Effects of miRNA-15 and miRNA-16 expression replacement in chronic lymphocytic leukemia : implication for therapy

This work was supported by: Associazione Italiana Ricerca sul Cancro (AIRC) Grant 5 x mille n.9980, (to M.F., F.M. A. N., P.T. and M.N.) ; AIRC I.G. n. 14326 (to M.F.), n.10136 and 16722 (A.N.), n.15426 (to F.F.). AIRC and Fondazione CaRiCal co-financed Multi Unit Regional Grant 2014 n.16695 (to F.M.). Italian Ministry of Health 5x1000 funds (to S.Z. and F.F). A.G R. was supported by Associazione Italiana contro le Leucemie-Linfomi-Mielomi (AIL) Cosenza - Fondazione Amelia Scorza (FAS). S.M. C.M., M.C., L.E., S.B. were supported by AIRC.Peer reviewedPostprin

Risk of Recurrence of Chronic Subdural Hematomas After Surgery: A Multicenter Observational Cohort Study

Background: Chronic Subdural Hematoma (CSDH) is a common condition in the elderly population. Recurrence rates after surgical evacuation range from 5 to 30%. Factors predicting recurrence remain debated and unclear. Objective: To identify factors associated with increased risk of recurrence. Methods: Cases of CSDHs that underwent surgical treatment between 2005 and 2018 in the Neurosurgery Units of two major Italian hospitals were reviewed. Data extracted from a prospectively maintained database included demographics, laterality, antithrombotic therapy, history of trauma, corticosteroid therapy, preoperative and postoperative symptoms, type of surgical intervention, use of surgical drain, and clinical outcomes. Results: A total of 1313 patients was analyzed. The overall recurrence rate was 10.1%. The risk of recurrence was not significantly different between patients with unilateral or bilateral CSDH (10.4 vs. 8.8%, p = 0.39). The risk of recurrence was higher in patients that underwent surgical procedure without postoperative drainage (16.1 vs. 5.4%, p < 0.01). No relationship was found between recurrence rates and therapy with antithrombotic drugs (p = 0.97). The risk of recurrence was increasingly higher considering craniostomy, craniectomy, and craniotomy (9.3, 11.3, and 18.9%, respectively, p = 0.013). Lower recurrence rates following Dexamethasone therapy were recorded (p = 0.013). Conclusion: No association was found between the risk of recurrence of CSDH after surgical evacuation and age, use of antithrombotic medication, or laterality. Burr-hole craniostomy was found to be associated with lower recurrence rates, when compared to other surgical procedures. Placement of surgical drain and Dexamethasone therapy were significantly associated with reduced risk of recurrence of CSDHs

Biomarkers in post-reperfusion syndrome after acute lower limb ischaemia

Ischaemia reperfusion (I/R) injury refers to tissue damage caused when blood supply returns to the tissue after a period of ischaemia. Matrix metalloproteinases (MMPs), neutrophil gelatinase-associated lipocalin (NGAL) and cytokines are biomarkers involved in several vascular complications. The aim of this study was to evaluate the role of MMPs, NGAL and inflammatory cytokines in I/R syndrome. We conducted an open label, multicentric, parallel group study, between January 2010 and December 2013. Patients with acute limb ischaemia were enrolled in this study and were divided into two groups: (i) those subjected to fasciotomy and (ii) those not subjected to fasciotomy, according to the onset of compartment syndrome. Plasma and tissue values of MMPs and NGAL as well as plasma cytokines were evaluated. MMPs, NGAL and cytokine levels were higher in patients with compartment syndrome. Biomarkers evaluated in this study may be used in the future as predictors of I/R injury severity and its possible evolution towards post-reperfusion syndrome

Sector Neutral Portfolios: Long Memory Motifs Persistence in Market Structure Dynamics

