 2, ORs for death were higher in the presence of recent administration of IV heparin (OR: 2.077), platelet count

Multiple myeloma is a type of blood cancer arising from the uncontrolled clonal proliferation of malignant plasma cells resulting in impaired hematopoiesis, hyper production of monoclonal protein, bone tissue destruction leading and renal system alterations up to kidney failure. The aim is to review the state-of-the-art of radiological imaging in multiple myeloma. Radiological techniques as well as the advancements in imaging technology have been reviewed and summarized. The main radiological findings of different imaging techniques in patients suffering from multiple myeloma are also illustrated. Different radiological techniques provide structural and functional data. In the last years, conventional skeletal survey has gradually lost its utility and it has been replaced by whole body low-dose computed tomography which allows to identify also small lytic lesions, the medullary and the extramedullary involvement. Nowadays, magnetic resonance is the most sensitive imaging technique for detecting of skeletal as well as medullary involvement in patients with multiple myeloma. Thanks to the multiparametric evaluation (morphological, diffusion weighted and perfusion imaging sequences) and to the quantitative analysis, magnetic resonance imaging is proved to be useful in the early evaluation of response to therapy. Finally, positron emission tomography has greater sensibility compared to computed tomography as it provides quantitative data; however, the lower expression levels of the specific gene involved in the glycolysis pathway are associated with false-negative results with consequent underestimation of the disease. The only use of the advanced combined multimodal imaging allows a better evaluation, staging and early assessment of treatment response in patients with multiple myeloma.

Background: The combination of endocrine therapy with the cyclin-dependent kinases 4/6 inhibitor palbociclib was proven to be effective for the treatment of hormone receptor (HR)-positive/HER2-negative metastatic breast cancer (MBC). Although generally well tolerated, treatment delays and dose reductions are frequently observed with palbociclib, mainly due to severe neutropenia. Predictors of palbociclib-related toxicities are still unknown, as well as the clinical relevance of its relative dose intensity (RDI). Henceforth, this study aimed to identify baseline clinicopathological features associated with a RDI Methods: We reviewed data of 150 consecutive patients with HR-positive/HER2-negative MBC patients treated with palbociclib at two Italian cancer centers from 2017 to 2019. Eligible patients must have received at least 3 cycles of treatment. Those who experienced early suspension due to unacceptable toxicities were still eligible. RDI was calculated as the ratio of actual dose intensity (cumulative administered dose/treatment duration) and planned dose intensity (cumulative planned dose/planned treatment duration). The association of both RDI Results: Overall, 142 patients were deemed eligible. Of these patients, 98 (69.0%) were treated with palbociclib plus fulvestrant, 44 (31.0%) with palbociclib plus aromatase inhibitors, and 73 (51.4%) in the first-line setting. The median number of administered palbociclib cycles was 8 (range: 1-24) and 61 patients (43.0%) required at least a first-level dose reduction (29 within 3 months). Furthermore, the median time to first dose reduction was 3.22 months, with neutropenia being responsible for 85.24% of first-level dose reductions. In the whole cohort, median RDI was 90.5% (95.1% for patients without dose reduction and 80% for those who had received a dose reduction). Notably, 28 patients (19.7%) experienced a RDI Conclusions: In our analysis, baseline weight and WBC were statistically associated with a RDI Citation Format: Giacomo Pelizzari, Elisa Bertoli, Marco Giavarra, Carla Corvaja, Lorenzo Gerratana, Debora Basile, Michele Bartoletti, Camilla Lisanti, Lucia Bortot, Silvia Buriolla, Mattia Garutti, Debora Avoledo, Marta Bonotto, Lucia Da Ros, Silvia Bolzonello, Mauro Mansutti, Paola Di Nardo, Gianpiero Fasola, Simon Spazzapan, Alessandro M Minisini, Fabio Puglisi. Predictors of relative dose intensity and early dose reduction in patients with metastatic breast cancer treated with palbociclib and endocrine therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-08.

Diabetic foot syndrome (DFS) is a complex disease. The best outcomes are reported with the multi-disciplinary team (MDT) approach, where each member works collaboratively according to his/her expertise. However, which health provider should act as the team leader (TL) has not been determined. The TL should be familiar with the management of diabetes, related complications and comorbidities. He/she should be able to diagnose and manage foot infections, including prompt surgical treatment of local lesions, such as abscesses or phlegmons, in an emergent way in the first meeting with the patient. According to the Organization for Economic Co-operation and Development (OECD) reports, Italy is one of countries with a low amputation rate in diabetic patients. Many factors might have contributed to this result, including 1)the special attention directed to diabetes by the public health system, which has defined diabetes as a "protected disease", and accordingly, offers diabetic patients, at no charge, the best specialist care, including specific devices, and 2)the presence of a network of diabetic foot (DF) clinics managed by diabetologists with medical and surgical expertise. The health care providers all share a "patient centred model" of care, for which they use their internal medicine background and skills in podiatric surgery to manage acute or chronic needs in a timely manner. Therefore, according to Italian experiences, which are fully reported in this document, we believe that only a skilled diabetologist/endocrinologist should act as a TL. Courses and university master's degree programmes focused on DF should guarantee specific training for physicians to become a TL.

