Obesity in Hypertensive Patients Is Characterized by a Dawn Phenomenon in Systolic Blood Pressure Values and Variability.

One of the causes of hypertension is excess weight gain, which can also affect the course of this disease. Both the diagnosis and management of hypertension commonly use ambulatory blood pressure monitoring; the results of which correlate more strongly with cardiovascular diseases and cardiovascular death than office blood pressure monitoring. We evaluated blood pressure values and their variability from hour to hour to see if and when they differed between hypertensive patients with and without obesity. The study included 1345 patients who underwent 24 h ambulatory blood pressure monitoring and then were divided into groups according to body mass index and waist circumference. The obtained data were analyzed according to the subjects' wake-up time, and short-term blood pressure variability parameters were calculated as the mean of the absolute values of the differences between consecutive measurements. The systolic blood pressure in obese subjects was significantly higher between 1 and 5 h before waking than in normal-weighted individuals. In turn, the variability in systolic and diastolic blood pressure was higher with increasing body mass index. The difference in systolic blood pressure values and blood pressure variability was most prominent in the last 5 h of sleep in obese patients.

Risks and benefits of renal artery stenting in fibromuscular dysplasia: Lessons from the ARCADIA-POL study.

INTRODUCTION: Although renal stenting is the standard revascularization method for atherosclerotic renal artery stenosis (RAS) (FMD-RAS), stenting in fibromuscular dysplasia (FMD) RAS is usually limited to periprocedural complications of angioplasty and primary arterial dissection. The main aim of the study was to retrospectively analyze the immediate and long-term results of renal stenting versus angioplasty in patients with FMD. METHODS: Of 343 patients in the ARCADIA-POL registry, 58 patients underwent percutaneous treatment due to FMD-RAS (in 70 arteries). Percutaneous transluminal renal angioplasty (PTRA) was performed as an initial treatment in 61 arteries (PTRA-group), whereas primary stenting was undertaken in nine arteries (stent-group). Stent-related complications were defined as: in-stent restenosis > 50% (ISR); stent fracture; under-expansion; or migration. RESULTS: In the PTRA-group, the initial restenosis rate was 50.8%. A second procedure was then performed in 22 arteries: re-PTRA (12 arteries) or stenting (10 arteries). The incidence of recurrent restenosis after re-PTRA was 41.7%. Complications occurred in seven of 10 (70%) arteries secondarily treated by stenting: two with under-expansion and five with ISR. In the stent-group, stent under-expansion occurred in one case (11.1%) and ISR in three of nine stents (33.3%). In combined analysis of stented arteries, either primarily or secondarily, stent-related complications occurred in 11/19 stenting procedures (57.9%): three due to under-expansion and eight due to ISRs. Finally, despite several revascularization attempts, four of 19 (21%) stented arteries were totally occluded and one was significantly stenosed at follow-up imaging. CONCLUSION: Our study indicates that renal stenting in FMD-RAS may carry a high risk of late complications, including stent occlusion. Further observational data from large-scale registries are required.

Mechanisms of carboplatin- and paclitaxel-dependent induction of premature senescence and pro-cancerogenic conversion of normal peritoneal mesothelium and fibroblasts.

