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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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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 purpose Only a restricted number of elderly patients has been included in the majority of recent endovascular stroke trials. We provided an analysis about differences in outcomes after mechanical thrombectomy (MT) according to age. Methods A retrospective analysis of an observational registry of patients with anterior large vessel acute ischemic stroke was performed. Main analysis was performed comparing patients Results 615 patients were identified. 227 (36.9%) patients were ≥80 years old, with 115 (18.5%) ≥85 years old. Elderly (≥80 years) patients showed a higher modified Rankin Scale (mRS) at discharge and 3-months follow-up (F=9.819, p=0.001) [Figure 1]. Comparing the three groups ( Conclusions In our analysis elderly patients have an increased risk of death and composite outcome of disability and death. In particular, this risk appears to be significantly higher in very elderly patients (≥85 years old). Figure 1. mRS according to main analysis Funding Acknowledgement Type of funding source: None

Purpose To clarify the role of endovascular treatment in patients with Critical Hand Ischemia of the distal upper extremity. Methods From January 2012 to January 2017, 18 dialyzed patients presented chronic critical hand ischemia; 6 patients had a chronic occlusion of the ulnar artery and radial artery stenosis, 5 patients had a chronic occlusion of the radial artery and ulnar artery stenosis, 4 patients presented multiple stenosis of the ulnar, radial and interosseous arteries, 2 patients had only ulnar artery occlusion while one patient presented only radial artery occlusion. All patients underwent duplex ultrasound and a subsequent brachial angiography, in order to evaluate the distal run-off circulation. Revascularization was achieved via antegrade brachial puncture in all patients, with retrograde approach in 4 patients, with distal retrograde puncture in 3 patients and in one patient with loop technique. Results No complications were observed during the periprocedural follow-up. One patient was not successfully revascularized (technical success rate: 94.4%). The patient had no direct flow after ulnar artery angioplasty. The procedure was clinical effective in 15 patients (clinical success rate: 83.3%). Clinical evaluation and Duplex-US were performed in the follow up period. TcpO2 evaluated in the perilesional skin surface increased from 20.2 ± 6.5 mmHg to 53.8 ± 13.1 mmHg in the follow up period (P Conclusion Percutaneous intervention prevents hand loss and functional impairment in patients with Critical Hand Ischemia and multiple comorbidities.

The study aimed to evaluate clinical and vascular characteristics, as well as outcomes, for diabetic persons with foot ulceration and no-option critical limb ischemia (CLI). The study group included a sample of patients admitted to our diabetic foot unit because of a new diabetic foot ulcer and CLI. All subjects were managed using a limb salvage protocol which includes lower-limb revascularization. According to whether or not the revascularization procedure was a success, patients were respectively divided into two groups: successfully treated CLI patients (ST-CLI) and no-option CLI patients (NO-CLI). Failed revascularization was considered in the case of technical recanalization failure of occluded vessels (inability to overcome the obstruction) and/or absence of arterial flow to the foot. Limb salvage, major amputation, and death after 1 year of follow-up were evaluated and compared between the two groups. Overall, 239 patients were included, 74.9% belonging to ST-CLI and 25.1% to NO-CLI. NO-CLI patients reported more cases of ischemic heart disease (80 vs. 62.1, p = 0.008), heart failure (63.3 vs. 32.4%, p &lt, 0.0001), and end-stage renal disease (ESRD) (60 vs. 25.7%) than ST-CLI patients. In addition, more vessels were affected in the NO-CLI group (5.2 &plusmn, 1.6 vs. 4 &plusmn, 1.5, p &lt, 0.0001), and there was more involvement of tibio-peroneal trunk (50 vs. 30.2%, p = 0.006), anterior tibial (93.3 vs. 82.7, p = 0.03), posterior tibial (93.3 vs. 73.7%, p = 0.0005), peroneal (70 vs. 48%, p = 0.002), and below-the-ankle arteries (73.3 vs. 39.1%, p &lt, 0.0001) than ST-CLI. The 1 year outcomes for the whole population were 69.9% limb salvage, 10.9% major amputation, and 19.2% death. The outcomes for NO-CLI and ST-CLI were, respectively, as follows: limb salvage (13.8 vs. 73.4%, p &lt, 0.0001), amputation (30 vs. 4.5%, p = 0.0001), and mortality (50 vs. 8.9%, p &lt, 0.0001). NO-CLI patients showed a more severe pattern of peripheral arterial disease (PAD) with distal arterial lesions and worse outcomes than ST-CLI.