Introduction: The transition from adolescence to adulthood involves a variety of physical, behavioral, and social transformations, often including tobacco use. Because understanding smoking at this stage is important for tobacco control, we aimed to analyze the prevalence of cigarette smoking in the Brazilian youth population.Methods: This study included participants aged 16–25 years from all Brazilian capitals. A standardized questionnaire was administered by trained healthcare professionals to collect information about sociodemographic status, sexual behavior, and tobacco use. The samples from each capital were weighted by age range and sex.Results: Of the 8,581 participants, 15.1% were current smokers, and 20.0% were former smokers; the average age at first tobacco use was 15.5 years. The prevalence of smoking in men was higher than that in women (20.1 vs. 10.3%, p < 0.01). Education level was associated with current smoking and former smoking. Participants with an elementary education level had a higher smoking prevalence (PR: 5.84, 95%, CI: 4.29–7.95) than those with a secondary education (PR: 2.19, 95% CI: 1.63–2.93) and those with higher education. Those without current partners (PR: 1.27, 95% CI: 1.03–1.56) also had a higher prevalence of smoking than those with partners, and participants who had a previous same-sex sexual experience smoked more (PR: 2.29, 95% CI: 1.78–2.96) than those who did not. In addition, regular use of alcohol was associated with higher prevalence of cigarette smoking (PR: 5.65, 95% CI: 4.03–7.90) than a lack of alcohol consumption. Skin color and socioeconomic class did not exhibit significant relationships with tobacco use patterns.Conclusions: Smoking was associated with education level regardless of social class, and some specific behaviors associated with a same-sex sexual experience were associated with a higher prevalence of smoking. These findings are important for formulating policies and directing actions to combat and prevent smoking among young populations.

Background To prevent flu spread, Italian healthcare workers (HCWs) are annually recommended and given free flu vaccination. This measure of healthcare system protection resulted to be fundamental during COVID-19 pandemic to prevent staff shortage issue. Being the minimum coverage target set at 75%, we decided to evaluate vaccination adherence among HCWs at Udine University hospital. Methods The 2020 vaccination campaign started 4 weeks earlier than usual and was based on a multiple offer strategy including a daily-dedicated clinic, in-ward administrations along with wide vaccination agenda promotion within hospital. The prevalence and the characteristics of vaccinated HCWs were compared with the same 2019 data. Results During 2020, 1868 out of 3839 (48.7%) of HCWs were vaccinated, compared to 29.1% in 2019 (p < 0.0001). Doctors and residents were the most vaccinated categories in both years, being respectively 64.7% and 67.2% in 2020 vs 45.0% and 52.4% in 2019 (p < 0.0001). Midwives showed the best improvement in coverage passing from 44.4% to 20.4% (p = 0.0096). HCWs working in emergency areas and intensive care unit reached the highest adherence in 2020 (61.3%) and the best improvement compared to 2019 as well (37.9%; p < 0.0001). Conclusions Even if the target was not reached, strategies adopted for 2020 vaccination campaign significantly increased HCWs adherence. COVID-19 contribution in this achievement cannot be ruled out, possibly representing a strong reinforcing element for HCWs awareness towards infectious disease prevention. Key messages Despite the improvement in vaccination adherence, HCWs flu vaccination coverage still remains a concerning issue to be addressed. Increased flu shot adherence reached during COVID-19 pandemic should be not only a target to be maintained but even improved next year getting closer to herd immunity.

In fundamental papers from 1962, Heffener and Haus showed that it is not possible to construct a linear noiseless amplifier [Proc. IRE 50, 1604 (1962)PIREAE0096-839010.1109/JRPROC.1962.288130; Phys. Rev. Lett. 128, 2407 (1962)PHRVAO0031-899X10.1103/PhysRev.128.2407]. This implies that amplifier intrinsic noise sources induce random perturbations on the phase of the incoming optical signal, which translates into spectral broadening. Achieving the minimum induced phase fluctuation requires a phase measurement method that introduces minimum uncertainty, i.e., optimum phase measurement. We demonstrate that a measurement method based on heterodyne detection and extended Kalman filtering approaches optimum phase measurement in the presence of amplifier noise. A penalty of 5 dB (numerical) and 15 dB (experimental) compared to quantum limited spectral broadening is achieved. Spectral broadening reduction of 44 dB is achieved, compared to when using the widely employed phase measurement method, based purely on the argument of the signal field. Our results reveal new scientific insights by demonstrating a phase measurement method that enables to approach minimum phase fluctuation, induced by amplifier noise. An impact is envisioned for phase-based optical sensing systems, as optical amplification could increase sensing distance with minimum impact on the phase.

The paper presents recent advances in the design of controllable, highly accurate, and multi–band Raman gain profiles. The ultra–wideband programmable gain profiles are implemented using a machine learning approach based on the mapping between gain profiles and pump powers.

Purpose: Intracranial carotid artery occlusion represents an underinvestigated cause of acute ischemic stroke as well as an indication for mechanical thrombectomy. We investigated baseline and procedural characteristics, outcomes and predictors of outcome in patients with acute ischemic stroke secondary to intracranial carotid artery occlusion. Methods: A retrospective analysis of the Italian Registry of Endovascular Treatment in Acute Stroke was performed. Patients with intracranial carotid artery occlusion (infraclinoid and supraclinoid) with or without cervical artery occlusion but with patent intracranial arteries were included. The 3‑month functional independence, mortality, successful reperfusion and symptomatic intracranial hemorrhage were evaluated. Results: Intracranial carotid artery occlusion with patent intracranial arteries was diagnosed in 387 out of 4940 (7.8%) patients. The median age was 74 years and median baseline National Institute of Health Stroke Scale (NIHSS) was 18. Functional independence was achieved in 130 (34%) patients, successful reperfusion in 289 (75%) and symptomatic intracranial hemorrhage in 33 (9%), whereas mortality occurred in 111 (29%) patients. In univariate analysis functional independence was associated with lower age, lower NIHSS at presentation, higher rate of successful reperfusion and lower rate of symptomatic intracranial hemorrhage. Multivariable regression analysis found age (odds ratio, OR:1.03; P = 0.006), NIHSS at presentation (OR: 1.07; P < 0.001), diabetes (OR: 2.60; P = 0.002), successful reperfusion (OR:0.20; P < 0.001) and symptomatic intracranial hemorrhage (OR: 4.17; P < 0.001) as the best independent predictors of outcome. Conclusion: Our study showed a not negligible rate of intracranial carotid artery occlusion with patent intracranial arteries, presenting mostly as severe stroke, with an acceptable rate of 3‑month functional independence. Age, NIHSS at presentation and successful reperfusion were the best independent predictors of outcome. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

