Outcomes of drug-coated balloon angioplasty in patients with dyslipidemia in the BIOLUX P-III registry: A subgroup analysis.

OBJECTIVES: The aim of this study was to assess the mid-term outcomes of the use of drug-coated balloons (DCBs) to treat infrainguinal peripheral arterial disease (PAD) in patients with dyslipidemia. METHODS: BIOLUX P-III is a prospective, international, multicenter, all-comers registry-based study that was conducted at 44 sites with follow-ups at 6, 12 and 24 months. The present study is a subgroup analysis comparing the outcomes associated with endovascular revascularization with those associated with Passeo-18 lux DCBs in patients with and without dyslipidemia. The proportions of patients free from major adverse events (defined as device- or procedure-related mortality within 30 days, clinically driven target lesion revascularization (CD-TLR) and major target limb amputation), target vessel revascularization, and patient-reported outcomes within 24 months postintervention were compared between the two groups. RESULTS: A total of 876 patients with symptomatic PAD who underwent peripheral revascularization with DCBs and had information on their dyslipidemia status were included; 588 of those patients had dyslipidemia. There was no difference in the proportion of patients free from MAEs between the groups. The percentages of patients who were 6, 12 and 24 months free from CD-TLR were significantly lower in the dyslipidemia group than in the nondyslipidemia group (86.3% vs 91.9% at 2 years, p = .0183). Similarly, the percentage of patients free from target vessel revascularization was lower in the dyslipidemia group at all timepoints (83.3% vs 89.3% at 2 years, p = .0203). There was no difference in mortality or major or minor limb amputation rates. Other secondary outcomes were similar between the groups. CONCLUSIONS: Compared to those without dyslipidemia, patients with symptomatic PAD and dyslipidemia who underwent revascularization with a Passeo-18 lux DCB had greater rates of CD-TLR and TVR. However, having dyslipidemia did not increase the risk of mortality or limb amputation. CLINICAL TRIAL REGISTRATION: NCT02276313.

The Importance of Prion Research.

Over the past four decades, prion diseases have received considerable research attention owing to their potential to be transmitted within and across species as well as their consequences for human and animal health. The unprecedented nature of prions has led to the discovery of a paradigm of templated protein misfolding that underlies a diverse range of both disease-related and normal biological processes. Indeed, the "prion-like" misfolding and propagation of protein aggregates is now recognized as a common underlying disease mechanism in human neurodegenerative disorders such as Alzheimer's and Parkinson's disease and the prion principle has led to the development of novel diagnostic and therapeutic strategies for these illnesses. Despite these advances, research into the fundamental biology of prion diseases has declined, likely due to their rarity and the absence of an acute human health crisis. Given the past translational influence, continued research on the etiology, pathogenesis, and transmission of prion disease should remain a priority. In this review we highlight several important "unsolved mysteries" in the prion disease research field and how solving them may be crucial for the development of effective therapeutics, preventing future outbreaks of prion disease, and understanding the pathobiology of more common human neurodegenerative disorders.

Optimal surgical approach for mid-transverse colon cancer: a systematic review and meta-analysis.

BACKGROUND AND AIM: The incidence of cancer colon has increased dramatically. In addition, the database lacks a review to analyze the outcomes of surgeries for mid-transverse colon cancer with several recent controversial studies. We aimed to compare the outcomes of extended hemicolectomy versus transverse colectomy for mid-transverse colon cancer. METHOD: PubMed, Scopes, Web of Science and Cochrane Library were searched for eligible studies from inception to 1 December 2022 and a systematic review and meta-analysis were done to detect. RESULTS: According to eligibility criteria, 8 studies (2237 patients) were included in our study. The pooled results of the included studies showed no difference in the 5-year OS, 3-year DFS and 5-year DFS between the two types of surgery (5-year OS, RR = 1.15, 95% CI 0.94-1.39, P = 0.17), (3-year OS, RR = 0.96, 95% CI 0.88-1.06, P = 0.42) and (5-year DFS, RR = 1.21, 95% CI 0.91-1.62, P = 0.20). In addition to that, the recurrence rate and the incidence of complications were similar in the two groups (Recurrence rate, RR = 1.08, 95% CI 0.62-1.89, P = 0.79) and (Complications, RR = 1.07, 95% CI 0.74-1.54, P = 0.72). However, the number of LN harvest and the time of the operation were more in case of extended hemicolectomy. CONCLUSION: Despite harvesting less LN, transverse colectomy has similar oncological outcomes to extended hemicolectomy for mid-transverse colon cancer. In addition to that, there was no significant difference in the incidence of complications between the two surgeries.

Intraoperative Extravascular Ultrasound in the Identification of Flow-Limiting Dissections after Balloon Angioplasty in the Femoropopliteal Segment.

