Gupta Perioperative Risk for Myocardial Infarction or Cardiac Arrest score is a long-term cardiovascular risk predictor after aortoiliac revascularization.

INTRODUCTION: Gupta Perioperative Risk for Myocardial Infarction or Cardiac Arrest (MICA) is a validated self-explanatory score applied in cardiac or non-cardiac surgeries. This study aims to assess the predictive value of the MICA score for cardiovascular events after aortoiliac revascularization. METHODS: This prospective cohort underwent elective aortoiliac revascularization between 2013 and 2021. Patients' demographic, clinical characteristics and outcomes were registered. The patients were divided into two groups according to the MICA score using optimal binning. Survival analysis to test for time-dependent variables and multivariate Cox regression analysis for independent predictors were performed. RESULTS: This study included 130 patients with a median follow-up of 55 months. Preoperative MICA score was ≥ 6.5 in 41 patients. MICA ≥ 6.5 presented a statistically significant association with long-term occurrence of acute heart failure (HR=1.695, 95% CI 1.208-2.379, p=0.002), major adverse cardiovascular events (HR=1.222, 95% CI 1.086-1.376, p<0.001) and all-cause mortality (HR=1.256, 95% CI 1.107-1.425, p<0.001). Multivariable Cox regression confirmed MICA as a significant independent predictor of long-term major adverse cardiovascular events (aHR=1.145 95%CI 1.010-1.298, p=0.034) and all-cause mortality (aHR=1.172 95%CI 1.026-1.339, p=0.020). CONCLUSION: The MICA score is a quick, easy-to-obtain, predictive tool in identifying patients with a higher risk of post-aortoiliac revascularization cardiovascular events, such as acute heart failure, major adverse cardiovascular events and all-cause mortality. Additional research for validation of the MICA score in the context of aortoiliac revascularization and specific interventions are necessary.

Short-term outcomes after selective shunt during carotid endarterectomy: a propensity score matching analysis.

INTRODUCTION AND OBJECTIVES: Carotid cross-clamping during carotid endarterectomy might lead to intraoperative neurologic deficits, increasing stroke/death risk. If deficits are detected, carotid shunting has been recommended to reduce the risk of stroke. However, shunting may sustain a specific chance of embolic events and subsequently incurring harm. Current evidence is still questionable regarding its clear benefit. The aim is to determine whether a policy of selective shunt impacts the complication rate following an endarterectomy. MATERIAL AND METHODS: From January 2013 to May 2021, all patients undergoing carotid endarterectomy under regional anesthesia with intraoperative neurologic alteration were retrieved. Patients submitted to selective shunt were compared to a non-shunt group. A 1:1 propensity score matching (PSM) was performed. Differences between the groups and clinical outcomes were calculated, resorting to univariate analysis. RESULTS: Ninety-eight patients were selected, from which 23 were operated on using a shunt. After PSM, 22 non-shunt patients were compared to 22 matched shunted patients. Concerning demographics and comorbidities, both groups were comparable to pre and post-PSM, except for chronic heart failure, which was more prevalent in shunted patients (26.1%, P=0.036) in pre-PSM analysis. Regarding 30-day stroke and score Clavien-Dindo ≥2, no significant association was found (P=0.730, P=0.635 and P=0.942, P=0.472, correspondingly, for pre and post-PSM). CONCLUSIONS: In this cohort, resorting to shunting did not demonstrate an advantage regarding 30-day stroke or a Clavien-Dindo ≥ 2 rates. Nevertheless, additional more extensive studies are mandatory to achieve precise results concerning the accurate utility of carotid shunting in this subset of patients under regional anesthesia.

Prolonged survival of venereal Tritrichomonas foetus parasite in the gastrointestinal tract, bovine fecal extract, and water.

IMPORTANCE: Nowadays, the routine herd diagnosis is usually performed exclusively on bulls, as they remain permanently infected, and prevention and control of Tritrichomonas foetus transmission are based on identifying infected animals and culling practices. The existence of other forms of transmission and the possible role of pseudocysts or cyst-like structures as resistant forms requires rethinking the current management and control of this parasitic disease in the future in some livestock regions of the world.

In vitro bioevaluation and docking study of dihydrosphingosine and ethambutol analogues against sensitive and multi-drug resistant Mycobacterium tuberculosis.