Carboplatin (CPT) and paclitaxel (PCT) are the optimal non-surgical treatment of epithelial ovarian cancer (EOC). Although their growth-restricting influence on EOC cells is well known, their impact on normal peritoneal cells, including mesothelium (PMCs) and fibroblasts (PFBs), is poorly understood. Here, we investigated whether, and if so, by what mechanism, CPT and PCT induce senescence of omental PMCs and PFBs. In addition, we tested whether PMC and PFB exposure to the drugs promotes the development of a pro-cancerogenic phenotype. The results showed that CPT and PCT induce G2/M growth arrest-associated senescence of normal peritoneal cells and that the strongest induction occurs when the drugs act together. PMCs senesce telomere-independently with an elevated p16 level and via activation of AKT and STAT3. In PFBs, telomeres shorten along with an induction of p21 and p53, and their senescence proceeds via the activation of ERK1/2. Oxidative stress in CPT + PCT-treated PMCs and PFBs is extensive and contributes causatively to their premature senescence. Both PMCs and PFBs exposed to CPT + PCT fuel the proliferation, migration, and invasion of established (A2780, OVCAR-3, SKOV-3) and primary EOCs, and this activity is linked with an overproduction of multiple cytokines altering the cancer cell transcriptome and controlled by p38 MAPK, NF-κB, STAT3, Notch1, and JAK1. Collectively, our findings indicate that CPT and PCT lead to iatrogenic senescence of normal peritoneal cells, which paradoxically and opposing therapeutic needs alters their phenotype towards pro-cancerogenic. It cannot be excluded that these adverse outcomes of chemotherapy may contribute to EOC relapse in the case of incomplete tumor eradication and residual disease initiation. © 2023 The Pathological Society of Great Britain and Ireland.

Target Blood Pressure Values in Ambulatory Blood Pressure Monitoring.

INTRODUCTION: 2018 ESC/ESH guidelines have recommended 24-h ambulatory blood pressure monitoring to assess hypotensive therapy in many circumstances. Recommended target blood pressure in office blood pressure measurements is between 120/70 and 130/80 mmHg. Such targets for 24-h ambulatory blood pressure monitoring lacks. AIM: We aimed to define target values of blood pressure in 24-h ambulatory blood pressure monitoring in hypertensive patients. METHODS: Office blood pressure measurements and 24-h ambulatory blood pressure monitoring data were collected from 1313 hypertensive patients and sorted following increasing systolic (SBP)/diastolic (DBP) blood pressure in office blood pressure measurements. The corresponding 24-h ambulatory blood pressure monitoring to office blood pressure measurements values were calculated. RESULTS: Values 130/80 mmHg in office blood pressure measurements correspond in 24-h ambulatory blood pressure monitoring: night-time SBP/DBP mean: 113.74/66.95 mmHg; daytime SBP/DBP mean: 135.02/81.78 mmHg and 24-h SBP/DBP mean: 130.24/78.73 mmHg. Values 120/70 mmHg in office blood pressure measurements correspond in 24-h ambulatory blood pressure monitoring: night-time SBP/DBP mean: 109.50/63.43 mmHg; daytime SBP/DBP mean: 131.01/78.47 mmHg and 24-h SBP/DBP mean: 126.36/75.31 mmHg. CONCLUSIONS: The proposed blood pressure target values in 24-h ambulatory blood pressure monitoring complement the therapeutic target indicated in the ESC/ESH recommendations and improves 24-h ambulatory blood pressure monitoring usefulness in clinical practice.

Screening Services in a Community Pharmacy in Poznan (Poland) to Increase Early Detection of Hypertension.

BACKGROUND: Community pharmacies in many countries around the world provide healthcare services for patients. Pharmacists trained as medication experts provide a wide range of patient care services related to medication therapy, patient education, disease prevention, and health promotion. Professional training, expertise, and skills qualify pharmacists to engage in health screenings. These screening programs performed by community pharmacists can help to identify risk factors, facilitate early detection of common diseases, and assist physicians with making effective diagnoses. OBJECTIVES: In this study, we created and tested a novel model to provide professional monitoring and counseling on blood pressure by community pharmacists. The aims of the study were to identify the prevalence of elevated blood pressure among patients visiting a community pharmacy and describe the demographic characteristics of patients with hypertension (sex, age, education, body weight, and hypertension risk factors). METHODS: The research project was conducted in an accredited community pharmacy in Poznan, Poland, from January to April 2019. A total of 118 anonymous patients (30.5% men and 69.5% women) participated in this study. To qualify for this study, participants had to be older than 18 years of age and have no previous diagnosis of hypertension or other cardiovascular disease. RESULTS: Based on the blood pressure screenings, 61.9% of patients were qualified for the standard consultation (SC: normal blood pressure), 21.2% for the intensive consultation (IC: normal blood pressure and hypertension risk factor), 16.9% patients with elevated blood pressure for the high-risk consultation (HRC: referred to a physician), and 3.4% received a diagnosis of hypertension. We qualified 35.6% with a high-pressure value (greater than 140/90 mmHg). CONCLUSIONS: The novel model for blood pressure control screening and counseling implemented in a generally accessible community pharmacy may help with early detection of hypertension problems, lead to initiation of effective patient counseling by a community pharmacist, and result in early referral of the patient to a physician.

