MicroRNAs and angiosarcoma: are there promising reports?

In recent years, microRNAs (miRNAs) have garnered increasing attention for their potential implications in cancer pathogenesis, functioning either as oncogenes or tumor suppressors. Notably, angiosarcoma, along with various other cardiovascular tumors such as lipomas, rhabdomyomas, hemangiomas, and myxomas, has shown variations in the expression of specific miRNA subtypes. A substantial body of evidence underscores the pivotal involvement of miRNAs in the genesis of angiosarcoma and certain cardiovascular tumors. This review aims to delve into the current literature on miRNAs and their prospective applications in cardiovascular malignancies, with a specific focus on angiosarcoma. It comprehensively covers diagnostic methods, prognostic evaluations, and potential treatments while providing a recapitulation of angiosarcoma's risk factors and molecular pathogenesis, with an emphasis on the role of miRNAs. These insights can serve as the groundwork for designing randomized control trials, ultimately facilitating the translation of these findings into clinical applications. Moving forward, it is imperative for studies to thoroughly scrutinize the advantages and disadvantages of miRNAs compared to current diagnostic and prognostic approaches in angiosarcoma and other cardiovascular tumors. Closing these knowledge gaps will be crucial for harnessing the full potential of miRNAs in the realm of angiosarcoma and cardiovascular tumor research.

Social interactions and olfactory cues are required for contagious itch in mice.

The phenomenon of contagious itch, observed in both humans and rodents, remains a topic of ongoing debate concerning its modulators and underlying pathways. This study delves into the relationship between contagious itch and familiar olfactory cues, a non-visual factor contributing to this intriguing behavior. Our findings showed that contagious itch in observer mice occurs during physical interaction with the cagemate itch-demonstrator but not with a stranger demonstrator or in a non-physical encounter condition. Notably, itch-experienced observer mice displayed an increased contagious itch behavior, highlighting the relevance of itch-associated memory in this phenomenon. Furthermore, anosmic observer mice, whether itch-naïve or itch-experienced, displayed no contagious itch behavior. These results demonstrate that the familiar olfactory cues, specifically cagemate body odors, are required for contagious itch behaviors in mice. In line with these behavioral findings, our study reveals increased activity in brain regions associated with olfaction, emotion, and memory during contagious itch, including the olfactory bulb, the amygdala, the hypothalamus, and the hippocampus, with this activity diminished in anosmic mice. In conclusion, our study unveils the critical role of familiar olfactory cues in driving contagious itch in mice, shedding light on the interplay between social factors, sensory perception, and memory in this phenomenon.

Sex Dimorphism in Pain Threshold and Neuroinflammatory Response: The Protective Effect of Female Sexual Hormones on Behavior and Seizures in an Allergic Rhinitis Model.

Our previous research demonstrated that allergic rhinitis could impact behavior and seizure threshold in male mice. However, due to the complex hormonal cycles and hormonal influences on behavior in female mice, male mice are more commonly used for behavioral tests. In this study, we aimed to determine whether these findings were replicable in female mice and to explore the potential involvement of sexual hormones in regulating neuroinflammation in an allergic model. Our results indicate that pain threshold was decreased in female mice with allergic rhinitis and the levels of IL-23/IL-17A/IL-17R were increased in their Dorsal root ganglia. However, unlike males, female mice with AR did not display neuropsychological symptoms such as learning and memory deficits, depression, and anxiety-like behavior. This was along with decreased levels of DNA methyl transferase 1 (DNMT1) and inflammatory cytokines in their hippocampus. Ovariectomized mice were used to mitigate hormonal effects, and the results showed that they had behavioral changes and neuroinflammation in their hippocampus similar to male mice, as well as increased levels of DNMT1. These findings demonstrate sex differences in how allergic rhinitis affects behavior, pain sensitivity, and seizure thresholds. Furthermore, our data suggest that DNMT1 may be influenced by sexual hormones, which could play a role in modulating inflammation in allergic conditions.

Aortic Arch Debranching and Thoracic Endovascular Aortic Repair (TEVAR) for Type B Aortic Dissection.

