Real-World Evaluation of the Off-the-Shelf Precannulated Inner-Branched Endograft for Pararenal Aortic Aneurysms.

PURPOSE: To analyze the early performance and efficacy of the first commercially available off-the-shelf precannulated multibranched endograft in the endovascular repair of pararenal abdominal aortic aneurysms (PAAAs). The device received European marketing approval in late 2020. MATERIALS AND METHODS: Between January 2021 and June 2023, a retrospective analysis of prospectively collected data from all consecutive patients with pAAAs undergoing implantation of the E-nside precannulated inner-branched endograft was conducted in 2 centers. The primary outcome measure was technical success defined as the composite endpoint of successful (1) delivery of the 24F endograft, (2) use of the precannulation tubes, and (3) implantation of the bridging stent-grafts (BSGs) to the target vessels. Main secondary endpoints were mortality, target vessel instability (TVI), absence of type I or III endoleak, reintervention, spinal cord ischemia, and supra-celiac aortic coverage. RESULTS: Twenty-one patients (20 men, mean age: 71 years) were included in this study with a mean follow-up of 14±7.7 months. Nine patients had a symptomatic aneurysm (43%). Technical success amounted to 95% (in one patient, an iliofemoral conduit was necessary to advance the device). One out of 112 BSGs (1%, right renal artery) occluded at 30 days, resulting in freedom from TVI and reintervention rate at 12 months of 95%. No type I or III endoleaks were identified during follow-up. One patient (5%) died at 13 months due to non-aneurysm-related death, and 1 patient (5%) developed spinal cord ischemia. No other major perioperative complications were observed. Mean supra-celiac aortic coverage reached 52±8%. CONCLUSIONS: Given the imperative need for an off-the-shelf endograft tailored to address PAAAs, the E-nside stent-graft demonstrated encouraging outcomes in this study. Nevertheless, it is essential to emphasize that the extent of aortic coverage mandates the production of a truncated variant. CLINICAL IMPACT: The endovascular repair of urgent pararenal aortic aneurysms remains still an unsolved problem in the endovascular era since there are no available off-the-shelf dedicated fenestrated or branched endografts. This paper confirms the safety and efficacy of the off-the-shelf precannulated inner branched endograft for this specific indication.

The Effect of Cyclosporine and the Consequences in Hepatic and Renal Function Following Ischemic Stroke in a Rats' Model.

INTRODUCTION: Recent studies have indicated that the damaging effects of stroke are not only limited to the brain. We sought to examine the changes of liver and renal enzymes in the acute phase of ischemic stroke and to investigate possible explanations and therapeutic options, concerning in particular the functional alterations of peripheral organs after administration of an anti-inflammatory agent. MATERIAL/METHODS: Twelve-week-old Wistar male rats were randomly divided into control and Cyclosporine groups (n = 10 each). Cyclosporine was given orally by gavage for 5 days prior to cerebral ischemia at a total volume of 15 mg/kg/day. All animals were subjected to 60 minutes focal ischemia by filament occlusion of the middle cerebral artery. Serum concentrations of Creatinine, Urea, SGOT, SGPT, and γGT were determined at the time before surgery and after 60 minutes brain ischemia. RESULTS: Comparing data of 2 time-points, in both groups the serum liver enzyme levels increased progressively during the ischemic period. The liver enzymes and Urea were significantly lower in the Cyclosporine group than in the control group and the levels of Creatinine were slightly higher in the Cyclosporine group, in both time-points. CONCLUSIONS: The detection of high liver enzyme serum levels in the acute phase of ischemic stroke implies the secondary effect of cerebral infraction on the peripheral organs and particularly on the liver function. Cyclosporine seems to exhibit a protective activity and to affect both liver and renal function after ischemic stroke.

Expression of S100B Protein in Ischemia/Reperfusion-Induced Brain Injury After Cyclosporine Therapy: A Biochemical Serum Marker with Prognostic Value?