Systematic and Multidisciplinary Evaluation of Fibromuscular Dysplasia Patients Reveals High Prevalence of Previously Undetected Fibromuscular Dysplasia Lesions and Affects Clinical Decisions: The ARCADIA-POL Study.

Fibromuscular dysplasia (FMD), regarded as a generalized vascular disease, may affect all vascular beds and may result in arterial stenosis, occlusion, aneurysm, or dissection. It has been proposed to systematically evaluate all vascular beds in patients with FMD, regardless of initial FMD involvement. However, the impact of this approach on clinical decisions and on management is unknown. Within the prospective ARCADIA-POL study (Assessment of Renal and Cervical Artery Dysplasia-Poland), we evaluated 232 patients with FMD lesions confirmed in at least one vascular bed, out of 343 patients included in the registry. All patients underwent a detailed clinical evaluation including computed tomography angiography of intracranial and cervical arteries, as well as computed tomography angiography of the abdominal aorta, its branches, and upper and lower extremity arteries. In the study group, FMD lesions were most frequently found in renal arteries (87.5%). FMD was also found in cerebrovascular (24.6%), mesenteric (13.8%), and upper (3.0%) and lower extremity (9.9 %) arteries. Newly diagnosed FMD lesions were found in 34.1% of the patients, and previously undetected vascular complications were found in 25% of the patients. Among all FMD patients included in the study, one out of every 4 evaluated patients qualified for interventional treatment due to newly diagnosed FMD lesions or vascular complications. The ARCADIA-POL study shows for the first time that the systematic and multidisciplinary evaluation of patients with FMD based on a whole-body computed tomography angiography scan has an impact on their clinical management. This proved the necessity of the systematic evaluation of all vascular beds in patients with FMD, regardless of initial FMD involvement.

Association of intrarenal blood flow with renal function and target organ damage in hypertensive patients with fibromuscular dysplasia: the ARCADIA-POL study.

INTRODUCTION Data on the assessment of intrarenal blood flow parameters in patients with renal fibromuscular dysplasia (FMD) are scarce. OBJECTIVES The aim of the study was to evaluate intrarenal blood flow parameters in patients with FMD and significant or nonsignificant renal artery stenosis (RAS). PATIENTS AND METHODS We evaluated intrarenal blood flow parameters by Doppler ultrasonography in 153 patients with renal FMD enrolled in the ARCADIA­POL study: 32 and 121 patients with and without significant RAS, respectively, compared with 60 matched patients with essential hypertension and 60 healthy controls. RESULTS Patients with FMD and significant RAS had a lower renal resistive index (RRI) compared with patients with FMD without significant RAS, patients with essential hypertension, and normotensive controls (mean [SD], 0.51 [0.08] vs 0.60 [0.07], 0.62 [0.06], and 0.61 [0.06], respectively; P <0.001). In patients with nonsignificant RAS, RRI correlated significantly with carotid intima-media thickness, 24­hour diastolic blood pressure, 24­hour pulse pressure, left ventricular diastolic function, known duration time of hypertension, and age. In patients with significant RAS, there was a significant correlation between RRI and known duration time of hypertension, left ventricular diastolic function, and age. In a separate, "per­kidney" analysis, renal arteries with FMD and significant RAS were characterized by lower RRI values, higher maximal blood flow velocity, higher renal aortic ratio, and longer acceleration time compared with renal arteries with FMD and nonsignificant RAS as well as renal arteries without FMD. CONCLUSIONS In contrast to atherosclerotic RAS, intrarenal blood flow in patients with FMD and RAS is preserved, confirming that renal vasculature is relatively intact in these patients.

