Are Long Term Cryopreservation and Patency of Vein Allograft Truly Achievable?

Despite extensive experimental work, neither the effect of long term cryopreservation on vein graft architecture nor the failure of alloveins due to graft rejection have yet been investigated. Herein, we investigated ultrastructurally: a) the integrity of rabbit jugular veins following 1, 2 and 3 months of cryopreservation; b) the outcome of the three-month cryopreserved vein auto- and allografts after 1 month of implantation in the rabbit carotid artery; and c) the immunologic response to cryopreserved vein allografts with and without seeded autologous endothelium. Prior to implantation, the cryopreserved rabbit veins were well-maintained except for endothelial cell damage. Following implantation, the cryopreserved vein autografts were comparable to fresh veins with a complete endothelial lining. Conversely, only one of the allograft was still patent with features of acute rejection. After seeding with autologous endothelium , these explants failed shortly after surgery. We found absence of endothelium and necrosis of the media components with neutrophil infiltration. Although three months of cryopreservation does not affect vein graft architecture significantly, endothelial cells are damaged irrespective of the time of cryopreservation. Vein autografts promptly healed after one month of implantation at which time a viable endothelial cell lining was restored from the host artery. Conversely, vein allografts, with and without seeded autologous endothelium, failed due to graft rejection. This study highlights that current methods of cryopreservation do not reduce antigenicity of venous allografts significantly

Sex Influence on Fenestrated and Branched Endovascular Aortic Aneurysm Repair: Outcomes From a National Multicenter Registry

Introduction: Women are generally underrepresented in trials focusing on aortic aneurysm. Nevertheless, sex-related differences have recently emerged from several studies and registries. The aim of this research was to assess whether sex-related anatomical disparities existed in fenestrated and branched aortic repair candidates and whether these discrepancies could influence endovascular repair outcomes. Methods: Data from all consecutive patients treated during the 2008–2019 period within the Italian Multicenter fenestrated or branched endovascular aortic repair (F/BEVAR) Registry were included in the present study. Propensity matching was performed using a logistic regression model adjusted for demographic data and comorbidities to obtain comparable male and female samples. The selection model led to a final study population of 176 patients (88 women and 88 men) among the total initial cohort of 596. Study endpoints were technical and clinical success, overall survival, aneurysm-related death, and reintervention rates evaluated at 30 days and during follow-up. Results: Twenty-eight patients (15.9%) received urgent/emergent repair. In most of the cases (71.6%), women received treatment for extensive thoracoabdominal pathology (Crawford type I, II, or III aneurysm rather than type IV or juxta-pararenal) versus 46.6% of men (p=0.001). Female patients presented with more challenging iliac accesses with at least one side considered hostile in 27.3% of the cases (vs 13.6% in male patients, p=0.039). Finally, women had significantly smaller visceral vessels. Women had significantly worse operative outcomes, with an 86.2% technical success rate versus 96.6% in the male population (p=0.016). No differences were recorded in terms of 30-day reinterventions between men and women. The 5-year estimate of freedom from late reintervention, according to Kaplan-Meier analysis, was 85.6% in men versus 81.6% in women (p=ns). No aneurysm-related death was recorded during follow-up (median observational time, 23 months [interquartile range, 7–45 months]). Conclusion: Women presented a significantly higher incidence of thoracoabdominal aneurysms, smaller visceral vessels, and more complex iliofemoral accesses, resulting in a significantly lower technical success after F/BEVAR. Further studies assessing sex-related differences are needed to properly determine the impact on outcomes and stratify procedural risks. Clinical Impact: Women are generally underrepresented in trials focusing on aortic aneurysms. Aiming to assess whether sex may affect outcomes after a complex endovascular aortic repair, a propensity score selection was applied to a total population of 596 patients receiving F/BEVAR aortic repair with the Cook platform, matching each treated female patient with a corresponding male patient. Women presented more frequently a thoracoabdominal aneurysm extent, smaller visceral vessels, and complex iliofemoral accesses, resulting in significantly worse operative outcomes, with an 86.2% technical success versus 96.6% (p=0.016). No differences were recorded in terms of short-term and mid-term reinterventions. According to these results, careful and critical assessment should be posed in case of female patients receiving complex aortic repair, especially regarding preoperative anatomical evaluation and clinical selection with appropriate surgical risk stratification

Validation of a microarrays protocol for detection and genotyping isolates of Plum pox virus