BACKGROUND: Since its introduction, thoracic endovascular aortic repair (TEVAR) has revolutionized the treatment of type B aortic dissections (TBADs). However, the proximal aspect of the aortic pathology treated may infringe on the origin of the left subclavian artery or even more proximally. Hence, to ensure durable outcomes, the origin of these vessels needs to be covered, but an extra-anatomical bypass is required to perfuse vital branches, known as aortic arch debranching. This series aims to describe and delineate the disparities of aortic arch debranching during TEVAR for TBAD. METHODS: A retrospective review and analysis of a multicenter international database was conducted to identify patients with TBAD treated with TEVAR between 2005 and 2021. Data analyzed included patient demographics, disease characteristics, operative characteristics, and postoperative outcomes with follow-up on mortality and reintervention. All statistical analyses were carried out using IBM SPSS 26. Patient survival was calculated using a Kaplan-Meier survival analysis, and a P value of less than 0.05 was considered statistically significant. RESULTS: A total of 58 patients were included in the analysis, of which 27 (46.6%) presented with complicated disease and 31 were uncomplicated, of which 10 (17.2%) were classed as high risk and 21 (36.2%) low risk. Zone 2 was the most common proximal landing zone for the stent graft. Left subclavian artery bypass was performed selectively (26%), with 1 stroke occurring, likely due to embolic reasons. A further 6 underwent more proximal aortic debranching before TEVAR (10%) and was a significant risk factor for mortality and the number of stents deployed. The overall rates of reintervention and mortality were 17.2% (n = 10) and 29.3% (n = 17). CONCLUSIONS: Aortic arch debranching and TEVAR for TBAD is associated with significant mortality. Future developments to treat aortic arch pathology could incorporate branched graft devices, eliminating the need for debranching, improving stroke rates, and reducing future reinterventions.

Desmopressin enhances random-pattern skin flap survival in rats: Possible role of vasopressin Type-1a and 2 receptors.

BACKGROUND: Many drugs have been explored for their role in improving skin flap survival. 1-deamino-8-D-arginine vasopressin (DDAVP or desmopressin) is a synthesized form of anti-diuretic hormone (ADH) and a selective agonist for vasopressin type-2 receptors (V2 receptors). Desmopressin has been shown to improve endothelial function, induce vasodilation, and reduce inflammation. We aimed to evaluate its efficacy in enhancing flap survival and assess the role of vasopressin receptors in this process. MATERIALS AND METHODS: We randomly assigned six male Wistar rats to each study group. Different doses of desmopressin were injected intraperitoneally to find the most effective amount (8 µg/rat). SR-49059, a selective V1a receptor antagonist, was given at 2µg/rat before providing the most effective dose of desmopressin (8µg/rat). Histopathological assessments, quantitative measurements of interleukin-1ß (IL-1ß), Tumor necrosis factor-alpha (TNF-α), and Nuclear Factor-κB (NF-κB), optical imaging, and measurement of the expression levels of V2 receptor in the rat skin tissue were performed. RESULTS: Desmopressin (8µg/rat) significantly reduced the mean percentage of necrotic area compared to the control group (19.35% vs 73.57%). Histopathological evaluations revealed a notable reduction in tissue inflammation, edema, and degeneration following administration of desmopressin (8). The expression of the V2 receptor was increased following desmopressin administration. It also led to a reduction in IL-1ß, TNF-α, and NF-κB levels. The protective effect of desmopressin on flap survival was reversed upon giving SR-49059. The optical imaging revealed enhanced blood flow in the desmopressin group compared to the control group. CONCLUSIONS: Desmopressin could be repurposed to improve flap survival. V1a and V2 receptors probably mediate this effect.

Prevalence and associated factors of chronic venous disease among the modern Iranian urban population.