We study soft persistence (existence in subsequent temporal layers of motifs from the initial layer) of motif structures in Triangulated Maximally Filtered Graphs (TMFG) generated from time-varying Kendall correlation matrices computed from stock prices log-returns over rolling windows with exponential smoothing. We observe long-memory processes in these structures in the form of power law decays in the number of persistent motifs. The decays then transition to a plateau regime with a power-law decay with smaller exponent. We demonstrate that identifying persistent motifs allows for forecasting and applications to portfolio diversification. Balanced portfolios are often constructed from the analysis of historic correlations, however not all past correlations are persistently reflected into the future. Sector neutrality has also been a central theme in portfolio diversification and systemic risk. We present an unsupervised technique to identify persistently correlated sets of stocks. These are empirically found to identify sectors driven by strong fundamentals. Applications of these findings are tested in two distinct ways on four different markets, resulting in significant reduction in portfolio volatility. A persistence-based measure for portfolio allocation is proposed and shown to outperform volatility weighting when tested out of sample

Adjuvant treatment for elderly patients with colon cancer. An observational study

Background: Adjuvant. 5-fluoruracil-based chemotherapysignificantly reduces mortality in. patients with: stage II-III colon cancer, but is less prescribed with rising age. In this study we were interested in the pattern of adjuvant treatment and possible effects on survival among elderly patients. Patients and methods: From January to December 2004, 63 questionnaires on the management of stage II-III resected colon cancer patients aged over 70 years, collected from 10 Italian Centres, were retrospectively examined. Determinants of receipt of adjuvant chemotherapy and their relation to survival were considered. Results: The proportion of elderly patients receiving adjuvant chemotherapy was 79.4%, distinct of age, gender, educational level and comorbidities. Grade 3-4 toxicities were the following: haematological in 4 (8.5.%) patients, mucositis in 4 (8.5%), diarrhoea in 2 (4.2%) and nausea in 1 (2.1%). The disease-free survival (DFS) and overall survival (OS) at two years were 79.9% and 95.6%, respectively. Due to the paucity of events, the impact of prognostic factors (patient's age and comorbidity, tumour stage and grade) on DFS and OS could not be assessed. Conclusion: An increasing proportion of elderly patients with colon cancer may be treated with a tolerability and OS similar to those observed in the younger population. Development of age-based guidelines and increased awareness of both physicians and patients through education is important to prevent undertreatment of those elderly patients who are eligible for chemotherapy

TRH: Pathophysiologic and clinical implications

Thyrotropin releasing hormone is thought to be a tonic stimulator of the pituitary TSH secretion regulating the setpoint of the thyrotrophs to the suppressive effect of thyroid hormones. The peptide stimulates the release of normal and elevated prolactin. ACTH and GH may increase in response to exogenous TRH in pituitary ACTH and GH hypersecretion syndromes and in some extrapituitary diseases. The pathophysiological implications of extrahypothalamic TRH in humans are essentially unknown. The TSH response to TRH is nowadays widely used as a diganostic amplifier in thyroid diseases being suppressed in borderline and overt hyperthyroid states and increased in primary thyroid failure. In hypothyroid states of hypothalamic origin, TSH increases in response to exogenous TRH often with a delayed and/or exaggerated time course. But in patients with pituitary tumors and suprasellar extension TSH may also respond to TRH despite secondary hypothyroidism. This TSH increase may indicate a suprasellar cause for the secondary hypothyroidism, probably due to portal vessel occlusion. The TSH released in these cases is shown to be biologically inactive

Endovascular Abdominal Aortic Aneurysm Repair With Ovation Alto Stent Graft: Protocol for the ALTAIR (ALTo endogrAft Italian Registry) Study

