806 Scout post-PCI instantaneous wave-free ratio as a driver of functional complete

Abstract Aims Physiology assessment by means of instantaneous wave-free ratio (iFR) is non-inferior to fractional flow reserve for the assessment of intermediate coronary lesions that are candidates to percutaneous coronary intervention (PCI). However, in pivotal trials assessing iFR, tandem coronary lesions (i.e. two serial lesions located in the same coronary artery) were excluded. In addition, the role of iFR after PCI as a way to optimize its success is poorly understood, particularly in the context of ST-segment elevation myocardial infarction (STEMI) with multivessel disease and tandem stenoses. We describe an illustrative case of post-PCI iFR in a STEMI patient with multivessel disease that led to a significant change in the revascularization strategy. Methods A 71-year old man presented with infero-lateral STEMI and received PCI with 1 drug-eluting stent (DES) 2.25 × 18 mm on the distal right coronary artery. The left coronary artery presented a 30–40% stenosis of the proximal left circumflex (LCX) and a 90% bifurcation stenosis of the mid portion of the same artery. PCI of the distal lesion was performed with implantation of 1 DES 3.0 × 22 with flaring of the stent at the level of the side branch and proximal optimization technique. Post-PCI iFR of the LCX was performed to assess the success of the procedure, with a value of 0.74. To understand the relative contribution of the two tandem stenoses, a pullback of the iFR wire was performed, which showed an unexpectedly small jump of the pressure when the wire was between the two lesions (0.80). Results As such, the significant contribution of the proximal lesion was unravelled, which led to implantation of a second DES 4.0 × 26 mm, partially overlapping with the previously implanted DES. Post-PCI iFR confirmed the complete success of the procedure (1.00). Conclusions In the context of complete revascularization for STEMI presenting with non-infarct related artery tandem stenoses, post-PCI physiology contributes to unravel the relative contribution of low-grade angiographic stenoses corresponding to functionally significant atherosclerosis left untreated. This case example illustrates the emerging procedural value of post-PCI iFR in achieving the goal of complete functional revascularization

Bifidobacterium affects antitumor efficacy of oncolytic adenovirus in a mouse model of melanoma

Gut microbiota plays a key role in modulating responses to cancer immunotherapy in melanoma patients. Oncolytic viruses (OVs) represent emerging tools in cancer therapy, inducing a potent immunogenic cancer cell death (ICD) and recruiting immune cells in tumors, poorly infiltrated by T cells. We investigated whether the antitumoral activity of oncolytic adenovirus Ad5D24-CpG (Ad-CpG) was gut microbiota-mediated in a syngeneic mouse model of melanoma and observed that ICD was weakened by vancomycin-mediated perturbation of gut microbiota. Ad-CpG efficacy was increased by oral supplementation with Bifidobacterium, reducing melanoma progression and tumor-infiltrating regulatory T cells. Fecal microbiota was enriched in bacterial species belonging to the Firmicutes phylum in mice treated with both Bifidobacterium and Ad-CpG; furthermore, our data suggest that molecular mimicry between melanoma and Bifidobacterium-derived epitopes may favor activation of cross-reactive T cells and constitutes one of the mechanisms by which gut microbiota modulates OVs response

Key questions for modelling COVID-19 exit strategies

Combinations of intense non-pharmaceutical interventions ('lockdowns') were introduced in countries worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement lockdown exit strategies that allow restrictions to be relaxed while attempting to control the risk of a surge in cases. Mathematical modelling has played a central role in guiding interventions, but the challenge of designing optimal exit strategies in the face of ongoing transmission is unprecedented. Here, we report discussions from the Isaac Newton Institute 'Models for an exit strategy' workshop (11-15 May 2020). A diverse community of modellers who are providing evidence to governments worldwide were asked to identify the main questions that, if answered, will allow for more accurate predictions of the effects of different exit strategies. Based on these questions, we propose a roadmap to facilitate the development of reliable models to guide exit strategies. The roadmap requires a global collaborative effort from the scientific community and policy-makers, and is made up of three parts: i) improve estimation of key epidemiological parameters; ii) understand sources of heterogeneity in populations; iii) focus on requirements for data collection, particularly in Low-to-Middle-Income countries. This will provide important information for planning exit strategies that balance socio-economic benefits with public health

Sudden Unexpected Deaths and Vaccinations during the First Two Years of Life in Italy: A Case Series Study