A genomic strategy for PPV identification has been recently developed (Pasquini et al., 2008). The method is based on using a 70-mer oligonucleotide DNA microarray chip capable of simultaneously detecting and genotyping PPV strains. Universal and specific probes have been identified and used with a sensitive protocol of hybridization using an indirect fluorescent labelling of cDNA product with cyanine able to enhance the sensitivity of the virus detection avoiding the use of the PCR amplification step. In order to evaluate the protocol fitness for diagnostic use, about 30 samples belonging to a PPV isolates collection, including M, D, EA and C strains, have been used for its validation, that was determined, estimating the performance criteria that include the following parameters: diagnostic sensitivity (D-SN), diagnostic specificity (D-SP) and diagnostic accuracy (D-AC). Keywords: oligonucleotides chip, PPV, sensitivity, specificity, accuracy, performance criteri

Fenestrated and Branched Endografts for Post-Dissection Thoraco-Abdominal Aneurysms: Results of a National Multicentre Study and Literature Review

Objective: Fenestrated and branched endografting (F/B-EVAR) has been proposed as an endovascular solution for chronic post-dissection thoraco-abdominal aneurysms (PD-TAAAs). The aim of this study was to analyse the experience of four high volume centres nationwide and the current available literature. Methods: Data on patients undergoing F/B-EVAR in four Italian academic centres between 2008 and 2019 were collected, and those from patients with PD-TAAAs were analysed retrospectively. Peri-operative morbidity and mortality were assessed as early outcomes. Survival, freedom from re-intervention (FFR), target visceral vessel (TVV) patency, and aortic remodelling were assessed as follow up outcomes. A MEDLINE search was performed for studies published from 2008 to 2020 reporting on F/B-EVAR in PD-TAAAs. Results: Among 351 patients who underwent F/B-EVAR for TAAAs, 37 (11%) had PD-TAAAs (Crawford's extent I–III: 35% – 95%). Overall, 135 TVVs (from true lumen 120; false lumen seven; both true and false lumen eight) were accommodated by fenestrations (96% – 71%) and branches (39% – 29%). Technical success (TS) was achieved in 34 (92%) cases with three failures due to endoleaks (Ia: 1; Ic: 1; III: 1). There were no 30 day deaths. No cases of permanent spinal cord ischaemia (SCI) were recorded and six (16%) patients suffered from transient deficits. Renal function worsening (eGFR < 30% than baseline) and pulmonary complications were reported in two (5%) and four (11%) cases, respectively. From the Kaplan–Meier analysis, three year survival, FFR, and TVV patency were 81%, 66%, and 97%, respectively. Radiological imaging was available for 30 (81%) patients at 12 months with complete false lumen thrombosis in 26 (87%). Two hundred and fifty-six patients were reported in seven published papers with TS, 30 day mortality, and SCI ranging from 99% to 100%, 0 to 6%, and 0 to 16%, respectively. The mean follow up ranged from 12 to 26 months, with estimated two year survival between 81% and 90% and a re-intervention rate between 19% and 53%. Conclusion: F/B-EVAR is effective to treat PD-TAAAs. A high re-intervention rate is necessary to complete the aneurysm exclusion and promote aortic remodelling successfully

S.13.1 Safety and efficacy of rituximab in SSc: an analysis from the European Scleroderma Trial and Research Group

Objectives. Objective of this multicentre, observational study was to assess effects and safety of rituximab (RTX) using the European Scleroderma Trial and Research Group (EUSTAR) cohort. Methods. EUSTAR centres were asked to provide specific data about SSc patients treated with RTX. Primary endpoints were predefined for different disease manifestations and compared between baseline and follow-up. Normally distributed data, analysed by paired t-test, are shown as mean (s.d.), and non-parametric data, analysed by Wilcoxon matched paired signed-rank test, are shown as median and interquartile range. Results. Data on 72 SSc patients treated with RTX were captured from 27 EUSTAR centres (51 females/21 males, 52 diffuse/19 limited, age 51 (44-60) years, disease duration 6 (3-10) years, 47 anti-Scl-70 positive). The most frequent RTX application scheme was 1000 mg × 2 within 2 weeks (57/72 patients). Co-treatment with other immunosuppressive drugs was reported in 28 patients. The modified Rodnan skin score (mRSS) significantly decreased vs baseline at 7 (5-9) months follow-up (n = 47, 18.2 + 10.9 vs 14.5 + 9.9, P = 0.0002). This was true for both patients with later disease stages and also for patients with earlier, extended skin fibrosis (dSSc with mRSS >16 at baseline, n = 26; 26.5 + 6.8 vs 20.4 + 8.9, P < 0.0001, reduction by 29.9%). S-HAQ was unchanged, but the European SSc activity score improved after rituximab treatment [n = 10; 3.7 (2.6-6.4) vs 1.7 (0.9-2.5), P = 0.01]. RTX had no effects on lung fibrosis (FVC, DLCO, TLC, HRCT score) in n = 11 patients with evidence for SSc-ILD. In SSc-polyarthritis patients, the DAS-28 declined at 6 months follow-up without reaching statistical significance [n = 8; 4.8 (2.5-7.5) vs 3.7 (2.6-6.6); p = 0.3]. Of 8, 5patients were RF and/or anti-CCP antibody positive. Similar results were obtained for secondary outcome measures (tender and swollen joint count, VAS, CRP, ESR). Additional positive effects of RTX were seen on SSc-related myopathy (CK levels, 273 + 177 vs 184 + 139; n = 12, P = 0.03) and on digital ulcers [total number per patient 1 (1-3) vs 0 (0-1); n = 23; P = 0.0086]. During RTX treatment 14 patients had infections, 3 serum sickness, 2 allergic reactions and 1 lung fibrosis aggravation, 29 fatigue and 9 nausea. Four patients died, one possibly related to RTX treatment (pneumonia and cardiac failure 1.5 months after RTX infusion). Conclusion. This large EUSTAR cohort study points at positive effects of RTX in particular on skin fibrosis, and suggests randomized controlled trial in SSc patient