Tuberculosis remains a major public health problem and one of the top ten causes of death worldwide. The alarming increase in multidrug-resistant and extensively resistant variants (MDR, pre-XDR, and XDR) makes the disease more difficult to treat and control. New drugs that act against MDR/XDR strains are needed for programs to contain this major epidemic. The present study aimed to evaluate new compounds related to dihydro-sphingosine and ethambutol against sensitive and pre-XDR Mycobacterium strains, as well as to characterize the pharmacological activity through in vitro and in silico approaches in mmpL3 protein. Of the 48 compounds analyzed, 11 demonstrated good to moderate activity on sensitive and MDR Mycobacterium tuberculosis (Mtb), with a Minimum Inhibitory Concentration (MIC) ranging from 1.5 to 8 µM. They presented 2 to 14 times greater potency of activity when compared to ethambutol in pre-XDR strain, and demonstrated a selectivity index varying between 2.21 and 82.17. The substance 12b when combined with rifampicin, showed a synergistic effect (FICI = 0.5) on sensitive and MDR Mtb. It has also been shown to have a concentration-dependent intracellular bactericidal effect, and a time-dependent bactericidal effect in M. smegmatis and pre-XDR M. tuberculosis. The binding mode of the compounds in its cavity was identified through molecular docking and using a predicted structural model of mmpL3. Finally, we observed by transmission electron microscopy the induction of damage to the cell wall integrity of M. tuberculosis treated with the substance 12b. With these findings, we demonstrate the potential of a 2-aminoalkanol derivative to be a prototype substance and candidate for further optimization of molecular structure and anti-tubercular activity in preclinical studies.

Role of cytoneme structures and extracellular vesicles in Trichomonas vaginalis parasite-parasite communication.

Trichomonas vaginalis, the etiologic agent of the most common non-viral sexually transmitted infection worldwide. With an estimated annual prevalence of 276 million new cases, mixed infections with different parasite strains are expected. Although it is known that parasites interact with their host to enhance their own survival and transmission, evidence of mixed infections call into question the extent to which unicellular parasites communicate with each other. Here, we demonstrated that different T. vaginalis strains can communicate through the formation of cytoneme-like membranous cell connections. We showed that cytonemes formation of an adherent parasite strain (CDC1132) is affected in the presence of a different strain (G3 or B7RC2). Our findings provide evidence that this effect is contact-independent and that extracellular vesicles (EVs) are responsible, at least in part, of the communication among strains. We found that EVs isolated from G3, B7RC2, and CDC1132 strains contain a highly distinct repertoire of proteins, some of them involved in signaling and communication, among other functions. Finally, we showed that parasite adherence to host cells is affected by communication between strains as binding of adherent T. vaginalis CDC1132 strain to prostate cells is significantly higher in the presence of G3 or B7RC2 strains. We also observed that a poorly adherent parasite strain (G3) adheres more strongly to prostate cells in the presence of an adherent strain. The study of signaling, sensing, and cell communication in parasitic organisms will enhance our understanding of the basic biological characteristics of parasites, which may have important consequences in pathogenesis.

Extracellular vesicle-localized miR-203 mediates neural crest-placode communication required for trigeminal ganglia formation.

While interactions between neural crest and placode cells are critical for the proper formation of the trigeminal ganglion, the mechanisms underlying this process remain largely uncharacterized. Here, we show that the microRNA-(miR)203, whose epigenetic repression is required for neural crest migration, is reactivated in coalescing and condensing trigeminal ganglion cells. Overexpression of miR-203 induces ectopic coalescence of neural crest cells and increases ganglion size. Reciprocally, loss of miR-203 function in placode, but not neural crest, cells perturbs trigeminal ganglion condensation. Demonstrating intercellular communication, overexpression of miR-203 in the neural crest in vitro or in vivo represses a miR-responsive sensor in placode cells. Moreover, neural crest-secreted extracellular vesicles (EVs), visualized using pHluorin-CD63 vector, become incorporated into the cytoplasm of placode cells. Finally, RT-PCR analysis shows that small EVs isolated from condensing trigeminal ganglia are selectively loaded with miR-203. Together, our findings reveal a critical role in vivo for neural crest-placode communication mediated by sEVs and their selective microRNA cargo for proper trigeminal ganglion formation.

Red blood cell distribution width as a predictor of cardiovascular outcomes in extensive aortoiliac disease.

