The Effect of Retinoids in Vascular Smooth Muscle Cells: From Phenotyping Switching to Proliferation and Migration.

Atherosclerosis, a term derived from the Greek "athero" (atheroma) and "sclerosis" (hardening), is a long-standing process that leads to the formation of atheromatous plaques in the arterial wall, contributing to the development of atherosclerotic cardiovascular disease. The proliferation and migration of vascular smooth muscle cells (VSMCs) and the switching of their phenotype play a crucial role in the whole process. Retinoic acid (RA), a natural derivative of vitamin A, has been used in the treatment of various inflammatory diseases and cell proliferation disorders. Numerous studies have demonstrated that RA has an important inhibitory effect on the proliferation, migration, and dedifferentiation of vascular smooth muscle cells, leading to a significant reduction in atherosclerotic lesions. In this review article, we explore the effects of RA on the pathogenesis of atherosclerosis, focusing on its regulatory action in VSMCs and its role in the phenotypic switching, proliferation, and migration of VSMCs. Despite the potential impact that RA may have on the process of atherosclerosis, further studies are required to examine its safety and efficacy in clinical practice.

Is it time for a retinoic acid-eluting stent or retinoic acid-coated balloon? Insights from experimental studies of systemic and local delivery of retinoids.

Although the incidence of restenosis and stent thrombosis has substantially declined during the last decades, they still constitute the two major causes of stent failure. These complications are partially attributed to the currently used cytostatic drugs, which can cause local inflammation, delay or prevent re-endothelialization and essentially cause arterial cell toxicity. Retinoic acid (RA), a vitamin A (retinol) derivative, is a naturally occurring substance used for the treatment of cell proliferation disorders. The agent has pleiotropic effects on vascular smooth muscle cells and macrophages: it influences the proliferation, migration, and transition of smooth muscle cells to other cell types and modulates macrophage activation. These observations are supported by accumulated evidence from in vitro and in vivo experiments. In addition, systemic and topical administration of RA can decrease the development of atherosclerotic plaques and reduce or inhibit restenosis after vascular injury (caused by embolectomy, balloon catheters, or ligation of arteries) in various experimental models. Recently, an RA-drug eluting stent (DES) has been tested in an animal model. In this review, we explore the effects of RA in atherosclerosis and the potential of the local delivery of RA through an RA-DES or RA-coated balloon for targeted therapeutic percutaneous vascular interventions. Despite promising published results, further experimental study is warranted to examine the safety and efficacy of RA-eluting devices in vascular artery disease.

Non-Cardiogenic Pulmonary Edema Due to Administration of Atosiban.

We report the case of a pregnant woman, treated with atosiban for premature labor, who developed non-cardiogenic pulmonary edema. She corresponded initially to oxygen supplementation and furosemide administration to induce diuresis but the onset of preterm contractions combined with aggravation of respiratory failure led the patient to a cesarean section, and subsequently to the intensive care unit where she remained intubated for 24 hours. In this case report, we emphasize the importance of distinguishing between two types of pulmonary edema: cardiogenic and non-cardiogenic. The instant separation between these two categories, most of the time with transthoracic echocardiography while the patient is on early support of ventilation, increases the optimum outcome for the patient.

Systemic Thrombolysis for Treatment of Acute Life-threatening Pulmonary Embolism During Cesarean Section Followed by Post-partum Rescue Hysterectomy: A Case Report and Review of the Literature.

BACKGROUND/AIM: Acute pulmonary embolism during cesarean section is extremely rare and only a limited number of cases have been reported in literature. The aim of this study was to report a case of acute high risk pulmonary embolism during elective cesarean section treated with systemic thrombolysis and discuss the multidisciplinary management in both early recognition and prompt treatment. CASE REPORT: A 39-year-old, G5P2, ASA II parturient presented for repeat cesarean section under general anesthesia. A sudden drop in end-tidal CO2 after placenta delivery combined with significant hemodynamic instability after an uneventful intraoperative course was strongly indicative of pulmonary embolism. Urgent transthoracic ultrasound revealed a sizable thrombus in the inferior vena cava and the right atrium. Thrombolysis was carried out intraoperatively using recombinant tissue plasminogen activator, which was administered under continuous US monitoring until thrombus resolution. This resulted in significant bleeding that was treated in a stepwise manner beginning with implementation of massive transfusion protocol, Bakri balloon placement, and rescue hysterectomy several hours after the event. Follow-up was uneventful and she was discharged on the 12th postoperative day. CONCLUSION: Though pregnancy is one of the major risk factors of the development of venous thromboembolism, acute intraoperative pulmonary embolism is extremely rare. Specific guidelines for the management of such cases are difficult to issue due to the paucity of relevant data. Thus, an individualized approach by a multidisciplinary team for diagnosis and intervention is mandated.

Safety and Efficacy of an Innovative Everolimus-Coated Balloon in a Swine Coronary Artery Model.