Early and Late Response and Glucocorticoid-Sparing Effect of Belimumab in Patients with Systemic Lupus Erythematosus with Joint and Skin Manifestations: Results from the Belimumab in Real Life Setting Study—Joint and Skin (BeRLiSS-JS)

Aim. To assess the efficacy of belimumab in joint and skin manifestations in a nationwide cohort of patients with SLE. Methods. All patients with skin and joint involvement enrolled in the BeRLiSS cohort were considered. Belimumab (intravenous, 10 mg/kg) effectiveness in joint and skin manifestations was assessed by DAS28 and CLASI, respectively. Attainment and predictors of DAS28 remission (&lt;2.6) and LDA (≥2.6, ≤3.2), CLASI = 0, 1, and improvement in DAS28 and CLASI indices ≥20%, ≥50%, and ≥70% were evaluated at 6, 12, 24, and 36 months. Results. DAS28 &lt; 2.6 was achieved by 46%, 57%, and 71% of patients at 6, 12, and 24 months, respectively. CLASI = 0 was achieved by 36%, 48%, and 62% of patients at 6, 12, and 24 months, respectively. Belimumab showed a glucocorticoid-sparing effect, being glucocorticoid-free at 8.5%, 15.4%, 25.6%, and 31.6% of patients at 6, 12, 24, and 36 months, respectively. Patients achieving DAS-LDA and CLASI-50 at 6 months had a higher probability of remission at 12 months compared with those who did not (p = 0.034 and p = 0.028, respectively). Conclusions. Belimumab led to clinical improvement in a significant proportion of patients with joint or skin involvement in a real-life setting and was associated with a glucocorticoid-sparing effect. A significant proportion of patients with a partial response at 6 months achieved remission later on during follow-up

Comparison of single- and multistage strategies during fenestrated-branched endovascular aortic repair of thoracoabdominal aortic aneurysms

Objective: The aim of this study was to compare outcomes of single or multistage approach during fenestrated-branched endovascular aortic repair (FB-EVAR) of extensive thoracoabdominal aortic aneurysms (TAAAs). Methods: We reviewed the clinical data of consecutive patients treated by FB-EVAR for extent I to III TAAAs in 24 centers (2006-2021). All patients received a single brand manufactured patient-specific or off-the-shelf fenestrated-branched stent grafts. Staging strategies included proximal thoracic aortic repair, minimally invasive segmental artery coil embolization, temporary aneurysm sac perfusion and combinations of these techniques. Endpoints were analyzed for elective repair in patients who had a single- or multistage approach before and after propensity score adjustment for baseline differences, including the composite 30-day/in-hospital mortality and/or permanent paraplegia, major adverse event, patient survival, and freedom from aortic-related mortality. Results: A total of 1947 patients (65% male; mean age, 71 ± 8 years) underwent FB-EVAR of 155 extent I (10%), 729 extent II (46%), and 713 extent III TAAAs (44%). A single-stage approach was used in 939 patients (48%) and a multistage approach in 1008 patients (52%). A multistage approach was more frequently used in patients undergoing elective compared with non-elective repair (55% vs 35%; P < .001). Staging strategies were proximal thoracic aortic repair in 743 patients (74%), temporary aneurysm sac perfusion in 128 (13%), minimally invasive segmental artery coil embolization in 10 (1%), and combinations in 127 (12%). Among patients undergoing elective repair (n = 1597), the composite endpoint of 30-day/in-hospital mortality and/or permanent paraplegia rate occurred in 14% of single-stage and 6% of multistage approach patients (P < .001). After adjustment with a propensity score, multistage approach was associated with lower rates of 30-day/in-hospital mortality and/or permanent paraplegia (odds ratio, 0.466; 95% confidence interval, 0.271-0.801; P = .006) and higher patient survival at 1 year (86.9±1.3% vs 79.6±1.7%) and 3 years (72.7±2.1% vs 64.2±2.3%; adjusted hazard ratio, 0.714; 95% confidence interval, 0.528-0.966; P = .029), compared with a single stage approach. Conclusions: Staging elective FB-EVAR of extent I to III TAAAs was associated with decreased risk of mortality and/or permanent paraplegia at 30 days or within hospital stay, and with higher patient survival at 1 and 3 years