BACKGROUND: Aortoiliac peripheral artery disease may lead to disabling lower limb claudication or to lower limb chronic threatening ischemia, which is associated with increased short and long-term morbi-mortality. The red blood cell distribution width-coefficient of variation (RDW-CV) has been able to predict outcomes in other atherosclerotic diseases, such as myocardial infarction and stroke. The main objective of this study was to assess the predictive ability of perioperative RDW-CV in accurately predicting short and long-term major adverse cardiovascular events (MACE) and all-cause mortality in patients submitted to aortoiliac revascularization due to extensive aortoiliac atherosclerotic disease. METHODS: From 2013 to 2020, patients who underwent aortoiliac revascularization due to severe aortoiliac disease were included in a prospective cohort. Blood samples were taken preoperatively and the patient's demographics, comorbidities, and postoperative outcomes were assessed. A multivariate Cox regression model was used to adjust for confounding and assess the independent effect of these prognostic factors on the outcomes. RESULTS: The study group included 107 patients. Median follow-up was 57 (95% CI: 34.4-69.6) months. Preoperative RDW-CV was increased in thirty-eight patients (35.5%). Increased RDW-CV was associated with congestive heart failure - adjusted odds ratio of 5.043 (95% CI: 1.436-17.717, P=0.012). It could predict long-term occurrence of MACE (adjusted hazard ratio [aHR] 1.065, 95% CI: 1.014-1.118, P=0.011), all-cause mortality (aHR=1.069, 95% CI: 1.014-1.126, P=0.013), acute heart failure (AHF) (aHR=1.569, 95% CI: 1.179-2.088, P=0.002), and stroke (aHR=1.343, 95% CI: 1.044-1.727, P=0.022). CONCLUSIONS: RDW is a widely available and low-cost marker that was able to independently predict long-term AHF, stroke, MACE, and all-cause mortality in patients with extensive aortoiliac disease submitted to revascularization. This biomarker could help assess which patients would likely benefit from stricter follow-up in the long-term.

The Gupta Perioperative Risk for Myocardial Infarct or Cardiac Arrest (MICA) Calculator as an Intraoperative Neurologic Deficit Predictor in Carotid Endarterectomy.

BACKGROUND: Patients undergoing carotid endarterectomy (CEA) may experiment intraoperative neurologic deficits (IND) during carotid cross-clamping. This work aimed to assess the impact of the Gupta Perioperative Myocardial Infarct or Cardiac Arrest (MICA) risk calculator in the IND. METHODS: From January 2012 to April 2021, patients undergoing CEA with regional anaesthesia for carotid stenosis with IND and consecutively control operated patients without IND were selected. A regressive predictive model was created, and a receiver operating characteristic (ROC) curve was applied for comparison. A multivariable dependence analysis was conducted using a classification and regression tree (CRT) algorithm. RESULTS: A total of 97 out of 194 included patients developed IND. Obesity showed aOR = 4.01 (95% CI: 1.66-9.67) and MICA score aOR = 1.21 (1.03-1.43). Higher contralateral stenosis showed aOR = 1.29 (1.08-1.53). The AUROC curve was 0.656. The CRT algorithm differentiated obese patients with a MICA score ≥ 8. Regarding non-obese patients, the model identified the presence of contralateral stenosis ≥ 55% with a MICA ≥ 10. CONCLUSION: MICA score might play an additional role in stratifying patients for IND in CEA. Obesity was determined as the best discrimination factor, followed by a score ≥ 8. A higher ipsilateral stenosis degree is suggested to have a part in avoiding procedure-related IND. Larger studies might validate the benefit of MICA score regarding the risk of IND.

Distinct mRNA and protein interactomes highlight functional differentiation of major eIF4F-like complexes from Trypanosoma brucei.

