The Value of Troponin Measurement in Carotid Revascularization: A Scoping Review.

PURPOSE: Patients undergoing carotid endarterectomy (CEA) or carotid artery stenting (CAS) are at substantially increased risk of short-term and long-term cardiac complications. Still, the role of perioperative troponin in predicting cardiac events remains unclear. The objective was to systematically summarize the existing evidence on the topic and provide directions for further research. MATERIALS AND METHODS: Studies that examined perioperative troponin values and its association with myocardial injury, and/or myocardial infarction (MI), and/or major adverse cardiac events (MACE) and postoperative mortality in exclusively CEA/CAS patients, published in English until March 15, 2022, were retrieved through a systematic search of MEDLINE and Web of Science. The study selection process was independently performed by 2 authors, while the third researcher resolved disagreements. RESULTS: Four studies with 885 participants met the inclusion criteria. Age, chronic kidney disease, presentation of carotid disease, type of closure (primary closure/venous patch/Dacron/polytetrafluoroethylene patch), coronary artery disease, chronic heart failure, and the long-term use of calcium channel blockers represent risk factors for troponin elevation, which occurred in 11% to 15.3%. Myocardial infarction and MACE occurred in 23.5% to 40%, that is, 26.5% of patients with troponin elevation, respectively, during the first 30 postoperative days. Elevated postoperative troponin levels were significantly associated with adverse cardiac events during the long-term surveillance period. The rates of cardiac-related and all-cause mortality were higher in patients with postoperative troponin elevation. CONCLUSION: Troponin measurement could be helpful in the prediction of adverse cardiac events. The predictive role of preoperative troponin, the patient population in whom routine troponin sampling should be used, and a comparison of different treatment methods/anesthesia techniques in carotid patients should be further examined. CLINICAL IMPACT: The present scoping review critically appraises the extent and nature of the existing literature data on the predictive value of troponin on the occurrence of cardiac complications in patients undergoing CEA and CAS. In particular, it provides clinicians with essential insights by systematically summarizing the core evidence and identifying knowledge gaps that may direct future research. This, in turn, may significantly alter the current clinical practice and perhaps even reduce the incidence of cardiac complications in patients undergoing CEA/CAS.

Case Control Study of Risk Factors for Occurrence of Postoperative Hematoma After Thyroid Surgery: Ten Year Analysis of 6938 Operations in a Tertiary Center in Serbia.

BACKGROUND: Post-thyroidectomy bleeding is rare, but potentially life-threatening complication. Early recognition with immediate intervention is crucial for the management of this complication. Therefore, it is very important to identify possible risk factors of postoperative hemorrhage as well as timing of postoperative hematoma occurrence. METHODS: Retrospective review of 6938 patients undergoing thyroidectomy in a tertiary center in a ten year period (2009-2019) revealed 72 patients with postoperative hemorrhage requiring reoperation. Each patient who developed postoperative hematoma was matched with four control patients that did not develop postoperative hematoma after thyroidectomy. The patients and controls were matched by the date of operation and surgeon performing thyroidectomy. RESULTS: The incidence of postoperative bleeding was 1.04%. On univariate analysis older age, male sex, higher BMI, higher ASA score, preoperative use of anticoagulant therapy, thyroidectomy for retrosternal goiter, larger thyroid specimens, larger dominant nodules, longer operative time, higher postoperative blood pressure and the use of postoperative subcutaneous heparin were identified as risk factors for postoperative bleeding. Sixty-nine patients (95.8%) bled within first 24 h after surgery. CONCLUSION: The rate of postoperative bleeding in our study is consistent with recent literature. Male sex, the use of preoperative anticoagulant therapy, thyroidectomy for retrosternal goiter and the use of postoperative subcutaneous heparin remained statistically significant on multivariate analysis (p < 0.001). When identified, these risk factors may be an obstacle to the outpatient thyroidectomy in our settings.

Preoperative Anxiety is Associated With Postoperative Complications in Vascular Surgery: A Cross-Sectional Study.