High incidence and clinical characteristics of fibromuscular dysplasia in patients with spontaneous cervical artery dissection: The ARCADIA-POL study.

The association between fibromuscular dysplasia (FMD) and spontaneous cervical artery dissection (SCeAD) has been recognized, but the available evidence on this relationship is scant. Therefore, the main goal of our study was to systematically evaluate FMD frequency, clinical characteristics and vascular bed involvement in patients with SCeAD. Among 230 patients referred to the ARCADIA-POL study, 43 patients (mean age 44.1 ± 8.9 years; 15 men and 28 women) with SCeAD were referred. Also, 135 patients with FMD were compared to patients with and without SCeAD. Patients underwent: ambulatory blood pressure measurements, biochemical evaluation, echocardiographic examination, and whole body computed tomographic angiography. FMD changes were found in 39.5% of patients with SCeAD. There were no differences in clinical characteristics between patients with SCeAD and FMD and those without FMD, except for a tendency towards a higher female ratio in SCeAD patients with FMD. There were no differences in other parameters describing target organ and SCeAD characteristics. Patients with SCeAD and FMD compared to those without SCeAD were characterized by a lower frequency of hypertension and a higher frequency of hyperlipidemia and history of contraceptive hormone use. Our study indicates a high incidence (39.5%) of FMD in subjects with SCeAD. Since there are no distinctive discriminating factors between patients with SCeAD and FMD and those without FMD, FMD should be suspected in all patients with SCeAD.

Mitochondria-related oxidative stress contributes to ovarian cancer-promoting activity of mesothelial cells subjected to malignant ascites.

Very little is known about the mechanisms by which malignant ascites modulates the cancer-promoting activity of human peritoneal mesothelial cells (HPMCs). Because malignant ascites induces pro-tumoral senescence in HPMCs, here we examined if this effect could be driven by oxidative stress. The study showed that malignant ascites generated by serous ovarian tumors induced oxidative damage to the DNA (γH2A.X, 53BP1, 8-hydroxy-2'-deoxyguanosine) and lipids (8-isoprostane) in HPMCs as well as increased the production of mitochondrial superoxides and cellular peroxides in these cells. This activity coincided with increased activity of two enzymes involved in the mitochondrial production of oxidants, i.e. cytochrome c oxidase and NADH dehydrogenase, decreased mitochondrial inner membrane potential, increased mitochondrial mass, and increased the activity of peroxisome proliferator-activated receptor gamma coactivator-1 alpha. Increased production of superoxides and peroxides in cells subjected to the malignant ascites was effectively reduced when the fluid was pre-incubated with neutralizing antibodies against hepatocyte growth factor. Moreover, when HPMCs subjected to the malignant ascites were protected against oxidative stress with a spin-trap scavenger of reactive oxygen species, they displayed decreased expression of senescence-associated ß-galactosidase and their potential to stimulate cancer cell adhesion, proliferation, and migration was significantly diminished. Collectively, our findings indicate that improved ovarian cancer cell progression in response to HPMCs exposed to malignant ascites may be associated with the development of profound oxidative stress in these cells.

Echocardiographic assessment of left ventricular morphology and function in patients with fibromuscular dysplasia: the ARCADIA-POL study.