Background Since the beginning of coronavirus disease 2019 (COVID-19), the development of predictive models has sparked relevant interest due to the initial lack of knowledge about diagnosis, treatment, and prognosis. The present study aimed at developing a model, through a machine learning approach, to predict intensive care unit (ICU) mortality in COVID-19 patients based on predefined clinical parameters. Results Observational multicenter cohort study. All COVID-19 adult patients admitted to 25 ICUs belonging to the VENETO ICU network (February 28th 2020-april 4th 2021) were enrolled. Patients admitted to the ICUs before 4th March 2021 were used for model training (“training set”), while patients admitted after the 5th of March 2021 were used for external validation (“test set 1”). A further group of patients (“test set 2”), admitted to the ICU of IRCCS Ca’ Granda Ospedale Maggiore Policlinico of Milan, was used for external validation. A SuperLearner machine learning algorithm was applied for model development, and both internal and external validation was performed. Clinical variables available for the model were (i) age, gender, sequential organ failure assessment score, Charlson Comorbidity Index score (not adjusted for age), Palliative Performance Score; (ii) need of invasive mechanical ventilation, non-invasive mechanical ventilation, O2 therapy, vasoactive agents, extracorporeal membrane oxygenation, continuous venous-venous hemofiltration, tracheostomy, re-intubation, prone position during ICU stay; and (iii) re-admission in ICU. One thousand two hundred ninety-three (80%) patients were included in the “training set”, while 124 (8%) and 199 (12%) patients were included in the “test set 1” and “test set 2,” respectively. Three different predictive models were developed. Each model included different sets of clinical variables. The three models showed similar predictive performances, with a training balanced accuracy that ranged between 0.72 and 0.90, while the cross-validation performance ranged from 0.75 to 0.85. Age was the leading predictor for all the considered models. Conclusions Our study provides a useful and reliable tool, through a machine learning approach, for predicting ICU mortality in COVID-19 patients. In all the estimated models, age was the variable showing the most important impact on mortality.

Objective: To describe the angiographic characteristics of peripheral arterial disease (PAD) in persons with diabetic foot ulcers (DFUs) on dialysis treatment. Method: The study is a retrospective analysis of patients with DFUs and PAD who had been referred to our diabetic foot clinic. All patients had been managed by a pre-set limb salvage protocol including revascularisation of the affected limb. Arterial lesions (stenosis between 50–99% and occlusions) were retrospectively evaluated through angiogram analysis. According to the presence or not of dialysis, patients were divided into two patient groups: renal-diabetic foot (RDF) and diabetic foot (DF). Distribution of PAD and immediate revascularisation outcome (technical revascularisation outcome) for RDF and DF were separately reported and compared. Results: The sample included 239 patients: mean age was 71.8 years; 72.4% were male; 87.4% had type 2 diabetes; mean diabetes duration was 21.4 years; and the mean HbA1c was 63±22mmol/mol. The RDF group compared with the DF group reported higher numbers of vessels affected (n=5±1.6 versus 3.9±1.5, respectively, pConclusion: In this study, RDF patients showed a widespread distribution of arterial lesions with a higher involvement of foot arteries in comparison with DF patients. BTA arterial disease was found to be an independent predictor of revascularisation failure.

BACKGROUND AND PURPOSE: Woven EndoBridge (WEB) devices are increasingly used to treat intracranial aneurysms. A1 asymmetry contributes to anterior communicating artery aneurysm formation and to treatment instability after coiling. We sought to evaluate whether A1 asymmetry had an impact on angiographic outcome in anterior communicating artery aneurysms treated with the WEB. MATERIALS AND METHODS: Anterior communicating artery aneurysms treated between July 2012 and July 2020 with the WEB from an institutional review board–approved database were reviewed. A1 asymmetry was categorized as the following: absence of the A1 segment on 1 side (unilateral A1) versus bilateral A1. Univariate and multivariable analyses assessed independent predictors of adequate (WEB Occlusion Scale A, B, and C) and complete occlusion (WEB Occlusion Scale A and B). RESULTS: Forty-eight individual aneurysms (47 patients) were included in the final analysis, of which 16 (33%) were acutely ruptured. The mean size was 6.5 (SD, 2.2) mm. Adequate and complete occlusion was achieved in 33 (69%) and 30 (63%) cases, respectively. Unilateral A1 was associated with significantly higher rates of adequate (92% versus 60% for bilateral A1; P = .03) and complete occlusion (92% versus 50% for bilateral A1; P < .01). Multivariable logistic regression confirmed unilateral A1 as an independent predictor of both adequate (OR = 10.6; 95% CI, 1.6–220.7; P = .04) and complete occlusion (OR = 9.5, 95% CI, 1.5–190.2; P = .04. A sensitivity analysis comparing unilateral “functional” A1 with bilateral “functional” A1 showed similar results. WEB shape modification was not influenced by the unilateral A1 configuration (P = .70). CONCLUSIONS: Anterior communicating artery aneurysms with a unilateral A1 configuration treated with WEB devices are associated with better angiographic outcome than those with bilateral A1. This finding supports the hypothesis that WEB devices are resistant to unilateral flow in the aneurysm as opposed to coils.