OBJECTIVES: Chronic venous disease (CVD) of the lower extremities is one of the common venous diseases in different populations, with a wide range of clinical manifestations and undetermined exact prevalence owing to different population characteristics and measurement methods. This study aimed to estimate the prevalence of CVD among the modern Iranian urban population and determine its associated risk factors. METHODS: The Heart Assessment and Monitoring in Rajaie Hospital study, a longitudinal population-based cohort, aims to investigate the baseline prevalence and the 10-year incidence of cardiovascular diseases and associated risk factors in the adult population aged 30 to 75 years with no overt cardiovascular diseases in Tehran. Two instructed interventional cardiologists performed CVD evaluation using the Clinical-Etiology-Anatomy-Pathophysiology classification. CVD was graded as C1 to C6, and chronic venous insufficiency (CVI) as C3 to C6. A multivariable regression model was used to analyze the association between CVD and prespecified covariates of age, sex, body mass index (≥30 kg/m2), smoking, hypertension, diabetes mellitus, physical activity, dyslipidemia, and delivery method. RESULTS: CVD prevalence among 1176 participants was 36.5% (95% confidence interval [CI], 33.8-39.3) and was higher in women than men (44.2% vs 23.5%). CVI prevalence was only 0.7% (95% CI, 0.3-1.3). Multivariable analysis showed that advanced age (odds ratio [OR], 1.06; 95% CI, 1.04-1.08), female sex (OR, 2.98; 95% CI, 2.14-4.14), and body mass index of ≥30 (OR, 1.36; 95% CI, 1.03-1.81) were independently associated with CVD. Physical activity (OR, 0.77; 95% CI, 0.58-1.02) was nearly protective, whereas other factors, including traditional cardiovascular risk factors, had no meaningful association with CVD. CONCLUSIONS: Our findings showed that CVD was prevalent in the modern Iranian urban population. However, considering the very low prevalence of the higher stages of the disease, the benefit of mass screening is debatable, and better risk discriminators should be investigated.

Ten-year follow-up report and neurologic sequelae in a case of neonatal severe primary hyperparathyroidism.

We present a 10-year follow-up and describe our experience in managing a case of neonatal severe primary hyperparathyroidism (NSHPT) for the first time in Iran. Microcephaly, mental retardation, and epilepsy may be long time sequels of NSHPT. The brain MRI findings are compatible with an old hypoxic-ischemic event.

The current state of knowledge on how to improve skin flap survival: A review.

The incorporation of skin flaps in wound closure management with its cosmetic implications has appeared as a gleam of hope in providing desirable outcomes. Given the influence of extrinsic and intrinsic factors, skin flaps are prone to several complications, including ischemia-reperfusion injury (IRI). Numerous attempts have been undertaken to enhance the survival rate of skin flaps entailing pre/post-conditioning with surgical and pharmacological modalities. Various cellular and molecular mechanisms are employed in these approaches in order to reduce inflammation, promote angiogenesis and blood perfusion, and induce apoptosis and autophagy. With the emerging role of multiple stem cell lineages and their ability to improve skin flap viability, these approaches are increasingly being used to develop even more translationally applicable methods. Therefore, this review aims at providing current evidence around pharmacological interventions for improving skin flap survival and discussing their underlying mechanism of action.

Therapeutic potential of bromhexine for acute itch in mice: Involvement of TMPRSS2 and kynurenine pathway.

Itching is an unpleasant sensation on the skin that could negatively impact the quality of life. Over the years, many non-pharmacological and pharmacological approaches have been introduced to mitigate this burdensome condition; However, the effectiveness of these methods remains questioned. Bromhexine, derived from the Adhatoda vasica plant, is a safe drug with minimal side effects. It has been widely used in managing respiratory symptoms over the years. The results of our study revealed that bromhexine has the potential to alleviate acute itch induced by Compound 48/80, a known mast cell destabilizer. According to our findings, bromhexine exerts its antipruritic effects primarily by inhibiting the Transmembrane Protein Serine Protease 2 (TMPRSS2) and, to a lesser extent, by decreasing the activation of the Kynurenine Pathway (KP). We further investigated the KP involvement by administrating 1-Methyl Tryptophan (1-MT), a known indoleamine-2,3-dioxygenase (IDO) inhibitor. 1-MT was found to be effective in reducing the itch itself. Moreover, co-administration of bromhexine and 1-MT resulted in synergistic antipruritic effects, suggesting that KP plays a role in acute itch. To conclude, we have presented for the first time a repositioning of bromhexine as a treatment for acute itch. In addition, we addressed the involvement of TMPRSS2 and KP in this process.

Ethnic & Sex Disparities in Type B Aortic Dissection Patients Undergoing Thoracic Endovascular Aortic Repair: An International Perspective.

