Objectives The current treatment of acute lower limb ischemia (ALLI) includes open surgical and percutaneous pharmaco-mechanical thromboembolectomy (TE). We hereby report our results with open surgical TE over a 10-year period and compare our outcomes using routine fluoroscopic assisted TE (FATE) with blind and selective on demand fluoroscopic-assisted TE (BSTE). Methods This is a retrospective analysis of all patients who underwent open surgical TE for acute lower limb ischemia at a single tertiary center between 2008 and 2018. Patients were divided into a group who underwent BSTE and another who underwent routine FATE. Data on presentation, medical history, surgery performed, and short-term outcomes were retrieved from medical record. Comparison between baseline characteristics and outcomes of both groups were made using t-test and chi-square analysis. Results Over 10 years, 108 patients underwent surgical TE. Thirty-day mortality rate and 30-day major lower extremity amputation rate in the cohort were 12.0% and 6.5%, respectively. On subgroup analysis, 53 patients were treated by BSTE and 55 patients by FATE. There was no significant difference in 30-day mortality rate (11.3% vs 12.7%, p-value = .82) and 30-day major amputation rate (9.4% vs 3.6%, p-value = .454) between the two groups. Local anesthesia was more frequently performed in patients undergoing FATE (58.2% vs 24.5%, p-value < .001). More than one arteriotomy was more frequently required in patients undergoing BSTE (2.6% vs 45.5%, p-value < .001). Patients with infrapopliteal involvement undergoing FATE required less further interventions such as patch angioplasty (2.6% vs 36.4%, p-value < .001) and bypass (2.6% vs 22.7%, p-value = .01). Conclusion ALLI remains a disease of high morbidity and mortality. Open surgical TE offers an effective approach to treat ALLI. The addition of fluoroscopy to the conduction of TE could be associated with valuable benefits, especially in patients with infra-popliteal involvement. Randomized controlled trials are needed to objectively assess the therapeutic potential of FATE.

01 Mar 2023·Molecular Therapy - Oncolytics

Oncolytic adenovirus coding for bispecific T cell engager against human MUC-1 potentiates T cell response against solid tumors

Article

Author: Havunen, Riikka ; Heiniö, Camilla ; Clubb, James H A ; Hemminki, Akseli ; Kanerva, Anna ; Quixabeira, Dafne C A ; Pakola, Santeri ; Basnet, Saru ; Santos, Joao M ; Arias, Victor ; Sorsa, Suvi ; Anttila, Marjukka ; Cervera-Carrascon, Victor ; Grönberg-Vähä-Koskela, Susanna A M ; Kudling, Tatiana V

Immunotherapy with bispecific T cell engagers has shown efficacy in patients with hematologic malignancies and uveal melanoma. Antitumor effects of bispecific T cell engagers in most solid tumors are limited due to their short serum half-life and insufficient tumor concentration. We designed a novel serotype 5/3 oncolytic adenovirus encoding a human mucin1 antibody and the human CD3 receptor, Ad5/3-E2F-d24-aMUC1aCD3 (TILT-321). TILT-321 is engineered to replicate only in cancer cells, leading to a high concentration of the aMUC1aCD3 molecule in the tumor microenvironment. Infection and cell viability assays were performed to determine the oncolytic potential of the novel construct. The functionality of the virus-derived aMUC1aCD3 was evaluated in vitro. When TILT-321 was combined with allogeneic T cells, rapid tumor cell lysis was observed. TILT-321-infected cells secreted functional aMUC1aCD3, as shown by increased T cell activity and its binding to MUC1 and CD3. In vivo, TILT-321 treatment led to effective antitumor efficacy mediated by increased intratumoral T cell activity in an A549 and patient-derived ovarian cancer xenograft mouse model humanized with peripheral blood mononuclear cells (PBMC). This study provides a proof of concept for an effective strategy to overcome the key limitations of recombinant bispecific T cell engager delivery for solid tumor treatment.

Healthcare

Four-Dimensional Flow Echocardiography: Blood Speckle Tracking in Congenital Heart Disease: How to Apply, How to Interpret, What Is Feasible, and What Is Missing Still

Review

Author: Franchi, Eliana ; Marchese, Pietro ; Santoro, Giuseppe ; Assanta, Nadia ; Cantinotti, Massimiliano ; Giordano, Raffaele

Blood speckle tracking echocardiography (BSTE) is a new, promising 4D flow ultrafast non-focal plane imaging technique. The aim of the present investigation is to provide a review and update on potentialities and application of BSTE in children with congenital heart disease (CHD) and acquired heart disease. A literature search was performed within the National Library of Medicine using the keywords “echocardiography”, “BST”, and “children”. The search was refined by adding the keywords “ultrafast imaging”, “CHD”, and “4D flow”. Fifteen studies were finally included. Our analysis outlined how BSTE is highly feasible, fast, and easy for visualization of normal/abnormal flow patterns in healthy children and in those with CHD. BSTE allows for visualization and basic 2D measures of normal/abnormal vortices forming the ventricles and in the main vessel. Left ventricular vortex characteristics and aortic flow patterns have been described both in healthy children and in those with CHD. Complex analysis (e.g., energy loss, vorticity, and vector complexity) are also highly feasible with BSTE, but software is currently available only for research. Furthermore, current technology allows for BSTE only in neonates and low-weight children (e.g., <40 kg). In summary, the feasibility and potentialities of BSTE as a complementary diagnostic tool in children have been proved; however, its systemic use is hampered by the lack of (i) accessible tools for complex quantification and for acquisition at all ages/weight, (ii) data on the diagnostic/prognostic significance of BSTE, and (iii) consensus/recommendation papers indicating when and how BSTE should be employed.

100 Deals associated with aMUC1aCD3 coding virus(TILT)

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Indication	Highest Phase	Country/Location	Organization	Date
Lung Cancer	Preclinical	FI	University of Helsinki	08 Dec 2022
Lung Cancer	Preclinical	FI	TILT Biotherapeutics Oy	08 Dec 2022

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