Endothelial function assessment in atherosclerosis: Comparison of brachial artery flow‑mediated vasodilation and peripheral arterial tonometry

INTRODUCTION Endothelial dysfunction, characterized by the loss of nitric oxide bioavailability, is a key element in the pathogenesis of atherosclerosis and an important prognostic factor in cardiovascular diseases. Therefore, the development of reliable, safe, and noninvasive methods of endothelial function assessment is important for their use in cardiovascular risk stratification. Brachial artery flow‑mediated dilation (FMD) is widely used in research but technical difficulties and problems with calibration between laboratories limit its clinical use. Reactive hyperemia–peripheral artery tonometry (RH‑PAT, EndoPAT) has been developed as a simpler, cheaper, and potentially more reproducible method. OBJECTIVES We aimed to investigate associations between RH‑PAT and FMD in relation to atherosclerotic risk factor profile. PATIENTS AND METHODS The study involved 80 subjects (52 men, 28 women) aged 43.6 ±14.8 years, with moderate‑to‑low cardiovascular risk (mean SCORE, 2.2% ±2%), in whom FMD, RH‑PAT, and intima–media thickness (IMT) were determined. RESULTS The reactive hyperemia index (RHI) measured by RH‑PAT correlated with FMD (r = 0.35, P <0.01). However, no significant correlation was observed between RHI and IMT, SCORE, or the number of classical atherosclerotic risk factors (hypertension, smoking, diabetes, hypercholesterolemia), while FMD was significantly correlated with IMT (r = –0.53, P <0.001), risk factors (r = –0.55, P <0.05), and SCORE (r = –0.4, P <0.05). CONCLUSIONS Despite its technical requirements, FMD is a more sensitive method than RH‑PAT in evaluating the effect of classical atherosclerotic risk factors on vascular endothelial function. Microvasculature response during RH‑PAT needs to be further studied, including the assessment of nonendothelial factors that may affect the measurements, before RH‑PAT becomes the universal tool for the evaluation of the endothelial cells

Wczesne wyniki leczenia skolioz idiopatycznych z zastosowaniem gorsetu dynamicznego SpineCor

Wstęp: Skolioza idiopatyczna to trójpłaszczyznowa deformacja kręgosłupa. Leczenie uzależnione jest od wielu czynników, spośród których wielkość skrzywienia i stopień dojrzałości kostnej wydają się być najbardziej istotne. W przypadku progresujących skrzywień o kącie <40° zalecane jest stosowanie gorsetu. Dostępnych jest wiele rodzajów gorsetów, najczęściej o sztywnej konstrukcji. Gorset dynamiczny SpineCor to system elastycznych taśm, które po założeniu bezpośrednio korygują deformację kręgosłupa nieograniczając jego ruchomości. Cel pracy: Celem pracy jest przedstawienie wczesnych wyników leczenia skolioz idiopatycznych z zastosowaniem gorsetu dynamicznego SpineCor. Materiał i metodyka: Kryterium rozpoczęcia leczenia gorsetem była obecność progresującego skrzywienia kręgosłupa u chorych z dojrzałością kostną według Rissera 0-3. Aplikacja gorsetu odbywało się według założeń metody. Badaną grupę stanowiło 42 chorych, 36 dziewcząt i 6 chłopców. Wiek w chwili rozpoczęcia leczenia wynosił średnio 11,9 lat. Okres obserwacji wynosił średnio 11 miesięcy. Wyjściowy kąt skrzywienia w odcinku piersiowym wynosił średnio 33,1°, zaś w odcinku lędźwiowym 29,4°. Badana grupa została podzielona na podgrupy na podstawie: wielkości wyjściowego skrzywienia, lokalizacji skrzywienia, płci. Wyniki oceniano jako korekcję (zmniejszenie kąta o >=5°), stabilizację (zmiana kąta +/- 5°) lub progresję (zwiększenie kąta o >=5°). Wyniki: Wielkość kąta skrzywienia w ostatniej kontroli w odcinku piersiowym wyniosła średnio 29,7°, zaś w odcinku lędźwiowym 25,5°. U 21 chorych skrzywienie uległo korekcji (50%), 14 osiągnęło stabilizację (33,3%) a 7 progresję (16,6%). Najlepsze wyniki osiągnięto w grupie chorych z wyjściowym kątem <25° (p < 0,05) - 60% chorych z korekcją. Przeciwnie w grupie chorych z wyjściowym kątem >45° tylko 37,5% osiągnęło korekcję. Nie zanotowano znaczących różnic w wynikach leczenia w zależności od płci. Wnioski: Gorset SpineCor stanowi dobrą alternatywę dla sztywnych gorsetów, zwłaszcza w przypadkach małych skrzywień. Pozwala on na zachowanie ruchomości kręgosłupa. Tego typu gorset jest dobrze akceptowalny przez młodych chorych. Niezbędne są dalsze długofalowe obserwacje celem ostatecznych wniosków.Introdcution: Idiopathic scoliosis is a three-dimensional deformation of the spine. Treatment of this condition depends on many factors, with curve magnitude (Cobb angle) and skeletal maturity (Risser sign) being the most important indices. In progressing curves of <40°, bracing is recommended. Different types of braces are available, most of them are of a rigid type. The SpineCor dynamic brace is a system of elastic bands designed to directly correct the spinal column deformity without restricting motion of the spine. Aim of the paper: The aim of this paper is to present early results of adolescent idiopathic scoliosis treatment with the SpineCor brace. Material and methods: Inclusion criteria for brace the application included the presence of a progressing curve in a skeletally immature child (Risser 0 - 3). The SpineCor brace was applied according to the principles of the method. The study group comprised 42 patients: 36 girls, 6 boys. The mean age at brace application was 11.9 years. The mean follow-up was 11 months. The mean initial curve size in the whole group was 33.1° in the thoracic spine and 29.4° in the lumbar spine. The evaluated group was subsequently divided into different subgroups depending on: initial curve size, curve type and sex. Results were classified as correction (decrease of curve size of >=5°), stablisation (curve change +/- 5°) or progression (increase of curve size of >=5°). Results: Mean curve size at the final follow-up was 29.7° in the thoracic spine and 25.5° in the lumbar spine. Twenty one patients improved (50%), 14 had curve stabilisation (33.3%) and 7 progressed (16.6%). The best results were achieved in curves lower than 25° Cobb angle (p < 0.05) - 60% of patients improved. In contrast, in the over-45° group, only 37.5% of patients improved. No significant differences were found between treatment results with regard to sex. Conclusion: SpineCor brace seems to be a good alternative for rigid braces, especially in minor curves. It enables preservation of motion of the spine. This type of brace is easily accepted by young patients. Further follow-up is needed to present long-term results