Helsinki-Vantaan lentoaseman tilannekuvakeskus : Häiriö- ja poikkeamatilanteiden eteneminen lentoasemalla

Tämän opinnäytetyön tavoitteena oli selvittää, miten Finavian ylläpitämällä Helsinki-Vantaa lentoasemalla tapahtuvat häiriö- ja poikkeamatilanteet vaikuttavat lentoasemalla toimiviin Finavian omiin organisaatioihin sekä lentoasemalla toimiviin viranomaisiin. Häiriö- ja poikkeamatilanteella tarkoitetaan lentoaseman normaaliin toimintaan häiritsevästi vaikuttavaa tapahtumaa, esimerkiksi sähkökatkoa. Työ tehtiin Helsinki-Vantaa lentoaseman tilannekuvakeskuksen päällikön pyynnöstä. Tilannekuvakeskuksessa huomattiin, että vaikka häiriö- ja poikkeamatilanteessa toiminta eri tahojen kanssa on ollut kitkatonta ja sujuvaa, ei toisen organisaation sisällä tapahtuvasta toiminnasta ollut kuvaa. Työn avulla selvitettiin, onko häiriö- tai poikkeamatilanteella vaikutusta eri organisaatioiden ja viranomaisten toimintaan. Opinnäytetyö auttaa rakentamaan kokonaiskäsitystä poikkeamatilanteiden aiheuttamasta toiminnasta koko lentoaseman alueella. Tätä kautta voidaan myös lisätä ymmärrystä eri organisaatioiden ja viranomaisten välillä. Opinnäytetyö toteutettiin yhteistyössä Helsinki-Vantaa lentoaseman tilannekuvakeskuksen kanssa. Työn edetessä rakennetta muokattiin yhteistyössä tilaajan kanssa niin, että se palvelisi mahdollisimman tarkoituksenmukaisesti eri organisaatioita. Työ toteutettiin tekemällä laadullinen tutkimus, jonka runkona oli puolistrukturoitu haastattelu. Haastatteluita kertyi yhteensä 19 kappaletta ja haastateltavia 21. Haastateltavina olivat Finavian eri organisaatioiden johtajia tai päälliköitä ja lentoaseman toimintaan liittyvien viranomaisten lentoaseman toimipisteiden päälliköt. Työstä rajattiin pois kaupalliset yritykset, koska haastatteluiden määrä olisi kasvanut liian suureksi. Lentoaseman tilannekuvakeskus on luonut useita valmiita toimintamalleja erilaisiin häiriö- ja poikkeamatilanteisiin. Tilannekuvakeskuksen päällikkö valitsi näistä häiriö- ja poikkeamatilanteista ne, jotka ovat todennäköisiä tai merkittäviä ja vaikuttavat haitallisesti lentoaseman toimintaan. Erilaisia häiriö- ja poikkeamatilanteita valikoitui 17 kappaletta. Näiden tilanteiden vaikutuksia ja toimintamalleja käsiteltiin haastatteluissa. Haastatteluissa saatu informaatio liitettiin tilannekuvakeskuksen toimintamalleihin ja luotiin jokaiseen valittuun poikkeamatilanteeseen kronologinen kuvaus eri organisaatioiden toiminnasta. Opinnäytetyöstä on myöhemmin tarkoitus tehdä pelkistetympi käsikirja Finavian ja viranomaisten käyttöön.The aim of this study was to find out how to Finavia’s Helsinki-Vantaa airport take place in crisis and emergency situations and how they affecting operating at the airport Finavia's own organizations as well as authorities operating at the airport. The work was done at the request of the Head of the Helsinki-Vantaa airport operation center. The airport operation center noted that although the crisis and emergency situations operation with various parties has been smooth, but nobody didn’t have a picture how these crisis and emergency situations was handled in the another organizations. The work purpose was to find out whether the fault or deviation situation could affect the functioning of the various organizations and public authorities. The thesis helps to build the overall understanding of the actions caused by the deviation of situations throughout the airport. This period may also increase the understanding of the different organizations and authorities. The research was conducted in cooperation with the Helsinki-Vantaa airport operation center. As work progresses, the structure was modified in cooperation with the client so that it would serve as appropriately as possible the different organizations. The work was carried out by qualitative research, whose backbone was the semi-structured interview. Interviews were a total of 19 tracks and 21 interviewees were interviewed leaders or managers in different organizations and Finavia's airport activities related to airport authorities, heads of offices. Work were excluded trading companies, because the number of interviews had grown too large. The airport operation center has created a number of ready-made models for different crisis and emergency situations. Head of the Centre chose a snapshot of the crisis and emergency situations, those who are likely or significant and adversely affect the operation of the airport. 17 various types of crisis and emergency situations was selected. Effects and models of these situations addressed in the interviews. The information obtained in the interviews attached a airport operation center’s operational models and was created for each selected deviation situation chronological description of the activities of various organizations. The thesis is later to be made simpler manual for use by Finavia and the authorities