Gene expression in pathogenic protozoans of the family Trypanosomatidae has several novel features, including multiple eIF4F-like complexes involved in protein synthesis. The eukaryotic eIF4F complex, formed mainly by eIF4E and eIF4G subunits, is responsible for the canonical selection of mRNAs required for the initiation of mRNA translation. The best-known complexes implicated in translation in trypanosomatids are based on two related pairs of eIF4E and eIF4G subunits (EIF4E3/EIF4G4 and EIF4E4/EIF4G3), whose functional distinctions remain to be fully described. Here, to define interactomes associated with both complexes in Trypanosoma brucei procyclic forms, we performed parallel immunoprecipitation experiments followed by identification of proteins co-precipitated with the four tagged eIF4E and eIF4G subunits. A number of different protein partners, including RNA binding proteins and helicases, specifically co-precipitate with each complex. Highlights with the EIF4E4/EIF4G3 pair include RBP23, PABP1, EIF4AI and the CRK1 kinase. Co-precipitated partners with the EIF4E3/EIF4G4 pair are more diverse and include DRBD2, PABP2 and different zinc-finger proteins and RNA helicases. EIF4E3/EIF4G4 are essential for viability and to better define their role, we further investigated their phenotypes after knockdown. Depletion of either EIF4E3/EIF4G4 mRNAs lead to aberrant morphology with a more direct impact on events associated with cytokinesis. We also sought to identify those mRNAs differentially associated with each complex through CLIP-seq with the two eIF4E subunits. Predominant among EIF4E4-bound transcripts are those encoding ribosomal proteins, absent from those found with EIF4E3, which are generally more diverse. RNAi mediated depletion of EIF4E4, which does not affect proliferation, does not lead to changes in mRNAs or proteins associated with EIF4E3, confirming a lack of redundancy and distinct roles for the two complexes.

Revised cardiac score index is a predictor of long-term outcomes after carotid endarterectomy.

Background: Cardiac complications represent the main cause of mortality after non-cardiac surgery and the Revised Cardiac Risk Index (RCRI) was created to estimate the perioperative risk of these events. It considers history of ischaemic heart disease, congestive heart failure, diabetes requiring preoperative insulin, stroke or transient ischaemic attack and renal impairment. We aim to describe the accuracy of the RCRI for predicting perioperative major adverse cardiovascular events (MACE) - a composite of heart failure, ischemic events and all-cause death. Also, the authors aimed to review the score for better prediction of cardiovascular outcomes. Patients and methods: From January 2012 to January 2020, patients who underwent Carotid endarterectomy (CEA) with regional anaesthesia (RA) were selected. RCRI was calculated for each case. Estimated and reported cardiovascular complications were compared using multivariate logistic regression and cox proportional hazards. An alternative and optimized carotid-RCRI (CtRCRI) was obtained. Overall predictive accuracy was assessed and compared by measuring model discrimination. Adjustments for overfitting and evaluation of the new model were performed by bootstrap. Results: 186 patients were selected, of which 80% were male with a mean age of 70.0±9.05 years old. The median follow-up was 50 months, interquartile range 21-69 months. None of the scores were able to predict MACE in the perioperative period. Both were associated with 30-day Clavien-Dindo ≥2 (p=0.022 and p=0.041, respectively). Regarding long-term prognosis, both were able to predict MACE (RCRI: hazard ratio (HR) 3.54 (95% confidence interval [CI] 1.04-11.48) vs. CtRCRI: HR 2.08 (95%CI 1.08-3.98) and all-cause mortality (RCRI: HR 3.33, 95%CI 0.99-11.11 vs. CtRCRI: HR 1.57, 95%CI 1.14-7.04). Conclusions: RCRI and CtRCRI did not predict MACE in the perioperative period but are good predictors of 30-day complications (Clavien-Dindo ≥2). Both RCRI and CtRCRI have good prognostic value as predictors of long-term cardiovascular events.

The Impact of the First COVID-19 Wave on European Vascular Education.

INTRODUCTION: Public health was severely affected by the first wave of the COVID-19 pandemic, imposing major daily life changes across the world, including health services that had to restructure significantly. REPORT: Considering the potential side effects on the quality of vascular training, a digital survey (Survey Monkey®) was developed and submitted to vascular trainees from 7 July to 20 September 2020 through European mailing lists and social media platforms. The aim was to evaluate the standpoint of vascular education across Europe during the first wave of the COVID-19 pandemic and to identify possible measures to mitigate the negative effects on vascular trainees. A total of 104 answers across 27 European countries were received. The mean age of the responders was 31.2 ± 3.58 years, of whom 60.6% were male. Forty-four (42.3%) of the vascular trainees actively participated on the COVID-19 front line; 76.9% of them reported a decrease in surgical procedures performed and/or assisted, with 60% reporting a reduction >50%. Emergency procedures were the only surgical activities for 7.5% of the trainees. Annual or final examinations were re-scheduled or cancelled for 16.3% and 10.6% of the participants, respectively. According to the survey, 73.5% of the responders claimed that the first wave of the COVID-19 pandemic had a negative impact on vascular education and 73.4% agreed the need for "compensation measures" to be taken. DISCUSSION: The first wave of the COVID-19 pandemic brought a significant negative impact on vascular education. Considering an extended pandemic situation, it is believed that compensatory measures should be addressed to maintain the high standards of vascular education and develop new educational tools for future trainees.