Th17 responses are not altered by natural exposure to seasonal allergens in pollen-sensitive patients

Background: Allergic rhinitis affects 10–30 % of the global population and this number is likely to increase in the forthcoming years. Moreover, it commonly co-exists with allergic asthma as a chronic allergic respiratory syndrome. While the involvement of Th2 cells in allergy is well understood, alterations of pro-inflammatory Th17 responses remain poorly characterized. The aim of our study was to determine whether natural seasonal allergen exposure causes changes in T cell subset characteristics in patients with allergic rhinitis and asthma. Methods: Sixteen patients with allergic rhinitis/atopic asthma (9M, 7F; age 31.8 ± 12.1) and 16 healthy controls were recruited into the study (9M, 7F; age 31.2 ± 5.3). Blood samples were collected from the patients 1–3 months before pollen season (visit 1), within 7 days of the appearance of pollen/initiation of allergic symptoms (visit 2) and 2 weeks after visit 2 following the introduction of symptomatic treatment with antihistamines (visit 3). Flow cytometry was used to assess major T cell subsets (naïve, central memory, effector memory and CD45RA+ effector) and key T cell cytokine production (IFNγ, IL-17A, TNF and IL-4) using intracellular staining. Data were analyzed using repeated measures ANOVA and paired t test. Results: As expected, an increase in the percentage of IL‐4+ CD4+ cells was observed during natural pollen exposure in patients with allergic respiratory syndrome. No significant changes were observed in the production of other cytokines, including Th17 cells, which tended to be lower than in the control population but unchanged during pollen exposure. Introduction of antihistamine treatment led to only moderate changes in cytokine production from CD4 and CD8 T cells. Selective changes in CD8+ T cells were observed during natural pollen exposure including a decrease in transient cells (with features of CD45RA+ and CD45RO+ cells) and a decrease in the percentage of central memory cells in the peripheral circulation. Within the CD4 cell group the total percentage of CD45RA positive CD4 cells was increased during pollen exposure. Conclusions: Th1 and Th17 responses are not altered during pollen season but allergen exposure affects T cell activation and memory cell status in patients with allergic respiratory syndrome

Spine deformities in patients with Ehlers-Danlos syndrome, type IV - late results of surgical treatment

<p>Abstract</p> <p>Background</p> <p>Spinal deformities in Ehlers-Danlos syndrome are usually progressive and may require operative treatment. There is limited number of studies describing late results of surgery in this disease.</p> <p>Methods</p> <p>This is a retrospective study of the records of 11 patients with Ehlers-Danlos syndrome type IV, treated surgically between 1990 and 2007. All patients underwent surgical treatment for spinal deformity. Duration of operation, type of instrumentation, intraoperative blood loss, complications and number of additional surgeries were noted. Radiographic measurement was performed on standing AP and lateral radiographs acquired before surgery, just after and at final follow up.</p> <p>Results</p> <p>The mean follow up period was 5.5 ± 2.9 years (range 1-10 years). The mean preoperative thoracic and lumbar curve were 109.5 ± 19.9° (range 83° - 142°) and 75.6 ± 26.7° (range 40° - 108°) respectively. Posterior spine fusion alone was performed on 6 patients and combined anterior and posterior fusion (one- or two stage) on 5 cases. Posterior segmental spinal instrumentation was applied with use of hooks, screws and wires. The mean postoperative thoracic and lumbar curve improved to 79.3 ± 16.1° (range 56° - 105°) and 58.5 ± 27.7° (range 10° - 95°) respectively, with a slight loss of correction during follow up. The average thoracic and lumbar correction was 26.4 ± 14.9% (range 5.3 - 50.4%) and 26.3 ± 21.2% (range 7.9 - 75%). Postoperatively, the mean kyphosis was 79.5 ± 40.3° (range 21° -170°), and lordosis was 50.8 ± 18.6° (range 20° -79°). Hyperkyphosis increased during follow up while lordosis remained stable. Mean Th12-L2 angle was -3.5 ±9.9° (range -19° - 15°) postoperatively and did not change significantly during follow up.</p> <p>Conclusions</p> <p>Huge spinal deformities in patients with Ehlers-Danlos syndrome require complex and extensive surgery. There is a big risk of sagittal imbalance in this group.</p

