Cardiovascular Disturbances Research Articles

Dural manipulation coinciding with transient asystole during lumbar spine surgery: illustrative case.

Hemodynamic disturbances during lumbar spine surgeries have proven to be exceptionally rare, with only seven published cases demonstrating instances where intraoperative dural manipulation coincided with bradycardia, hypotension, and/or asystole. The authors present the case of a 39-year-old male with a history of chronic low-back pain and leg weakness. Imaging demonstrated a disc herniation at L5-S1, resulting in impingement of the left S1 traversing nerve root. The patient agreed to surgery. The preoperative workup was unremarkable. While retracting the S1 nerve root, transient asystole occurred when the S1 nerve root was manipulated, causing the patient's heart rate to drop from 51 to 0 bpm. Manipulating the nerve root once again triggered a similar event, and upon cessation of the surgical stimulus, the patient's heart rate spontaneously returned to baseline. Other potential causes of these hemodynamic perturbations were excluded. As in other reported cases, each cardiovascular disturbance corresponded with either direct or indirect dural manipulation. Given the limited number of lumbar spinal cases reported to have undergone hemodynamic perturbances via dural manipulation, this case report provides evidence for the likelihood of a spinal-cardiac reflex between the cardiovascular system and the spinal dura mater. https://thejns.org/doi/10.3171/CASE24158.

Long-Term Persistence Rate of Secukinumab in Psoriatic Patients: A Six-Year Multicenter, Real-World Experience, Retrospective Study.

Background: Psoriatic disease, a chronic immune-mediated systemic inflammatory condition, significantly impairs patients' quality of life. The advent of highly targeted biological therapies has transformed treatment strategies, emphasizing the importance of selecting the most effective and cost-efficient option. Secukinumab, an IL-17A inhibitor, has demonstrated efficacy and safety in treating moderate-to-severe plaque psoriasis (PsO). However, long-term real-world data on its effectiveness and persistence rate are limited. Methods: This retrospective study, conducted across eight Italian dermatology centers, aimed to evaluate the 6-year persistence rate and effectiveness of secukinumab in patients with PsO. Additionally, the study investigated the onset of psoriatic arthritis during treatment. Results: Overall, 166 adult patients were analyzed. Their median age was 53.9 years. The mean BMI was 26.5. Of the 166 patients, 64 were bio-experienced while 102 were bio-naïve. A progressive reduction in PsO severity measured by PASI scores over 6 years of treatment was revealed: the PASI score decreased from a baseline value of 18.1 (±9.1) to 0.7 (±1.6) after 6 years of follow-up. Adverse events, including mucocutaneous fungal infections and cardiovascular disturbances, were reported in 19.9% of patients. The persistence rate was 86.8% at 24 months, decreasing to 66.4% at 72 months. Psoriatic arthritis onset during treatment was observed in 15 (9.0%) of patients. Conclusions: This study highlights the sustained effectiveness and favorable safety profile of secukinumab over 6 years, providing valuable real-world evidence. Understanding the long-term persistence rate and predictors of discontinuation could help clinicians optimize treatment decisions and improve patient outcomes in PsO management. We found that the absence of scalp PsO, no involvement of the genital area and normal weight were the best factors of persistence in secukinumab treatment in the long term.

Musculoskeletal Disorders Related to Upper Limb Disability after One-Year Lung Cancer Resection.

Lung resection represents the main curative treatment in lung cancer; however, this surgical process leads to several disorders in tissues and organs. Previous studies have reported cardiovascular, pulmonary, and muscular disturbances that affect the functional capacity of these patients in the short, mid, and long term. However, upper limb impairment has been scarcely explored in the long term, despite the relevance in the independence of the patients. The aim of this study was to characterize the upper limb impairment in survivors of lung cancer one year after pulmonary resection. In this observational trial, patients who underwent lung cancer surgery were compared to control, healthy subjects matched by age and gender. Upper limb musculoskeletal disorders (shoulder range of motion, pain pressure threshold, nerve-related symptoms) and functional capacity (upper limb exercise capacity) were evaluated one-year post-surgery. A total of 76 survivors of lung cancer and 74 healthy subjects were included in the study. Significant differences between groups were found for active shoulder mobility (p < 0.05), widespread hypersensitivity to mechanical pain (p < 0.001), mechanosensitivity of the neural tissue (p < 0.001), and upper limb exercise capacity (p < 0.001). Patients who undergo lung cancer surgery show upper limb musculoskeletal disorders and upper limb functional impairment after a one-year lung resection. This clinical condition could limit the functionality and quality of life of patients with lung cancer.