BACKGROUND AND PURPOSE: The Woven Endobridge has proved to be a safe and effective treatment, especially for wide-neck intracranial aneurysms. The recent fifth-generation Woven Endobridge came with smaller devices. The purpose of this study was to assess the safety and efficiency of Woven Endobridge treatment of small and very small aneurysms. MATERIALS AND METHODS: Between September 2017 and March 2020, all consecutive patients treated with a 3- or 3.5 mm-width Woven Endobridge device were included in this retrospective intention-to-treat study. Clinical and radiologic findings were evaluated at immediate and last-available follow-up. Angiographic outcome was assessed by an external expert reader. RESULTS: One hundred twenty-eight aneurysms were treated with a fifth-generation Woven Endobridge device including 29 with a width of ≤3.5 mm. Ten aneurysms were ruptured (34%). In 3 cases (10%), Woven Endobridge treatment could not be performed because the aneurysm was still too small for the smallest available Woven Endobridge device and another endovascular strategy was chosen. The median follow-up time was 11.2 months. Complete and adequate occlusion was obtained in 71% and 90% of the treated aneurysms, respectively. Retreatment was needed in 2 cases (10%). Symptomatic ischemic complications leading to transient neurologic deficits occurred in 2 cases (7%) (1 procedure-related and 1 device-related) but with full spontaneous recovery at discharge. CONCLUSIONS: The fifth-generation Woven Endobridge device seems to be a safe and technically feasible treatment for both ruptured and unruptured small and very small intracranial aneurysms, with satisfactory occlusion rates on midterm follow-up. However, further study is needed to evaluate longer-term efficiency.

Highlights • Vascular myelopathies include different aetiology and mechanism of damage. • The level of the lesion and the localization within the SC correlates with the clinical symptoms. • CT, MRI and angiography are essential for diagnosis and treatment playing a complementary role. • MRI is the gold standard for the evaluation of spinal cord lesions. • Spinal angiography is the gold standard for evaluation of spinal cord vasculature and vascular malformations., Background Vascular lesions of the spinal cord are rare but potentially devastating conditions whose accurate recognition critically determines the clinical outcome. Several conditions lead to myelopathy due to either arterial ischemia, venous congestion or bleeding within the cord. The clinical presentation varies, according with the different aetiology and mechanism of damage. Purpose The aim is to provide a comprehensive review on the radiological features of the most common vascular myelopathies, passing through the knowledge of the vascular spinal anatomy and the clinical aspects of the different aetiologies, which is crucial to promptly address the diagnosis and the radiological assessment.

We propose a Convolutional Neural Network (CNN) to learn the mapping between the 2D power profiles, (distance and frequency), and the Raman pumps. Using the CNN, the pump powers and wavelengths for arbitrary 2D profiles can be determined with high accuracy.

Graft-versus-host disease (GVHD) is an immune triggered process leading to severe immune dysregulation and organ dysfunction until death and it is one of the worst medical complications after a transplant. Patients with GVHD may have several neurological alterations: during this acute severe phase there is coexistence of various and nonspecific neurological symptoms. We are reporting a case of a 53 year old woman with severe GVHD after bone marrow transplant with acute neurological signs and symptoms. MRI study showed findings consistent with Posterior reversible encephalopathy syndrome and Wernicke encephalopathy. Keywords: Acute graft-versus-host disease, Posterior reversible encephalopathy syndrome, Wernicke encephalopathy, Magnetic resonance imaging

To compare outcomes of minor stroke patients with intracranial vessel occlusions (IVO) underwent mechanical thrombectomy (MT) versus those treated with intravenous thrombolysis alone (IVT).We retrospectively reviewed two large prospective stroke databases from two European centers searching for patients admitted with minor stroke (i.e. NIHSS Score░≤░5), baseline mRS░=░0 and occlusion of the M1-M2 segment of the middle cerebral artery (MCA). Groups receiving (A) IVT alone and (B) MT+/-IVT were compared. Primary outcome measures were MT safety, successful recanalization rate (mTICI 2b-3) and NIHSS shift (discharge NIHSS minus admission NIHSS); secondary outcomes included discharge rates and excellent outcome (mRS 0-1) at 3 months. Univariate and multivariate analyses were performed.Thirty-two patients were enrolled in Group B (19░MT alone; 13 MT░+░IVT) and 24 in Group A. Successful recanalization (mTICI 2b-3) was obtained in 100% of cases in Group B vs 38% in Group A. Symptomatic hemorrhagic transformation rate did not differ between the two groups. Multivariate analysis reported MT as the only predictor of early (░12░h) favorable NIHSS shift and lower NIHSS at discharge. Moreover, discharge at home and excellent outcome at 3-month follow-up were statistically associated with MT.MT in patients with minor strokes and intracranial vessel occlusion (IVO) is safe and can determine a rapid improvement of NIHSS Score. MT seems also associated with a higher rate of patients discharged at home after hospitalization and better clinical outcome at 3-month follow-up. Larger randomized trials are warranted to confirm these results.

