Closed-Loop Microreactor on PCB for Ultra-Fast DNA Amplification: Design and Thermal Validation.

Polymerase chain reaction (PCR) is the most common method used for nucleic acid (DNA) amplification. The development of PCR-performing microfluidic reactors (µPCRs) has been of major importance, due to their crucial role in pathogen detection applications in medical diagnostics. Closed loop (CL) is an advantageous type of µPCR, which uses a circular microchannel, thus allowing the DNA sample to pass consecutively through the different temperature zones, in order to accomplish a PCR cycle. CL µPCR offers the main advantages of the traditional continuous-flow µPCR, eliminating at the same time most of the disadvantages associated with the long serpentine microchannel. In this work, the performance of three different CL µPCRs designed for fabrication on a printed circuit board (PCB) was evaluated by a computational study in terms of the residence time in each thermal zone. A 3D heat transfer model was used to calculate the temperature distribution in the microreactor, and the residence times were extracted by this distribution. The results of the computational study suggest that for the best-performing microreactor design, a PCR of 30 cycles can be achieved in less than 3 min. Subsequently, a PCB chip was fabricated based on the design that performed best in the computational study. PCB constitutes a great substrate as it allows for integrated microheaters inside the chip, permitting at the same time low-cost, reliable, reproducible, and mass-amenable fabrication. The fabricated chip, which, at the time of this writing, is the first CL µPCR chip fabricated on a PCB, was tested by measuring the temperatures on its surface with a thermal camera. These results were then compared with the ones of the computational study, in order to evaluate the reliability of the latter. The comparison of the calculated temperatures with the measured values verifies the accuracy of the developed model of the microreactor. As a result of that, a total power consumption of 1.521 W was experimentally measured, only ~7.3% larger than the one calculated (1.417 W). Full validation of the realized CL µPCR chip will be demonstrated in future work.

Association of Pressure Wave Reflections With Left Ventricular Mass: a Systematic Review and Meta-Analysis.

BACKGROUND: Pressure wave reflections (PWRs) within the circulation are assessed at various arterial sites by various noninvasive methods. We aimed at reviewing the conflicting data regarding the hypothesis that higher PWRs are associated with higher left ventricular mass and tested whether this association stands for all available indices of PWRs, all (proximal or distal to the heart) sites of assessment, and is modified by sex, age and heart rate. METHODS: Based on a predefined protocol applying the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines, we identified eligible for meta-analysis data regarding: augmentation index, augmentation pressure, backward pressure (Pb), reflection index, and their association with left ventricular mass index (19 studies, total population n=8686). RESULTS: We found statistically significant associations, independent from blood pressure level, for all indices of PWRs at all arterial sites (carotid augmentation index; odds ratio; standardized beta coefficient [ß]: 0.14 [95% CI, 0.07% to 0.21%], per SD increase), radial augmentation index (ß: 0.21; 0.11 to 0.31), central augmentation pressure (ß: 0.15; 0.03 to 0.27), central Pb (ß: 0.23; 0.05 to 0.42), and central reflection index (ß: 0.14; 0.06 to 0.22), except for aortic augmentation index as estimated by generalized transfer functions. Meta-regression analysis showed that the association between carotid augmentation index and left ventricular mass was higher among populations with higher heart rate (P=0.036, beta: 0.017 [95% CI, 0.001 to 0.033]) and tended to be higher in middle-aged (P=0.07, beta: -0.001; -0.021 to 0.001). CONCLUSIONS: A clinically meaningful association between PWRs and left ventricular mass, assessed at either central or peripheral arterial sites by most available methods was shown, suggesting that PWR reduction strategies might be useful. Based on the present evidence, such trials should target middle-aged populations with high normal heart rate.

