Unraveling tumor specific neoantigen immunogenicity prediction: a comprehensive analysis

IntroductionIdentification of tumor specific neoantigen (TSN) immunogenicity is crucial to develop peptide/mRNA based anti-tumoral vaccines and/or adoptive T-cell immunotherapies; thus, accurate in-silico classification/prioritization proves critical for cost-effective clinical applications. Several methods were proposed as TSNs immunogenicity predictors; however, comprehensive performance comparison is still lacking due to the absence of well documented and adequate TSN databases.MethodsHere, by developing a new curated database having 199 TSNs with experimentally-validated MHC-I presentation and positive/negative immune response (ITSNdb), sixteen metrics were evaluated as immunogenicity predictors. In addition, by using a dataset emulating patient derived TSNs and immunotherapy cohorts containing predicted TSNs for tumor neoantigen burden (TNB) with outcome association, the metrics were evaluated as TSNs prioritizers and as immunotherapy response biomarkers.ResultsOur results show high performance variability among methods, highlighting the need for substantial improvement. Deep learning predictors were top ranked on ITSNdb but show discrepancy on validation databases. In overall, current predicted TNB did not outperform existing biomarkers.ConclusionRecommendations for their clinical application and the ITSNdb are presented to promote development and comparison of computational TSNs immunogenicity predictors

A simple device to secure ventricular assist device driveline and prevent exit-site infection

Objectives: Driveline infections are one of the most common and important complications in patients with left ventricular assist device (LVAD). One of the causes favouring the development of this complication is the traumatism of the exit site, which occurs in response to movement of the driveline. In this work, we present a simple and feasible method to immobilize the driveline at the level of the exit site. Methods: From April 2013 until November 2013, 6 patients underwent implantation of HeartWare LVAD (HVAD) for an end-stage heart failure. When the patient has begun to mobilize after the implantation of the device, we have combined the use of two components with the aim of securing the driveline to the patient's skin: a StatLock system and a silicone suture. Results: No case of local traumatism and no case of local infection at the driveline were observed during the follow-up. No patient reported pain or swelling at the driveline exit site. All patients were satisfied with their quality-of-life and they do not report any limitations in their daily activities. Conclusions: One of the major long-term complications in patients with LVAD is the development of infections of the exit site of the driveline. The trauma of this skin region promotes the onset and maintenance of an inflammatory process and local infectious. Avoiding excessive mobilization of the driveline is likely to reduce the incidence of infections of the exit site and improve the quality-of-life. \ua9 The Author 2013

A retrospective comparative analysis of Latissimus Dorsi (LD) flap versus Thoracodorsal Artery Perforator (TDAP) flap in total breast reconstruction with implants: a pilot study

Introduction In breast surgery, an autologous flap combined with implant may reduce the risk or repair the soft-tissue defects in several cases. Traditionally, the preferred flap is the myocutaneous latissimus dorsi (LD) flap. In the perforator flap era, the evolution of LD flap is the thoracodorsal artery perforator (TDAP) flap. The aim of this study is the comparison between LD flap and TDAP flap with implants in terms of early complications and shoulder function. Methods We performed a retrospective cohort study in accordance with the STROBE guidelines. Between January 1 2015 and January 1 2020, 27 women underwent a unilateral total breast reconstruction with LD or TDAP flap combined with an implant at our institution. 15 women were operated with LD flap and 12 with TDAP flap. The most frequent indications for intervention were results of mastectomy and radiation-induced contracture. We evaluated several data in terms of clinical and demographical characteristics, operative and perioperative factors, and follow-up variables. We assessed shoulder function through the Disability of the Arm, Shoulder and Hand Questionnaire (DASH). Results The rate of complications was significantly lower in the TDAP group compared with the LD group (16.7% vs 60.0%, p = 0.047. Table 3). Although the small sample size limited further detailed statistical analyses, we particularly noticed no cases of donor site seroma in the TDAP group, as compared with four in the LD group. Patients in the TDAP group had an ∼11-point lower mean DASH score compared with the LD group (9.8 vs 20.5). This difference was statistically significant (p = 0.049). Conclusions TDAP flap seems to be a reliable technique for soft-tissue coverage in total breast reconstruction with implants. In comparison with the traditional LD flap, it could be a more favorable option in terms of less complications and better quality of life

Advanced heart failure in critical patients (INTERMACS 1 and 2 levels): Ventricular assist devices or emergency transplantation?