To evaluate, by Magnetic Resonance Imaging, if there is a typical pattern or severity of PRES in transplanted children for hemoglobinopathy. Secondary point was to investigate the pattern and severity of PRES in children with thalassemia-THAL and sickle-cell disease-SCD after autologous hematopoietic stem cell transplantation (aHSCT). Finally, we evaluate the presence of atypical PRES presentation and the involved area of central nervous system. Two neuroradiologists analyzed retrospectively MRI of 21 transplanted children for THAL or SCD treated with CI, with neurological symptoms and signs of PRES. The Bartynski and Boardman classification has been used for PRES pattern while McKinney scale for PRES severity. Fisher Exact Probability test or Chi-square test were used to compare the categorical data. In the 21 transplanted children the PRES severity was typically mild (85.7%) without preferring radiological pattern at MRI. The analysis didn't show significant association between PRES pattern or PRES severity and previous hemoglobinopathy (THAL or SCD). No atypical PRES presentation has been found. PRES severity in transplanted children for hemoglobinopathy is typically mild. Notwithstanding children affected by SCD have a damage on the capillary endothelium, after aHSCT our data didn't show a different PRES severity and pattern than THAL children. Keywords: PRES, aHSCT, MRI, Thalassemia, Sickle-cell disease, Hemoglobinopathy

Background Osimertinib became the standard treatment for patients with untreated EGFR-mutant advanced non-small cell lung cancer (aNSCLC) following results reported in the phase III randomized FLAURA trial. Because of strict exclusion criteria, patient populations included in pivotal trials are only partially representative of real-world patients. Methods We designed an observational, prospective, multicenter study enrolling patients with EGFR-mutant aNSCLC receiving first-line osimertinib to evaluate effectiveness, safety, and progression patterns in the real-world. Results At data cutoff, 126 White patients from nine oncology centers were included. At diagnosis, 16 patients (12.7%) had a performance status (PS) ≥2 and 38 (30.2%) had brain metastases. Overall response rate (ORR) was 73%, disease control rate (DCR) 96.0%. After a median follow-up of 12.3 months, median time to treatment discontinuation (mTTD) was 25.3 months, median progression-free-survival (mPFS) was 18.9 months and median overall survival (mOS) was not reached (NR). One hundred and ten patients (87%) experienced adverse events (AEs), 42 (33%) of grade 3–4, with venous thromboembolism (VTE) as the most common (n = 10, 7.9%). No difference in rates of VTE was reported according to age, PS, comorbidity, and tumor load. We observed longer mTTD in patients without symptoms (NR vs. 18.8 months) and with fewer than three metastatic sites at diagnosis (NR vs. 21.4 months). Patients without brain metastases experienced longer mPFS (NR vs. 13.3 months). No difference in survival outcome was observed according to age, comorbidity, and type of EGFR mutation. Isolated progression and progression in fewer than three sites were associated with longer time to treatment discontinuation (TTD). Conclusion Osimertinib confirmed effectiveness and safety in the real world, although thromboembolism was more frequent than previously reported.

Ultra-wideband (UWB) optical communication systems, envision to operate in O+E+S+C+l band, are a viable solution to cope with the network’s exponential traffic growth [1] . One of the main challenges to provide beyond C-band transmission is a lack of optical amplifiers. Since the erbium-doped fiber amplifiers (EDFAs) are limited to C and L bands only, new technologies will have to be explored to cover the remaining bands. Some examples of amplifiers able to provide amplification beyond C–band are: bismuth doped fibre amplifiers (BDFA) [2] , semiconductor optical amplifiers, (SOAs) [3] and Raman amplifiers (RAs) [4] . Compared to the solutions based on BDFA and SOA, optical amplifiers based RAs offer a higher degree of commercial maturity [5] . Most importantly, RA amplifiers can provide gain in any band provided a proper allocation of pump powers and wavelength.

This paper presents an overview of fiber nonlinearity compensation (NLC) methods based on digital signal processing (DSP) algorithms assisted by forward error correction (FEC) decoders in coherent optical receivers. The work focuses on DSP schemes that are able to improve the performance of NLC by using hard or soft information feedback from FEC-decoders. Challenges and new research directions are discussed.

An essential element for many management decisions is an accurate forecasting. There are several methods and techniques to forecast time series that include traditional forecasting techniques with theoretical foundations in statistics. These methods present some obstacles and complexities to overcome; one of the most important ones is the difficulty to select the model that can provide the best adjustment for a specific dataset, many attempts have to be usually done until the best model can be obtained. Considering this scenario, different machine learning techniques have been recently used in this problem, such as Artificial Neural Network (ANN), Evolutionary Computation (EC), in particular, Genetic Programming (GP), which is considered a promising approach to forecast noisy complex series (Kaboudan, 2000), there are many other works founded in the literature that use (GP) to Time Series Prediction. On the other hand, recently advances in the machine learning field show that the application of the Boosting algorithm is a powerful approach to increase the accuracy of forecasting methods. Boosting algorithm was proposed and developed by Freund and Schapire (1996). According to Allwein et al. (2000), Boosting is a method of finding a highly accurate hypothesis by combining many "weak" hypotheses, each of which is only moderately accurate. Paris et al. (2004) proposed GPBoost that uses the Boosting algorithm with the GP as base learner. We have proposed a new formula for the updating of the weights and for obtain the final hypothesis of the predictor. This algorithm was called of Boosting Correlation Coefficients (BCC) and it is based on the correlation coefficient instead of the loss function used by traditional Boosting algorithms. To evaluate this approach we conducted three experiments. In the first one, the BCC was used to forecast real time series, in this experiment the mean squared error (MSE) has been used to compare the accuracy of the proposed method against the results obtained by GP, GPBoost and the traditional statistical methodology (ARMA). In the second, to prove the efficiency of the proposed methodology a widespread Monte Carlo simulation was done covering the entire ARMA spectrum, in which artificial series were generated from the parametric space of the principal ARMA models, they are AR(1), AR(2), MA(1), MA(2) e ARMA(1,1). The database generated was composed by 214.000 time series with 150 observations each one. The training set was composed by 90% of date and the others 10% composes the test set. The results were compared out of sample and the BCC showed better performance than ARMA O pe n A cc es s D at ab as e w w w .in te ch w eb .o rg