Pharmacological interventions for antipsychotic-induced weight gain in schizophrenia: A network meta-analysis

ObjectiveAntipsychotic-induced weight gain (AIWG) is a significant but frequently neglected adverse effect of first- and second-generation antipsychotic therapy, which may lead to cardiovascular disturbances. The present network meta-analysis (NMA) was conducted to evaluate and compare the effects of available treatment options in antipsychotic-induced weight gain (AIWG). MethodsThe data was extracted from 68 relevant clinical trials after a literature search on MEDLINE/PubMed, Embase, Scopus, Cochrane databases and clinical trial registries. Random-effects Bayesian NMA was done to pool the effects across the interventions for the change in body weight from baseline. A network graph was built, a consistency model was run, node split analysis was performed, treatments were ranked as per the SUCRA score and meta-regression was done for the duration of therapy, baseline body weight and treatment strategy as the predictor variables. Finally, the results were sorted based on the certainty of evidence. ResultsThe drugs showing significant reduction in body weight in order of magnitude of effect size include sibutramine 10 mg (−8.0 kg; −16. to −0.21), metformin 750 mg + lifestyle modification (−7.5 kg; −12 to −2.8), topiramate 200 mg (−7 kg; −10 to −3.4), metformin 750 mg (−5.7 kg; −9.3 to −2.1), topiramate 100 mg (−5.7 kg; −8.8 to −2.5), topiramate 50 mg (−5.2 kg; −10 to −0.57), liraglutide 1.8 mg (−5.2 kg; −10., −0.080), sibutramine 15 mg (−4.5 kg; −8.9 to −0.59), nizatidine 300 mg (−3.0 kg; −5.9 to −0.23) and metformin 1000 mg (−2.3 kg; −4.6 to −0.0046). There was no effect of duration of follow-up, baseline body weight and, preventive versus therapeutic strategy on weight reduction in AIWG. ConclusionMetformin 750 mg with lifestyle modification was the most effective treatment for AIWG, followed by topiramate 200 mg, metformin 750 mg, and topiramate 100 mg with moderate certainty of evidence.

Linking wall shear stress and vorticity topologies: Toward a unified theory of cardiovascular flow disturbances

Broadening current knowledge about the complex relationship at the blood-vessel wall interface is a main challenge in hemodynamics research. Moving from the consideration that wall shear stress (WSS) provides a signature for the near-wall velocity dynamics and vorticity is considered the skeleton of fluid motion, here we present a unified theory demonstrating the existing link between surface vorticity (SV) and WSS topological skeletons, the latter recently emerged as a predictor of vascular disease. The analysis focused on WSS and SV fixed points, i.e., points where the fields vanish, as they play a major role in shaping the main vector field features. The theoretical analysis proves that: (i) all SV fixed points on the surface must necessarily be WSS fixed points, although with differences in nature and stability and (ii) a WSS fixed point is not necessarily a SV fixed point. In the former case, WSS fixed points are the consequence of flow patterns where only shear contributes to vorticity; in the latter case, WSS fixed points are the consequence of flow impingement to/emanation from the vessel wall. Moreover, fluid structures interacting with the wall characterized by zero or non-zero rotational momentum generate WSS fixed points of different nature/stability. High-fidelity computational fluid dynamics simulations in intracranial aneurysm models confirmed the applicability of the theoretical considerations. The presented unified theory unambiguously explains the mechanistic link between near-wall flow disturbances and the underlying intravascular flow features expressed in terms of vorticity, ultimately facilitating a clearer interpretation of the role of local hemodynamics in vascular pathophysiology.