Assessment of Early Markers of Cardiovascular Risk in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome, with long-term sequelae from birth to senescence. The long-term effects of PCOS are attributed to several metabolic aberrations ensuing the syndrome. In a systematic review of literature regarding the cardiovascular risk factors that accompany PCOS, we found that macrovascular function has been assessed by flow-mediated dilatation (FMD), microvascular function by venous occlusion plethysmography (VOP), and arterial structure by ultrasonographic assessment of intima-media thickness (IMT) usually of the carotid artery. Contradictory results have been reported; however, in most studies, endothelial dysfunction, an early marker of atherosclerosis assessed either by haemodynamic methods such as FMD or by biochemical methods such as endothelin-1 levels, was found to be impaired. VOP is a less-studied method, with few indices altered. IMT was found to be altered in most of the included studies, but the population was more heterogeneous. Inflammatory markers, including C-reactive protein, were also found to be altered in most studies. On the other hand, a number of interventions have been shown beneficial for the markers of cardiovascular risk, in the context of insulin-sensitizers. However, other interventions such as oral contraceptive pills or statins did not consistently show a similar beneficial effect. In summary, the early identification and eventual treatment of cardiovascular clinical and biochemical risk factors may be used in clinical practice to prevent potential 'silent' triggers of cardiovascular disease.

Role of Receptor Profiling for Personalized Therapy in a Patient with a Growth Hormone-Secreting Macroadenoma Resistant to First-Generation Somatostatin Analogues.

BACKGROUND: Acromegaly is almost always caused by a pituitary adenoma and is associated with high morbidity and mortality when uncontrolled. Trans-sphenoidal removal of the adenoma is the mainstay of therapy, but fails to control the disease in a significant number of patients who require further treatment. Somatostatin analogues (SSAs) as monotherapy or in combination with growth hormone (GH)-receptor antagonists and/or dopamine agonists are used either alone or in combination following surgical failure to achieve disease control. The use of specific biomarkers may help to individualize the therapeutic plan after surgical failure and direct towards a more personalized approach. METHODS: We report a 41-year-old man with acromegaly and residual disease after repeated surgery that was resistant to first-generation SSAs. RESULTS: Biochemical and tumor control were achieved following the administration of a second-generation SSA, pasireotide, combined with pegvisomant, both at maximal doses and along with cabergoline. Histology specimens showed a sparsely-granulated GH-immunostaining pituitary adenoma with intense positivity for somatostatin receptors 2 and 5 and low levels of E-cadherin. CONCLUSION: Personalized medical therapy guided by currently available biomarkers, such as immunohistochemically-characterized receptor profiling or adhesion molecules, resulted in controlled insulin-like growth factor-1 (IGF-1) and GH levels and symptom alleviation following the combination of three drug-classes.

Differential Expression of Apoptotic and Low-Grade Inflammatory Markers in Alzheimer Disease Compared to Diabetes Mellitus Type 1 and 2.

BACKGROUND: Neuroinflammation, impaired brain insulin signaling, and neuronal apoptosis may be interrelated in the pathophysiology of people with Alzheimer disease (AD) and diabetes, either type 1 or 2 diabetes (T1D or T2D, respectively). METHODS: We studied 116 patients: 41 with AD, 20 with T1D, 21 with T2D, and 34 healthy controls. The number (n) of cytokine-secreting peripheral blood mononuclear cells (PBMCs) before and after mitogenic stimulation was determined for interleukin 1ß (IL1ß), interleukin 6 (IL6), tumor necrosis factor (TNF) by the enzyme-linked-immuno-spot assay. Serum concentrations of C-reactive protein (CRP) and Fas ligand (FASLG) were determined by ELISA. RESULTS: The studied subgroups did not differ in sex but differed in age. Higher CRP concentrations were detected in the AD group than in the T1D group (P = 0.02) and lower in controls (P < 0.001). The nPBMCs was higher in AD patients after stimulation than in basal conditions: after stimulation in nTNF (P < 0.001 vs T2D; P < 0.001 vs T1D; P = 0.001 vs control), nIL6 (P = 0.039 vs T2D; P < 0.001 vs T1D; P = 0.007 vs control), and nIL1ß (P = 0.03 vs control). The nPBMCs increased after stimulation with ΡΜA in all the subgroups (P < 0.001). FASLG in the AD group displayed statistically higher concentrations than in all other subgroups (P < 0.001 vs T2D; P < 0.001 vs T1D; P = 0.012 vs control). The nPBMCs was positively correlated with plasma concentrations of FASLG in the AD subgroup. CONCLUSIONS: Patients with AD display a low-grade systemic inflammation compared to people with diabetes. The FAS-FASLG pathway has a potential role because FASLG concentrations are positively correlated with the inflammatory response in AD. However, this positive correlation cannot be seen in people with diabetes, at least not with the apoptotic markers used in the present study.