Bone marrow (BM) microenvironment contributes to the regulation of normal hematopoiesis through a finely tuned balance of self-renewal and differentiation processes, cell-cell interaction and secretion of cytokines that during leukemogenesis are altered and favor tumor cell growth. In pediatric acute myeloid leukemia (AML), chemotherapy is the standard of care, but still >30% of patients relapse. The need to accelerate the evaluation of innovative medicines prompted us to investigate the mesenchymal stromal cells (MSCs) role in the leukemic niche to define its contribution to the mechanisms of leukemia escape. We generated humanized three-dimensional (3D) niche with AML cells and MSCs derived from either patients (AML-MSCs) or healthy donors. We observed that AML cells establish physical connections with MSCs, mediating a reprogrammed transcriptome inducing aberrant cell proliferation and differentiation, and severely compromising their immunomodulatory capability. We confirmed that AML cells modulate h-MSCs transcriptional profile promoting functions similar to the AML-MSCs when co-cultured in vitro, thus facilitating leukemia progression. Conversely, MSCs derived from BM of patients at time of disease remission showed recovered healthy features, at transcriptional and functional levels, including the secretome. We proved that AML blasts alter MSCs activities in the BM niche, favoring disease development and progression. We discovered that a novel AML-MSCs selective CaV1.2 channel blocker drug, Lercanidipine, is able to impair leukemia progression in 3D niche both in vitro and when implanted in vivo, if used in combination with chemotherapy, supporting the hypothesis that synergistic effects can be obtained by dual targeting approaches.

The multidisciplinary management represents a crucial part of the care for cancer patients, resulting in better clinical and process outcomes, with evidence of improved survival among different cancer primary sites, including breast. According with international recommendations established by the European Society of Breast Cancer Specialists (EUSOMA), all breast-cancer patients have to be evaluated by a multidisciplinary team including radiologist, pathologist, surgeon, medical oncologist and radiation oncologist. Thus, variations in clinical practice of each specialty should be discussed and shared with all team members to guarantee a fruitful cooperation among the involved specialists. During the last decades, radiation treatment was deeply changed by the evidence-based adoption of hypofractionated radiotherapy (HFRT) as standard of treatment in patients with early-stage breast cancer undergoing conservative surgery. Moreover, mature randomized data have showed that partial breast irradiation (PBI) is an effective and safe alternative to whole breast irradiation in selected patients with low-risk early-stage breast cancer. Based on this background, we reviewed indications and critical issues of HFRT and PBI analyzing impact of their adoption from a multidisciplinary perspective.

Stroke remains one of the leading causes of death and disability in Europe. The European Stroke Action Plan (ESAP) defines four main targets for the years 2018 to 2030. The COVID-19 pandemic forced the use of innovative technologies and created pressure to improve internet networks. Moreover, 5G internet network will be helpful for the transfer and collecting of extremely big databases. Nowadays, the speed of internet connection is a limiting factor for robotic systems, which can be controlled and commanded potentially from various places in the world. Innovative technologies can be implemented for acute stroke patient management soon. Artificial intelligence (AI) and robotics are used increasingly often without the exception of medicine. Their implementation can be achieved in every level of stroke care. In this article, all steps of stroke health care processes are discussed in terms of how to improve them (including prehospital diagnosis, consultation, transfer of the patient, diagnosis, techniques of the treatment as well as rehabilitation and usage of AI). New ethical problems have also been discovered. Everything must be aligned to the concept of “time is brain”.

OBJECTIVE Different etiologies of extracranial internal carotid artery steno-occlusive lesions (ECLs) in patients with acute ischemic stroke (AIS) and tandem occlusion (TO) have been pooled together in randomized trials. However, carotid atherosclerosis (CA) and carotid dissection (CD), the two most common ECL etiologies, are distinct nosological entities. The authors aimed to determine if ECL etiology has impacts on the endovascular management and outcome of patients with TO. METHODS A multicenter, retrospective study of prospectively collected data was conducted. AIS patients were included who had TO due to internal CA or CD and ipsilateral M1 middle cerebral artery occlusion and underwent endovascular treatment (EVT). Comparative analyses including demographic data, safety, successful recanalization rates, and clinical outcome were performed according to EVT and ECL etiology. RESULTS In total, 214 AIS patients with TOs were included (77.6% CA related, 22.4% CD related). Patients treated with a retrograde approach were more often functionally independent at 3 months than patients treated with an antegrade approach (OR 0.6, 95% CI 0.4–0.9). Patients with CD-related TOs achieved 90-day clinical independence more often than patients with CA-related TOs (OR 1.4, 95% CI 1.1–2.0). Emergency stenting use was associated with good 3-month clinical outcome only in patients with CA-related TOs (OR 1.4, 95% CI 1.1–2.1). Symptomatic intracranial hemorrhage (sICH) occurred in 10.7% of patients, without differences associated with ECL etiology. CONCLUSIONS ECL etiology impacts both EVT approach and clinical outcome in patients with TOs. Patients with CD-related TO achieved higher 3-month functional independence rates than patients with CA-related TOs. A retrograde approach can be desirable for both CA- and CD-related TOs, and emergency stenting is likely better justified in CA-related TOs.