BACKGROUND: Drug-coated balloons have been used as a non-stenting treatment in coronary and peripheral artery disease. Until recently, only sirolimus- and paclitaxel-coated balloons have been investigated in clinical trials. We evaluated the safety and efficacy of an innovative everolimus-coated balloon (ECB) in a swine coronary artery model. METHODS: thirty-two swine coronary arteries were prepared through dilatation with a non-coated angioplasty balloon in a closed-chest model. During a period of 90 days, the following four groups (four animals per group, two coronary arteries per animal) were compared for safety and efficacy: A, Rontis ECB with 2.5 µg/mm2 of drug per balloon surface; B, Rontis ECB with 7.5 µg/mm2; C, Rontis Europa Ultra bare balloon; and D, Magic Touch, Concept Medical, sirolimus-coated balloon with a drug load of 1.3 µg/mm2. RESULTS: Differences in local biological effects (arterial reaction scores) and surface of intimal area (mm2) were not statistically significant between the treatment groups. Numerically, group A showed the lowest intimal area and intimal mean thickness, while group B showed the lowest stenosis among all groups. CONCLUSIONS: ECB was safe and effective in a porcine coronary artery model. The dose of everolimus may play a role in the biocompatibility of the balloon.

Histopathological evaluation of a retinoic acid eluting stent in a rabbit iliac artery model.

This study aimed to evaluate the safety and efficacy of innovative retinoic acid (RA) eluting stents with bioabsorbable polymer. Sixty stents divided in ten groups were implanted in the iliac arteries of 30 rabbits. Two polymers ("A", poly (lactic-co-glycolic acid) and "B", polylactic acid), and three doses ("Low", "Medium" and "High") of RA (groups: AL, AM, AH, BL, BM, BH) were used on cobalt chromium stents (Rontis Corporation), one group of bare stent (C), one group (D) of Everolimus eluting stent (Xience-Pro, Abbot Vascular), and two groups of Rontis Everolimus eluting stents coated with polymer A (EA) and B (EB). Treated arteries were explanted after 4 weeks, processed by methyl methacrylate resin and evaluated by histopathology. None of the implanted stents was related with thrombus formation or extensive inflammation. Image analysis showed limited differences between groups regarding area stenosis (BH, D and EB groups had the lower values). Group BH had lower intimal mean thickness than AH (105.1 vs 75.3 µm, p = 0.024). Stents eluting RA, a non-cytotoxic drug, were not related with thrombus formation and had an acceptable degree of stenosis 4 weeks post implantation. RA dose and type of polymer may play role in the biocompatibility of the stents.

Elderly patients with non-cardiac admissions and elevated high-sensitivity troponin: the prognostic value of renal function.

BACKGROUND: High-sensitivity cardiac troponin (hs-cTn) levels are frequently elevated in elderly patients presenting to the emergency department for non-cardiac events. However, most studies on the role of elevated hs-cTn in elderly populations have investigated the prognostic value of hs-cTn in patients with a specific diagnosis or have assessed the relationship between hs-cTn and comorbidities. AIM: To investigate the in-hospital prognosis of consecutive elderly patients admitted to the Internal Medicine Department with acute non-cardiac events and increased hs-cTnI levels. METHODS: In this retrospective study, we selected patients who were aged ≥ 65 years and admitted to the Internal Medicine Department of our hospital between January 2019 and December 2019 for non-cardiac reasons. Eligible patients were those who had hs-cTnI concentrations ≥ 100 ng/L. We investigated the independent predictors of in-hospital mortality by multivariable logistic regression analysis. RESULTS: One hundred and forty-six patients (59% female) were selected with an age range from 65 to 100 (mean ± SD: 85.4 ± 7.61) years. The median hs-cTnI value was 284.2 ng/L. For 72 (49%) patients the diagnosis of hospitalization was an infectious disease. The overall in-hospital mortality was 32% (47 patients). Individuals who died did not have higher hs-cTnI levels compared with those who were discharged alive (median: 314.8 vs 282.5 ng/L; P = 0.565). There was no difference in mortality in patients with infectious vs non-infectious disease (29% vs 35%). Multivariable analysis showed that age (OR 1.062 per 1 year increase, 95%CI: 1.000-1.127; P = 0.048) and creatinine levels (OR 2.065 per 1 mg/dL increase, 95%CI: 1.383-3.085; P < 0.001) were the only independent predictors of death. Mortality was 49% in patients with eGFR < 30 mL/min/1.73 m2. CONCLUSION: Myocardial injury is a malignant condition in elderly patients admitted to the hospital for non-cardiac reasons. The presence of severe renal impairment is a marker of extremely high in-hospital mortality.

Persistent decline of hospitalizations for acute stroke and acute coronary syndrome during the second wave of the COVID-19 pandemic in Greece: collateral damage unaffected.