BACKGROUND: Preoperative anxiety is associated with increased morbidity and/or mortality in surgical patients. This study investigated the incidence, predictors, and association of preoperative anxiety with postoperative complications in vascular surgery. METHODS: Consecutive patients undergoing aortic, carotid, and peripheral artery surgery, under general and regional anesthesia, from February until October 2019 were included in a cross-sectional study. Anesthesiologists assessed preoperative anxiety using a validated Serbian version of the Amsterdam Preoperative Anxiety and Information Scale. Patients were divided into groups with low/high anxiety, both anesthesia- and surgery-related. Statistical analysis included multivariate linear logistic regression and point-biserial correlation. RESULTS: Of 402 patients interviewed, 16 were excluded and one patient refused to participate (response rate 99.7%). Out of 385 patients included (age range 39-86 years), 62.3% had previous surgery. High-level anesthesia- and surgery-related anxieties were present in 31.2 and 43.4% of patients, respectively. Independent predictors of high-level anesthesia-related anxiety were having no children (OR = 0.443, 95% CI: 0.239-0.821, p = 0.01), personal bad experiences with anesthesia (OR = 2.294, 95% CI: 1.043-5.045, p = 0.039), and time since diagnosis for ≥ 4 months (OR = 1.634, 95% CI: 1.023-5.983, p = 0.04). The female sex independently predicted high-level surgery-related preoperative anxiety (OR = 2.387, 95% CI: 1.432-3.979, p = 0.001). High-level anesthesia-related anxiety correlated with postoperative mental disorders (rpb = 0.193, p = 0.001) and pulmonary complications (rpb = 0.104, p = 0.042). Postoperative nausea (rpb = 0.111, p = 0.03) and postoperative mental disorders (rpb = 0.160, p = 0.002) correlated with high-level surgery-related preoperative anxiety. CONCLUSIONS: Since preoperative anxiety affects the postoperative course and almost every third patient experiences anxiety preoperatively, routine screening might be recommended in vascular surgery.

Identification of Risk Factors and Development of Predictive Risk Score Model for Mortality after Open Ruptured Abdominal Aortic Aneurysm Repair.

Background and Objectives: Despite the relatively large number of publications concerning the validation of these models, there is currently no solid evidence that they can be used with absolute precision to predict survival. The goal of this study is to identify preoperative factors that influenced 30-day mortality and to create a predictive model after open ruptured abdominal aortic aneurysm (RAAA) repair. Materials and Methods: This was a retrospective single-center cohort study derived from a prospective collected database, between 1 January 2009 and 2016. Multivariate logistic regression analysis was used to identify all significant predictive factors. Variables that were identified in the multivariate analysis were dichotomized at standard levels, and logistic regression was used for the analysis. To ensure that dichotomized variables were not overly simplistic, the C statistic was evaluated for both dichotomized and continuous models. Results: There were 500 patients with complete medical data included in the analysis during the study period. Of them, 37.6% were older than 74 years, and 83.8% were males. Multivariable logistic regression showed five variables that were predictive of mortality: age > 74 years (OR = 4.01, 95%CI 2.43−6.26), loss of consciousness (OR = 2.21, 95%CI 1.11−4.40), previous myocardial infarction (OR = 2.35, 95%CI 1.19−4.63), development of ventricular arrhythmia (OR = 4.54, 95%CI 1.75−11.78), and DAP < 60 mmHg (OR = 2.32, 95%CI 1.17−4.62). Assigning 1 point for each variable, patients were stratified according to the preoperative RAAA mortality risk score (range 0−5). Patients with 1 point suffered 15.3% mortality and 3 points 68.2% mortality, while all patients with 5 points died. Conclusions: This preoperative RAAA score identified risk factors readily assessed at the bedside and provides an accurate prediction of 30-day mortality after open repair of RAAA.

Patients' Fears and Perceptions Associated with Anesthesia.