The impact of financial crisis on coronary artery disease burden in Greece.

BACKGROUND: Economic crisis poses an immense threat to public health worldwide and has been linked to cardiovascular morbidity and mortality. Greece is facing a distinctive recession over the recent years. However, the exact impact on coronary artery disease (CAD) burden has not been adequately addressed. METHODS: Demographic, clinical, and angiographic data of 3895 hospitalized patients were retrospectively studied. Patients were classified into two groups: those before crisis (2006-2007, n = 1228) and those during crisis (2011-2015, n = 2667). RESULTS: All data before and during crisis were compared. During crisis, patients presented with less acute coronary syndrome (ACS - 45.5% vs. 39.9%, p < 0.001). Subsequently, there were more patients without CAD (23.7% vs. 35.1%, p < 0.001) or one-vessel disease (20.5% vs. 23%, p < 0.001). The prevalence of traditional risk factors decreased significantly or remained stable except obesity (26.3% vs. 31.4%, p = 0.002). A significant increase in the examined females (23.6% vs. 26.7%, p = 0.04) was also observed. CONCLUSIONS: The burden of CAD in Greece was partially affected during the financial crisis. Even though the incidence of ACS was decreased, more women and more patients with no- or single-vessel disease were referred for cardiac catheterization. In addition, the prevalence of traditional risk factors for CAD did not increase except obesity confirming the "obesity paradox." It seems that the impact of traditional risk factors for CAD is not an immediate process and is somewhat related to living conditions or other exogenous and social factors.

Prevalence, Incidence, and Contributors of Subclinical Atheromatosis, Arteriosclerosis, and Arterial Hypertrophy in HIV-Infected Individuals: A Single-Center, 3-Year Prospective Study.

Cardiovascular disease (CVD) is an important comorbidity for people living with HIV infection (PLWH) in the combined antiretroviral therapy era. We prospectively examined the presence of subclinical arterial disease in 138 consecutive CVD-free, HIV-infected individuals compared to 664 HIV-negative individuals. We studied 10 arterial sites in 4 beds using 5 distinct biomarkers of subclinical atheromatosis, arteriosclerosis, and hypertrophy and evaluated the association of subclinical arterial damage with CVD-related and HIV-related factors at baseline and at 3-year follow-up. Atheromatosis, arteriosclerosis, and arterial hypertrophy were present in 36.1%, 59.7%, and 34.3% of HIV-infected individuals, respectively, at baseline. HIV infection was independently associated with carotid atheromatosis and hypertrophy. The presence of carotid atheromatosis was independently associated with age, years of smoking, and exposure to nonnucleoside reverse transcriptase inhibitors (NNRTIs). The annual incidence of atheromatosis, arteriosclerosis, and arterial hypertrophy was 5.5, 18.6, and 12.5 cases/100 patients, respectively. Carotid atheromatosis progression was significantly associated with NNRTI exposure. People living with HIV infection exhibited high prevalence and incidence of subclinical arterial damage and site-specific predilection for the carotids. These investigations may help optimize HIV-specific CVD prediction models. The NNRTIs may contribute to atheromatosis, emphasizing the need to consider the atherogenic potential of antiretroviral drugs in management strategies.

Effectiveness of artificial pancreas in the non-adult population: A systematic review and network meta-analysis.