Background and aims Diabetic foot (DF) disease is a current health and social burden. The authors aimed to identify the barriers to the DF management across Italy. Methods and results A questionnaire was submitted to Italian centres dedicated to DF care. The questionnaire was composed of 12 questions focused on the barriers to the DF management including timing of referral, hospital management, and community follow-up. Each centre could answer by choosing a score from 1 to 5 for every item with the following numerical variables: 1 = never; 2 = rarely; 3 = sometimes; 4 = often; 5 = always. Accordingly, for each item a national and regional score was reported and a comparison between regions was carried out. National and regional scores were estimated using the total score for each item as a numerator and the number of national centres included as a denominator. Among 102 centres, 99 were included and 3 were excluded due to missing data. The 99 centres belonged to 16 regions with the following distribution: Calabria 4, Campania 5, Emilia-Romagna 14, Friuli-Venezia-Giulia 4, Lazio 12, Liguria 4, Lombardy 10, Marche 1, Molise 1, Piedmont 5, Apulia 5, Sardinia 5, Sicily 4, Tuscany 11, Veneto 9, Umbria 5. The items with the highest score were late referral (3.3) and urgent surgery (3.2). The regions with the highest score were Molise (3.9) and Calabria (3.5). Conclusion The main issues across Italy were late referral and the requirement for urgent surgery for acute DF. In the regional scenario, the southern central areas showed more barriers than northern regions.

A disfunção erétil (DE) é uma condição médica muito prevalente onde mais da metade dos homens adultos apresentam alguma queixa relacionada a suas ereções. A DE é mais comumente encontrada nos homens com vários componentes da síndrome metabólica, que reúne fatores de risco para diabetes e doença cardiovascular. A disfunção endotelial é um fator etiológico unificador para muitos dos aspectos da síndrome metabólica, especialmente para o diabetes e a doença cardiovascular. A etiologia multifatorial da DE, especialmente em pacientes com síndrome metabólica, aumenta a complexidade no manejo deste problema. Deve-se estar ciente dos fatores fisiopatológicos relacionados à DE para buscar as melhores alternativas e resultados no tratamento destes pacientes. Quaisquer fatores de risco (tabagismo, diabetes, sedentarismo, obesidade, hipertensão e dislipidemia) para doença cardiovascular devem ser modificados ou tratados.

Background Endocrine therapy (ET) is the mainstay of treatment for hormone receptor-positive human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer; however, adaptive mechanisms emerge in about 25-30% of cases through alterations in the estrogen receptor ligand-binding domain, with a consequent ligand-independent estrogen receptor activity. Epigenetic-mediated events are less known and potentially involved in alternative mechanisms of resistance. The aim of this study was to test the feasibility of estrogen receptor 1 (ESR1) epigenetic characterization through liquid biopsy and to show its potential longitudinal application for an early ET sensitivity assessment. Methods A cohort of 49 women with hormone receptor-positive HER2-negative MBC was prospectively enrolled and characterized through circulating tumor DNA using methylation-specific droplet digital PCR (MS-ddPCR) before treatment start (BL) and after 3 months concomitantly with computed tomography (CT) scan restaging (EV1). ESR1 epigenetic status was defined by assessing the methylation of its main promoters (promA and promB). The most established cell-free tumor DNA (ctDNA) factors associated with ET resistance [ESR1 and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations] were assessed through next-generation sequencing. Associations were tested through Mann-Whitney U test, matched pairs variations through Wilcoxon signed rank test, and survival was analyzed by log-rank test. Results The ET backbone was mainly based on aromatase inhibitors (AIs) (70.83%) in association with CDK4/6 inhibitors (93.75%). Significantly lower promA levels at baseline were observed in patients with liver metastases (P = 0.0212) and in patients with ESR1 mutations (P = 0.0091). No significant impact on PFS was observed for promA (P = 0.3777) and promB (P = 0.7455) dichotomized at the median while a ≥2-fold increase in promB or in either promA or promB at EV1 resulted in a significantly worse prognosis (respectively P = 0.0189, P = 0.0294). A significant increase at EV1 was observed for promB among patients with PIK3CA mutation (P = 0.0173). A trend was observed for promB in ESR1 wild-type patients and for promA in the ESR1 mutant subgroup. Conclusion The study proofed the concept of an epigenetic characterization strategy based on ctDNA and is capable of being integrated in the current clinical workflow to give useful insights on treatment sensitivity.