BACKGROUND: There has been a revolution in the management of type B aortic dissection (TBAD) over the last 2 decades due to the increasing development of endovascular techniques, with the prime example being thoracic endovascular aortic repair (TEVAR). However, many controversies concerning the use of TEVAR in TBAD exist. For instance, there is little available evidence suggesting any differences in demographics, disease characteristics, intervention technicalities, and clinical outcomes between males and females as well as different ethnicities when undergoing TEVAR for TBAD, both in the short and long term. Also, there is no risk prediction model/tool available. The objective of this international study is to describe and delineate the disparities between male and female patients of different ethnicities in terms of demographics, disease and interventional characteristics, and clinical outcomes. METHODS: Over 17 years a total of 58 TBAD patients were admitted to 2 tertiary vascular centres and treated using TEVAR. Mortality, postoperative complications and reintervention data were recorded for the first 30 days after the procedure as well as during follow-up. Follow-up for all patients lasted until the study endpoint or until a patient's death. Data were analysed retrospectively using IBM SPSS statistical package 26 for Windows. RESULTS: The mean age was similar between the 2 groups, with the majority of patients in both being Caucasian. More than half of the males had complicated TBAD, while the majority of females were classed as having uncomplicated disease. The most commonly utilized proximal and distal landing zone for the TEVAR stent graft was zone 2 and zone 4, respectively. The mean proximal stent diameter was significantly larger in males compared to females (P = 0.004). The difference in mean distal diameter between the 2 groups was insignificant (P = 0.721). The mean total stent coverage of the thoracic aorta was 251.3 mm in male patients compared to 291.2 mm in females (P = 0.203). A total of 32 patients underwent adjunctive procedures. Seven (17%) of the males had one or more postoperative complications compared to 2 (12%) females. Nine (22%) males underwent a reintervention procedure post TEVAR compared to only 1 (6%) female (P = 0.136). Overall, males had a mortality rate of 24% (n = 10) compared to 41% of females (n = 7) (P = 0.201). Estimated survival of males and females post TEVAR was 80.4 ± 9.6 months and 69.7 ± 14.4 months (P = 0.428). For the total population, the number of stent grafts was inversely correlated with mortality. CONCLUSIONS: Despite the favourable clinical outcomes achieved by TEVAR in TBAD, there remains a grey area concerning its management. Thus, it is important to perform risk stratification of individual patients using their demographics and comorbidities, particularly scrutinizing patient sex and ethnic origin, when considering intervention for TBAD to achieve optimum results.

Balloon-Expandable Cheatham-Platinum Stents Versus Self-Expandable Nitinol Stents in Coarctation of Aorta: A Randomized Controlled Trial.

OBJECTIVES: This study sought to compare the safety and efficacy of the balloon-expandable stent (BES) and the self-expandable stent (SES) in the endovascular treatment of coarctation of aorta. BACKGROUND: Coarctoplasty with stents has conferred promising results. Although several nonrandomized studies have approved the safety and efficacy of the BES and the SES, no high-quality evidence exists for this comparison. METHODS: In the present open-label, parallel-group, blinded endpoint randomized pilot clinical trial, adult patients with de novo native aortic coarctation were randomized into Cheatham-platinum BES and uncovered nitinol SES groups. The primary outcome of the study was a composite of procedural and vascular complications. The secondary outcomes of the study consisted of the incidence of aortic recoarctation, thoracic aortic aneurysm/pseudoaneurysm formation, and residual hypertension at a 12-month follow-up. RESULTS: Among 105 patients who were screened between January 2017 and December 2019, 92 eligible patients (32 women [34.8%]) with a median age of 30 years (IQR: 20-36 years) were randomized equally into the BES and SES groups. The composite of procedural and vascular complications occurred in 10.9% of the BES group and 2.2% of the SES group (odds ratio: 0.18; 95% CI: 0.02-1.62; P = 0.20). Aortic recoarctation occurred in 5 patients (5.4%), 3 patients (6.5%) in the BES group and 2 patients (4.3%) in the SES group (odds ratio: 0.65; 95% CI: 0.10-4.09; P = 0.64). Only 1 patient (1.1%) was complicated by aortic pseudoaneurysm. Hypertension control was achieved in 50% of the study population, with an equal distribution in the 2 study groups at the 12-month follow-up. CONCLUSIONS: Both the BES and the SES were safe and effective in the treatment of native coarctation.