Purpose:
Mitral valve repair is a complex minimally invasive surgery of the heart valve. In this context, suture detection from endoscopic images is a highly relevant task that provides quantitative ...information to analyse suturing patterns, assess prosthetic configurations and produce augmented reality visualisations. Facial or anatomical landmark detection tasks typically contain a fixed number of landmarks, and use regression or fixed heatmap-based approaches to localize the landmarks. However in endoscopy, there are a varying number of sutures in every image, and the sutures may occur at any location in the annulus, as they are not semantically unique.
Method:
In this work, we formulate the suture detection task as a multi-instance deep heatmap regression problem, to identify entry and exit points of sutures. We extend our previous work, and introduce the novel use of a 2D
Gaussian
layer followed by a differentiable 2D spatial
Soft-Argmax
layer to function as a local non-maximum suppression.
Results:
We present extensive experiments with multiple heatmap distribution functions and two variants of the proposed model. In the intra-operative domain, Variant 1 showed a mean
F
1
of
+
0.0422
over the baseline. Similarly, in the simulator domain, Variant 1 showed a mean
F
1
of
+
0.0865
over the baseline.
Conclusion:
The proposed model shows an improvement over the baseline in the intra-operative and the simulator domains. The data is made publicly available within the scope of the MICCAI AdaptOR2021 Challenge
https://adaptor2021.github.io/
, and the code at
https://github.com/Cardio-AI/suture-detection-pytorch/
.
Background and aim of the study
Cardiac implantable electronic device (CIED) implantation is associated with an increase in CIED infection. For pacemaker‐dependent patients, temporary pacemaker leads ...are implanted until infection remission, which allows new CIED implantation. We compared the outcome of pacemaker‐dependent patients with infected CIED based on whether a combined single procedure of epicardial pacemaker implantation with system extraction or a temporary transjugular pacemaker implantation with interval system implantation was performed.
Methods
This retrospective study included pacemaker‐dependent patients with CIED infection who were divided into two groups: the Tempo and Epi groups. The Tempo group received temporary transvenous pacemaker connected to an external pulse generator. After infection remission, a new permanent pacemaker was implanted, and the temporary pacemaker leads were removed. The Epi group received implantable epicardial right‐ventricular pacemaker through infrasternal inferior pericardiotomy, and a permanent pulse generator was implanted through the same incision between the subcutaneous tissue and abdominal fascia.
Results
Sixty‐six patients were included. Forty‐two patients with epicardial pacemakers were discharged after 9.5 ± 8.8 days without infection of the newly implanted epicardial pacemaker. Patients with temporary transjugular pacemaker lead were discharged 23 ± 15 days after receiving permanent pacemakers. No serious complications were recorded in the Epi group.
Conclusions
CIED infections in pacemaker‐dependent patients can be treated through epicardial pacemaker implantation that allows early patient mobility and reduces hospital stay with no risk of epicardial pacemaker infection. Epicardial pacemakers can be used as a bridge until permanent intravenous CIED is implanted or as a replacement for permeant intravenous CIED.
Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, poorly immunogenic cancer with increasing incidence and a poor 5-year survival rate of 12%. PDAC tumors are refractory to all ...currently available treatments, including immune checkpoint blockade (ICB) therapies, and demonstrate limited infiltration of cytotoxic CD8+ T cells that kill tumor cells. There is therefore an urgent, unmet need for novel therapeutic options. Analysis of single-cell RNA-sequencing data of patient PDAC revealed high expression of the novel immune checkpoint, PSGL-1, on infiltrating CD8+ T cells. We hypothesize that PSGL-1-mediated immune suppression is a critical barrier to effective anti-tumor immunity in PDAC. To test this, we utilized a preclinical model of PDAC where orthotopic injection of the KPC.4662 tumor cell line into pancreata recapitulates patient tumor responses with limited T cell infiltrates and uncontrolled tumor growth in C57BL/6 (wildtype) control mice and compared to PSGL-1KO (C57BL/6 background) mice. At endpoint, tumor burden in PSGL-1KO mice was reduced by >50% compared to controls, with 45% of PSGL-1KO animals exhibiting >70% reduction. Total immune infiltration (CD45+) was 2-fold greater in tumors from PSGL-1KO mice, with a significant increase in infiltrating CD3+ T cells. Detailed analyses revealed that infiltrating CD8+ T cells from PSGL-1KO mice were not only more abundant, but also less differentiated towards terminal exhaustion with sustained TCT-1 expression compared to controls. Moreover, PSGL-1KO mice showed protection against metastatic disease. Since our data support a critical role for T cell driven anti-tumor immunity to PDAC, we transiently depleted CD4+ T cells, CD8+ T cells, or both just prior to tumor cell implantation. While depletion of CD8+ T cells did not impede tumor control by PSGL-1KO mice, depletion of all T cells or only CD4+ T cells resulted in the loss of PDAC tumor growth inhibition, demonstrating a key role of CD4+ cells in the response. Given our previous studies demonstrating an intrinsic role for PSGL-1 in development of terminal T cell exhaustion in melanoma, including loss of TCF-1+ CD8+ T cells, we hypothesized that PSGL-1-deficiency would promote responsiveness to PD-1 ICB, which is ineffective as a monotherapy in PDAC patients and mouse models. To test this prediction, PD-1 ICB was therapeutically administered to control and PSGL-1KO mice. While treatment with anti-PD-1 had no effect on the tumor growth in the control animals, PD-1 ICB resulted in complete tumor ablation in 85% of PSGL-1KO animals, demonstrating a profound synergistic effect of PD-1 inhibition in the absence of PSGL-1. From these studies, we conclude that PSGL-1 is a critical inhibitor of T cell anti-tumor responses in PDAC. PSGL-1 therefore represents a novel ICB target with high translational potential for promoting immune responses to PDAC tumors. Citation Format: Jennifer L. Hope, Yijuan Zhang, Hannah A. Hetrick, Gabriele Romano, Sreeja Roy, Michelle Lin, Ashley B. Palete, Swetha Maganti, Dennis C. Otero, Cosimo Commisso, Linda M. Bradley. Rewiring CD8+T cell responses to PD-1 immune checkpoint blockade in PDAC by preventing terminal exhaustion via the inhibitory receptor PSGL-1 abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1359.
