Vascular Morbidity Research Articles

Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework.

It is well-established that patients with sickle cell disease (SCD) are at substantial risk of neurological complications, including overt and silent stroke, microstructural injury, and cognitive difficulties. Yet the underlying mechanisms remain poorly understood, partly because findings have largely been considered in isolation. Here, we review mechanistic pathways for which there is accumulating evidence and propose an integrative systems-biology framework for understanding neurological risk. Drawing upon work from other vascular beds in SCD, as well as the wider stroke literature, we propose that macro-circulatory hyper-perfusion, regions of relative micro-circulatory hypo-perfusion, and an exhaustion of cerebral reserve mechanisms, together lead to a state of cerebral vascular instability. We suggest that in this state, tissue oxygen supply is fragile and easily perturbed by changes in clinical condition, with the potential for stroke and/or microstructural injury if metabolic demand exceeds tissue oxygenation. This framework brings together recent developments in the field, highlights outstanding questions, and offers a first step toward a linking pathophysiological explanation of neurological risk that may help inform future screening and treatment strategies.

Hibiscus ameliorates salt-induced carotid intima-media thickness in albino rats

Objectives: The carotid intima-media thickness (CIMT) is a known biomarker of clinical and subclinical cardiovascular events and evaluation of therapeutic action. Excessive salt directly causes changes in the common carotid intima and media layers and has been linked to hypertensive disease resulting to changes on vascular structure. Hibiscus sabdariffa is a traditional herbal drink with antihypertensive effects. The anatomical aspects of its effects however, are largely unknown. This study therefore, investigated the effects of hibiscus extract on CIMT in rats fed with a high-salt diet. Methods: Young albino rats (Rattus norvegicus) were divided into three groups: (A) high-salt diet alone, (B) high-salt diet and Hibiscus sabdariffa extract and (C) control group fed a normal diet for 8 weeks. Specimens from carotid arteries of rats were fixated and processed for paraffin embedding. Seven-micrometer thick sections were stained with Hematoxylin and Eosin stain and examined under light microscopy. Morphometric measurements were taken to determine the CIMT. Results: High-salt diet increased CIMT from 497.86 µm to 697.85 µm in 8 weeks. In Hibiscus sabdariffa extract fed rats, the CIMT decreased to 542.85 µm (p<0.05) by week 8. Conclusion: Hibiscus sabdariffa extract ameliorates salt-induced increase in CIMT in rats in a time-dependent manner. This implies that Hibiscus sabdariffa products may have therapeutic value in salt-induced vascular morbidity.

Update on the Diagnosis and Anticoagulant Treatment of the Antiphospholipid Syndrome

Antiphospholipid syndrome (APS) is an acquired form of thrombophilia characterised by the presence of antiphospholipid antibodies and arterial/venous thrombosis or obstetric complications. Although antiphospholipid antibodies are reported in 1–5% of the general population, only a minority of these individuals will develop the clinical manifestations of APS. The typical expressions of APS are thrombotic events that can involve veins, arteries, or small vessels in any organ or tissue. Pregnancy morbidity refers mainly to early and late fetal loss, but pre-eclampsia, eclampsia, or placental insufficiency can also occur. Extra-criteria manifestations include thrombocytopenia, APS-associated nephropathy, valvular heart disease, neurological manifestations, and livedo reticularis. The diagnosis of APS is currently based on the Sydney criteria: i.e., meeting at least one clinical criterion (vascular thrombosis or pregnancy morbidity) and one laboratory criterion (lupus anticoagulant, anticardiolipin antibodies, or anti-β2 glycoprotein-I antibodies). Anticoagulation with unfractionated or low molecular weight heparin followed by vitamin K antagonist is the standard treatment for APS patients presenting with venous thromboembolism. There is not enough evidence regarding the use of the direct oral anticoagulants in this population. Patients presenting with arterial thrombosis may receive a combination of vitamin K antagonists and low-dose aspirin. In women with obstetrical APS, the combination of low molecular weight heparin and low-dose aspirin is usually prescribed to prevent pregnancy complications. The aim of this narrative review is to summarise the latest evidence on the diagnosis and antithrombotic treatment of APS.

National and subnational estimation of the prevalence of peripheral artery disease (PAD) in China: a systematic review and meta-analysis