Background and Objectives: It has been suggested that intense feelings of fear/anxiety and significant patient concerns may affect the perioperative course. Those findings emphasize the importance of surgical patients' preoperative feelings. Still, current knowledge in this area is based on a limited number of studies. Thus, we think that there is a need to further explore patients' preoperative fears, better characterize risk factors and reasons for their occurrence, and evaluate patients' perspectives associated with anesthesia. Materials and Methods: A total of 385 patients undergoing vascular surgery were preoperatively interviewed using a questionnaire that included demographics and questions related to patients' fears and perceptions of anesthesia. Statistical analyses included descriptive statistics, Pearson's χ2 and McNemar tests, and multivariate ordinal logistic regression. Results: The main causes of patients' preoperative fear were surgery (53.2%), potential complications (46.5%), and anesthesia (40%). Female sex was a predictor of surgery and anesthesia-related fear (OR = 3.07, p = 0.001; OR = 2.4, p = 0.001, respectively). Previous experience lowered the fear of current surgery (OR = 0.65, p = 0.031) and anesthesia (OR = 0.6, p = 0.017). Type of surgery, type of anesthesia, educational and socioeconomic status, and personal knowledge of an anesthesiologist affected specific anesthesia-related fears. Over 25% of patients did not know that an anesthesiologist is a physician, and only 17.7% knew where anesthesiologists work. Level of education and place of residence influenced patients' perceptions of anesthesia. Conclusions: Anesthesia-related fears are affected by the type of surgery/anesthesia, experience with previous surgery, and personal knowledge of an anesthesiologist. Women, patients with lower education levels, and patients with poorer socioeconomic status are at higher risk of developing those fears. The perception of anesthesiologists is inadequate, and knowledge of anesthesia is poor. Promotion of patient education regarding anesthesia is needed to alleviate those fears and increase understanding of anesthesia.

Regulatory T cell differentiation: turning harmful into useful.

In this issue of Immunity, Lee et al. (2012) demonstrate a surprisingly broad "window of opportunity" for regulatory T (Treg) cell induction and provide evidence for an avidity model of Treg cell differentiation versus deletion.

Induced miR-99a expression represses Mtor cooperatively with miR-150 to promote regulatory T-cell differentiation.

Peripheral induction of regulatory T (Treg) cells provides essential protection from inappropriate immune responses. CD4(+) T cells that lack endogenous miRNAs are impaired to differentiate into Treg cells, but the relevant miRNAs are unknown. We performed an overexpression screen with T-cell-expressed miRNAs in naive mouse CD4(+) T cells undergoing Treg differentiation. Among 130 candidates, the screen identified 29 miRNAs with a negative and 10 miRNAs with a positive effect. Testing reciprocal Th17 differentiation revealed specific functions for miR-100, miR-99a and miR-10b, since all of these promoted the Treg and inhibited the Th17 program without impacting on viability, proliferation and activation. miR-99a cooperated with miR-150 to repress the expression of the Th17-promoting factor mTOR. The comparably low expression of miR-99a was strongly increased by the Treg cell inducer "retinoic acid", and the abundantly expressed miR-150 could only repress Mtor in the presence of miR-99a. Our data suggest that induction of Treg cell differentiation is regulated by a miRNA network, which involves cooperation of constitutively expressed as well as inducible miRNAs.

Regulatory T cell lineage commitment in the thymus.

A substantial fraction of the Foxp3(+) CD4(+) regulatory T (T(reg)) cell repertoire is generated through instructive and/or selective processes in the thymus, and there is some consensus that clonal deviation into the T(reg) lineage is a result of self-antigen recognition. Paradoxically, the same holds true for a diametrically different cell fate decision of developing thymocytes, namely their removal from the repertoire through apoptotic cell death (clonal deletion). Here, we will review our current understanding of how T cell receptor stimulation, cytokine signaling, co-stimulation, epigenetic modifications and T cell intrinsic developmental tuning synergize during T(reg) cell differentiation, and how instructive signals converge at the Foxp3 gene-locus during entry into the T(reg) cell lineage. We will also discuss how these parameters relate to known determinants of negative selection.

Effects of successful parathyroidectomy on neuropsychological and cognitive status in patients with asymptomatic primary hyperparathyroidism.