Optimal Management of Asymptomatic Carotid Stenosis: Counterbalancing the Benefits with the Potential Risks.

no abstract availabl

Differential baseline and response profile to IFN-γ gene transduction of IL-6/IL-6 receptor-α secretion discriminate primary tumors versus bone marrow metastases of nasopharyngeal carcinomas in culture

<p>Abstract</p> <p>Background</p> <p>Understanding of immunobiology of bone marrow metastases (designated BM-NPC) <it>versus </it>primary tumors (P-NPC) of the nasopharynx is far from complete. The aim of this study was to determine if there would be differences between cultured P-NPCs and BM-NPCs with respect to (i) constitutive IL-6 and the IL-6 receptor gp80 subunit (IL-6Rα) levels in the spent media of nontransduced cells, and (ii) IL-6 and IL-6Rα levels in the spent media of cells transduced with a retroviral vector containing the <it>IFN-γ </it>gene.</p> <p>Methods</p> <p>A panel of NPC cell lines were transduced with the <it>IFN-γ </it>gene through a retroviral vector. Four clonal sublines were isolated <it>via </it>limiting dilution methods. Cytofluorometric analysis was performed for the detection of cell surface antigens of HLA class I, HLA class II and ICAM-1. ELISA was used to assay for IFN-γ, IL-6 and IL-6Rα in the spent media of cultured cell lines.</p> <p>Results</p> <p>Our results showed that in day 3 culture supernatants, low levels of soluble IL-6 were detected in 5/5 cultured tumors derived from P-NPCs, while much higher constitutive levels of IL-6 were detected in 3/3 metastasis-derived NPC cell lines including one originated from ascites; the difference was significant (<it>p </it>= 0.025). An inverse relationship was found between IL-6Rα and IL-6 in their release levels in cultured P-NPCs and metastasis-derived NPCs. In <it>IFN-γ</it>-transduced-P-NPCs, IL-6 production increased and yet IL-6Rα decreased substantially, as compared to nontransduced counterparts. At variance with P-NPC cells, the respective ongoing IL-6 and IL-6Rα release patterns of BM-NPC cells were not impeded as much following <it>IFN-γ </it>transduction. These observations were confirmed by extended kinetic studies with representative NPC cell lines and clonal sublines. The latter observation with the clonal sublines also indicates that selection for high IL-6 or low IL-6Rα producing subpopulations did not occur as a result of <it>IFN-γ</it>-transduction process. P-NPCs, which secreted constitutively only marginal levels of IFN-γ (8.4 ~ 10.5 pg/ml), could be enhanced to produce higher levels of IFN-γ (6.8- to 10.3-fold increase) after <it>IFN-γ </it>transduction. Unlike P-NPCs, BM-NPCs spontaneously released IFN-γ at moderate levels (83.8 ~ 100.7 pg/ml), which were enhanced by 1.3- to 2.2-fold in the spent media of their <it>IFN-γ</it>-transduced counterparts.</p> <p>Conclusion</p> <p>Our results showed that cultured P-NPCs and BM-NPCs could be distinguished from one another on the basis of their differential baseline secretion pattern of IFN-γ, IL-6 and IL-6Rα, and their differential response profiles to <it>IFN-γ </it>gene transfer of the production of these three soluble molecules. These results suggest that the IL-6 and IFN-γ pathways in a background of genetic instability be involved in the acquisition of metastatic behaviour in BM-NPCs.</p