OBJECTIVE: Artificial pancreas is a technology that minimizes user input by bridging continuous glucose monitoring and insulin pump treatment, and has proven safety in the adult population. The purpose of this systematic review and meta-analysis is to evaluate the efficacy of closed-loop (CL) systems in the glycemic control of non-adult type 1 diabetes patients in both a pairwise and network meta-analysis (NMA) context and investigate various parameters potentially affecting the outcome. METHODS: Literature was systematically searched using the MEDLINE (1966-2018), Scopus (2004-2018), Cochrane Central Register of Controlled Trials (CENTRAL) (1999-2018), Clinicaltrials.gov (2008-2018) and Google Scholar (2004-2018) databases. Studies comparing the glycemic control in CL (either single- or dual-hormone) with continuous subcutaneous insulin infusion (CSII) in people with diabetes (PWD) aged <18 years old were deemed eligible. The primary outcome analysis was conducted with regard to time spent in the target glycemic range. All outcomes were evaluated in NMA in order to investigate potential between-algorithm differences. Pairwise meta-analysis and meta-regression were performed using the RevMan 5.3 and Open Meta-Analyst software. For NMA, the package pcnetmetain R 3.5.1 was used. RESULTS: The meta-analysis was based on 25 studies with a total of 504 PWD. The CL group was associated with significantly higher percentage of time spent in the target glycemic range (Mean (SD): 67.59% (SD: 8.07%) in the target range and OL PWD spending 55.77% (SD: 11.73%), MD: -11.97%, 95% CI [-18.40, -5.54%]) and with lower percentages of time in hyperglycemia (MD: 3.01%, 95% CI [1.68, 4.34%]) and hypoglycemia (MD: 0.67%, 95% CI [0.21, 1.13%]. Mean glucose was also decreased in the CL group (MD: 0.75 mmol/L, 95% CI [0.18-1.33]). The NMA arm of the study showed that the bihormonal modality was superior to other algorithms and standard treatment in lowering mean glucose and increasing time spent in the target range. The DiAs platform was superior to PID in controlling hypoglycemia and mean glucose. Time in target range and mean glucose were unaffected by the confounding factors tested. CONCLUSIONS: The findings of this meta-analysis suggest that artificial pancreas systems are superior to the standard sensor-augmented pump treatment of type 1 diabetes mellitus in non-adult PWD. Between-algorithm differences are also addressed, implying a superiority of the bihormonal treatment modality. Future large-scale studies are needed in the field to verify these outcomes and to determine the optimal algorithm to be used in the clinical setting.

Mechanisms of pulse pressure amplification dipping pattern during sleep time: the SAFAR study.

The difference in pulse pressure (PP) between peripheral arteries and the aorta, called pulse pressure amplification (PPamp), is a well-described physiological phenomenon independently associated with cardiovascular events. Recent studies suggest that it exhibits circadian variability. Our aim was to detect the factors associated with the circadian variability of PPamp. In 497 consecutive subjects (aged 54 years, 56.7% male, 79.7% hypertensives), we assessed the circadian pattern of peripheral and central arterial hemodynamics by 24-hour evaluation of brachial and aortic blood pressure (BP), augmentation index (AI), and pulse wave velocity (PWV) using a validated oscillometric device (Mobil-O-Graph). All parameters exhibited a circadian variation. Sleep dipping (decrease) pattern was observed for PPamp, brachial and aortic systolic BP, mean BP, and PWV, whereas a rising pattern (higher sleep than wake values) was observed for brachial PP, aortic PP, and AI. The factors independently associated with the less sleep dipping in PPamp were older age, lower height, the use of antihypertensive medication, and sleep decrease in arterial stiffness (PWV), whereas female gender, the presence of hypertension, sleep increase of pressure wave reflections (AI), sleep decrease in heart rate, and mean BP were associated with a greater sleep-dipping in PPamp. These data provide further pathophysiological understanding of the mechanisms leading to PPamp dipping. Several implications regarding the clinical use of the aortic and brachial BP, especially during sleep time, are raised that should be addressed in future research.

Antiepileptic Treatment Strategy in Vascular Malformations.