Mean Platelet Volume Predicts Restenosis After Carotid Endarterectomy.

BACKGROUND: Carotid restenosis following carotid endarterectomy (CEA) has a cumulative risk at 5-years up to 32%, which may impact the well-being of patients following CEA. Haematological parameters in the standard complete blood cell count (CBC) are emerging as potential biomarkers, but their application in CEA is scarce. The primary aim of this study was to investigate haematological markers for restenosis following CEA. The secondary aim was to characterize clinical risk factors for restenosis. METHODS: From January 2012 to January 2019, 151 patients who underwent CEA under regional anaesthesia due to carotid stenosis were selected from a prospectively maintained cohort database. Patients were included if a preoperative CBC was available in the 2 weeks preceding CEA. Multivariable analysis was performed alongside propensity score matching (PSM) analysis, using the preoperative CEA parameters, to reduce confounding factors between categories. RESULTS: The study group comprised 28 patients who developed carotid restenosis. The remaining 123 patients without restenosis composed the control group. Mean age of the patients did not differ significantly between groups (70.25 ± 8.05 vs. 70.32 ± 9.61 YO, P = 0.973), neither did gender (male gender 89.3% vs. 78.9%, P = 0.206). Regarding haematological parameters, only MPV remained statistically significant within multivariable analysis (1.855, aOR [1.174-2.931], P = 0.008), a result supported by PSM analysis (2.072, aOR [1.036-4.147], P = 0.042). CONCLUSIONS: MPV was able to predict restenosis 2 years after CEA. Thus, MPV can be incorporated into score calculations to identify patients at greater risk of restenosis, who could benefit from specific monitoring during follow-up. While results are promising, more research is necessary to corroborate them.

Outcome Analysis Using the Modified Frailty Index-5 in Patients With Complex Aortoiliac Disease.

OBJECTIVES: Vascular surgery patients commonly have several comorbidities that cumulatively lead to a frailty status. The cumulative comorbidities disproportionately increase the risk of adverse events and are also associated with worsened long-term prognosis. In recent years, several tools have been elaborated with the objective of quantifying a patient's frailty. One of them is the modified frailty index-5 (mFI-5), a simplified and easy to use index. There is scarce data regarding its value as a prognostic factor in aortoiliac occlusive disease. The aim of this work is to validate mFI-5 as a potential postoperative prognostic indicator in this population. METHODS: From January 2013 to January 2020, 109 patients who underwent elective revascularizations, either endovascular or open surgery, having Trans-Atlantic Inter-Society Consensus II type D aortoiliac lesions in a tertiary and a regional hospital were selected from a prospective vascular registry. Demographic data was collected including diabetes mellitus, chronic heart failure, chronic obstructive pulmonary disease, arterial hypertension requiring medication and functional status. The 30-d and subsequent long-term surveillance outcomes were also collected including major adverse cardiovascular events (MACE), major adverse limb events (MALE) and all-cause mortality were assessed in the 30-d post-procedure and in the subsequent long-term surveillance period. The mFI-5 was applied to this population to evaluate the prognostic impact of this frailty marker on mortality and morbidity. RESULTS: In the long-term follow-up, mFI-5 was significantly associated with MACE (hazard ratio [HR] 2.469; 95% confidence interval [CI]: 1.267-4.811; P = .008) and all-cause mortality (HR 2.585; 95% CI: 1.270-5.260; P = .009). However, there was no significant association with 30-day outcomes. Along with the presence of chronic kidney disease, mFI-5 was the prognostic factor better able of predicting MACE. No prognostic value was found regarding short-term outcomes. CONCLUSION: The mFI-5 index may have a role in predicting long term outcomes, namely MACE and all-cause mortality, in the subset of patients with extensive aortoiliac occlusive disease. Its ease of use can foster its application in risk stratification and contribute for the decision-making process.

Contralateral Carotid Stenosis is a Predictor of Long-term Adverse Events in Carotid Endarterectomy.