BACKGROUND Accumulating evidence has indicated that S100B protein may be involved in the pathophysiology of ischemia-reperfusion brain injury. Cyclosporine has been shown to have neuroprotective functions. This study investigated the effect of cyclosporine on S100B serum levels and the severity of brain tissue damage in a rat model of cerebral ischemia-reperfusion (I/R). MATERIAL AND METHODS Twelve-week-old Wistar male rats were randomly divided into Control I/R and Cyclosporine I/R groups (n=10 each). Cyclosporine was given orally by gavage for 5 days prior to cerebral I/R, at a total volume of 15 mg/kg/day. The Control group received an equal volume of saline. Body weight was measured and all animals were subjected to 60-min focal ischemia by filament occlusion of the middle cerebral artery. ELISA was used to assess the concentrations of serum S100B and development of brain infarct size and neurological outcomes were determined at 2 and 24 h after occlusion withdrawal. RESULTS Cyclosporine improved the neurological deficit score and decreased the cerebral infarct size and body weight. S100B serum levels were significantly elevated in Cyclosporine-treated rats compared with untreated Control rats during the reperfusion phase. Total infarct size was positively associated with S100B serum levels in the Control I/R group, but no significant correlation was observed in the Cyclosporine I/R group. CONCLUSIONS Cyclosporine seems to affect both ischemia-reperfusion brain tissue damage and S100B protein serum levels. S100B serum level appears to be a state marker for the severity of the cerebral ischemia-reperfusion, rather than a trait marker for Cyclosporine responsiveness.

Endovascular Treatment of a Forty-Year-Old Post-Traumatic Knee Arteriovenous Fistula.

Arteriovenous fistulas (AVFs) of the lower extremity are uncommon. The main causes are traumatic or iatrogenic, with 15% of traumatic AVFs occurring in the popliteal vessels. Herein, we present a 60-year-old female with a traumatic AVF caused after a car accident 40 years ago. The patient presented with right leg venous claudication and symptoms of congestive heart failure. Duplex ultrasound of lower limb vessels revealed an AVF at the distal part of the tibiofibular trunk. The patient was successfully managed with an endovascular approach using a coil-assisted covered endovascular repair technique of the tibiofibular bifurcation (CERTIFIB) with excellent results and distal vessels patency. At 3 months follow-up, patient presented with an impressive regression of 3 cm of the lower extremity oedema and improvement of both claudication and heart failure.

Time-dependent effects of cellulose and gelatin-based hemostats on cellular processes of wound healing.

Introduction: Oxidized regenerated cellulose-based (ORC - TABOTAMP), oxidized non-regenerated cellulose-based (ONRC - RESORBA CELL), and gelatin-based (GELA - GELITA TUFT-IT) hemostats are commonly used in surgery. However, their impact on the wound healing process remains largely unexplored. We here assess time-dependent effects of exposure to these hemostats on fibroblast-related wound healing processes. Material and methods: Hemostats were applied to fibroblast cell cultures for 5-10 (short-), 30 and 60 min (intermediate-) and 24 h (long-term). Representative images of the hemostat degradation process were obtained, and the pH value was measured. Cell viability, apoptosis and migration were analyzed after the above exposure times at 3, 6 and 24 h follow-up. Protein levels for tumor necrosis factor α (TNF-α) and transforming-growth factor ß (TGF-ß) were assessed. Results: ORC and ONRC reduced pH values during degradation, while GELA proved to be pH-neutral. Hemostat structural integrity was prolonged for GELA (vs. ORC and ONRC). TGF-ß and TNF-α levels were reduced for ORC and ONRC (vs. GELA and control) (p < 0.05). Further, exposure of ORC and ONRC for longer than 5-10 min reduced cell viability vs. GELA and control at 3 h post-exposure (p < 0.05). Similarly, cell migration was impaired with ORC and ONRC exposure longer than 60 min at 24 h follow-up (p < 0.05). Conclusions: Short-term exposure to ORC and ONRC impairs relevant wound healing-related processes in fibroblasts, and alters protein levels of key mediating cytokines. GELA does not show similar effects. We conclude that GELA may be preferred over ORC and ONRC over short-, intermediate- and long-term exposures. Future validation of the clinical relevance is warranted.

Cytolytic activity correlates with the mutational burden and deregulated expression of immune checkpoints in colorectal cancer.