BACKGROUND: Antiepileptic treatment strategy plays an important role in the management of intracranial vascular malformations. The intracranial vascular malformations can be divided into cavernous hemangiomas, arteriovenous malformations, developmental venous anomalies and capillary telangiectasias. Seizures and hemorrhage are among their most common clinical manifestations. OBJECTIVE: The aim of this article is to review the current literature on the antiepileptic treatment in the setting of intracranial vascular malformations and offer an updated view on when antiepileptic drug treatment should be employed for each type of vascular malformation. METHODS AND MATERIALS: Current literature has been reviewed on cavernous malformations, arteriovenous malformations, developmental venous anomalies and capillary telangiectasias. Epidemiological features, epileptogenesis, clinical presentation and antiepileptic treatment have been analyzed. RESULTS: A variety of treatment modalities exist for the management of intracranial vascular malformations, including antiepileptic treatment, microsurgery, radiosurgery and embolization. The decision-making process is different for each type of intracranial vascular malformation. Moreover, a plethora of other clinical factors needs to be taken into consideration during the decision-making process, such as the patient's age and comorbidities, the risk of hemorrhage the need for definitive treatment of the malformation, the seizure rates after the definitive treatment, the efficacy and side effects profile of antiepileptic drugs. CONCLUSION: Antiepileptic treatment strategy is a multifactorial decision that should be individualized and ideally be made by multidisciplinary teams.

Hallmarks in history of esophageal carcinoma.

Esophageal cancer is one of the deadliest cancers due to its aggressive behavior and poor survival. It was mentioned in the works of ancient Chinese and Arabo-islamic physicians, centuries before the recognition of high incidence in the Asian esophageal cancer belt. Till the 19th century the disease was considered incurable and the main goal of the proposed treatments was to alleviate dysphagia and pain. The introduction of esophagoscope in 1868 by Adolf Kussmaul (1822-1902) contributed to the observation of the living esophagus and to the diagnosis of esophageal pathologies, paving the way for new therapeutic approaches. In 1877, Vincenz Czerny (1842-1916) performed the first successful resection of the cervical esophagus for carcinoma, followed by Franz Torek (1861-1938) who carried out in 1913 the first successful subtotal thoracic esophagectomy and Tohru Ohsawa (1882-1984) who performed the world's first esophagectomy with an intrathoracic esophagogastric anastomosis. Nowadays, despite the advent of biomedical technology and the development of operation techniques, the surgical treatment of esophagus still remains a challenge.

Concomitant alterations of metabolic parameters, cardiovascular risk factors and altered cortisol secretion in patients with adrenal incidentalomas during prolonged follow-up.

OBJECTIVE: Adrenal incidentalomas (AI) are associated with metabolic and hormonal abnormalities, most commonly autonomous cortisol secretion (ACS). Data regarding alterations of insulin resistance (IR) and ACS after prolonged follow-up are limited. We investigated the evolution of IR, cortisol secretion and ACS development in patients with AI during prolonged follow-up. DESIGN: Prospective study in a tertiary hospital. PATIENTS AND MEASUREMENTS: Seventy-one patients with AI [51 nonfunctioning (NFAI) and 20 ACS] and 5·54 ± 1·7 years follow-up underwent testing for ACS and oral glucose tolerance test to determine IR indices and adrenal imaging. RESULTS: At follow-up, 16/51 (31%) NFAI patients converted to ACS, while two with previous ACS reverted to NFAI; 21% (7/33) of patients who did not covert to ACS exhibited high urinary-free cortisol (H-UFC) levels. All AI patients developed deterioration of IR irrespective of their cortisol secretory status. Eight patients developed newly diagnosed type 2 diabetes (9·8% NFAI and 15% ACS, respectively) and 14 IR (17·6% NFAI and 25% ACS, respectively). Adenoma size increased from 2·1 ± 0·8 to 2·3 ± 0·8 cm, whereas IR correlated with postdexamethasone cortisol level and adenoma size increase. IR showed an incremental continuum trend from normal UFC (Ν-UFC), to H-UFC, C-ACS and ACS patients. CONCLUSIONS: New-onset ACS developed in 31% patients with NFAI, whereas 21% of NFAI patients had H-UFC levels. All AI patients as a group and the subgroups of N-UFC, H-UFC, C-ACS and ACS patients developed deterioration of metabolic parameters during follow-up that was more prominent in ACS patients.