Contralateral carotid stenosis (clCS) has been described as a perioperative predictor of mortality after carotid endarterectomy (CEA). However, its predictive value on long-term cardiovascular events remains controversial. The study aims to assess the potential role of clCS as a long-term predictor of major adverse cardiovascular events (MACE) in patients who underwent CEA. From January 2012 to July 2020, patients undergoing CEA under regional anesthesia for carotid stenosis in a tertiary care and referral center were eligible from a prospective database, and a post hoc analysis was performed. The primary outcome consisted in the occurrence of long-term MACE. Secondary outcomes included all-cause mortality, stroke, myocardial infarction, acute heart failure, and major adverse limb events. A total of 192 patients were enrolled. With a median 50 months follow-up, chronic kidney disease (CKD) (mean survival time (MST) 51.7 vs. 103.3, P < 0.010) and peripheral artery disease (PAD) (MST 75.1 vs. 90.3, P = 0.001) were associated with decreased survival time. After propensity score matching (PSM), CKD (MST 49.1 vs. 106.0, P = 0.001) and PAD (MST 75.7 vs. 94.0, P = 0.001) maintained this association. On multivariate Cox regression analysis, contralateral stenosis was associated with higher MACE (hazard ratio (HR) = 2.035; 95% CI: 1.113-3.722, P = 0.021 and all-cause mortality (HR = 2.564; 95% CI: 1.276-5,152 P = 0.008). After PSM, only all-cause mortality (HR 2.323; 95% CI: 0.993-5.431, P = 0.052) maintained a significant association with clCS. On multivariable analysis, clCS (aHR 2.367; 95% CI: 1.174-4.771, P = 0.016), age (aHR 1.039, 95% CI: 1.008-1.070), CKD (aHR 2.803; 95% CI: 1.409-5.575, P = 0.003) and PAD (aHR 3.225, 95% CI: 1.695-6.137, P < 0.001) were independently associated with increased all-cause mortality. Contrary to MACE, clCS is a strong predictor of long-term all-cause mortality after CEA. However, MACE risk may compromise CEA benefits by other competitive events. Therefore, further studies are needed to establish the role of clCS on postoperative events and on patients' specific assessments in order to determine the best medical treatment and easy access to surgical intervention.

Ultrastructural and Functional Analysis of a Novel Extra-Axonemal Structure in Parasitic Trichomonads.

Trichomonas vaginalis and Tritrichomonas foetus are extracellular flagellated parasites that inhabit humans and other mammals, respectively. In addition to motility, flagella act in a variety of biological processes in different cell types, and extra-axonemal structures (EASs) have been described as fibrillar structures that provide mechanical support and act as metabolic, homeostatic, and sensory platforms in many organisms. It has been assumed that T. vaginalis and T. foetus do not have EASs. However, here, we used complementary electron microscopy techniques to reveal the ultrastructure of EASs in both parasites. Such EASs are thin filaments (3-5 nm diameter) running longitudinally along the axonemes and surrounded by the flagellar membrane, forming prominent flagellar swellings. We observed that the formation of EAS increases after parasite adhesion on the host cells, fibronectin, and precationized surfaces. A high number of rosettes, clusters of intramembrane particles that have been proposed as sensorial structures, and microvesicles protruding from the membrane were observed in the EASs. Our observations demonstrate that T. vaginalis and T. foetus can connect to themselves by EASs present in flagella. The protein VPS32, a member of the ESCRT-III complex crucial for diverse membrane remodeling events, the pinching off and release of microvesicles, was found in the surface as well as in microvesicles protruding from EASs. Moreover, we demonstrated that the formation of EAS also increases in parasites overexpressing VPS32 and that T. vaginalis-VPS32 parasites showed greater motility in semisolid agar. These results provide valuable data about the role of the flagellar EASs in the cell-to-cell communication and pathogenesis of these extracellular parasites.

VPS32, a member of the ESCRT complex, modulates adherence to host cells in the parasite Trichomonas vaginalis by affecting biogenesis and cargo sorting of released extracellular vesicles.

Trichomonas vaginalis is a common sexually transmitted extracellular parasite that adheres to epithelial cells in the human urogenital tract. Extracellular vesicles (EVs) have been described as important players in the pathogenesis of this parasite as they deliver proteins and RNA into host cells and modulate parasite adherence. EVs are heterogeneous membrane vesicles released from virtually all cell types that collectively represent a new dimension of intercellular communication. The Endosomal Sorting Complex Required for Transport (ESCRT) machinery contributes to several key mechanisms in which it reshapes membranes. Based on this, some components of the ESCRT have been implicated in EVs biogenesis in other cells. Here, we demonstrated that VPS32, a member of ESCRTIII complex, contribute to the biogenesis and cargo sorting of extracellular vesicles in the parasite T. vaginalis. Moreover, we observe that parasites overexpressing VPS32 have a striking increase in adherence to host cells compared to control parasites; demonstrating a key role for this protein in mediating host: parasite interactions. These results provide valuable information on the molecular mechanisms involved in extracellular vesicles biogenesis, cargo-sorting, and parasite pathogenesis.