OBJECTIVE: For patients in advanced heart failure, emergency transplantation or ventricular assist devices (VADs) are possible strategies. The aim of this single-centre, retrospective study was to evaluate early and long-term results for these two strategies.METHODS: From 2005 to 2011, we analysed 49 INTERMACS level 1 and 2 patients, who were divided into the following two groups: group A comprised 26 patients on the waiting list for heart transplantation with urgent conditions; and group B comprised 23 patients who underwent VAD implantation as a bridge to candidacy.RESULTS: In group A, 25 patients underwent transplantation. In group B, 19 patients were supported with left VAD and four with biventricular VAD. Of these 23 patients, 13 underwent transplantation (mean time 279 \ub1 196 days). The 30 day mortality was 42.3 and 4.3% in group A and B, respectively. Survival at 6 and 12 months was significantly better in group B than in group A (87 vs 53%, P = 0.018 at 6 months; and 77 vs 48%, P = 0.045 at 12 months).CONCLUSION: Improved outcomes may justify the use of mechanical assistance devices as a bridge to candidacy or bridge to transplantation in INTERMACS 1 and 2 patients in order to avoid high-risk transplants. Evaluation of long-term multicentre outcomes is needed to assess future strategies. \ua9 2012 The Author 2012. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved

Thrombosis in left ventricular assistance device with centrifugal technology: Is early thrombolysis a better solution?

Background: Continuous flow left ventricular assistance devices (CF-LVADs) have revolutionized the treatment of advanced heart failure. Pump replacement for thrombosis is a high-risk procedure with a high perioperative mortality rate with possible recurrence. We aim to summarize our experience using a conservative approach with medical therapy. Methods: We retrospectively reviewed records of patients who experienced pump thrombosis after LVAD implantation with HeartWare HVAD at our institution, from November 2010 to March 2016. Device thrombosis (DT) was divided into suspected (SDT) and confirmed (CDT). A conservative approach using thrombolysis and heparin was used in all patients. Results: A total of 32 HeartWare HVAD pumps were implanted. Mean age was 59 \ub1 10 years and the mean time on mechanical support was 19.29 months (\ub114.06). Pump thrombosis occurred in 7 patients (0.14 patients/year) after a mean time of 733 (231-1,606) days after LVAD implantation. Three out of 7 cases had thrombosis recurrence (43%). Overall 19 episodes were recorded (0.38 event per patient/year). Eighteen out of 19 thrombolytic treatments were successful (94.7%). No patient required LVAD replacement or transfusion of blood products. There was no significant difference in terms of survival between patients who experienced thrombotic events and patients who did not. No major complications related to thrombolysis were recorded. Conclusions: Systemic thrombolysis plus heparin was an excellent therapeutic option. Early intervention in clinically stable patients without signs of heart failure but with indirect signs of device thrombosis has led to better outcomes

Management of cardiogenic shock: a proposal for a shared protocol

Cardiogenic shock (CS) is a complex and relatively rare disease. Whilst its mortality remains unacceptably high, a multidisciplinary approach based on pre-established and shared protocols may improve prognosis and ensure appropriate resource allocation. Comprehensive hemodynamic assessment and monitoring as well as tailored, goal-directed medical therapy are part of an optimal management. Moreover, mechanical support devices may be helpful as they sustain hemodynamics to a greater extent as compared to inotropes and vasopressors, while lacking their cardiotoxic effects. Therefore, they are increasingly used in CS patients. In 2019, a new protocol for the management of patients with CS was adopted at the Ospedale Policlinico San Martino (HSM) in Genoa, Italy. Following in the footsteps of similar international experiences, the HSM protocol aims at streamlining the management of these high-risk patients improving the cooperation among healthcare specialists, and also addressing the key issues of mechanical support device implantation and appropriate referral for palliative care