Melanoma cells display distinct intrinsic phenotypic states. Here, we seek to characterize the molecular regulation of these states using multi-omic analyses of whole exome, transcriptome, microRNA, ...long non-coding RNA and DNA methylation data together with reverse-phase protein array data on a panel of 68 highly annotated early passage melanoma cell lines. We demonstrate that clearly defined cancer cell intrinsic transcriptomic programs are maintained in melanoma cells ex vivo and remain highly conserved within melanoma tumors, are associated with distinct immune features within tumors, and differentially correlate with checkpoint inhibitor and adoptive T cell therapy efficacy. Through integrative analyses we demonstrate highly complex multi-omic regulation of melanoma cell intrinsic programs that provide key insights into the molecular maintenance of phenotypic states. These findings have implications for cancer biology and the identification of new therapeutic strategies. Further, these deeply characterized cell lines will serve as an invaluable resource for future research in the field.
Purpose
Minimally invasive mitral valve surgery (MIMVS) and transcatheter edge-to-edge repair (TEER) are complex procedures used to treat mitral valve (MV) pathologies, but with limited training ...opportunities available. To enable training, a realistic hemodynamic environment is needed. In this work we aimed to develop and validate a simulator that enables investigation of MV pathologies and their repair by MIMVS and TEER in a hemodynamic setting.
Methods
Different MVs were installed in the simulator, and pressure, flow, and transesophageal echocardiographic measurements were obtained. To confirm the simulator’s physiological range, we first installed a biological prosthetic, a mechanical prosthetic, and a competent excised porcine MV. Subsequently, we inserted two porcine MVs—one with induced chordae tendineae rupture and the other with a dilated annulus, along with a patient-specific silicone valve extracted from echocardiography with bi-leaflet prolapse. Finally, TEER and MIMVS procedures were conducted by experts to repair the MVs.
Results
Systolic pressures, cardiac outputs, and regurgitations volumes (RVol) with competent MVs were 119 ± 1 mmHg, 4.78 ± 0.16 l min
−1
, and 5 ± 3 ml respectively, and thus within the physiological range. In contrast, the pathological MVs displayed increased RVols. MIMVS and TEER resulted in a decrease in RVols and mitigated the severity of mitral regurgitation.
Conclusion
Ex-vivo modelling of MV pathologies and repair procedures using the described simulator realistically replicated physiological in-vivo conditions. Furthermore, we showed the feasibility of performing MIMVS and TEER at the simulator, also at patient-specific level, thus providing new clinical perspectives in terms of training modalities and personalized planning.
Purpose
According to literature, interruptions during drug administration lead to a significant proportion of medication errors. Evidence on the effectiveness of interventions to reduce interruption ...is still limited. The purpose of this paper is to explore main reasons for interruptions during drug administration rounds in a geriatric ward of an Italian secondary hospital and test the effectiveness of a combined intervention.
Design/methodology/approach
This is a pre and post-intervention observational study based on direct observation. All nurse staff (24) participated to the study that lead to observe a total of 44 drug dispensing rounds with 945 drugs administered to 491 patients in T0 and 994 drugs to 506 patients in T1.
Findings
A significant reduction of raw number of interruptions (mean per round from 17.31 in T0 to 9.09 in T1,
p
<0.01), interruptions/patient rate (from 0.78 in T0 to 0.40 in T1,
p
<0.01) and interruptions/drugs rate (from 0.44 in T0 to 0.22 in T1,
p
<0.01) were observed. Needs for further improvements were elicited (e.g. a greater involvement of support staff).