BackgroundWhile the recommended laboratory diagnosis of COVID-19 is a molecular based assay, population-based studies to determine the prevalence of COVID-19 usually use serological assays.ObjectiveTo evaluate the sensitivity and specificity of a rapid diagnostic test for COVID-19 compared to quantitative reverse transcription polymerase chain reaction (qRT-PCR).MethodsWe evaluated the sensitivity using a panel of finger prick blood samples from participants >18 years of age that had been tested for COVID-19 by qRT-PCR. For assessing specificity, we used serum samples from the 1982 Pelotas (Brazil) Birth Cohort participants collected in 2012 with no exposure to SARS-CoV-2.ResultsThe sensitivity of the test was 77.1% (95% CI 66.6 - 85.6), based upon 83 subjects who had tested positive for qRT-PCR at least 10 days before the rapid diagnostic test (RDT). Based upon 100 sera samples, specificity was 98.0% (95% CI 92.9 - 99.8). There was substantial agreement (Kappa score 0.76) between the qRT-PCR results and the RDT.InterpretationThe validation results are well in line with previous assessments of the test, and confirm that it is sufficiently precise for epidemiological studies aimed at monitoring levels and trends of the COVID-19 pandemic.

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 AND PURPOSE: There is no consensus on the optimal antithrombotic medication for patients with acute ischemic stroke with anterior circulation tandem occlusions treated with emergent carotid stent placement and mechanical thrombectomy. The identification of factors influencing hemorrhagic risks can assist in creating appropriate therapeutic algorithms for such patients. This study aimed to investigate the impact of medical therapy on functional and safety outcomes in patients treated with carotid stent placement and mechanical thrombectomy for tandem occlusions. MATERIALS AND METHODS: A multicenter retrospective study on prospectively collected data was conducted. Only patients treated with carotid stent placement and mechanical thrombectomy for tandem occlusions of the anterior circulation were included. Univariate and multivariate analyses were performed on preprocedural, procedural, and postprocedural variables to assess factors influencing clinical outcome, symptomatic intracranial hemorrhage, stent patency, and successful intracranial vessel recanalization. RESULTS: Ninety-five patients with acute ischemic stroke and tandem occlusions were included. Good clinical outcome (mRS ≤ 2) at 3 months was reached by 33 (39.3%) patients and was associated with baseline ASPECTS ≥ 8 (OR = 1.53; 95% CI, 1.16–2.00), ≤2 mechanical thrombectomy attempts (OR = 0.71; 95% CI, 0.55–0.99), and the absence of symptomatic intracranial hemorrhage (OR = 0.13; 95% CI , 0.03–0.51). Symptomatic intracranial hemorrhage was associated with a higher amount of intraprocedural heparin, ASPECTS ≤ 7, and ≥3 mechanical thrombectomy attempts. No relationships among types of acute antiplatelet regimen, intravenous thrombolysis, and symptomatic intracranial hemorrhage were observed. Patients receiving dual-antiplatelet therapy after hemorrhagic transformation had been ruled out on 24-hour CT were more likely to achieve functional independence and had a lower risk of symptomatic intracranial hemorrhage. CONCLUSIONS: During carotid stent placement and mechanical thrombectomy for tandem occlusion treatment, higher intraprocedural heparin dosage (≥3000 IU) increased symptomatic intracranial hemorrhage risk when the initial ASPECTS was ≤7, and mechanical thrombectomy needs more than one passage for complete recanalization. Antiplatelets antiplatelets use were safe, and dual-antiaggregation therapy was related to better functional outcomes.

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.

BackgroundNeo-intimal hyperplasia (NIH) is frequently observed after flow-diverter stent (FDS) implantation. Although mostly asymptomatic, this vascular response can sometimes lead to delayed ischemic strokes. This study intended to evaluate the factors potentially influencing the rates of NIH following FDS treatment.Material and MethodsAll aneurysm treatments performed with a Pipeline embolization device (PED) or a SILK stent from May 2011 to May 2015 were collected in a prospectively maintained database. Patient demographics, clinical, and angiographic outcomes including both digital subtraction angiography and C-arm cone-beam CT were registered. Two blind reviewers rated the presence of NIH on a binary scale (present/absent).ResultsFrom 148 patients, 63 datasets were available for analysis. Inter-reader agreement was excellent (Kappa=0.88). NIH was positively correlated with smoking, dyslipidemia, and high blood pressure, but not with aneurysm characteristics. At early follow-up (ConclusionNIH is a dual-vessel reaction after FDS implant. When planning a treatment in locations at risk of ischemic complications if severe NIH would occur, then the stent design should be considered. However, minimal NIH might also be needed as it is involved in aneurysm healing. Before treatment patients should be recommended best medical management of their cardiovascular risks factors to prevent an excessive NIH reaction.