Il piede diabetico rappresenta una delle complicanze più severe del Diabete Mellito (DM) oltre che la prima causa di amputazione non traumatica degli arti inferiori; si stima, infatti, che ogni anno più di un milione di persone con DM siano sottoposte a trattamento demolitivo come conseguenza di questa condizione. Nonostante l’esistenza di linee guida nazionali ed internazionali sul management del piede diabetico, per alcuni aspetti gestionali le raccomandazioni proposte non raggiungono un forte livello di evidenza. Ciò rappresenta una potenziale fonte di incertezza decisionale, ma anche uno spunto da cui partire per chiarire aspetti legati al management del piede diabetico nella realtà italiana. L’obiettivo del presente documento è, quindi, quello di riadattare le raccomandazioni internazionali sulla gestione del piede diabetico alla luce dell’opinione di esperti italiani.

A machine learning framework predicting pump powers and noise figure profile for a target distributed Raman amplifier gain profile is experimentally demonstrated. We employ a single-layer neural network to learn the mapping from the gain profiles to the pump powers and noise figures. The obtained results show highly-accurate gain profile designs and noise figure predictions, with a maximum error on average of ~0.3dB. This framework provides the comprehensive characterization of the Raman amplifier and thus is a valuable tool for predicting the performance of the next-generation optical communication systems, expected to employ Raman amplification., 4 pages, 5 figures

The cloud edge data center will enable reliable and low latency options for the network, and the interconnection among these data-centers will demand a scalable low-complexity scheme. An intensity-modulated and directed detected transmission system is an attractive solution, but chromatic dispersion is the main limitation for higher symbol rate systems. To overcome this challenge, we have proposed and experimentally demonstrated a receiver with shared-complexity between optical and digital domains that enables 80 km transmission reach below KP4 FEC limit for a 32 GBd on-off keying signal. The optical stage consists of optical filters that slices the signal into smaller sub-bands and each is detected by a photodetector. A feedforward neural network and reservoir computing are compared to reconstruct the full signal from the slices and mitigate the chromatic dispersion. Both equalizers have shown similar performance with the advantage of the reservoir computing requiring fewer inputs and easier training process. In this work, we have compared the linear and nonlinear activation functions in the feedforward neural network to investigate the gain of using a nonlinear equalizer. The maximum transmission reach is reduced almost to half, $\approx$ 45 km, when using the linear. The performance is also reduced if a reduced number of slices is used in the receiver, as we have demonstrated. In this case, using 2 slices to reduce the complexity of the system, instead of the total 4, we have shown a $\approx$ 55 km transmission reach below KP4 FEC limit. In this work we have also provided a numerical comparison with 4x8 GBd subcarriers system. The results have shown a 40 km increase in transmission reach compared to the proposed optoelectronic system. The trade-off between performance and complexity should be analyzed for each case, as a different hardware is required in each situation.

The benefit of mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) and baseline mild neurological symptoms remains unclear. The purpose of this study was to evaluate the effectiveness of MT in this subgroup of patients. The databases of 9 high-volume Italian stroke centers were retrospectively screened for patients with LVO in the anterior circulation and a baseline National Institute of Health Stroke Scale (NIHSS) score ≤ 5 that received either immediate MT or best medical management (BMM) with the possibility of rescue MT upon neurological worsening. Primary outcome measure was a modified Rankin Scale score of 0–1 at 90 days. Propensity score matching (PSM) analysis was used to estimate the treatment effect of immediate MT compared to BMM/rescue MT. Two hundred and seventy-two patients received immediate MT (MT group). The BMM/rescue MT group included 41 patients. The primary outcome was achieved in 78.6% (n = 246) of overall patients, with a higher proportion in the MT group (80.5% vs. 65.9%, p = 0.03) in unadjusted analysis. After PSM, patients in the MT group had a 19.5% higher chance of excellent outcome at 90 days compared to the BMM/Rescue MT group with a similar risk of death from any cause. Our experience is in favor of a potential benefit of MT also in patients with LVO and a NIHSS score ≤ 5 at the time of groin puncture. Nonetheless, this issue waits for a clear-cut recommendation in a dedicated clinical trial.

We present a convolutional neural network architecture for inverse Raman amplifier design. This model aims at finding the pump powers and wavelengths required for a target signal power evolution in both distance along the fiber and in frequency. Using the proposed framework, the prediction of the pump configuration required to achieve a target power profile is demonstrated numerically with high accuracy in C-band considering both counter-propagating and bidirectional pumping schemes. For a distributed Raman amplifier based on a 100 km single-mode fiber, a low mean set (0.51, 0.54, and 0.64 dB) and standard deviation set (0.62, 0.43, and 0.38 dB) of the maximum test error are obtained numerically employing two and three counter-, and four bidirectional propagating pumps, respectively.