Theories About Blood Coagulation in the Writings of Ancient Greek Medico-philosophers.

Anaxagoras and Empedocles both established during the Presocratic era a pioneering theory for the creation of everything in the universe. Macrocosmos' impact through the "Four Elements Theory" explained the conglomeration of the blood inside the vessels. Hippocrates, who instituted the "Four Humours theory", clearly understood blood's coagulation and introduced the term "thrombus". Plato, Aristotle and Galen, all engaged with the clotting phenomenon trying to interpret it. After eons of inquiry, it was the innovative thinking of the ancient Greek medico philosophers that set the scientific bases towards the understanding of a process that had been analyzing until our era.

Phenotypes of office systolic blood pressure according to both brachial and aortic measurements: frequencies and associations with carotid hypertrophy in 1861 adults.

BACKGROUND/AIM: Aortic SBP (aSBP) associates with arterial damage more consistently than brachial SBP (bSBP). However, it is unknown how often aSBP is normal in the presence of elevated bSBP, and vice versa; if SBP phenotyping on the basis of bSBP and aSBP cut-off values improves cardiovascular risk stratification. We tested the frequency of four office SBP phenotypes: type I (both normal bSBP and aSBP); type II (high bSBP but normal aSBP); type III (normal bSBP but high aSBP), and type IV (both high bSBP and aSBP), the probability of each phenotype to be associated with increased arterial damage, using type Ia (i.e. normal bSBP and low-normal aSBP) as reference. METHODS: In 1861 participants (age: 54 years, 49.1% men), we measured simultaneously bSBP, aSBP, and carotid cross-sectional wall area with ultrasound. RESULTS: Depending on the applied cut-off values, type II and type III phenotypes represented together 5-11% of the population (0.9-3.4 and 1.8-10.3%, respectively) and type IV around 20%. Subgroups with phenotypes, Ib (i.e. normal bSBP and high-normal aSBP), II, III, and IV had gradually significantly higher probability (by 1.37-1.91, 2.3-3.3, 3.3-8.9 times, and 4.18-6.25, respectively) to present elevated carotid artery cross-sectional wall area compared with the reference group, even after adjustment for DBP and other confounders. CONCLUSIONS: Type II (i.e. isolated high bSBP) and type III (i.e. isolated high aSBP) office SBP phenotypes were common and had intermediate level (between types I and IV) of arterial damage.

Racial variation and cancer: a historical approach.

At the end of the 19th century, in an attempt to define cancer's etiology, scientists considered that cancer was mainly affecting the white race and the temperate zone countries. In their turn, epidemiological studies held in the early 20th century sustained the dogma of cancer's racial distribution, targeting and stigmatizing ethnic groups.

Ambulatory Aortic Stiffness Is Associated With Narrow Retinal Arteriolar Caliber in Hypertensives: The SAFAR Study.

BACKGROUND: Arterial stiffness measured under static conditions reclassifies significantly cardiovascular (CV) risk and associates with narrower retinal arterioles. However, arterial stiffness exhibits circadian variation, thus single static stiffness recordings do not correspond to the "usual" 24 hr, awake, and asleep average arterial stiffness. We aimed to test the hypothesis that ambulatory 24 hr, awake, and asleep aortic (a) pulse wave velocity (PWV) associate with retinal vessel calibers, independently of confounders and of static arterial stiffness, in hypertensive individuals free from diabetes and CV disease. METHODS: Digital retinal images were obtained (181 individuals, age: 53.9±10.7 years, 55.2% men) and retinal vessel calibers were measured with validated software to determine central retinal arteriolar and venular equivalents (CRAE and CRVE, respectively); ambulatory (24 hr, awake, asleep) and static office aPWV were estimated by Mobil-O-Graph; and static office carotid to femoral (cf) PWV by SphygmoCor. RESULTS: Regression analysis performed in 320 gradable retinal images showed that, after adjustment for confounders: (i) ambulatory aPWV was significantly associated with narrower retinal arterioles but not with venules; (ii) asleep aPWV had stronger associations with CRAE than awake aPWV; (iii) both ambulatory aPWV and cfPWV were associated mutually independently with narrower retinal arterioles; aPWV introduction in the model of cfPWV, improved model's R2 (P = 0.012). Similar discriminatory ability of 24 hr aPWV and of cfPWV to detect the presence of retinal arteriolar narrowing was found. CONCLUSION: Ambulatory aPWV, estimated by an operator-independent method, provides additional information to cfPWV regarding the associations of arterial stiffness with the retinal vessel calibers.

Intact calibers of retinal vessels in patients with systemic sclerosis.

OBJECTIVE: A primary endothelial cell dysfunction is thought to be involved in systemic sclerosis (SSc)-associated fibroproliferative vasculopathy of the microcirculation and small arterioles, even in sites not affected by fibrosis. Because the role of fibroblasts in pathologic modifications and vascular wall remodeling is relatively unclear, and because the retina provides a unique opportunity to assess microcirculation in the absence of resident fibroblasts, we systematically evaluated retinal vessels in patients with SSc. METHODS: Digital retinal images were obtained from both eyes of 93 consecutive patients with fully characterized SSc and 29 healthy controls matched 1:1 for age and sex with selected patients without diabetes, hypertension history, or antihypertensive treatment. Internal microvascular calibers (erythrocyte column width in µm) by central retinal arteriolar and venular equivalents and arteriolar to venular ratio were measured using validated software. RESULTS: Arteriolar and venular calibers were similar in patients and their matched controls (mean ± SEM; 187 ± 2 vs 184 ± 3, p = 0.444, and 211 ± 2 vs 216 ± 3, p = 0.314, respectively). Both arteriolar and venular calibers and their ratio in patients with SSc were not associated with disease duration, extent of skin involvement, pulmonary fibrosis, digital ulcers or pitting scars, amputations, digital capillaroscopic findings, inflammatory indices, or autoantibodies. CONCLUSION: The evidence that retinal microcirculation is spared in SSc suggests that fibroproliferative vasculopathy may depend on specific cellular or soluble factors not present in the retinal environment.

Left-ventricular hypertrophy is associated better with 24-h aortic pressure than 24-h brachial pressure in hypertensive patients: the SAFAR study.

OBJECTIVE: To test the hypothesis that left-ventricular hypertrophy (LVH) is better associated with aortic, than brachial, 24-h average blood pressure (BP) in individuals with hypertension. BACKGROUND: The office aortic BP is associated better with organ damage, such as LVH, than the office brachial BP; whether the 24-h average aortic BP associates better with LVH, than the 24-h average brachial BP, has never been tested. METHODS: Aortic ambulatory BP monitoring (ABPM) was performed with a novel validated oscillometric cuff-based BP recording device, also used for simultaneous brachial ABPM, and the application of pulse wave analysis method. Office brachial and aortic BP were assessed with validated oscillometric recording device and pulse wave analysis, respectively; left-ventricular mass was measured by ultrasound. RESULTS: Regression analysis performed in 229 individuals (aged 54.3 ±â€Š14.6 years; 56% men; 75% hypertensive patients) showed that the 24-h average aortic SBP was significantly better associated with left-ventricular mass index and LVH than the 24-h average brachial, as well as, office (brachial or aortic) SBP, independently of age, sex, obesity or treatment. Receiver operator characteristics curve analysis showed a higher discriminatory ability of 24-h average aortic than brachial SBP to detect the presence of LVH (area under the curve: 0.73 versus 0.69; P = 0.007). A high degree of interindividual overlap regarding aortic 24-h average SBP level was found in individuals in whom the corresponding brachial measurements denoted different hypertension levels. CONCLUSION: These data suggest that aortic ABPM, when compared to brachial ABPM, improves the individualized assessment of the BP-associated heart damage.