Background Stroke is a major cause of severe and long-term disability in adult individuals. Treatment of this disease is limited by the narrow therapeutic window in which intervention is crucial. An alternative therapy for stroke could be cellular growth factors, which participate in several pathways that mediate neuronal cell death. Methods We evaluated the neuroprotective ability of different doses of granulocyte colonystimulating factor (G-CSF; 5, 50 and 100 μg/kg/day) in the mouse model of global cerebral ischemia induced by bilateral occlusion of the common carotid arteries for 80 minutes. The control group received vehicle (5% glucose solution) and the treated group was administered with G-CSF at two postsurgery time-points: immediately after and 24 hours after. Subsequently, muscle strength, leukocyte count, infarcted cortical area, and apoptosis/TUNEL were evaluated. Results The global ischemia promoted an impairment of the strength (16%) and a cerebral infarction (0.437±0.08 cm2) which were accompanied by apoptosis evaluated by TUNEL in control mice. In mice treated with G-CSF the strength function was maintained, the infarcted area (~70%) and apoptosis were decreased in a similar magnitude in all treated groups. Accordingly, the cytokine activities were confirmed by blood leukocyte count that was increased approximately 2-fold than that observed in the control group. Conclusion The results indicate a neuroprotective effect of G-CSF, even in small doses, in mice subjected to global cerebral ischemia, thereby reducing the neurofunctional impairment caused by stroke, when considering the maintenance of muscle strength in the treated animals.

// Elisa De Carlo 1 , Maria Chiara Del Savio 1 , Jerry Polesel 2 , Valentina Da Ros 1 , Eleonora Berto 1 , Sandra Santarossa 1 , Emanuela Chimienti 1 , Lucia Fratino 1 and Alessandra Bearz 1 1 Medical Oncology Department, CRO-IRCCS, Aviano, Italy 2 Epidemiology Unit, CRO-IRCCS, Aviano, Italy Correspondence to: Alessandra Bearz, email: abearz@cro.it Keywords: non-small cell lung cancer; anaplastic lymphoma kinase (ALK); ALK inhibitors; brain metastasis Received: September 11, 2017 Accepted: February 21, 2018 Epub: February 26, 2018 Published: March 16, 2018 ABSTRACT Rearrangement in the anaplastic lymphoma kinase (ALK) gene is one of the oncogenic drivers in non-small cell lung cancer (NSCLC) patients. Several ALK inhibitors (ALKis) have been developed and have demonstrated their efficacy, however the best treatment strategy for ALK positive NSCLC patients has yet to be determined. Our retrospective study has investigated the outcome of 40 ALK-rearranged NSCLC patients treated with two different sequential strategies in our Institute; a “classical group”, treated with crizotinib followed by second or third generation ALKis, and the “experimental group”, treated upfront with a second generation ALK inhibitor. The primary endpoints investigated were Progression-free survival (PFS) and intracranial activity. The analysis has revealed a significant improvement in PFS ( p = 0.050) in the experimental group, furthermore none of these patients developed brain metastasis. There was no statistically significant difference in OS, but all patients in the experimental group were still alive after a median follow up of 15 months. Our retrospective analysis suggests that systemic and intracranial efficacy tends to be better in the experimental group; randomized prospective studies could confirm our observations.