Do steroid abusers have more temporomandibular joint symptoms? A study with 97 bodybuilders

ABSTRACT Objectives Anabolic androgenic steroids (AAS) are derivatives of testosterone, used to treat gonadal disturbances, performance enhancement, and aesthetic purposes. AAS abuse can lead to side effects, including androgenic, cardiovascular, and liver disturbances, effects on libido, gynecomastia, and behavioral effects. There is a hypothesis that some joint tissues may be targets for sex hormones, and the use of AAS without medical follow-up may exacerbate temporomandibular joint problems in patients seeking performance and aesthetics. Methods In this study, a cross-sectional survey was conducted on AAS abusers who voluntarily presented themselves for clinical evaluation. Patients were subdivided by sex and age group, and the length of AAS use and symptoms such as headache, tinnitus, and temporomandibular joint pain were evaluated. Results It was observed that drug usage is related to symptoms. Conclusion The results suggest that AAS use without medical follow-up may exacerbate temporomandibular joint problems, especially in patients with low estrogen levels.

An Epidemiological Study to Assess the Risk Factors and Symptoms of PCOS

The aim to present this study was to assess the most affected age group of girls from PCOD and to make them aware by our questionnaire in this descriptive study, 200 girls were selected randomly from hostels of MMDU, MULLANA. A questionnaire was formulated to obtain information regarding symptoms, changes, dietary patterns, etc. This data was differentiated, tabulated, and tested. The data collected shows that the majority of the respondents who participated in the survey were on the edge of PCOD. Stein and Leventhal are regarded to have been the first investigators of polycystic ovary syndrome however, in 1721 Vallisneri, an Italian scientist; he described a married, infertile woman with shiny ovaries with a white surface, and the size of pigeon eggs. It was not until early 1990 at a national institute of Health (NIH) sponsored conference on PCOD that formal diagnostic criteria were proposed and afterward largely utilized. Many scientists tried to explain the pathophysiology of PCOS and many studies were made. It is now accepted that it is multifactorial, partly genetic, however, a number of candidate genes have been postulated. Insulin resistance has been noted consistently among many women with PCOS, especially in those with Hyperandrogenism, but it is not included in any of the diagnostic criteria. Now there is strong evidence that cardiovascular diseases risk factors and disturbances in carbohydrate metabolism are all increased in patients with PCOS compared to healthy populations. The criteria was established by a group of experts during a conference in ROTTERDAM held in 2003 are obligatory. The subsequent ROTTERDAM CRITERIA incorporated the size and morphology as determined by an ultrasound of the ovary into the diagnostic criteria. The Center for Disease Control and Prevention, obesity among children in the U.S. has tripled since 1980 due to various factors like bad eating habits, and lack of physical exercise, and many more children are getting more and more obese. Many researchers have found that PCOD findings are increasing with time. Finding insulin resistance in obese adolescents gave a different diagnosis of PCOD. Upon further clinical testing, many other symptoms are found like Hirsutism, acne, and menstrual abnormalities. Emans (2005) described PCOS as a diagnosis related to the diagnosis of insulin resistance, not being overweight. For insulin resistance, females don't need to be overweight, they will have insulin resistance even a normal weight female adolescents also have insulin resistance.

Should Glucokinase be Given a Chance in Diabetes Therapeutics? A Clinical-Pharmacological Review of Dorzagliatin and Lessons Learned So Far.