BACKGROUND: Microsatellite unstable colorectal cancers (MSI+ CRCs) expressing PD-L1, respond to anti-PD-1 or anti-PD-L1 checkpoint blockade, whereas microsatellite-stable tumors do not respond the same. Our aim was to examine how the immune landscape relates to different aspects of the CRC's biology, including neoepitope burden. METHODS: We used TCGA data to stratify patients based on a cytolytic T-cell activity expression index and correlated immune cytolytic activity (CYT) with mutational, structural, and neoepitope features of each tumor sample. The expression of several immune checkpoints was verified in an independent cohort of 72 CRC patients, relative to their MSI status, using immunohistochemistry and RT-qPCR. RESULTS: CRC exhibits a range of intertumoral cytolytic T-cell activity, with lower cytolytic levels in the tumor, compared to the normal tissue. We separated CRC patients into CYT-high and CYT-low subgroups. High cytolytic activity correlated with increased mutational load in colon tumors, the count of MHC-I/-II classically defined and alternatively defined neoepitopes, high microsatellite instability and deregulated expression of several inhibitory immune checkpoints (VISTA, TIGIT, PD-1, IDO1, CTLA-4, and PD-L1, among others). Many immune checkpoint molecules (IDO1, LAG3, TIGIT, VISTA, PD-1, PD-L1 and CTLA-4) expressed significantly higher in MSI+ CRCs compared to MSS tumors. The expression of Treg markers was also significantly higher in CYT-high tumors. Both individual and simultaneous high levels of CTLA-4 and PD-L1 had a positive effect on the patients' overall survival. On the reverse, simultaneous low expression of both genes led to a significant shift towards negative effect. Assessed globally, CYT-low CRCs contained more recurrent somatic copy number alterations. PD-L1 protein was absent in most samples in the independent cohort and stained lowly in 33% of MSI CRCs. PD-L1+ CRCs stained moderately for CD8 and weakly for FOXP3. CYT-high colon tumors had higher TIL load, whereas CYT-high rectum tumors had higher TAN load compared to their CYT-low counterparts. CONCLUSIONS: Overall, we highlight the link between different genetic events and the immune microenvironment in CRC, taking into consideration the status of microsatellite instability. Our data provide further evidence that MSI+ and CYT-high tumors are better candidates for combinatorial checkpoint inhibition.

Clinical outcomes after direct and indirect surgical venous thrombectomy for inferior vena cava thrombosis.

OBJECTIVE: Inferior vena cava thrombosis is rare, but patients are at high risk for development of a post-thrombotic syndrome (PTS) in the long term. Surgical approaches include indirect transfemoral venous thrombectomy (iTFVT) and direct open venous thrombectomy (dOVT). This study reports patient outcomes after iTFVT and dOVT for inferior vena cava thrombosis covering a 25-year follow-up period. METHODS: The study period was from January 1, 1982, to December 31, 2013. Data were retrieved from archived medical records, and patients were invited for a detailed phlebologic follow-up examination (DPFE). Health-related quality of life was assessed with the 36-Item Short Form Health Survey questionnaire. Patient survival, patency rates, and freedom from PTS were calculated using Kaplan-Meier estimation with log-rank testing. The χ2 test with Yates continuity correction and logistic regression analysis were applied to identify associations between risk factors or coagulation disorders, mortality, and PTS. RESULTS: Complete medical records were available for 152 patients. Patients' 5-year survival was 91% ± 3%, and 5-year primary and secondary patency rates were 80% ± 3% and 94% ± 2%. Freedom from PTS after 25 years was 84% ± 6%. No differences for patient survival, patency rates, or freedom from PTS were identified between iTFVT, dOVT, and a combination of both procedures. Antithrombin III deficiency was the most common coagulation disorder, and patients' physical function and social function were impaired compared with those found in German normative data (P < .05). No risk factor or coagulation disorder was associated with survival or PTS. CONCLUSIONS: Open surgical venous thrombectomy is safe and delivers satisfying short- and long-term outcomes compared with endovascular approaches. It remains valuable for patients who are not eligible for other interventional therapies.

The Expression and Prognostic Impact of Immune Cytolytic Activity-Related Markers in Human Malignancies: A Comprehensive Meta-analysis.