The Diagnostic Accuracy of Intra-Operative Near Infrared Spectroscopy in Carotid Artery Endarterectomy Under Regional Anaesthesia: Systematic Review and Meta-Analysis.

OBJECTIVE: Intra-operative near infrared spectroscopy (NIRS) is a non-invasive tool used to monitor regional cerebral oxygen saturation during carotid endarterectomy (CEA), for which accuracy remains unclear. Therefore, this systematic review and meta-analysis aimed to determine the diagnostic accuracy of NIRS in patients undergoing CEA under regional anaesthesia (RA). DATA SOURCES: MEDLINE, Scopus, and Web of Science were searched for studies that compared NIRS with the "awake test" in patients undergoing CEA under RA. REVIEW METHODS: Bivariable random effects meta-analysis was performed to determine the diagnostic accuracy of NIRS to detect cerebral ischaemia. Meta-regression was performed to explore causes of heterogeneity. Meta-analysis of proportions was also performed to determine the accuracy of NIRS in predicting 30 day stroke. Study quality was evaluated using the QUADAS-2 criteria. RESULTS: Eleven primary studies were included, assessing 1 237 participants. The meta-analysis obtained a partial area under the summary receiver operating characteristic curve for diagnosing brain ischaemia of 0.646, with a summary sensitivity of 72.0% (95% confidence interval [CI] 58.1 - 82.7; I2 = 48.6%) and a specificity of 84.1% (95% CI 78.5-88.4; I2 = 48.6%). In meta-regression analysis, the frequency of hypertension (p = .011) and patients with symptomatic carotid stenosis (p = .031) were significant effect modifiers. Higher frequency of arterial hypertension (z score = -2.15; p = .032) and diabetes (z score = -2.12; p = .034) were associated with lower summary sensitivity, while a higher frequency of symptomatic carotid stenosis (z score = 2.11; p = .035) was associated with higher summary sensitivity. Point estimate sensitivity and specificity for predicting 30 day stroke occurrence were 41% (95% CI 19.5 - 66.6; I2 = 0%) and 81.4% (95% CI 74.4 - 86.9, I2 = 65.6%), respectively. CONCLUSION: The results of this study suggest that NIRS as a cerebral monitoring technique does not have sufficiently high sensitivity or specificity to be used alone in the neurological monitoring of patients undergoing CEA under RA.

THE IMPACT OF NEUTROPHIL-TOLYMPHOCYTE RATIO AND PLATELETTO- LYMPHOCYTE RATIO IN CAROTID ARTERY DISEASE.

INTRODUCTION: Inflammation is a common underlying feature of atherosclerosis. Several inflammatory biomarkers have been reported to have prognostic value, in several areas, including in vascular surgery. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) may permit to identify patients at greater risk for cerebrovascular events, tailor patient management, improve preoperative status and possibly develop target anti-atherosclerotic therapy. However, studies reporting usefulness of these hematological biomarkers in the context of carotid artery disease are still scarce. The aim of this study was to review the literature concerning the prognostic ability of NLR and PLR in the subpopulation of vascular patients with carotid artery disease. METHODS: A Medline search was performed in order to identify publications focused on the physiopathology of NLR and PLR and their impact in the management of patients with carotid artery disease. RESULTS: The study identified 18 articles with a total of 5339 patients. NLR is associated with carotid intima-media thickness, carotid plaques, carotid stenosis, symptomatic stenosis and intra-stent restenosis after carotid artery stenting and cognitive dysfunction after carotid endarterectomy. PLR is associated with carotid stenosis, symptomatic stenosis and predicts post-operative outcomes after carotid artery revascularization, including post-operative stroke, acute coronary syndrome and all-cause mortality. CONCLUSIONS: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have the ability to predict sub-clinic atherosclerosis, atherosclerosis progression in carotid artery disease and propensity for carotid stenosis to become symptomatic along with morbidity following CEA and carotid stenting. Consequently, these parameters may be considered to tailored therapy and improve patient management.