Despite advances in the management of type 2 diabetes mellitus (T2DM), one-third of patients with diabetes do not achieve the desired glycemic goal. Considering this inadequacy, many agents that activate glucokinase have been investigated over the last two decades but were withdrawn before submission for marketing permission. Dorzagliatin is the first glucokinase activator that has been granted approval for T2DM, only in China. As overstimulation of glucokinase is linked with pathophysiological disturbances such as fatty liver and cardiovascular issues and a loss of therapeutic efficacy with time. This review aims to highlight the benefits of glucokinase activators vis-à-vis the risks associated with chronic enzymatic activation. We discuss the multisystem disturbances expected with chronic activation of the enzyme, the lessons learned with glucokinase activators of the past, the major efficacy and safety findings with dorzagliatin and its pharmacological properties, and the status of other glucokinase activators in the pipeline. The approval of dorzagliatin in China was based on the SEED and the DAWN trials, the major pivotal phase III trials that enrolled patients with T2DM with a mean glycosylated hemoglobin of 8.3-8.4%, and a mean age of 53-54.5years from multiple sites in China. Patients with uncontrolled diabetes, cardiac diseases, organ dysfunction, and a history of severe hypoglycemia were excluded. Both trials had a randomized double-blind placebo-controlled phase of 24weeks followed by an open-label phase of 28weeks with dorzagliatin. Drug-naïve patients with T2DM with a disease duration of 11.7months were enrolled in the SEED trial while the DAWN trial involved patients with T2DM with a mean duration of 71.5months and receiving background metformin therapy. Compared with placebo, the decline in glycosylated hemoglobin at 24weeks was more with dorzagliatin with an estimated treatment difference of -0.57% in the SEED trial and -0.66% in the DAWN trial. The desired glycosylated hemoglobin (<7%) was also attained at more than two times higher rates with dorzagliatin. The glycemic improvement was sustained in the SEED trial but decreased over 52weeks in the DAWN trial. Hyperlipidemia was observed in 12-14% of patients taking dorzagliatin versus 9-11% of patients receiving a placebo. Additional adverse effects noticed over 52weeks with dorzagliatin included an elevation in liver enzymes, hyperuricemia, hyperlacticacidemia, renal dysfunction, and cardiovascular disturbances. Considering the statistically significant improvement in glycosylated hemoglobin with dorzagliatin in patients with T2DM, the drug may be given a chance in treatment-naïve patients with a shorter disease history. However, with the waning therapeutic efficacy witnessed in patients with long-standing diabetes, which was also one of the potential concerns with previously tested molecules, extended studies involving patients with chronic and uncontrolled diabetes are needed to comment upon the long-term therapeutic performance of dorzagliatin. Likewise, evidence needs to be generated from other countries, patients with organ dysfunction, a history of severe hypoglycemia, cardiac diseases, and elderly patients before extending the use of dorzagliatin. Apart from monitoring lipid profiles, long-term safety studies of dorzagliatin should involve the assessment of serum uric acid, lactate, renal function, liver function, and cardiovascular parameters.

Effectiveness of antianemic therapy for patients with severe iron deficiency anemia

Aim. To assess the effectiveness of antianemic therapy in patients with severe iron deficiency anemia.Material and Methods. For inpatient treatment, 30 patients with severe iron deficiency anemia, who exhibited significant cardiovascular system disturbances in the form of developed cardiomyopathy of anemic origin, were selected.Results and discussion. Therefore, the therapy conducted on average contributes to an increase in hemoglobin level by 5.0-6.0 g/l, serum iron by 1.25 µmol/l, and erythrocytes up to 4.0±0.03. In addition to the pronounced clinical effect, patients showed an increase in hemoglobin levels from 75.0±4.5 g/l to 95.0±5.0 g/l. The content of total lipids did not change significantly.Conclusion. The treatment course conducted in patients with severe forms of anemia was found to contribute to an increase in the number of erythrocytes, and levels of hemoglobin, hematocrit, serum iron, and ferritin. This suggests its effectiveness and safety as a treatment method for patients with iron deficiency anemia in the context of developed cardiomyopathy of anemic origin.

Microvascular Capillary and Precapillary Cardiovascular Disturbances Strongly Interact to Severely Affect Tissue Perfusion and Mitochondrial Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Evolving from the Post COVID-19 Syndrome.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent, debilitating and still enigmatic disease. There is a broad overlap in the symptomatology of ME/CFS and the Post-COVID-19 Syndrome (PCS). A fraction of the PCS patients develop the full clinical picture of ME/CFS. New observations in microvessels and blood from patients suffering from PCS have appeared and include microclots and malformed pathological blood cells. Capillary blood flow is impaired not only by pathological blood components but also by prothrombotic changes in the vascular wall, endothelial dysfunction, and the expression of adhesion molecules in the capillaries. These disturbances can finally cause a low capillary flow and even capillary stasis. A low cardiac stroke volume due to hypovolemia and the inability of the capacitance vessels to adequately constrict to deliver the necessary cardiac preload generate an unfavorable low precapillary perfusion pressure. Furthermore, a predominance of vasoconstrictor over vasodilator influences exists, in which sympathetic hyperactivity and endothelial dysfunction play a strong role, causing the constriction of resistance vessels and of precapillary sphincters, which leads to a fall in capillary pressure behind the sphincters. The interaction of these two precapillary cardiovascular mechanisms causing a low capillary perfusion pressure is hemodynamically highly unfavorable in the presence of a primary capillary stasis, which is already caused by the pathological blood components and their interaction with the capillary wall, to severely impair organ perfusion. The detrimental coincidence of microcirculatory and precapillary cardiovascular disturbances may constitute the key disturbance of the Post-COVID-19 syndrome and finally lead to ME/CFS in predisposed patients because the interaction causes a particular kind of perfusion disturbance-capillary ischemia/reperfusion-which has a high potential of causing mitochondrial dysfunction by inducing sodium- and calcium-overload in skeletal muscles. The latter, in turn, worsens the vascular situation through the generation of reactive oxygen species to close a vicious cycle from which the patient can hardly escape.