Practical implications
Nurse staff should be adequately trained on the risks related to interruptions during drug administration since routine activity is at high risk of distractions due to its repetitive and skill-based nature.
Originality/value
A strong involvement of both MB and leadership, together with the frontline staff, helped to raise staff motivation and guide a bottom-up approach, able to identify tailored interventions and serve concurrently as training instrument tool.
Patients with BRAF-mutant melanoma show substantial responses to combined BRAF and MEK inhibition, but most relapse within 2 years. A major reservoir for drug resistance is minimal residual disease ...(MRD), comprised of drug-tolerant tumor cells laying in a dormant state. Towards exploiting potential therapeutic vulnerabilities of MRD, we established a genetically engineered mouse model of BrafV600E-driven melanoma MRD wherein genetic BrafV600E extinction leads to strong but incomplete tumor regression. Transcriptional time-course analysis after BrafV600E extinction revealed that after an initial surge of immune activation, tumors later became immunologically "cold" after MRD establishment. Computational analysis identified candidate T-cell recruiting chemokines as strongly upregulated initially and steeply decreasing as the immune response faded. Therefore, we hypothesized that sustaining chemokine signaling could impair MRD maintenance through increased recruitment of effector T cells. We found that intratumoral administration of recombinant Cxcl9 (rCxcl9), either naked or loaded in microparticles, significantly impaired MRD relapse in BRAF-inhibited tumors, including several complete pathologic responses after microparticle-delivered rCxcl9 combined with BRAF and MEK inhibition. Our experiments constitute proof of concept that chemokine-based microparticle delivery systems are a potential strategy to forestall tumor relapse and thus improve the clinical success of first-line treatment methods.
Atherosclerosis is a slowly progressing, chronic multifactorial disease characterized by the accumulation of lipids, inflammatory cells, and fibrous tissue that drives to the formation of asymmetric ...focal thickenings in the tunica intima of large and mid-sized arteries. Despite the high therapeutic potential of ApoA-1 proteins, the purification and delivery into the disordered organisms of these drugs is still limited by low efficiency in these processes.
We report here a novel production and delivery system of anti-atherogenic APOA-1Milano muteins (APOA-1M) by means of genetically modified rice plants. APOA-1M, delivered as protein extracts from transgenic rice seeds, significantly reduced macrophage activation and foam cell formation in vitro in oxLDL-loaded THP-1 model. The APOA-1M delivery method and therapeutic efficacy was tested in healthy mice and in Apoe−/− mice fed with high cholesterol diet (Western Diet, WD). APOA-1M rice milk significantly reduced atherosclerotic plaque size and lipids composition in aortic sinus and aortic arch of WD-fed Apoe−/− mice as compared to wild type rice milk-treated, WD-fed Apoe−/− mice. APOA-1M rice milk also significantly reduced macrophage number in liver of WD-fed Apoe−/− mice as compared to WT rice milk treated mice.
The delivery of therapeutic APOA-1M full length proteins via oral administration of rice seeds protein extracts (the ‘rice milk’) to the disordered organism, without any need of purification, might overcome the main APOA1-based therapies' limitations and improve the use of this molecules as therapeutic agents for cardiovascular patients.
•A novel production and delivery system, via oral administration, of anti-atherogenic APOA-1Milano muteins (APOA-1M)•APOA-1M muteins expressed in rice seeds retained anti-atherogenic and anti-inflammatory properties in vitro and in vivo•Orally delivered full length APOA-1M proteins are athero-protective even if the organism is still exposed to high fat diet
Purpose
According to literature, interruptions during drug administration lead to a significant proportion of medication errors. Evidence on the effectiveness of interventions to reduce interruption ...is still limited. The purpose of this paper is to explore main reasons for interruptions during drug administration rounds in a geriatric ward of an Italian secondary hospital and test the effectiveness of a combined intervention.
Design/methodology/approach
This is a pre and post-intervention observational study based on direct observation. All nurse staff (24) participated to the study that lead to observe a total of 44 drug dispensing rounds with 945 drugs administered to 491 patients in T0 and 994 drugs to 506 patients in T1.
Findings
A significant reduction of raw number of interruptions (mean per round from 17.31 in T0 to 9.09 in T1, p<0.01), interruptions/patient rate (from 0.78 in T0 to 0.40 in T1, p<0.01) and interruptions/drugs rate (from 0.44 in T0 to 0.22 in T1, p<0.01) were observed. Needs for further improvements were elicited (e.g. a greater involvement of support staff).
Practical implications
Nurse staff should be adequately trained on the risks related to interruptions during drug administration since routine activity is at high risk of distractions due to its repetitive and skill-based nature.
Originality/value
A strong involvement of both MB and leadership, together with the frontline staff, helped to raise staff motivation and guide a bottom-up approach, able to identify tailored interventions and serve concurrently as training instrument tool.
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