PURPOSE: Besides typical clinical symptoms, primary hyperparathyroidism (pHPT) is associated with impaired quality of life and cognitive status. The aim of this study was to evaluate the quality of life and cognitive impairment in patients with pHPT, before and after parathyroidectomy. METHODS: We conducted a panel study, which included asymptomatic pHPT patients scheduled for parathyroidectomy. Besides demographic and clinical data, patients' quality of life and cognitive capacity were recorded before, 1 month, and 6 months following parathyroidectomy using the Short Form 36 questionnaire (RAND-36), Beck Depression Inventory (BDI), Depression Anxiety Stress Scales (DASS), Mini-Mental State Examination (MMSE), and Symptom Check List 90-revised version (SCL90R). RESULTS: During a 2-year follow-up, 101 patients entered the study (88 women), with an average age of 60.7 years. The Global score of RAND-36 test ameliorated by almost 50% 6 months after parathyroidectomy. The most sustained subscores of the RAND-36 test were role functioning/physical and health change, with an improvement of more than 125%. According to the BDI, DASS depression subscore, and SCL90R depression subscore, the extent of depressive symptoms reduction was approximately 60% 6 months postoperatively. The level of anxiety was reduced by 62.4%, measured by both the DASS and SCL90R anxiety subscores. The stress level was almost halved according to the DASS stress subscore (from 10.7 to 5.6 points). The results of the MMSE test showed a significant improvement postoperatively, for 1.2 points (4.4%). A worse preoperative score of each tool was related to the higher magnitude of improvement 6 months after parathyroidectomy. CONCLUSION: A considerable number of pHPT patients, even without other typical symptoms, show signs of impaired quality of life and neurocognitive status preoperatively. After a successful parathyroidectomy, there is an improvement in quality of life, declined levels of depression, anxiety, and stress, as well as amelioration of cognitive status. Patients with more impaired quality of life and pronounced neurocognitive symptoms may expect more benefits from the surgery.

Translation and validation of the Amsterdam preoperative anxiety and information scale (APAIS) in Serbia.

OBJECTIVES: Preoperative anxiety is common and might affect surgical treatment outcomes. The aim was to translate and validate the Serbian version of the Amsterdam Preoperative Anxiety and Information Scale (APAIS). METHODS: Following translation and initial evaluation, the Serbian version (S-APAIS) was administered to 385 patients. Internal consistency, construct validity, prognostic criteria validity, and concurrent validity between S-APAIS and Visual Analogue Scale for Anxiety (VAS-A) were evaluated. RESULTS: Factor analysis revealed two factors: APAIS-anesthesia (items 1, 2, 3) and APAIS-procedure (items 4, 5, 6). The whole scale, APAIS-anesthesia, and APAIS-procedure subscales showed an adequate level of internal consistency (Cronbach's αs: 0.787, 0.806, and 0.805, respectively). High concurrent validity was observed between APAIS-anesthesia and VAS-A (ρ = 0.628, p < .001). A moderate correlation was found between APAIS-procedure and VAS-A scale (ρ = 0.537, p < .001). At the cut-off point of 9, the area under the curve (AUC) of APAIS-anesthesia was 0.815 (95% CI: 0.77-0.85, p < .001). For the APAIS-procedure, AUC was 0.772 (95% CI: 0.73-0.81, p < .001) at the cut-off point of 8. CONCLUSION: The structure of S-APAIS substantially differs from the original and allows separate measurement of anesthesia- and procedure-related anxieties. S-APAIS is a comprehensive, valid, and reliable instrument for the measurement of preoperative anxiety.

Morphology of brachial segments in mudpuppy (Necturus maculosus) spinal cord studied with confocal and electron microscopy.