Background The signal of an association between vaccination in the second year of life with a hexavalent vaccine and sudden unexpected deaths (SUD) in the two days following vaccination was reported in Germany in 2003. A study to establish whether the immunisation with hexavalent vaccines increased the short term risk of SUD in infants was conducted in Italy. Methodology/Principal Findings The reference population comprises around 3 million infants vaccinated in Italy in the study period 1999–2004 (1.5 million received hexavalent vaccines). Events of SUD in infants aged 1–23 months were identified through the death certificates. Vaccination history was retrieved from immunisation registries. Association between immunisation and death was assessed adopting a case series design focusing on the risk periods 0–1, 0–7, and 0–14 days after immunisation. Among the 604 infants who died of SUD, 244 (40%) had received at least one vaccination. Four deaths occurred within two days from vaccination with the hexavalent vaccines (RR = 1.5; 95% CI 0.6 to 4.2). The RRs for the risk periods 0–7 and 0–14 were 2.0 (95% CI 1.2 to 3.5) and 1.5 (95% CI 0.9 to 2.4). The increased risk was limited to the first dose (RR = 2.2; 95% CI 1.1 to 4.4), whereas no increase was observed for the second and third doses combined. Conclusions The RRs of SUD for any vaccines and any risk periods, even when greater than 1, were almost an order of magnitude lower than the estimates in Germany. The limited increase in RRs found in Italy appears confined to the first dose and may be partly explained by a residual uncontrolled confounding effect of age

Difficult tracheal intubation in neonates and infants. NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE): a prospective European multicentre observational study

BACKGROUND: Neonates and infants are susceptible to hypoxaemia in the perioperative period. The aim of this study was to analyse interventions related to anaesthesia tracheal intubations in this European cohort and identify their clinical consequences. METHODS: We performed a secondary analysis of tracheal intubations of the European multicentre observational trial (NEonate and Children audiT of Anaesthesia pRactice IN Europe [NECTARINE]) in neonates and small infants with difficult tracheal intubation. The primary endpoint was the incidence of difficult intubation and the related complications. The secondary endpoints were the risk factors for severe hypoxaemia attributed to difficult airway management, and 30 and 90 day outcomes. RESULTS: Tracheal intubation was planned in 4683 procedures. Difficult tracheal intubation, defined as two failed attempts of direct laryngoscopy, occurred in 266 children (271 procedures) with an incidence (95% confidence interval [CI]) of 5.8% (95% CI, 5.1–6.5). Bradycardia occurred in 8% of the cases with difficult intubation, whereas a significant decrease in oxygen saturation (SpO2<90% for 60 s) was reported in 40%. No associated risk factors could be identified among co-morbidities, surgical, or anaesthesia management. Using propensity scoring to adjust for confounders, difficult anaesthesia tracheal intubation did not lead to an increase in 30 and 90 day morbidity or mortality. CONCLUSIONS: The results of the present study demonstrate a high incidence of difficult tracheal intubation in children less than 60 weeks post-conceptual age commonly resulting in severe hypoxaemia. Reassuringly, the morbidity and mortality at 30 and 90 days was not increased by the occurrence of a difficult intubation event

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Oltre il Segno/OltreMare

La realizzazione di un volume contenente le incisioni scelte all’interno della Scuola di Grafica d’Arte dell’Accademia di Belle Arti di Palermo, coordinata dai Proff. Giovanni D’Alessandro e Riccardo Mazzarino rappresenta motivo di orgoglio e di soddisfazione per la nostra Istituzione che costruisce i percorsi didattici dei propri corsi a partire dall’esperienza laboratoriale. L’incisione grafica è tra le tecniche artistiche più antiche ma nel contempo più contemporanee. La gestualità intrinseca al segno, che si manifesta nella carta, svela universi della visione inaspettati.(Mario Zito - Direttore dell’Accademia di Belle Arti di Palermo) Il segno è il risultato di un gesto a volte deciso, a volte contorto, a volte leggero, i cui risultati spesso sono inattesi e sorprendenti. Il volume contiene esemplari di incisioni fortemente caratterizzanti della scuola di Grafica d’Arte che vanta all’interno del proprio corso di studi docenti-artisti che consapevoli della ricchezza del loro bagaglio esperienziale offrono agli studenti gli strumenti necessari per far sì che l’arte del saper fare artigianale, si trasformi in mera poetica artistica