OBJECTIVE: To provide a comprehensive assessment of left ventricle (LV) structure, and function and to detect alterations in cardiac properties in relationship to presence, subtypes and extent of fibromuscular dysplasia (FMD). METHODS: We studied 144 patients with FMD. The control group consisted of 50 matched individuals. Office and ambulatory blood pressure levels were evaluated. Echocardiography was employed to assess: left ventricular mass index (LVMI), systolic function including speckle tracking echocardiography and diastolic function assessed by mitral flow and tissue Doppler imaging. RESULTS: There were no differences in LV morphology and function between patients with FMD and the control group. Among 128 patients with renal FMD, there were no differences in LVMI and LV systolic function between patients with unifocal and multifocal FMD. The patients with multifocal FMD were characterized by lower early diastolic velocity (e') as compared with unifocal FMD and control groups. However, in a multivariate regression model, e' was not independently correlated with FMD. There were no associations between echocardiographic indexes and vascular involvement of FMD. Also, there were no differences in LV morphology and function in patients with significant renal artery stenosis (RAS) compared with patients with history of significant RAS and patients with nonsignificant RAS. CONCLUSION: Our study in contrast to those with atherosclerotic RAS, did not show differences in LV morphology and function between FMD patients and matched controls. Although FMD can result in hypertension and serious vascular complications, there is no proof that it can alter LV regardless of FMD type and its extent.

Procancerogenic activity of senescent cells: A case of the peritoneal mesothelium.

Human peritoneal mesothelial cells belong to a narrow group of somatic cells in which both the triggers and the mechanisms of senescence have already been well defined. Importantly, senescent mesothelial cells have been found in the peritoneal cavity in vivo. From a clinical point of view, peritoneal mesothelial cells have been recognized as playing a critical role in the intraperitoneal development of tumor metastases. The pro-cancerogenic behavior of mesothelial cells is even more pronounced when the cells exhaust their proliferative capacity and become senescent. In this review, we summarize the current state of art regarding the contribution of peritoneal mesothelial cells in the progression of ovarian, colorectal, and pancreatic carcinomas, with particular attention paid to the cancer-promoting activity of their senescent counterparts. Moreover, we delineate the mechanisms, mediators, and signaling pathways that are engaged by the senescent mesothelial cells to support such vital elements of cancer progression as adhesion, proliferation, migration, invasion, epithelial-mesenchymal transition, and angiogenesis. Finally, we discuss the experimental evidence regarding both natural and synthetic compounds that may either prevent or restrict cancer development by delaying senescence of mesothelial cells.

Assessment of expression of toll-like receptors 2, 3 and 4 in laryngeal carcinoma.

Head and neck cancers remain a big challenge for oncology. Among them laryngeal carcinomas predominate. In spite of abundant inflammatory cell infiltrates containing several immunologically competent cells, patients with head and neck cancers show markedly suppressed anti-tumor response. In general, cancer cells use strategies to avoid recognition and destruction by the immune system. Toll-like receptors 1-13 (TLRs) are crucial for activation of innate immunity and secondarily for the induction of acquired response. TLRs are mainly expressed on cells of the immune system, but they have been demonstrated on endothelial and epithelial cells. Ligand binding to TLR leads to the activation of several genes, predominantly proinflammatory ones such as IL-1 and TNF-alpha and maturation of professional antigen presenting cells (APC) i.e., dendritic cells. It can cause better tumor antigen presentation by APC. The aim of this study was the evaluation of expression of TLR-2, TLR-3 and TLR-4 in the microenvironment of laryngeal carcinoma. Tumor specimens (n = 20, male patients aged 43-77 years, mean 57 years) from patients subjected to total laryngectomy. Immunohistochemistry and indirect immunoflourescence on frozen tissue sections. Cancer tissue: portion of cancer cells manifested membrane and/or cytoplasmic expression of TLR-2, TLR-3 and TLR-4. The most frequent expression on tumor cells was TLR-2 and the least expression of TLR-4. Inflammatory infiltrates: in all cases inflammatory cell infiltrates of various intensities were present, both in tumor mass and tumor stroma. Expression of all TLRs tested, both, membrane and cytoplasmic ones were shown on inflammatory cells, but distinct in quantitative terms. TLR-4 positive cells were the most frequent. A portion of cells expressed both, TLR and HLA-DR. It is of interest that TLRs tested were expressed not only on cells of inflammatory infiltrate, but also on tumor cells. This fact may be an important factor in tumor escape from immune surveillance. It is notable, that both, TLRs and HLA-DR were shown to be co-expressed, what may favor the role and impact of TLRs in antigen presentation. Further studies are needed to elucidate TLRs function in the course of neoplastic process.