The isolated brachial spinal cord of Necturus maculosus is useful for studies of neural networks underlying forelimb locomotion, but information about its cellular morphology is scarce. We addressed this issue by using confocal and electron microscopy. Remarkably, the central region of gray matter was aneural and consisted exclusively of a tenuous meshwork of glial fibers and large extracellular spaces. Somata of motoneurons (MNs) and interneurons (INs), labeled by retrograde transport of fluorescent tracers from ventral roots and axons in the ventrolateral funiculus, respectively, were confined within a gray neuropil layer abutting the white matter borders, whereas their dendrites projected widely throughout the white matter. About one-third of labeled INs were found contralaterally, with axons crossing ventral to a thick layer of ependyma surrounding the central canal. Lateral MN dendrites proliferated under the pial surface to form a dense, thin (1-2 microm) plexus immediately beneath a thin layer of glial fibrillary acidic protein-positive glia limitans. The latter contained arrays of unusual tubular structures (diameter 200-400 nm, length 3 microm) that resembled mitochondria but lacked double membranes or cristae. Dorsal roots (DRs) produced dense presynaptic arbors within a wedge-shaped afferent termination zone medial to the dorsal root entry, within which dendrites of MNs and INs mingled with dense collections of synaptic boutons. Our data suggest that a major fraction of synaptic interactions takes place within the white matter. This study provides a detailed foundation for designing electrophysiological experiments to study the neural circuits involved in locomotor pattern generation.

The use of PRV-Bartha to define premotor inputs to lumbar motoneurons in the neonatal spinal cord of the mouse.

BACKGROUND: The neonatal mouse has become a model system for studying the locomotor function of the lumbar spinal cord. However, information about the synaptic connectivity within the governing neural network remains scarce. A neurotropic pseudorabies virus (PRV) Bartha has been used to map neuronal connectivity in other parts of the nervous system, due to its ability to travel trans-neuronally. Its use in spinal circuits regulating locomotion has been limited and no study has defined the time course of labelling for neurons known to project monosynaptically to motoneurons. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigated the ability of PRV Bartha, expressing green and/or red fluorescence, to label spinal neurons projecting monosynaptically to motoneurons of two principal hindlimb muscles, the tibialis anterior (TA) and gastrocnemius (GC). As revealed by combined immunocytochemistry and confocal microscopy, 24-32 h after the viral muscle injection the label was restricted to the motoneuron pool while at 32-40 h the fluorescence was seen in interneurons throughout the medial and lateral ventral grey matter. Two classes of ipsilateral interneurons known to project monosynaptically to motoneurons (Renshaw cells and cells of origin of C-terminals) were consistently labeled at 40 h post-injection but also a group in the ventral grey matter contralaterally. Our results suggest that the labeling of last order interneurons occurred 8-12 h after motoneuron labeling and we presume this is the time taken by the virus to cross one synapse, to travel retrogradely and to replicate in the labeled cells. CONCLUSIONS/SIGNIFICANCE: The study establishes the time window for virally-labelling monosynaptic projections to lumbar motoneurons following viral injection into hindlimb muscles. Moreover, it provides a good foundation for intracellular targeting of the labeled neurons in future physiological studies and better understanding the functional organization of the lumbar neural networks.

Anatomical organization of motoneurons and interneurons in the mudpuppy (Necturus maculosus) brachial spinal cord: the neural substrate for central pattern generation.

The isolated brachial spinal cord of the mudpuppy is useful for studies of neural networks underlying forelimb locomotion, but information about its anatomy is scarce. We addressed this issue by combining retrograde labeling with fluorescent tracers and confocal microscopy. Remarkably, the central region of gray matter was aneural and contained only a tenuous meshwork of glial fibers and large extracellular spaces. Somata of motoneurons (MNs) and interneurons (INs), labeled retrogradely from ventral roots or axons in the ventro-lateral funiculus, respectively, were confined within a gray neuropil layer abutting the white matter borders, while their dendrites projected widely throughout the white matter. A considerable fraction of labeled INs was found contralaterally with axons crossing beneath a thick layer of ependyma surrounding the central canal. Dorsal roots (DRs) produced dense presynaptic arbors within a restricted dorsal region containing afferent terminations, within which dorsally directed MN and IN dendrites mingled with dense collections of synaptic boutons. Our data suggest that a major fraction of synaptic interactions takes place within the white matter. This study provides a detailed foundation for electrophysiological experiments aimed at elucidating the neural circuits involved in locomotor pattern generation.