// Anna Lisa Iorio 1 , Martina da Ros 1 , Lorenzo Genitori 1 , Maurizio Lucchesi 1 , Fabiana Colelli 2 , Giacomo Signorino 2 , Francesco Cardile 2 , Giacomo Laffi 3 , Maurizio de Martino 1 , Claudio Pisano 2 and Iacopo Sardi 1 1 Neuro-Oncology Unit, Department of Pediatric Oncology, Meyer Children’s Hospital, Florence, Italy 2 BIOGEM Research Institute, Ariano Irpino, Italy 3 Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy Correspondence to: Iacopo Sardi, email: iacopo.sardi@meyer.it Keywords: temozolomide, glioblastoma, morphine, blood-brain barrier, animal model Received: November 15, 2016 Accepted: July 13, 2017 Published: August 03, 2017 ABSTRACT Despite multimodal treatments comprising, radiation therapy (RT) and chemotherapy with temozolomide (TMZ), the prognosis of glioblastoma multiforme (GBM) remains dismal and consolidated therapy yields a median survival of 14.6 months. Blood Brain Barrier (BBB) mediated chemoresistance and high dose related toxicity make necessary the development of new therapeutic approach to sensitize GBM to TMZ. The aim of the present study was to investigate the potential of the treatment morphine plus TMZ metronmic doses (1,77 and 0,9 mg/kg) in GBM therapy. The effect of morphine, on tumor cell growth and P-glycoprothein (P-gp) activity, was investigate in in vitro models. The results demonstrated that GBM cells growth is not influenced by morphine treatment and, for the first time, we show that morphine is an inhibitor of the activity of P-gp efflux transporter who is markedly expressed on BBB. In vivo , response to the treatments TMZ plus morphine was investigated in an orthotopic nude mice model of GBM. Animals treated with TMZ metronomic doses showed a significant tumor growth inhibition compared to untreated mice and association with morphine appears to improve TMZ efficacy. Moreover, the combination of morphine with lower dose of TMZ result in a cytostatic effect on tumor growth over the period of the pharmacological treatments. In conclusion this novel approach could be a successful strategy to overcome chemoresistance and side effects TMZ mediated, reducing drug dosage and improving long term response, in GBM therapy.

Background Recent reports have revealed a worsening of aneurysm occlusion between WEB treatment baseline and angiographic follow-up due to “compression” of the device. Objective We utilized computational fluid dynamics (CFD) in order to determine whether the underlying mechanism of this worsening is flow related. Methods We included data from all consecutive patients treated in our institution with a WEB for unruptured aneurysms located either at the middle cerebral artery or basilar tip. The CFD study was performed using pre-operative 3D rotational angiography. From digital subtraction follow-up angiographies patients were dichotomized into two groups: one with WEB “compression” and one without. We performed statistical analyses to determine a potential correlation between WEB compression and CFD inflow ratio. Results Between July 2012 and June 2015, a total of 22 unruptured middle cerebral artery or basilar tip aneurysms were treated with a WEB device in our department. Three patients were excluded from the analysis and the mean follow-up period was 17 months. Eleven WEBs presented “compression” during follow-up. Interestingly, device “compression” was statistically correlated to the CFD inflow ratio ( P = 0.018), although not to aneurysm volume, aspect ratio or neck size. Conclusion The mechanisms underlying the worsening of aneurysm occlusion in WEB-treated patients due to device compression are most likely complex as well as multifactorial. However, it is apparent from our pilot study that a high arterial inflow is, at least, partially involved. Further theoretical and animal research studies are needed to increase our understanding of this phenomenon.

BACKGROUND AND PURPOSE: The treatment of wide-neck, large basilar apex aneurysms is challenging with either an endovascular or a surgical approach. The aim of the present study was to report our experience treating basilar apex aneurysms with flow-diverter stents and to evaluate their efficacy and safety profile in this specific anatomic condition. MATERIALS AND METHODS: We retrospectively analyzed data from all consecutive patients treated with flow-diverter stents at our institution between January 2011 and January 2015. Patients with large basilar apex aneurysms treated with a flow-diverter stent were included in the study. Clinical presentations, technical details, intra- and perioperative complications, and clinical and angiographic outcomes were recorded, with a midterm follow-up. RESULTS: Of the 175 aneurysms treated with flow-diverter stents at our institution, 5 patients (2 women and 3 men; age range, 44–58 years) received flow-diverter stent for basilar apex aneurysms. The mean follow-up after stent deployment was 21 months (range, 15–24 months). One patient died on day 31 from an early postprocedural midbrain hemorrhage. One patient had a right cerebellar hemispheric ischemic lesion with a transient cerebellar syndrome resolved within 24 hours without neurologic sequelae at the latest follow-up. The mRS was 0 in 4 patients and 6 in 1 patient at last follow-up. CONCLUSIONS: Flow diversion is a feasible technique with an efficacy demonstrated at a midterm follow-up, especially in the case of basilar apex aneurysm recurrences after previous endovascular treatments. Concern about its safety profile still exists.