Imipramine influences body distribution of supplemental zinc which may enhance antidepressant action

Zinc (Zn) was found to enhance the antidepressant efficacy of imipramine (IMI) in human depression and animal tests/models of depression. However, the underlying mechanism for this effect remains unknown. We measured the effect of intragastric (p.o.) combined administration of IMI (60 mg/kg) and Zn (40 mg Zn/kg) in the forced swim test (FST) in mice. The effect of Zn + IMI on serum, brain, and intestinal Zn concentrations; Zn transporter (ZnT, ZIP) protein levels in the intestine and ZnT in the brain; including BDNF (brain-derived neurotrophic factor) and CREB (cAMP response element-binding protein) protein levels in the brain were evaluated. Finally, the effect of IMI on Zn permeability was measured in vitro in colon epithelial Caco-2 cells. The co-administration of IMI and Zn induced antidepressant-like activity in the FST in mice compared to controls and Zn or IMI given alone. This effect correlated with increased BDNF and the ratio of pCREB/CREB protein levels in the prefrontal cortex (PFC) compared to the control group. Zn + IMI co-treatment increased Zn concentrations in the serum and brain compared to the control group. However, in serum, co-administration of IMI and Zn decreased Zn concentration compared to Zn alone treatment. Also, there was a reduction in the Zn-induced enhancement of ZnT1 protein level in the small intestine. Zn + IMI also induced an increase in the ZnT4 protein level in the PFC compared to the control group and normalized the Zn-induced decrease in the ZnT1 protein level in the hippocampus (Hp). The in vitro studies revealed enhanced Zn permeability (observed as the increased transfer of Zn through the intestinal cell membrane) after IMI treatment. Our data indicate that IMI enhances Zn transfer through the intestinal tract and influences the redistribution of Zn between the blood and brain. These mechanisms might explain the enhanced antidepressant efficacy of combined IMI/Zn treatment observed in the FST in mice

Hypertension and increased endothelial mechanical stretch promote monocyte differentiation and activation: roles of STAT3, interleukin 6 and hydrogen peroxide

Aims: Monocytes play an important role in hypertension. Circulating monocytes in humans exist as classical, intermediate and non-classical forms. Monocyte differentiation can be influenced by the endothelium, which in turn is activated in hypertension by mechanical stretch. We sought to examine the role of increased endothelial stretch and hypertension on monocyte phenotype and function. Methods and Results: Human monocytes were cultured with confluent human aortic endothelial cells undergoing either 5% or 10% cyclical stretch. We also characterized circulating monocytes in normotensive and hypertensive humans. In addition, we quantified accumulation of activated monocytes and monocyte-derived cells in aortas and kidneys of mice with Angiotensin II-induced hypertension. Increased endothelial stretch enhanced monocyte conversion to CD14++CD16+ intermediate monocytes and monocytes bearing the CD209 marker and markedly stimulated monocyte mRNA expression of interleukin (IL)-6, IL-1β, IL-23, chemokine (C-C motif) ligand 4 and tumor necrosis factor α. STAT3 in monocytes was activated by increased endothelial stretch. Inhibition of STAT3, neutralization of IL-6 and scavenging of hydrogen peroxide prevented formation of intermediate monocytes in response to increased endothelial stretch. We also found evidence that nitric oxide inhibits formation of intermediate monocytes and STAT3 activation. In vivo studies demonstrated that humans with hypertension have increased intermediate and non-classical monocytes and that intermediate monocytes demonstrate evidence of STAT3 activation. Mice with experimental hypertension exhibit increased aortic and renal infiltration of monocytes, dendritic cells and macrophages with activated STAT3. Conclusions: These findings provide insight into how monocytes are activated by the vascular endothelium during hypertension. This is likely in part due to a loss of nitric oxide signaling and increased release of IL-6 and hydrogen peroxide by the dysfunctional endothelium and a parallel increase in STAT activation in adjacent monocytes. Interventions to enhance bioavailable nitric oxide, reduce IL-6 or hydrogen peroxide production or to inhibit STAT3 may have anti-inflammatory roles in hypertension and related conditions

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat