Real-World Implementation of Digital Pathology: Results From an Intercontinental Survey.

The past 70 years have been characterized by rapid advancements in computer technology, and the health care system has not been immune to this trend. However, anatomical pathology has remained largely an analog discipline. In recent years, this has been changing with the growing adoption of digital pathology, partly driven by the potential of computer-aided diagnosis. As part of an international collaboration, we conducted a comprehensive survey to gain a deeper understanding of the status of digital pathology implementation in Europe and Asia. A total of 127 anatomical pathology laboratories participated in the survey, including 75 from Europe and 52 from Asia, with 72 laboratories having established digital pathology workflow and 55 without digital pathology. Laboratories using digital pathology for diagnostic (n = 29) and nondiagnostic (n = 43) purposes were thoroughly questioned about their implementation strategies and institutional experiences, including details on equipment, storage, integration with laboratory information system, computer-aided diagnosis, and the costs of going digital. The impact of the digital pathology workflow was also evaluated, focusing on turnaround time, specimen traceability, quality control, and overall satisfaction. Laboratories without access to digital pathology were asked to provide insights into their perceptions of the technology, expectations, barriers to adoption, and potential facilitators. Our findings indicate that although digital pathology is still the future for many, it is already the present for some. This decade may be a time when anatomical pathology finally embraces digital revolution on a larger scale.

Advanced Levels of Chronic Venous Insufficiency are Related to an Increased in Arterial Stiffness.

BACKGROUND: Chronic venous insufficiency (CVI) is characterized by progressive inflammatory changes. Inflammatory damage occurs in the veins, adjacent tissues, and can lead to structural changes in the arteries. The aim of this study is to analyze whether the degree of CVI is associated with arterial stiffness. METHODS: Cross-sectional study including patients with CVI classified by clinical, etiological, anatomical, and pathophysiological classification (CEAP) 1 to 6. We performed correlation between the degree of CVI, central and peripheral arterial pressure, and arterial stiffness measured by brachial artery oscillometry. RESULTS: We evaluated 70 patients, 53 of whom were women with a mean age of 54.7 years. Patients with advanced degrees of venous insufficiency CEAP 4,5,6, had higher levels of systolic, diastolic, central, and peripheral arterial pressures compared to those with early stages (CEAP 1,2,3). The CEAP 4,5,6 group had higher arterial stiffness indices than the CEAP 1,2,3 group: pulse wave velocity (PWV) 9.3 m/s vs. 7.0 m/s, P < 0.001; augmentation pressure (AP) 8.0 mm Hg vs. 6.3 mm Hg; P = 0.04. There was a positive correlation between the degree of venous insufficiency measured by the venous clinical severity score, villalta score and CEAP classification, and the arterial stiffness indices (Spearman's coefficient = 0.62 for PWV and CEAP, P < 0.01). The factors influencing PWV were age, peripheral systolic arterial pressure (SAPp), and AP. CONCLUSIONS: There is a correlation between the degree of venous disease and arterial structural changes characterized by arterial pressure and stiffness indices. Degenerative changes secondary to venous insufficiency are associated with impairment of the arterial system, which has implications for the development of cardiovascular disease.

Cost-effectiveness analysis of overground robotic training versus conventional locomotor training in people with spinal cord injury.

BACKGROUND: Few, if any estimates of cost-effectiveness for locomotor training strategies following spinal cord injury (SCI) are available. The purpose of this study was to estimate the cost-effectiveness of locomotor training strategies following spinal cord injury (overground robotic locomotor training versus conventional locomotor training) by injury status (complete versus incomplete) using a practice-based cohort. METHODS: A probabilistic cost-effectiveness analysis was conducted using a prospective, practice-based cohort from four participating Spinal Cord Injury Model System sites. Conventional locomotor training strategies (conventional training) were compared to overground robotic locomotor training (overground robotic training). Conventional locomotor training included treadmill-based training with body weight support, overground training, and stationary robotic systems. The outcome measures included the calculation of quality adjusted life years (QALYs) using the EQ-5D and therapy costs. We estimate cost-effectiveness using the incremental cost utility ratio and present results on the cost-effectiveness plane and on cost-effectiveness acceptability curves. RESULTS: Participants in the prospective, practice-based cohort with complete EQ-5D data (n = 99) qualified for the analysis. Both conventional training and overground robotic training experienced an improvement in QALYs. Only people with incomplete SCI improved with conventional locomotor training, 0.045 (SD 0.28), and only people with complete SCI improved with overground robotic training, 0.097 (SD 0.20). Costs were lower for conventional training, $1758 (SD $1697) versus overground robotic training $3952 (SD $3989), and lower for those with incomplete versus complete injury. Conventional overground training was more effective and cost less than robotic therapy for people with incomplete SCI. Overground robotic training was more effective and cost more than conventional training for people with complete SCI. The incremental cost utility ratio for overground robotic training for people with complete spinal cord injury was $12,353/QALY. CONCLUSIONS: The most cost-effective locomotor training strategy for people with SCI differed based on injury completeness. Conventional training was more cost-effective than overground robotic training for people with incomplete SCI. Overground robotic training was more cost-effective than conventional training for people with complete SCI. The effect estimates may be subject to limitations associated with small sample sizes and practice-based evidence methodology. These estimates provide a baseline for future research.

Immunohistochemistry Applied to Breast Cytological Material.

Fine-needle aspiration biopsies (FNABs) of the breast are minimally invasive procedures enabling the diagnosis of suspicious breast lesions. Unfortunately, they are often perceived as inferior to core-needle biopsies, namely because they are supposedly unable to differentiate between high-grade ductal carcinoma in situ and invasive carcinoma or provide material for ancillary testing. Several studies have shown, however, that FNAB samples, when handled properly, are indeed capable of providing sufficient and adequate material for ancillary testing, namely immunocytochemistry (ICC). We reviewed the published literature regarding the use of ICC for both diagnostic and theranostic uses in the different types of cytological samples obtained from FNABs of the breast, including smears, liquid-based cytology samples, and cellblocks. We found that p63 and 34ßE12 show promise in aiding in the differential diagnosis between in situ and invasive lesions and that most other diagnostic markers may be used as in tissue. Regarding theranostic ICC markers, results vary between publications, but with care, these can successfully be performed in cytological samples. Air-dried smears should be avoided, and cellblocks are overall more versatile than cytology slides, enabling the evaluation of not only hormonal receptors and HER2 by ICC, but also of Ki-67. Particular attention should be paid to fixation and antigen retrieval procedures in all cases. We recommend that laboratories without experience perform short validation runs before adopting these techniques into clinical practice.

Pediatric obstructive sleep-disordered breathing is associated with arterial stiffness.

The association between obstructive sleep-disordered breathing (oSDB) and arterial stiffness, an independent predictor of cardiovascular outcomes, is not well established in children. This study compared cardiovascular parameters between healthy and oSDB children and aimed to identify predictors of arterial stiffness indices in children with oSDB. Cross-sectional study realized in a tertiary hospital from June 2018 to January 2020. Forty-eight children (3 to 10 years old) with clinical diagnosis of oSDB and indication for adenotonsillectomy and 24 controls were evaluated. Cardiovascular parameters were measured non-invasively by brachial artery oscillometry with a portable device. The main arterial stiffness indices assessed were augmentation index and pulse wave velocity, both derived from the aortic pulse wave. In the oSDB group, the questionnaires Obstructive Sleep Apnea-18 (OSA-18) and Pediatric Quality of Life Inventory version 4.0 (PedsQL 4.0) were applied. The oSDB group had higher values of reflection coefficient (p = 0.044) and augmentation index (p = 0.003) than the control group. Stepwise multiple regression analysis revealed that age, female sex, reflection coefficient, and systolic volume were independent predictors of augmentation index. Higher pulse wave velocity values were associated with worse quality of life assessed by PedsQL 4.0 questionnaire. There was no association with OSA-18. The vascular and hemodynamic parameters were similar in both groups.Conclusion: Children with oSDB have increased augmentation index, an independent predictor of cardiovascular outcomes. The early identification of subclinical cardiovascular changes reinforces the importance of treating the disease, as well as changing lifestyle habits, to prevent complications in adulthood. What is Known: • The association between oSDB and cardiovascular risk in adults is well described in the literature. • Children with oSDB, regardless of their weight or sex, have higher PWV values when compared to non-snoring children. What is New: • Children with oSDB have augmented arterial stiffness, evidenced by the increase in AIx@75, measured non-invasively by brachial artery oscillometry with a portable device. • Low quality of life and therefore a high disease burden in children with oSDB may be a risk factor for arterial stiffness.

Cost-Effectiveness of High-intensity Training vs Conventional Therapy for Individuals With Subacute Stroke.

OBJECTIVE: This investigation estimated the incremental cost-effectiveness of high-intensity training (HIT) compared with conventional physical therapy in individuals with subacute stroke, based on the additional personnel required to deliver the therapy. DESIGN: Secondary analysis from a pilot study and subsequent randomized controlled trial. SETTING: Outpatient laboratory setting. PARTICIPANTS: Data were collected from individuals with locomotor impairments 1-6 months poststroke (N=44) who participated in HIT (n=27) or conventional physical therapy (n=17). INTERVENTIONS: Individuals performing HIT practiced walking tasks in variable contexts (stairs, overground, treadmill) while targeting up to 80% maximum heart rate reserve. Individuals performing conventional therapy practiced impairment-based and functional tasks at lower intensities (<40% heart rate reserve). MAIN OUTCOME MEASURES: Costs were assessed based on personnel use with availability of similar equipment. Incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves were calculated for quality-adjusted life years (QALYs) derived from the Medical Outcomes Short Form-36 questionnaire and gains in self-selected speeds (SSSs). RESULTS: Personnel costs were higher after HIT (mean, $1420±234) vs conventional therapy (mean, $1111±219), although between-group differences in QALYs (0.05 QALYs; 95% confidence interval [CI], 0.0-0.10 QALYs) and SSS (0.20 m/s; 95% CI, 0.05-0.35 m/s) favored HIT. ICERs were $6180 (95% CI, -$96,364 to $123,211) per QALY and $155 (95% CI, 38-242) for a 0.1 m/s gain in SSS. CONCLUSIONS: Additional personnel to support HIT are relatively inexpensive but can add substantial effectiveness to subacute rehabilitation. Future research should evaluate patient factors that increase the likelihood of improvement to maximize the cost-effectiveness of treatment post stroke.

Predicting Duration of Outpatient Physical Therapy Episodes for Individuals with Spinal Cord Injury Based on Locomotor Training Strategy.

OBJECTIVE: To characterize individuals with spinal cord injuries (SCI) who use outpatient physical therapy or community wellness services for locomotor training and predict the duration of services, controlling for demographic, injury, quality of life, and service and financial characteristics. We explore how the duration of services is related to locomotor strategy. DESIGN: Observational study of participants at 4 SCI Model Systems centers with survival. Weibull regression model to predict the duration of services. SETTING: Rehabilitation and community wellness facilities at 4 SCI Model Systems centers. PARTICIPANTS: Eligibility criteria were SCI or dysfunction resulting in motor impairment and the use of physical therapy or community wellness programs for locomotor/gait training. We excluded those who did not complete training or who experienced a disruption in training greater than 45 days. Our sample included 62 participants in conventional therapy and 37 participants in robotic exoskeleton training. INTERVENTIONS: Outpatient physical therapy or community wellness services for locomotor/gait training. MAIN OUTCOME MEASURES: SCI characteristics (level and completeness of injury) and the duration of services from medical records. Self-reported perceptions of SCI consequences using the SCI-Functional Index for basic mobility and SCI-Quality of Life measurement system for bowel difficulties, bladder difficulties, and pain interference. RESULTS: After controlling for predictors, the duration of services for the conventional therapy group was an average of 63% longer than for the robotic exoskeleton group, however each visit was 50% shorter in total time. Men had an 11% longer duration of services than women had. Participants with complete injuries had a duration of services that was approximately 1.72 times longer than participants with incomplete injuries. Perceived improvement was larger in the conventional group. CONCLUSIONS: Locomotor/gait training strategies are distinctive for individuals with SCI using a robotic exoskeleton in a community wellness facility as episodes are shorter but individual sessions are longer. Participants' preferences and the ability to pay for ongoing services may be critical factors associated with the duration of outpatient services.

Cdk9 and H2Bub1 signal to Clr6-CII/Rpd3S to suppress aberrant antisense transcription.

Mono-ubiquitylation of histone H2B (H2Bub1) and phosphorylation of elongation factor Spt5 by cyclin-dependent kinase 9 (Cdk9) occur during transcription by RNA polymerase II (RNAPII), and are mutually dependent in fission yeast. It remained unclear whether Cdk9 and H2Bub1 cooperate to regulate the expression of individual genes. Here, we show that Cdk9 inhibition or H2Bub1 loss induces intragenic antisense transcription of ∼10% of fission yeast genes, with each perturbation affecting largely distinct subsets; ablation of both pathways de-represses antisense transcription of over half the genome. H2Bub1 and phospho-Spt5 have similar genome-wide distributions; both modifications are enriched, and directly proportional to each other, in coding regions, and decrease abruptly around the cleavage and polyadenylation signal (CPS). Cdk9-dependence of antisense suppression at specific genes correlates with high H2Bub1 occupancy, and with promoter-proximal RNAPII pausing. Genetic interactions link Cdk9, H2Bub1 and the histone deacetylase Clr6-CII, while combined Cdk9 inhibition and H2Bub1 loss impair Clr6-CII recruitment to chromatin and lead to decreased occupancy and increased acetylation of histones within gene coding regions. These results uncover novel interactions between co-transcriptional histone modification pathways, which link regulation of RNAPII transcription elongation to suppression of aberrant initiation.

Chronic Methylmercury Intoxication Induces Systemic Inflammation, Behavioral, and Hippocampal Amino Acid Changes in C57BL6J Adult Mice.

Methylmercury (MeHg) is highly toxic to the human brain. Although much is known about MeHg neurotoxic effects, less is known about how chronic MeHg affects hippocampal amino acids and other neurochemical markers in adult mice. In this study, we evaluated the MeHg effects on systemic lipids and inflammation, hippocampal oxidative stress, amino acid levels, neuroinflammation, and behavior in adult male mice. Challenged mice received MeHg in drinking water (2 mg/L) for 30 days. We assessed weight gain, total plasma cholesterol (TC), triglycerides (TG), endotoxin, and TNF levels. Hippocampal myeloperoxidase (MPO), malondialdehyde (MDA), acetylcholinesterase (AChE), amino acid levels, and cytokine transcripts were evaluated. Mice underwent open field, object recognition, Y, and Barnes maze tests. MeHg-intoxicated mice had higher weight gain and increased the TG and TC plasma levels. Elevated circulating TNF and LPS confirmed systemic inflammation. Higher levels of MPO and MDA and a reduction in IL-4 transcripts were found in the hippocampus. MeHg-intoxication led to increased GABA and glycine, reduced hippocampal taurine levels, delayed acquisition in the Barnes maze, and poor locomotor activity. No significant changes were found in AChE activity and object recognition. Altogether, our findings highlight chronic MeHg-induced effects that may have long-term mental health consequences in prolonged exposed human populations.

Thromboprophylaxis in lower limb varicose vein surgery in Brazil.

Background: Despite all the investment in primary venous thromboembolism (VTE) prophylaxis for surgical patients in recent years, there are still no specific guidelines for those who undergo procedures to treat lower limb varicose veins. Objectives: To evaluate the profile of VTE prophylaxis practices among Brazilian vascular surgeons conducting lower limb varicose vein procedures. Methods: Survey design, sending an electronic questionnaire to Brazilian vascular surgeons. Respondents were divided between those who perform saphenous vein treatment with conventional surgery and those who perform thermoablation for the purpose of comparison between groups. Results: Of 765 respondents, 405 (53%) treat saphenous veins with conventional surgery for, 44 (6%) with foam, and 199 (26%) with thermoablation (endolaser or radiofrequency). Surgeons who perform thermoablation prescribed more pharmacoprophylaxis after varicose vein surgery than those who perform conventional surgery (67/199, 34% vs. 112/405, 28%; p = 0.002). The thermoablation group stratifies patients for thromboembolism risk more frequently than the conventional surgery group (102/199, 51% vs. 179/405, 44%; p = 0.004). Both groups use enoxaparin as the most frequent drug for prophylaxis, but the thermoablation group uses proportionally more direct oral anticoagulants than the conventional surgery group (26% vs. 10%, p<0.001). Conclusions: Brazilian vascular surgeons who perform saphenous vein treatment by thermoablation prescribe pharmacoprophylaxis more frequently and for a longer period than those who use conventional surgery.

Extracellular vesicles from HTLV-1 infected cells modulate target cells and viral spread.

BACKGROUND: The Human T-cell Lymphotropic Virus Type-1 (HTLV-1) is a blood-borne pathogen and etiological agent of Adult T-cell Leukemia/Lymphoma (ATLL) and HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). HTLV-1 has currently infected up to 10 million globally with highly endemic areas in Japan, Africa, the Caribbean and South America. We have previously shown that Extracellular Vesicles (EVs) enhance HTLV-1 transmission by promoting cell-cell contact. RESULTS: Here, we separated EVs into subpopulations using differential ultracentrifugation (DUC) at speeds of 2 k (2000×g), 10 k (10,000×g), and 100 k (100,000×g) from infected cell supernatants. Proteomic analysis revealed that EVs contain the highest viral/host protein abundance in the 2 k subpopulation (2 k > 10 k > 100 k). The 2 k and 10 k populations contained viral proteins (i.e., p19 and Tax), and autophagy proteins (i.e., LC3 and p62) suggesting presence of autophagosomes as well as core histones. Interestingly, the use of 2 k EVs in an angiogenesis assay (mesenchymal stem cells + endothelial cells) caused deterioration of vascular-like-tubules. Cells commonly associated with the neurovascular unit (i.e., astrocytes, neurons, and macrophages) in the blood-brain barrier (BBB) showed that HTLV-1 EVs may induce expression of cytokines involved in migration (i.e., IL-8; 100 k > 2 k > 10 k) from astrocytes and monocyte-derived macrophages (i.e., IL-8; 2 k > 10 k). Finally, we found that EVs were able to promote cell-cell contact and viral transmission in monocytic cell-derived dendritic cell. The EVs from both 2 k and 10 k increased HTLV-1 spread in a humanized mouse model, as evidenced by an increase in proviral DNA and RNA in the Blood, Lymph Node, and Spleen. CONCLUSIONS: Altogether, these data suggest that various EV subpopulations induce cytokine expression, tissue damage, and viral spread.

New connections between ubiquitylation and methylation in the co-transcriptional histone modification network.

Co-transcriptional histone modifications are a ubiquitous feature of RNA polymerase II (RNAPII) transcription, with profound but incompletely understood effects on gene expression. Unlike the covalent marks found at promoters, which are thought to be instructive for transcriptional activation, these modifications occur in gene bodies as a result of transcription, which has made elucidation of their functions challenging. Here we review recent insights into the regulation and roles of two such modifications: monoubiquitylation of histone H2B at lysine 120 (H2Bub1) and methylation of histone H3 at lysine 36 (H3K36me). Both H2Bub1 and H3K36me are enriched in the coding regions of transcribed genes, with highly overlapping distributions, but they were thought to work largely independently. We highlight our recent demonstration that, as was previously shown for H3K36me, H2Bub1 signals to the histone deacetylase (HDAC) complex Rpd3S/Clr6-CII, and that Rpd3S/Clr6-CII and H2Bub1 function in the same pathway to repress aberrant antisense transcription initiating within gene coding regions. Moreover, both of these histone modification pathways are influenced by protein phosphorylation catalyzed by the cyclin-dependent kinases (CDKs) that regulate RNAPII elongation, chiefly Cdk9. Therefore, H2Bub1 and H3K36me are more tightly linked than previously thought, sharing both upstream regulatory inputs and downstream effectors. Moreover, these newfound connections suggest extensive, bidirectional signaling between RNAPII elongation complexes and chromatin-modifying enzymes, which helps to determine transcriptional outputs and should be a focus for future investigation.

A comprehensive review of COVID-19 biology, diagnostics, therapeutics, and disease impacting the central nervous system.

The ongoing COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a highly transmissible disease. SARS-CoV-2 is estimated to have infected over 153 million people and to have caused over 3.2 million global deaths since its emergence in December 2019. SARS-CoV-2 is the seventh coronavirus known to infect humans, and like other coronaviruses, SARS-CoV-2 infection is characterized by a variety of symptoms including general flu-like symptoms such as a fever, sore throat, fatigue, and shortness of breath. Severe cases often display signs of pneumonia, lymphopenia, acute kidney injury, cardiac injury, cytokine storms, lung damage, acute respiratory distress syndrome (ARDS), multiple organ failure, sepsis, and death. There is evidence that around 30% of COVID-19 cases have central nervous system (CNS) or peripheral nervous system (PNS) symptoms along with or in the absence of the previously mentioned symptoms. In cases of CNS/PNS impairments, patients display dizziness, ataxia, seizure, nerve pain, and loss of taste and/or smell. This review highlights the neurological implications of SARS-CoV-2 and provides a comprehensive summary of the research done on SARS-CoV-2 pathology, diagnosis, therapeutics, and vaccines up to May 5.

Arterial stiffness predicts amputation and death in patients with chronic limb-threatening ischemia.

OBJECTIVE: Arterial stiffness indices predict cardiovascular outcomes in patients with coronary or kidney disease; however, there is little data on the prognostic value of arterial stiffness in patients with advanced peripheral arterial disease. We determined whether arterial stiffness indices predict the outcomes of major amputation or death in patients with chronic limb-threatening ischemia (CLTI). METHODS: Arterial stiffness was prospectively measured using brachial oscillometry in patients with CLTI. After measuring arterial stiffness, patients were followed in 6-month intervals for up to 3 years and evaluated for limb preservation, occurrence of major amputation, or death. Hemodynamic variables and arterial stiffness indices were used to define predictors of amputation or death. RESULTS: A total of 136 patients presented with CLTI, and 134 (99%) of these patients required limb revascularization. At the end of follow-up (mean, 14 months), 24 patients (18%) were alive with a major amputation, and mortality was 7% (9 patients); 33 patients (24%) progressed to the combined outcome of major amputation or death. Patients having amputation and/or death (n = 33; 24%) initially presented with elevated pulse wave velocity (PWV) (13.41 ± 1.21 m/s vs 11.54 ± 1.65 m/s; P < .001), elevated augmentation index corrected to 75 beats per minute (40.42 ± 6.65% vs 27.12 ± 9.19%; P < .001), and high augmentation pressure (AP) (29.98 ± 4.32 mm Hg vs 13.40 ± 7.05 mm Hg; P < .001) compared with patients with preserved limbs. The initial ankle-brachial index (ABI) was lower in patients having amputation and/or death (0.43 ± 0.94 vs 0.62 ± 0.12; P < .001). Multivariable analysis identified PWV (odds ratio [OR], 2.62; P = .013), AP (OR, 1.56; P < .001), and ABI (OR, 0.01; P < .001) as predictors of amputation or death. ROC analysis identified patients with PWV ≤12.7 m/s (hazard ratio, 4.71; P < .001), AP ≤22.15 mm Hg (hazard ratio, 13.03; P < .001), or ABI >0.52 with an increased rate of limb preservation. CONCLUSIONS: PWV and AP, measurements of arterial stiffness, as well as the ABI, predict amputation or death in patients with CLTI.

Anabolic androgenic steroid-induced hypogonadism, a reversible condition in male individuals? A systematic review.

The anabolic-androgenic steroids (AAS) are clinically used as an androgen replacement, in hypogonadism treatment, to induce puberty, and also in the treatment of chronic degenerative diseases. The AAS use out of clinical context is becoming massively, being used merely for aesthetic reasons. AAS abuse may cause severe disarrangement on the HPG axis and generate a significant decrease in testosterone synthesis and secretion by the testes. This review aims to evaluate whether the hypogonadism induced by AAS abuse is reversible and under what circumstances the reversibility is possible. For this, PRISMA guidelines and several databases are used between July and September 2020. Altogether, this systematic review identified and analysed 179 cases of AAS users. Of these, 168 cases had the hypogonadism clearly diagnosed and proven to be linked exclusively to AAS abuse. However, between these 168 cases, only 38 cases presented fully known outcomes and among these, merely in 4, the hypogonadism was completely reversible (2 based on drug therapy) with HPG axis recovery. In conclusion, this review presents evidences that AAS-induced hypogonadism is a seriously underestimated problem, and in the majority of cases, full recovery is very difficult to succeed.

Treatment of upper limb arterial occlusion caused by a cervical rib.

The cervical rib syndrome occurs when the interscalene triangle is occupied by a cervical rib, displacing the brachial plexus and the subclavian artery forward, which can cause pain and muscle spasms. The objective of this study is to discuss diagnosis of the cervical rib syndrome and treatment possibilities. This therapeutic challenge describes clinical and surgical management of a 37-year-old female patient with upper limb arterial occlusion caused by a cervical rib.

Results of venous reflux treatment with 1,470 nm endolaser and correlation with degree of venous insufficiency.

BACKGROUND: Patients with advanced chronic venous disease are more likely to need additional procedures for relapsed varicose veins. It has not yet been established whether severity of venous insufficiency is a factor that influences the occlusion rate of saphenous veins treated with endolasers. OBJECTIVES: To analyze occlusion rate of venous segments treated with endolaser and correlate it with patients' Venous Clinical Severity Score (VCSS) and Clinical-Etiological-Anatomical-Pathological (CEAP) classification. METHODS: Retrospective analysis of a cohort of patients operated using a 1,470 nm endolaser from November 2012 to March 2020. Descriptive statistics were calculated and Kaplan-Meier survival curves were plotted with Cox regression for groups stratified by VCSS and CEAP. RESULTS: A total of 180 venous segments were analyzed in 170 patients. Mean age was 44.3 ± 9.2 and the majority of patients were female (71%). Mean energy density used in the great saphenous vein was 49.2 ± 8.3 J/cm. The most common complications were pain along the course of the saphenous vein (12.2%) and paresthesias at 6 months (17.2%). There was no difference in venous occlusion rate between groups with VCSS ≤ 7 and VCSS > 7 (p = 0.067). A group of patients classified as CEAP classes C4, C5, or C6 had a lower occlusion rate than a group at classes C2 or C3 (hazard ratio [HR] = 3.22; confidence interval [CI] 1.85, 5.61; p = 0.001]. CONCLUSIONS: The occlusion rates of venous segments treated with endolaser were lower in patients with higher CEAP classes. It is probably necessary to use more energy in these patients to achieve effective treatment of saphenous veins.

Daily Patterns of Emotional Functioning on Drinking and Nondrinking Days.

BACKGROUND: Alcohol misuse continues to be a significant public health problem. Understanding the factors that may contribute to the harmful progression in drinking is an important aspect of public health. Previous research has shown that affect regulation is associated with problematic alcohol use. Additionally, emotion instability has been found as a predictor of alcohol-related problems and may be linked to reinforcement mechanisms. METHODS: The current study examined positive mood, negative mood, and mood instability in real time across drinking and nondrinking days utilizing ecological momentary assessment (EMA). Current drinkers (n = 74) were recruited for a 21-day EMA study. Participants completed up to 10 random assessments of positive mood, negative mood, and alcohol use per day. Mood instability was assessed as the squared difference in current mood from mood in the previous assessment. Data were analyzed using piecewise multilevel regression to examine mood trajectories across drinking and nondrinking days. RESULTS: Positive emotion across the day was higher on drinking days than nondrinking days and continued to increase after drinking initiation. In contrast, negative emotion across the day was lower on drinking days than nondrinking days and continued to decrease after drinking initiation. Emotional functioning was stable across the day on nondrinking days. However, on drinking days there was a steady increase in emotional instability leading up to drinking initiation, followed by a rapid stabilization after initiation. CONCLUSIONS: This study highlights the potentially reinforcing impact of alcohol via emotional stability. Overall, these findings highlight the importance of mood dynamics when examining the reinforcing effects of alcohol consumption.

Association Between Critical Limb Ischemia, the Society for Vascular Surgery Wound, Ischemia and Foot Infection (WIfI) Classification System and Arterial Stiffness.

BACKGROUND: Arterial stiffness analysis has been done to classify cardiovascular risk. The aim of this article is to analyze whether the group of patients with chronic limb-threatening ischemia (CLTI) has higher arterial stiffness indices than controls. The secondary objectives are to assess whether patients with advanced stages of Wound, Ischemia, and foot Infection (WIfI) classification have high levels of arterial stiffness, through multiple linear regressions to analyze whether the ankle-brachial index (ABI) and other variables are predictive of arterial stiffness. METHODS: We conducted a cross-sectional study with 66 patients with CLTI and 66 age- and sex-matched controls using brachial artery oscillometry. Hemodynamic and arterial stiffness measurements, clinical characteristics, laboratory data, and stages of WIfI classification were compared between the groups CLTI and controls. Through multiple linear regression, we identified predictors of pulse wave velocity (PWV) and augmentation index normalized to 75 beats/min (AIx@75). RESULTS: Patients with CLTI had PWV (11.8 ± 1.6 m/sec vs. 10.0 ± 1.8 m/sec, P < 0.01) and AIx@75 (29.2 ± 9.8% vs.18. ± 10.35%, P < 0.01) higher than controls. In the multiple regression model, there was influence of age (ß = 0.17, P < 0.01), antiplatelet therapy (ß = -0.15, P = 0.04), peripheral systolic pressure (ß = 0.03, P < 0.01), and clustered WIfI stages 3 and 4 (ß = 0.17, P = 0.02) of benefit of revascularization on PWV. Multiple regression analysis identified diabetes (ß = 7.51, P < 0.01) and the degree of ischemia measured by ABI (ß = -23.89, P < 0.01) as predictors of elevated AIx@75. WIfI stages 3 and 4 of estimate risk of amputation at 1 year predicts a high AIx@75 (ß = 9.77, P < 0.001) compared with stages 1 and 2. CONCLUSIONS: The degree of ischemia in CLTI patients determined by the ABI is associated with elevated arterial stiffness as measured by the AIx@75. Advanced WIfI stages were predictors of elevated PWV and AIx@75.

Pollutants and nutrition: Are methylmercury effects on blood pressure and lipoprotein profile comparable to high-fat diet in mice?

Human exposure to methylmercury (MeHg) due to contaminated fish intake as part of a high-fat (HFD), high-carbohydrate diets is a reality today for many populations. HFD is associated with hypertension and hyperlipidemia, primary cardiovascular disease (CVD) risk factors. Some studies suggest that MeHg induces those risk factors. We evaluated the effect of MeHg exposure in mice fed with HFD or control diet for eight weeks. In the last experimental 15 days, the half group received a MeHg solution (20 mg/L) replacing water. Blood pressure (BP), heart rate, lipoprotein concentrations, and paraoxonase activity were evaluated. Liver cholesterol, triacylglycerol, and IBA-1+ cells, as well as transcriptional levels of genes related to lipid metabolism and inflammatory response, were also assessed. HFD and both MeHg groups presented increased BP and total cholesterol (TC). In the liver, HFD but not MeHg was related to an increase in TC. Also, MeHg intoxication reduced paraoxonase activity regardless of diet. MeHg intoxication and HFD increased steatosis and the number of IBA-1+ cells and modified some gene transcripts associated with lipid metabolism. In conclusion, we demonstrated that MeHg effects on CVD risk factors resemble those caused by HFD.