Acute myeloid leukemia (AML) is a heterogeneous disease where selected subgroups of patients, linked by the presence of biological and clinical high-risk features, are candidates to receive allogenic hematopoietic stem cell transplantation HSCT) as post-remission consolidation treatment. The achievement of morphological complete remission (CR) before HSCT is an important pre-requisite to optimize the chance of successful post-transplant outcome. Minimal residual disease (MRD) assessment by quantitative polymerase chain reaction (q-PCR) has been shown to increase the ability to monitor therapy response in AML, improving prognostic accuracy and allowing to refine transplant strategies. Although MRD assessment was shown to have potential benefit when measured after induction and consolidation therapy courses, its role before HSCT remains to be fully elucidated. In order to contribute to better clarify this issue, we conducted a q-PCR I-BFM-AML collaborative study to measure MRD in bone marrow samples collected within 5 weeks prior to HSCT of 108 pediatric AML patients harboring one of the main recurrent AML aberrancies t(8;21)(q22;q22); RUNX1-RUNX1T1, inv(16)(p13.1q22)/t(16;16)(p13.1;q22); CBFB-MYH11, t(9;11)(p22;q23); KMT2A-MLLT3 or FLT3-ITD. Sixty patients underwent HSCT in first complete remission (CR1) with an overall survival (OS) of 84% versus 54% for the 48 transplanted in CR2 achieved after an initial relapse. Sixty patients showed q-MRD negativity (defined as a value lower than 2.1x10-4 calculated by ROC curve analysis with respect to diagnosis or relapse), whereas in 48 patients we detected q-MRD levels >2.1x10-4. Five-year OS after HSCT was 83% for patients with q-MRD negativity, while that of patients with q-MRD above the cutoff was 57% (p=0.012). As regards, cumulative incidence of relapse (CIR), q-MRD above the cutoff was associated with a high risk of recurrence (26% versus 10% for patients with q-MRD 2-log versus 73% for q-MRD2.1x10-4 and 2-log, HR). This combined stratification by q-MRD resulted into a better subdivision of the OS probability, which was 83%, 69% and 39% for LR, IR and HR respectively (p=0.004). Finally, a multivariate Cox regression model revealed that, together with CR status at time of the allograft (CR2, hazard ratio 4.4, p=0.001), q-MRD was an independent factor (hazard ratio 0.5, p=0.001) predicting HSCT outcome. In conclusion, this study supports the role of q-MRD pre-HSCT as a useful prognostic tool in childhood AML, able to provide information to tailor transplant strategies involving conditioning regimen intensity and graft-versus-host disease prophylaxis. Disclosures Reinhardt: AbbVie: Consultancy; Novartis: Consultancy, Other: Institutional Research Funding; Jazz: Consultancy, Other: Institutional Research Funding; Celgene: Consultancy, Other: Institutional Research Funding; bluebird bio: Consultancy; Roche: Consultancy, Other: Institutional Research Funding; Biotest: Other: Institutional Research Funding; Novo Nordisk: Other: Institutional Research Funding; Behring: Other: Institutional Research Funding. Merli:Bellicum Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; SOBI: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Honoraria; Sanofi-Genzyme: Honoraria; Atara Therapeutics: Honoraria.

Background Aging induces meaningful changes in the immune system and inflammation response with increase in monocyte-lymphocyte ratio (MLR) and serum lactate dehydrogenase (LDH) levels. Aim of this study was to explore the prognostic role of MLR and LDH levels in older patients (pts) with metastatic colorectal cancer (mCRC). Methods We conducted a retrospective analysis of a consecutive cohort of 168 older (>70 years) patients with mCRC. The prognostic impact of MLR and LDH levels on overall survival (OS) was investigated through uni-and multivariate Cox regression analyses. Moreover, we categorized patients into three groups according to MLR and LDH levels (group 1: MLR-low and LDH-low; group 2: MLR-high or LDH-high; group 3: MLR-high and LDH-high). Results By univariate analysis, high LDH level (HR 1.74, 95% CI 1.05–2.90) and high MLR level (HR 2.19, 95% CI 1.48–3.44) were significantly associated with a worse OS. Conversely, primary tumor resection and left-sidedness were significantly associated with a longer OS. By multivariate analysis, high LDH level (HR 2.00, 95% CI 1.13–3.55) and high MLR level (HR 2.99, 95% CI 1.68–5.33) were independent prognostic factors of worse prognosis. Compared to group 1, a shorter survival was reported for patients included in group 2 (HR 1.97, 95% CI 1.21–3.23 in univariate; HR 2.54, 95% CI 1.43–4.51 in multivariate) or in group 3 (HR 2.42, 95% CI 24–4.74, p = .010 in univariate; HR 5.59, 95% CI 2.15-14.54 in multivariate) Conclusions High baseline levels of LDH, MLR or both are independent unfavorable prognostic factors in older patients treated with first-line chemotherapy for mCRC.