BACKGROUND: Recently, immune-checkpoint blockade has shown striking clinical results in different cancer patients. However, a significant inter-individual and inter-tumor variability exists among different cancers. The expression of the toxins granzyme A (GZMA) and perforin 1 (PRF1), secreted by effector cytotoxic T cells and natural killer (NK) cells, were recently used as a denominator of the intratumoral immune cytolytic activity (CYT). These levels are significantly elevated upon CD8+ T-cell activation as well as during a productive clinical response against immune-checkpoint blockade therapies. Still, it is not completely understood how different tumors induce and adapt to immune responses. METHODS: Here, we calculated the CYT across different cancer types and focused on differences between primary and metastatic tumors. Using data from 10,355, primary tumor resection samples and 2,787 normal samples that we extracted from The Cancer Genome Atlas and Genotype-Tissue Expression project databases, we screened the variation of CYT across 32 different cancer types and 28 different normal tissue types. We correlated the cytolytic levels in each cancer type with the corresponding patient group's overall survival, the expression of several immune-checkpoint molecules, as well as with the load of tumor-infiltrating lymphocytes (TILs), and tumor-associated neutrophils (TANs) in these tumors. RESULTS: We found diverse levels of CYT across different cancer types, with highest levels in kidney, lung, and cervical cancers, and lowest levels in glioma, adrenocortical carcinoma (ACC), and uveal melanoma. GZMA protein was either lowly expressed or absent in at least half of these tumors; whereas PRF1 protein was not detected in almost any of the different tumor types, analyzing tissue microarrays from 20 different tumor types. CYT was significantly higher in metastatic skin melanoma and correlated significantly to the TIL load. In TCGA-ACC, skin melanoma, and bladder cancer, CYT was associated with an improved patient outcome and high levels of both GZMA and PRF1 synergistically affected patient survival in these cancers. In bladder, breast, colon, esophageal, kidney, ovarian, pancreatic, testicular, and thyroid cancers, high CYT was accompanied by upregulation of at least one immune-checkpoint molecule, indicating that similar to melanoma and prostate cancer, immune responses in cytolytic-high tumors elicit immune suppression in the tumor microenvironment. CONCLUSION: Overall, our data highlight the existence of diverse levels of CYT across different cancer types and suggest that along with the existence of complicated associations among various tumor-infiltrated immune cells, it is capable to promote or inhibit the establishment of a permissive tumor microenvironment, depending on the cancer type. High levels of immunosuppression seem to exist in several tumor types.

Development of a Robotic System for Enhancing Children's Motivation in Constraint Induced Movement Therapy (CIMT).

This paper presents a novel robotic system, which aims to enhance children's motivation through the gamification of the CIMT process. The system offers adjustability of the required movement skills, ensuring children will put increasingly more effort to achieve the rehabilitation goal, while keeping the task fun and engaging.

The concept of ageing in evolutionary algorithms: Discussion and inspirations for human ageing.

This paper discusses the concept of ageing as this applies to the operation of Evolutionary Algorithms, and examines its relationship to the concept of ageing as this is understood for human beings. Evolutionary Algorithms constitute a family of search algorithms which base their operation on an analogy from the evolution of species in nature. The paper initially provides the necessary knowledge on the operation of Evolutionary Algorithms, focusing on the use of ageing strategies during the implementation of the evolutionary process. Background knowledge on the concept of ageing, as this is defined scientifically for biological systems, is subsequently presented. Based on this information, the paper provides a comparison between the two ageing concepts, and discusses the philosophical inspirations which can be drawn for human ageing based on the operation of Evolutionary Algorithms.

Plexiglas (polymethylmethacrylate) implantation: technique, pre-clinical and clinical experience.

Over the past few decades, a great scientific effort has been made to treat gastroesophageal reflux disease (GERD). This reflects a trend in modem medicine toward optimizing quality of life, reducing health-related lost working hours, and minimizing costs of chronic treatments. It also reflects a revived interest in diseases that can be studied using novel equipment and that can be cured using minimally invasive techniques. In an effort to further minimize surgical trauma, novel endoscopic techniques are beginning to challenge the standard therapeutic approach to GERD.

A retroesophageal right subclavian artery originating from the left aortic arch -- a case report and review of the literature.

The retroesophageal right subclavian artery is an anatomical abnormality encountered by anatomists and pathologists and recently interventional cardiologists and thoracic surgeons have also come across this phenomenon. We report a case of a retroesophageal right subclavian artery arising from a normally located left aortic arch in a young male autopsied in the Department of Forensic Service of Warsaw Medical University. In addition to the aforementioned anomaly, the presence of a right non-recurrent inferior laryngeal nerve was noticed. The possible embryonic development of these branching patterns and their clinical significance is discussed.

The acute physicians unit in scarborough hospital.

AIM: The aim of Acute Physicians Unit (APU) in Scarborough Hospital is consultant led delivery of acute medical care. It operates weekdays from 9am to 5pm, staffed by a consultant physician, a trained nurse and an auxiliary nurse. We reviewed the APU activity over 38 months. RESULTS: 7170 patients were referred to APU, mainly from GPs (59.6%) and A&E (26.5%). The most common type of referrals: cardiovascular 21%, neurological 16.9% and respiratory 15.1%. It prevented admission in 2217 cases (30.9%): 22.4% were sent home after assessment in APU and in 8.5% telephone advice was sufficient. CONCLUSION: The APU has led to early consultant review in 53% of admissions, discharge of 31% of patients and is a useful source of consultation for GPs.