Background: Since 2010, the Ovation Abdominal Stent Graft System has offered an innovative sealing option for abdominal aortic aneurysm (AAA) by including a sealing ring filled with polymer 13 mm from the renal arteries. In August 2020, the redesigned Ovation Alto, with a sealing ring 6 mm closer to the top of the fabric, received CE Mark approval. Objective: This registry study aims to evaluate intraoperative, perioperative, and postoperative results in patients treated by the Alto stent graft (Endologix Inc.) for elective AAA repair in a multicentric consecutive experience. Methods: All consecutive eligible patients submitted to endovascular aneurysm repair (EVAR) by Alto Endovascular AAA implantation will be included in this analysis. Patients will be submitted to EVAR procedures based on their own preferences, anatomical features, and operators experience. An estimated number of 300 patients submitted to EVAR with Alto stent graft should be enrolled. It is estimated that the inclusion period will be 24 months. The follow-up period is set to be 5 years. Full data sets and cross-sectional images of contrast-enhanced computed tomography scan performed before EVAR, at the first postoperative month, at 24 or 36 months, and at 5-year follow-up interval will be reported in the central database for a centralized core laboratory review of morphological changes. The primary endpoint of the study is to evaluate the technical and clinical success of EVAR with the Alto stent graft in short- (90-day), mid- (1-year), and long-term (5-year) follow-up periods. The following secondary endpoints will be also addressed: operative time; intraoperative radiation exposure; contrast medium usage; AAA sac shrinkage at 12-month and 5-year follow-up; any potential role of patients' baseline characteristics, valuated on preoperative computed tomography angiographic study, and of device configuration (number of component) in the primary endpoint. Results: The study is currently in the recruitment phase and the final patient is expected to be treated by the end of 2023 and then followed up for 5 years. A total of 300 patients will be recruited. Analyses will focus on primary and secondary endpoints. Updated results will be shared at 1- and 3-5-year follow-ups. Conclusions: The results from this registry study could validate the safety and effectiveness of the new design of the Ovation Alto Stent Graft. The technical modifications to the endograft could allow for accommodation of a more comprehensive range of anatomies on-label

Outcomes of off-the-shelf preloaded inner branch device for urgent endovascular thoraco-abdominal aortic repair in the ItaliaN Branched Registry of E-nside EnDograft

Objective: The aim of this study was to report the outcomes of endovascular urgent thoracoabdominal aortic (TAAA) repair, using an off-the-shelf preloaded inner branch device (E-nside; Artivion). Methods: Data from a physician-initiated national multicenter registry, including patients treated with E-nside endograft (INBREED) were prospectively collected (2020-2024); only urgent cases were included in this study. Primary outcomes were technical success and mortality at 30 days. Secondary outcomes were spinal cord ischemia rate, stroke rate, major adverse events (MAE) as also branch instability at 12 months. Results: Of 185 patients enrolled in the INBREED, 64 (34.5%) were treated in a urgent setting and were included in the study. Reason for urgent repair was presence of aneurysm-related symptoms in 31 patients (48.4%), a contained rupture in eight (12.5%), and a large aneurysm >80 mm in 25 (39.1%). Extent of repair was I to III in 32 patients (50%) and IV in 32 (50%); 18 (28%) had a narrow (<25 mm) paravisceral aortic lumen. An adjunctive proximal thoracic endograft was deployed in 29 patients (45.3%); a distal bifurcated abdominal endograft was used in 33 (51.5%). Two hundred forty-nine target vessels (97.2%) were successfully incorporated through an inner branch from an upper arm (81.2%) or femoral (18.8%) access. A balloon expandable stent was used in 184 (75.7%) target vessels, a self-expandable stent in 59 (24.3%). Mean time for target vessel bridging was 39.9 ± 28.4 minutes per target vessel. Thirty-day cumulative major adverse event (MAE) rate was 28%, and mortality occurred in five patients (9.1%). There was one postoperative stroke (1.6%), and the spinal cord ischemia (SCI) rate was 8% (n = 5). For the 249 target vessels successfully incorporated through an inner branch, 1-year freedom from target vessel instability was 93% ± 3% after 1 year. Conclusions: The E-nside represents a valid solution for the urgent treatment of TAAAs, including symptomatic and ruptured TAAAs, as well as large asymptomatic TAAAs that cannot wait for a custom-made device. The preloaded inner branches and available proximal and distal graft diameters might be useful in urgent settings and provided satisfactory early and 1-year results, in terms of both endograft and target vessel stability. Further studies are required to assess the clinical role of E-nside for urgent TAAA repair