Background Endocrine therapy (ET) plus cyclin-dependent-kinases 4/6 inhibitors (CDK4/6i) represents the standard treatment for luminal-metastatic breast cancer (MBC). However, prospective head-to-head comparisons are still lacking for 1st line (L) options, and it is still crucial to define the best strategy between 1st and 2nd L. Materials and methods 717 consecutive luminal-MBC pts treated between 2008 and 2020 were analyzed at the Oncology Department of Aviano and Udine, Italy. Differences about survival outcomes (OS, PFS and PPS) were tested by log-rank test. The attrition rate (AR) between 1st and 2ndL was calculated. Results At 1stL, pts were treated with ET (49%), chemotherapy (CT) (31%) and ET-CDKi (20%) while, at 2ndL, 33% received ET, 33% CT and 8% ET-CDKi. Overall AR was 10%, 7% for CT, 8% for ET and 17% for ET-CDKi. By multivariate analysis, 1stL ET-CDK4/6i showed a better mPFS1 and OS. Moreover, 2ndL ET-CDK4/6i demonstrated better mPFS2 compared to ET and CT. Notably, 1stL ET-CDKi resulted in higher mPFS than 2ndL ET-CDKi. Intriguingly, 1stL ET-CDK4/6i was associated with worse mPPS compared to CT and ET. Secondarily, 1stL ET-CDK4/6i followed by CT had worse OS compared to 1stL ET-CDK4/6i followed by ET. Notably, none of baseline characteristics at 2ndL influenced 2ndL treatment choice (ET vs. CT) after ET-CDKi. Conclusion Our real-world data demonstrated that ET-CDKi represents the best option for 1stL luminal-MBC compared to ET and CT. Also, the present study pointed out that 2ndL ET, potentially combined with other molecules, could be a feasible option after CDK4/6i failure, postponing CT on later lines., Highlights • To define the best treatment strategy for 1st and 2nd L is crucial for luminal mBC. • 1st L CDK4/6i-based therapies represent the standard treatment in luminal mBC. • This study confirmed the key role of 1st L CDK4/6i on a real-world cohort. • This study suggested a preeminent role for ET after first-line CDK4/6i. • The 2nd line ET with other molecules could allow to further postpone CT.

IntroductionThe efficacy of non-invasive ventilation (NIV) in acute respiratory failure secondary to SARS-CoV-2 infection remains controversial. Current literature mainly examined efficacy, safety and potential predictors of NIV failure provided out of the Intensive Care Unit (ICU). On the contrary, the outcomes of ICU patients, intubated after NIV failure, remain to be explored. The aims of the present study are: 1) investigating in-hospital mortality in coronavirus disease 2019 (COVID-19) ICU patients receiving endotracheal intubation after NIV failure and 2) assessing whether the length of NIV application affects patient survival. MethodsThis observational multicenter study included all consecutive COVID-19 adult patients, admitted into the twenty-five ICUs of the COVID-19 VENETO ICU network (February-April 2020), who underwent endotracheal intubation after NIV failure. ResultsAmong the 704 patients admitted to ICU during the study period, 280 (40%) presented the inclusion criteria and were enrolled. The median age was 69 [60-76] years; 219 patients (78%) were male. In-hospital mortality was 43%. Only the length of NIV application before ICU admission (OR 2.03 (95% CI 1.06 - 4.98), p = 0.03) and age (OR 1.18 (95% CI 1.04 - 1.33), p < 0.01) were identified as independent risk factors of in-hospital mortality; whilst the length of NIV after ICU admission did not affect patient outcome. ConclusionsIn-hospital mortality of ICU patients intubated after NIV failure was 43%. Days on NIV before ICU admission and age were assessed to be potential risk factors of greater in-hospital mortality.

Background and Objectives: The term acrometastases (AM) refers to secondary lesions sited distally to the elbow and knee, representing 0.1% of all bony metastases. By frequency, pulmonary cancer and gastrointestinal and genitourinary tract neoplasms are the most responsible for the reported AM. Improvements in oncologic patient care favor an increase in the incidence of such rare cases. We performed a systematic review of acrometastases to the hand to provide further insight into the management of these fragile patients. We also present a peculiar case of simultaneous acrometastasis to the ring finger and pathological vertebral fracture. Material and Methods: A literature search according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement was conducted using the PubMed, Google Scholar, and Scopus databases in December 2020 on metastasis to the hand and wrist, from 1986 to 2020. MeSH terms included acrometastasis, carpal metastasis, hand metastasis, finger metastasis, phalangeal metastasis, and wrist metastasis. Results: In total, 215 studies reporting the follow-up of 247 patients were analyzed, with a median age of 62 years (range 10–91 years). Overall, 162 out of 247 patients were males (65.6%) and 85 were females (34.4%). The median reported follow-up was 5 months (range 0.5–39). The median time from primary tumor diagnosis to acrometastasis was 24 months (range 0.7–156). Acrometastases were located at the finger/phalanx (68.4%), carpal (14.2%), metacarpal (14.2%), or other sites (3.2%). The primary tumors were pulmonary in 91 patients (36.8%). The average interval from primary tumor diagnosis to acrometastasis varied according to the primary tumor type from 2 months (in patients with mesenchymal tumors) to 64.0 months (in patients with breast cancer). Conclusions: Acrometastases usually develop in the late stage of oncologic disease and are associated with short life expectancy. Their occurrence can no longer be considered rare; physicians should thus be updated on their surgical management and their impact on prognosis and survival.

In the surgical management of large incisional hernias, the main target is the closure of the abdominal wall defect on the midline without a dangerous increase in the intraabdominal pressure. In this setting, new intraperitoneal prosthesis and components separation techniques were proposed to solve this problem. Both solutions present some critical issues. A new surgical approach with a free lateral double layer prosthesis totally in polypropylene both sides (FLaPp (R)) is proposed to overcome this problem. This is a retrospective cohort analysis study with a prospectively collected database from two different Italian hospitals. Twenty-nine patients operated from April 2010 to December 2015 were treated using the new prosthesis. Four patients developed postoperative complications: one (3.4%) presented wound infection, two (6.9%) experienced seroma, and one had a hematoma (3.4%). No deaths were recorded. At a median follow-up of 28.5 months (IQR 22-36), no hernia relapse occurred. The application of FLaPp (R) mesh is a safe and feasible option that can be employed to manage Rives repair in cases of abdominal wall defects with difficult closure of the posterior plan when the conventional prosthetic meshes could be unsuitable.