Background: The BIO REACT study is designed to investigate the incremental value of Extravascular UltraSound (EVUS) added to conventional angiography, compared to conventional angiography only for the identification of Flow-Limiting Dissections (FLD) and to evaluate the safety and efficacy of the REsponse Adapted Combination Therapy (REACT) for the treatment of femoropopliteal lesions. Methods: The primary endpoints were the specificity and sensitivity of EVUS added to angiography for the detection of FLD. Secondary endpoints were primary patency of the REACT therapy within 12 months, fCD-TLR, freedom from MAE, major target limb amputations (mTLA) and survival rates within 24 months. Results: A total of 150 patients were included. EVUS added to angiography had an overall sensitivity of 29% and specificity of 93% for the detection of FLD. There was no PSVR cut-off offering a clinically acceptable trade-off between meaningful sensitivity and specificity values for the detection of FLD. At 12 months, treatment with the REACT resulted in primary patency and fCD-TLR of 81.6% and 94.3%, respectively. In addition, freedom from MAE was 94.3% at 12 months. At 24 months, the survival rate was 94.0%. No mTLA was reported up to the 24-month follow-up. Conclusions: The addition of DUS to angiography showed limited value for detecting FLD in femoropopliteal artery disease.

Pten regulates endocytic trafficking of cell adhesion and Wnt signaling molecules to pattern the retina.

The retina is exquisitely patterned, with neuronal somata positioned at regular intervals to completely sample the visual field. Here, we show that phosphatase and tensin homolog (Pten) controls starburst amacrine cell spacing by modulating vesicular trafficking of cell adhesion molecules and Wnt proteins. Single-cell transcriptomics and double-mutant analyses revealed that Pten and Down syndrome cell adhesion molecule Dscam) are co-expressed and function additively to pattern starburst amacrine cell mosaics. Mechanistically, Pten loss accelerates the endocytic trafficking of DSCAM, FAT3, and MEGF10 off the cell membrane and into endocytic vesicles in amacrine cells. Accordingly, the vesicular proteome, a molecular signature of the cell of origin, is enriched in exocytosis, vesicle-mediated transport, and receptor internalization proteins in Pten conditional knockout (PtencKO) retinas. Wnt signaling molecules are also enriched in PtencKO retinal vesicles, and the genetic or pharmacological disruption of Wnt signaling phenocopies amacrine cell patterning defects. Pten thus controls vesicular trafficking of cell adhesion and signaling molecules to establish retinal amacrine cell mosaics.

Efficacy of embolotherapy for the treatment of pelvic congestion syndrome: A systematic review.

Pelvic congestion syndrome (PCS) poses a significant health, diagnostic, and economic challenges. Transcatheter embolisation has emerged as a promising treatment for PCS. A systematic review was performed in order to assess the safety and efficacy of transcatheter embolisation in the treatment of PCS. A systematic search of electronic databases was performed using 'PubMed', 'Embase', 'Medline (OVID)', and 'Web of Science', for articles pertaining to efficacy of embolotherapy for the treatment of pelvic congestion syndrome. A total of 25 studies were included in this systematic review with a combined total of 2038 patients. All patients included were female with a mean average age of 37.65 (31-51). Of the 25 studies, 18/25 studies reported pre- and post-procedural pelvic pain outcomes using a visual analogue scale (VAS). All studies showed a reduction in VAS post-procedure. Transcatheter embolisation had a high technical success rate (94%) and an overall complication rate of 9.0%, of which 10.4% were major and 89.6% were minor. Fifteen out of 19 (78.9%) major complications required a subsequent intervention. Transcatheter embolisation using various techniques is effective and safe in treating PCS. A low quality of evidence limits the currently available literature; however, embolisation has shown to improve symptoms in the majority of patients with low complication rates and recurrence rates.

Injury Severity is a Key Contributor to Coagulation Dysregulation and Fibrinogen Consumption.

Background: Traumatic injury is a leading cause of death for those under the age of 45, with 40% occurring due to hemorrhage. Severe tissue injury and hypoperfusion lead to marked changes in coagulation, thereby preventing formation of a stable blood clot and increasing hemorrhage associated mortality. Objectives: We aimed to quantify changes in clot formation and mechanics occurring after traumatic injury and the relationship to coagulation kinetics, and fibrinolysis. Methods: Plasma was isolated from injured patients upon arrival to the emergency department. Coagulation kinetics and mechanics of healthy donors and patient plasma were compared with rheological, turbidimetric and thrombin generation assays. ELISA's were performed to determine tissue plasminogen activator (tPA) and D-dimer concentration, as fibrinolytic markers. Results: Sixty-three patients were included in the study. The median injury severity score (ISS) was 17, median age was 37.5 years old, and mortality rate was 30%. Rheological, turbidimetric and thrombin generation assays indicated that trauma patients on average, and especially deceased patients, exhibited reduced clot stiffness, increased fibrinolysis and reduced thrombin generation compared to healthy donors. Fibrinogen concentration, clot stiffness, D-dimer and tPA all demonstrated significant direct correlation to increasing ISS. Machine learning algorithms identified and highlighted the importance of clinical factors on determining patient outcomes. Conclusions: Viscoelastic and biochemical assays indicate significant contributors and predictors of mortality for improved patient treatment and therapeutic target detection. ESSENTIALS: Traumatic injury may lead to alterations in a patient's ability to form stable blood clotsA study was performed to assess how trauma severity affects coagulation kineticsKey alterations were observed in trauma patients, who exhibit weaker and slower forming clotsPaired with machine learning methods, the results indicate key aspects contributing to mortality.