A cross-sectional analysis of zinc and copper levels and their relationship to cardiovascular disease risk markers in Qatar biobank participants.

Cardiovascular diseases (CVD) are the leading cause of mortality and morbidity worldwide. Dietary intake, particularly zinc (Zn) and copper (Cu) has been strongly associated with CVD. These trace elements play a crucial role in human enzyme activity, suppressing inflammation, catalyzing lipid metabolism enzymes, reducing oxidative stress, and regulating glucose metabolism. However, imbalances in these elements are linked to cardiovascular disturbances. Thus, this study aimed to investigate the association between circulating levels of Zn, Cu, and Zn/Cu ratio with CVD risk factors in the Qatari population. Bivariate logistic regression, adjusted for age, nationality, gender, and education was performed to examine the impact of Zn, Cu, and Zn/Cu ratio (as independent variables) on major CVD risk markers (as dependent variables). Participants in the highest Zn tertiles (T2 and T3) were at greater odds ratio (OR) of unfavorable metabolic functions such as elevated HbA1C [OR = 2.5, p = 0.015 (T2) and OR = 3.2, p = 0.002 (T3)], triglycerides [OR = 2.17, p = 0.015 (T2), and TyG index [OR = 2.21, p = 0.004 (T2), and OR = 2.67, p < 0.001 (T3)] compared to T1. Conversely, they had significantly lower ORs for prolonged prothrombin time [OR = 0.37, p = 0.001 (T3)]. Higher levels of Cu (T2 and T3) had higher OR for elevated HDL-C levels [OR = 1.69, p = 0.046 (T2), and OR = 2.27, p = 0.002 (T3)] and lower OR for elevated levels of triglycerides (OR = 0.4, p = 0.009, T3), diastolic blood pressure [OR = 0.41, p = 0.024 (T2), and OR = 0.47, p = 0.049 (T3)], and creatinine kinase (OR = 0.27, p = 0.014, T3) compared to T1. Higher levels of Cu (T2 and T3) were associated with a higher risk for elevated fibrinogen levels [OR = 3.1, p = 0.035 (T2), and OR = 5.04, p = 0.002 (T3)]. Additionally, higher Zn/Cu ratio (T2 and T3) were associated with lower ORs for elevated fibrinogen levels [OR = 0.3, p = 0.005 (T2), and OR = 0.27, p = 0.005 (T3)] compared to T1, indicating a lower risk of developing CVD. The study reveals a link between Zn, Cu, and the Zn/Cu ratio and cardiovascular disease risk. A higher Zn/Cu ratio may protect against CVD, while elevated Cu levels are linked to obesity, fibrinogen levels, and HbA1C. Maintaining optimal levels of these trace elements, either through diet or supplementation, may help reduce CVD risk.

Systemic inflammatory response index as an independent predictor of severity in patients with obstructive sleep apnea

BackgroundChronic inflammation plays a crucial role in developing various cardiovascular and metabolic disorders. Obstructive sleep apnea (OSA) is a unique condition characterized by the coexistence of cardiovascular and metabolic disturbances, where chronic inflammation may exacerbate disease progression and severity. This study investigated how different hematological inflammatory cells and mediators can serve as predictive indicators of severe OSA.MethodsIn a retrospective cohort study, 150 patients suspected of having obstructive sleep apnea (OSA) underwent polysomnography (PSG) to confirm the diagnosis. Based on their apnea-hypopnea index (AHI), the patients were categorized into three groups: mild, moderate, and severe OSA. Blood samples were collected for the assessment of inflammatory blood cells and mediators at the time of diagnosis.ResultsAmong the 150 patients studied, 90 were diagnosed with OSA, and 43 had severe OSA, representing a prevalence rate of 47.7%. Patients with severe OSA were notably older and more likely to have diabetes mellitus and hypertension. After adjusting for age and sex, each one-unit increase in Systemic Inflammatory Response Index (SIRI), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) levels was associated with a doubling in the likelihood of having moderate and severe OSA (p < 0.05 for all). However, hypertension was linked to a 16-fold increase in the likelihood of moderate and severe OSA (p = 0.01).ConclusionOur research indicates that comorbidity and inflammatory cells and markers (SIRI, CRP, and ESR) are significantly related to the severity of OSA.

Physiological effects of alfaxalone anesthesia on rhesus monkeys during intravenous glucose tolerance testing.

Laboratory animal research with nonhuman primates (NHPs) requires anesthesia for most procedures to ensure safety and consistency in sample collection. However, anesthesia drugs can have adverse effects on the physiological measures of interest. Alfaxalone, most notably used in dogs and cats, offers rapid onset, short duration of action, and has a high safety margin. Here, we compared our current anesthesia protocol using Telazol, to three different doses of alfaxalone during a one-hour intravenous glucose tolerance test, the standard evaluation of glucose metabolism in NHPs. Results indicate there are no differences in the rate of glucose metabolism, anesthesia depth measurements, or total duration of sedation, but induction, number of supplemental doses required, and recovery time to eating were affected by the different doses of alfaxalone. Cardiovascular measures showed variability between the four protocols in respiratory rate and systolic blood pressure rates only. These results indicate that alfaxalone can produce a reliable state of anesthesia, similar to our current protocol, and confers minimal cardiovascular or metabolic disturbance, as well as enhanced recovery characteristics. As such, alfaxalone is a promising anesthetic for use in laboratory animals and further investigation is warranted.

Characterization of the oxidative stress and inflammatory markers in metabolically healthy obese individuals

Introduction and Objectives:&#x0D; Obesity has emerged as a global health problem. Although various studies have linked obesity to a wide spectrum of diseases mainly diabetes and cardiovascular disease, little is known concerning involvement of oxidative stress and inflammation in non-diseased conditions. The current study aims to explore the feasibility of inflammatory markers and oxidative stress markers in sera of metabolically healthy obese individuals. &#x0D; Methods:&#x0D; The current study involved one hundred healthy participants. Following obtaining relevant clinical data, sera were taken for further laboratory investigations including lipid profile, fasting serum glucose and HbA1c. Samples were also investigated for determining inflammatory and oxidative stress markers including highly sensitive C - reactive protein (hs-CRP), malondialdehyde (MDA) and gamma glutamyl transferase (GGT).&#x0D; Results: &#x0D; Total cholesterol, triglyceride and fasting blood glucose levels were statistically significantly higher in study group compared to controls (p &lt; 0.0001, 0.009 and &lt; 0.0001 respectively). The hs-CRP, MDA and GGT were also statistically significantly higher in healthy obese (p &lt; 0.001, 0.005 and 0.001 respectively). Moreover, MDA was positively correlated with GGT and was statistically significant (p &lt; 0.001). &#x0D; Conclusion:&#x0D; The obtained findings suggest that, there may be an existence of a low grade chronic inflammation consistent with oxidative stress which might be considered as a risk factor for developing metabolic diseases and cardiovascular disturbances mainly diabetes mellitus, hypertension and stroke.

Combined Ravitch and Nuss procedure for pectus excavatum with dyspnea following scoliosis repair

Abstract Pectus excavatum (PE) is often associated with scoliosis and can elicit cardiovascular disturbances under rare conditions. Here we report a patient who was treated with a combined Ravitch and Nuss procedure for PE with dyspnea following scoliosis repair to improve her symptoms. The patient was a 49-year-old woman with a history of PE and scoliosis. Right inferior pulmonary vein stenosis was caused by posterior spinal fusion for scoliosis prior to the PE repair. We could safely correct the chest wall deformity and treat dyspnea by performing a modified Ravitch repair in combination with the Nuss procedure.

FRI441 Antiestrogens To Treat Hypogonadotropic Hypogonadism In Male Users Of Anabolic-androgenic Steroids - A Clinical Pilot Study

Abstract Disclosure: H.C. Henriksen: None. A.P. Jørgensen: None. A. Bjørnebekk: None. S.P. Neupane: None. I.A. Havnes: None. Background: Anabolic-androgenic steroids (AAS) used recreationally in supra-physiological doses is a growing public health concern. The use is associated with cardiovascular, metabolic and endocrine disturbances including AAS induced hypogonadism (ASIH). ASIH is a form of hypogonadotropic hypogonadism caused by AAS’ long-term negative feedback on the hypothalamic-pituitary-gonadal (HPG) axis, promoting fatigue, depression and sexual dysfunction. Aims: The primary objective of the study is to explore the safety and efficacy of clomiphene citrate (CC) in treating ASIH. Secondary aims are to detect AAS associated health risks and assess whether these risks are reversed 12 months after cessation. Methods: In this open longitudinal pilot study at Oslo University Hospital in Norway, men with AAS dependence, continuous use and a desire to quit are treated for 16 weeks with an antiestrogen (CC). The CC is given to stimulate endogenous secretion of gonadotropin-releasing hormone (GnRH), gonadotropins (luteinizing hormone (LH)) and testosterone by blocking the estrogenic negative feedback on the HPG-axis. Transdermal testosterone is administered daily during the first four weeks to prevent a sudden drop in androgen levels. If HPG response is subpar, human chorionic gonadotropin (hCG), a synthetic LH analog, is added. The participants are monitored every 4th week during intervention, and at follow-up at 6 and 12 months. Physical health is assessed through clinical examinations, blood and fat tissue sampling, cardiovascular examination, dual-energy x-ray absorptiometry, testicular ultrasound and semen analysis. Results: Preliminary results are available from 11 men that were eligible for endocrine intervention with median age of 33 (range 26-57) and median cumulative lifetime AAS use of 11 years (1-20). Cardiovascular findings were recurrent and included hypertension, myocardial hypertrophy, increased arterial stiffness, reduced flow-mediated dilation and lower carotid artery reactivity. Polycythemia, testicular atrophy and oligozoospermia were other common findings at inclusion. Intervention with CC showed varying HPG response: While some participants responded poorly to treatment, others developed normalized endogenous levels of gonadotropins and testosterone after only 4-8 weeks of therapy. No serious adverse events from CC use were reported. Among the few reported less severe adverse effects were headache, nausea and mood swings. Conclusion: Preliminary results of this ongoing study indicate that treatment with CC and hCG is safe and effective in treating ASIH from long-term continuous AAS use. Insufficient HPG response after 16 weeks of intervention might indicate persisting hypogonadotropic hypogonadism, but further monitoring is needed. Presentation: Friday, June 16, 2023

Subacute administration of cilostazol modulates PLC-γ/PKC-α/p38/NF-kB pathway and plays vascular protective effects through eNOS activation in early stages of atherosclerosis development

AimsHypercholesterolemia is an important risk factor for development of cardiovascular disturbances, such as atherosclerosis, and its treatment remains challenging in modern medicine. Cilostazol is a selective inhibitor of phosphodiesterase 3 clinically prescribed for intermittent claudication treatment. Due to its pleiotropic properties, such as lipid lowering, anti-inflammatory, and antioxidant effects, the therapeutic repurposing of cilostazol has become a strategic approach for atherosclerosis treatment. This study aimed to investigate the effects of subacute administration of cilostazol on the aortas of hypercholesterolemic rats, focusing on the signaling pathways involved in these actions. Main methodsA murine model of hypercholesterolemia was employed to mimic the early stages of atherosclerosis development. Vascular reactivity assays were performed on thoracic aorta rings to assess the vascular response, as well as the non-invasive blood pressure was evaluated by plethysmography method. Pro-inflammatory markers and malondialdehyde (MDA) levels were measured to investigate the anti-inflammatory and antioxidant effects of cilostazol. Western Blot analysis was performed in aortas homogenates to evaluate the role of cilostazol on PLC-γ/PKC-α/p38-MAPK/IκB-α/NF-кB and PKA/eNOS/PKG pathways. Key findingsThe hypercholesterolemic diet induced the production of pro-inflammatory mediators such as TNF-α, TXB2, VCAM, and worsened vascular function, marked by increased contractile response, decreased maximum relaxation, and elevated systolic and diastolic blood pressure. Cilostazol seems to counteract the deleterious effects promoted by hypercholesterolemic diet, showing important anti-inflammatory and vasculoprotective properties possibly through the inhibition of the PLC-γ/PKC-α/p38-MAPK/IκB-α/NF-кB pathway and activation of the PKA/eNOS/PKG pathway. SignificanceCilostazol suppressed hypercholesterolemia-induced vascular dysfunction and inflammation. Our data suggest the potential repurposing of cilostazol as a pharmacological treatment for atherosclerosis.

Exploring Cardiovascular Manifestations in Vasculitides: An In-Depth Review.

Systemic vasculitides encompass a cluster of autoimmune diseases that affect blood vessels, and are characterized by immune-mediated injury to either small- or large-sized blood vessels. Individuals afflicted with systemic vasculitides experience notable morbidity and mortality attributable to cardiovascular manifestations. Noteworthy among these are ischemic heart disease, venous thromboembolism, aortic involvement, valvular irregularities, myocarditis, and pericarditis. This narrative review investigated and evaluated the prevalent cardiovascular disturbances commonly associated with different types of vasculitides. This review also discusses the mechanisms that underlie these manifestations. It also provides a thorough explanation of the many diagnostic techniques essential for detecting the disease at its occult stage. It is essential for healthcare professionals to have knowledge of the cardiovascular complications caused by vasculitides, as this enables them to promptly recognize these symptoms and employ suitable diagnostic techniques early on. By doing so, timely detection can be ensured, which will subsequently aid in initiating appropriate treatment strategies that are vital for decreasing morbidity and mortality in patients with systemic vasculitides.

Anesthetic Management of Patients with Dilated Cardiomyopathy Undergoing Noncardiac Surgery.

Dilated cardiomyopathy (DCM), a primary myocardial disease, is characterized by dilation of the left or both ventricles and systolic dysfunction with or without congestive heart failure. DCM per se is a well-recognized risk factor for sudden cardiac death and poor surgical outcomes following noncardiac surgery. Surgical trauma/stress represents unique challenges for DCM patient management. Unfortunately, there is a big knowledge gap in managing DCM patients undergoing non-cardiac surgery. Therefore, the aim of our review is to provide basic facts and current advances in DCM, as well as a practical guideline to perioperative care providers, for the management of surgical patients with DCM, who are quite rare compared with the general surgical population. This review summarizes recent advances in the medical management of DCM as well as perioperative assessment and management strategies for DCM patients undergoing noncardiac surgery. Optimal surgical outcomes depend on multiple-disciplinary care to minimize perioperative cardiovascular disturbances.

KIDNEY TRANSPLANTATION IN AN AGED PATIENT WITH MULTIPLE COMORBIDITIES: A REVIEW BASED ON UNUSUAL CLINICAL CASE

The article raises a question about the possible and effective kidney transplantation in elderly patients with various severe comorbidities. The analysis is based on an example of successful kidney transplantation from a deceased donor when a 67-year-old patient had severe concomitant background: obesity, diabetes mellitus, and cardiovascular disturbances. Despite unfavorable prognosis and further unpredictable illnesses such as COVID-19, candidal esophagitis, coronary attack, and pneumonia, the patient has not develop graft injury or rejection and kept sufficient kidney function.&#x0D; The research was mainly focused on coexisting illnesses and their influence on kidney transplantation consequences. Following disease groups were discussed regarding their impact on transplantation outcomes and prognosis: arterial hypertension, cardiac disorders, diabetes mellitus, and obesity. Patient’s age, previous interventions, and comorbidities were observed for association with outcomes and risk of graft rejection. A review of available publications compared approaches for recipient selection in different clinical centers as well.