BACKGROUND: An alarming cerebro/cardiovascular collateral damage, reflected by a decline in admissions for acute stroke (AS) and acute coronary syndrome (ACS), was observed during the initial phase of the COVID-19 pandemic, thereby leading to a re-design of public campaigns. However, there are limited data regarding the AS and ACS hospitalization rates during the second wave of the pandemic, which was followed by re-imposition of lockdowns. METHODS: We calculated the rate of AS and ACS hospitalizations from three representative tertiary care hospitals in Greece during a 2-month period (November-December 2020) of the second wave of the COVID-19 pandemic compared with the corresponding control period in 2019 from three representative tertiary care hospitals in Greece. This was a follow-up study with identical design to our previous report evaluating AS and ACS hospitalizations during the first wave of the pandemic (March-April 2020). RESULTS: Compared with 2019, there was a 34% relative reduction of AS hospitalizations [incidence rate ratio (IRR): 0.66, 95% confidence interval (CI): 0.48-0.92, p = 0.013] and 33% relative reduction of ACS hospitalizations (IRR: 0.67, 95% CI: 0.54-0.83, p < 0.001) during the second wave of the COVID-19 pandemic. The relative reduction was smaller and did not reach the level of statistical significance for the respective syndromes (haemorrhagic stroke: IRR 0.87, 95% CI: 0.41-1.82, p = 0.71; ST-elevation myocardial infarction: IRR 0.81, 95% CI: 0.57-1.14, p = 0.22). CONCLUSION: AS and ACS hospitalizations were persistently reduced during the second wave of the COVID-19 pandemic compared with 2019 in Greece. This decline was similar to the observations during the first wave despite the large differences in the epidemiological COVID-19 burden. Lockdowns, a common characteristic in both waves, appear to have a detrimental indirect impact on cerebro/cardiovascular diseases in the general population.

Laparoscopically assisted vaginal hysterectomy (LAVH) versus total abdominal hysterectomy (TAH) in endometrial carcinoma: prospective cohort study.

OBJECTIVE: To determine the feasibility and safety of laparoscopically assisted vaginal hysterectomy in the treatment of presumed stage I endometrial cancer. STUDY DESIGN: This was a prospective cohort study without randomization of 182 consecutive patients who underwent surgery for early endometrial cancer or atypical hyperplasia at the West Kent Gynaecological Oncology Centre, UK. Seventy-four had laparoscopically assisted vaginal hysterectomy and bilateral salpingo-oophorectomy (BSO), and 108 had a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Lymphadenectomy was performed in 153 patients, and lymph node sampling was performed in 2 patients. Twenty-seven patients with serous papillary endometrial cancer in addition had an omentectomy. The groups were compared for epidemiological and clinical characteristics, surgical outcomes, hospital stay, lymph node harvest, and intraoperative and postoperative complications. RESULTS: The patients in the laparoscopy group had less blood loss, similar number of lymph nodes removed, less need for analgesia, and shorter hospital stay but longer operative time than those treated by laparotomy. In our study, we had 4 conversions (5.4%) from laparoscopy to laparotomy. Twenty-eight (41%) patients who had laparoscopic surgery were obese (body mass index [BMI] >30 kg/m2). Postoperative complications were more common in the laparotomy group (34%) than in the laparoscopy group (6%). No major complications occurred in the laparoscopy group. Wound infection was the most common complication in laparotomy patients, and this invariably happened to obese patients (BMI >30 kg/m2). There were 6 readmissions, all from the laparotomy group. CONCLUSIONS: Laparoscopic surgery is a safe and reliable alternative to open surgery in the management of early endometrial cancer patients, with significantly reduced hospital stay and complications, especially in those patients with an elevated BMI.

Serum homocysteine levels and paraoxonase 1 activity in preschool aged children in Greece.

BACKGROUND: Over the past decade, it has been well established that elevated total serum homocysteine (tHcy) in adults is associated with increased risk of cardiovascular and thromboembolic diseases. Since risk factors for such diseases are established at a young age, the aim of the present study was to measure serum tHcy levels in 134 (71 boys, 63 girls) randomly selected healthy preschool children aged 4-6 years (mean 5.1), and to investigate possible correlation with paraoxonase 1 (PON1) activity, an antioxidant enzyme that contributes to the antiatherogenic properties of high-density lipoprotein (HDL). METHODS: tHcy was determined using an IMX tHcy assay (FPIA). PON1 was measured by a spectrophotometric method at 412 nm. RESULTS: Mean serum tHcy was 7.71+/-2.35 mumol/L. A relatively significant percentage (15.6%) of boys and girls had elevated serum tHcy levels (>10 mumol/L). tHcy levels were slightly higher in girls compared to boys (8.20+/-2.80 vs. 7.29+/-1.79 mumol/L, respectively; p<0.11). There was no significant interaction between age and tHcy levels. Mean PON1 activity was 124.86+/-66.62 U/L. No statistical difference in enzyme activity was observed between boys and girls (126.81+/-69.99 vs. 121.74+/-64.78 U/L) was observed. On the contrary, a weak negative relationship between tHcy concentration and PON1 activity was detected, with Pearson's correlation coefficient of r=-0.27. CONCLUSIONS: The significant percentage of elevated tHcy levels observed in healthy preschool cases and the negative tHcy correlation with PON1 activity are reported for the first time. Since children with a family history of cardiovascular disease have higher levels of serum Hcy, tHcy screening in children, even of this age, in relation to other parameters, such the protective PON1, might prove a useful prevention procedure for the genetic risk of premature atherosclerosis.