BackgroundPeripheral artery disease (PAD), the third leading cause of atherosclerotic vascular morbidity, affects approximately 202 million people worldwide, among whom more than two-thirds reside in low- and middle-income countries (LMIC). For China, the largest developing country, little is known about the epidemiology of PAD. We aimed to estimate the prevalence of PAD and the number of affected people in China, establish the main risk factors for PAD and assess the number of people with PAD at the sub-national level.MethodsWe searched China National Knowledge Infrastructure (CNKI), Wanfang, Chinese Biomedicine Literature Database (CBM-SinoMed), PubMed, Embase and Medline for population-based studies that have reported the prevalence of PAD in the general Chinese population from 1990 onwards. PAD was defined as an ankle-brachial index (ABI) lower than or equal to 0.90. We used a multilevel mixed-effects logistic regression to generate the gender- and age-specific prevalence of PAD, and a random-effects meta-analysis to pool the odds ratios (ORs) of major risk factors. United Nations population numbers were used to estimate and project the number of affected people from 2000 to 2020. Finally, we used the risk factors-based model to distribute the national number of people with PAD into different settings (urban and rural) and regions (East, Central and West) for the year 2010.ResultsOverall, 37 articles met all inclusion criteria and provided prevalence estimates, among which 14 also explored risk factors for PAD. The prevalence of PAD increased gradually by age until mid-60s, after which the increase accelerated. In males, the prevalence of PAD ranged from 2.81% (95% CI = 1.77-4.43) in those aged 25-29 years to 21.95% (95% CI = 15.39-30.31) in those 95-99 years old. In females, the PAD prevalence increased from 3.84% (95% CI = 2.44-5.98) in those aged 25-29 years to 27.95% (95% CI = 20.14-37.37) in those aged 95-99 years. The PAD prevalence was consistently higher in females than in males across all age groups. This difference was most significantly pronounced among the elderly, starting from 60 years. Between 2000 and 2020, the total number of Chinese people with PAD is expected to increase by 40%: from 29.44 million (95% CI = 22.51-38.62) in 2000 to 41.13 million (95% CI = 32.00-52.95) in 2020. Current smoking was the strongest risk factor for PAD, with a meta-odds ratio (OR) of 2.62 (95% CI = 1.44-4.76), followed by hypertension (1.94, 95% CI = 1.48-2.53) and diabetes (1.71, 95% CI = 1.45-2.01). In 2010, 15.18 million (95% CI = 11.74-19.67) people with PAD resided in the East China, 11.08 million (95% CI = 8.61-14.28) in the Central China and 8.65 million (95% CI = 6.71-11.16) in the West China. In addition, 24.20 million (95% CI = 18.82-31.16) people with PAD were living in rural areas, accounting for almost 70% of all PAD cases in China.ConclusionsWith rapid ageing in China, PAD has become a serious public health problem. More research and optimal interventions on PAD are required to better identify effective strategies for prevention and treatment of PAD in China.

Tight systolic blood pressure control with combination therapy decreases type 2 endoleaks in patients undergoing endovascular aneurysm repair

BackgroundEndovascular aneurysm repair (EVAR) has revolutionized the treatment of abdominal aortic aneurysm (AAA) disease. However, the survival advantage is lost in the long term due the occurrence of endoleaks affecting the late rupture of aneurism sac. Few data are available on the role of blood pressure control in affecting the incidence of type 2 endoleaks in patients undergoing EVAR. ObjectiveAim of this study was to evaluated whether systolic blood pressure (SBP) control to target 130 mmHg reached after preoperative cardiology consultant might decrease the incidence of type II endoleak(T2E), sac expansion and related aortic reintervention after elective endovascular aneurysm repair(EVAR). MethodsWe analyzed 386 patients undergoing EVAR between 2008 and 2016. The primary endpoints were T2E, sac expansion and related aortic re-intervention or sac shrinkage during a median follow-up of 24 months [12–48]. The secondary endpoint was every cause of vascular or cardiac morbidity and mortality. ResultsThe SBP value of 130 mmHg at the time of EVAR resulted, at ROC curve analysis, the most sensitive and specific for all the analyzed endpoints (T2E, n = 74; sac expansion n = 19; re-intervention, n = 10, sac shrinkage, n = 72). The combination antihypertensive therapy showed a significant inverse relationship with T2E occurrence. The incidence of primary endpoints was significantly higher (p < 0.001) in patients with SBP ≥ 130 mmHg. Cardiovascular death was significantly more prevalent (p < 0,001) in patients with SBP ≥130 mmHg. These findings were confirmed at the multivariable Cox regression analysis [primary endpoint HR = 0.09(0.06–0.15), p < 0.001; cardiovascular death HR = 0.33(0.12–0.85), p = 0.023]. ConclusionsTight SBP control at the target of 130 mmHg at the time of elective EVAR significantly decreases TE2 occurrence, need of re-intervention and cardiovascular death in a prolonged follow-up of a large sample of patients.

Noninvasive monitoring of the development and treatment response of ischemic hindlimb by targeting matrix metalloproteinase-2 (MMP-2).

Critical limb ischemia (CLI) is a common cause of high vascular morbidity and mortality. Monitoring the development and treatment response of hindlimb ischemia (HI) in an animal model enables a better understanding of the pathological mechanisms underlying CLI, and evaluation of the efficacy of novel therapeutic approaches. Matrix metalloproteinase (MMP) activity is essential for remodeling of ischemic tissue including extracellular matrix degradation and angiogenesis. Herein, a mouse HI model is established and subjected to noninvasive optical imaging with a novel and ultra-sensitive MMP activatable probe, termed MMP-P12, for analyzing the development and treatment response of HI. Our results show that angiogenesis development during HI was well correlated with MMP-2 activity alteration as examined by western blot, histological staining and MMP-P12 fluorescence signal recovery. Moreover, vascular endothelial growth factor (VEGF) mediated HI treatment was also monitored by MMP-P12. Up-regulated MMP-2 expression and an enhancement of angiogenesis were observed after VEGF treatment, which peaked at 7 days after the treatment. Overall, our results showed that MMP-2 plays an important role in the monitoring of angiogenesis during HI development and therapy. Application of MMP-P12 to visualize MMP-2 activity alteration can serve as a promising noninvasive optical imaging strategy to monitor angiogenesis and its response to therapy in CLI.

Clinical Phenotype of a First Unprovoked Acute Pulmonary Embolism Associated with Antiphospholipid Antibody Syndrome.

BackgroundAntiphospholipid antibody syndrome (APS), an important cause of acquired thrombophilia, is diagnosed when vascular thrombosis or pregnancy morbidity occurs with persistently positive antiphospholipid antibodies (aPL). APS is a risk factor for unprovoked recurrence of pulmonary embolism (PE). Performing laboratory testing for aPL after a first unprovoked acute PE is controversial. We investigated if a specific phenotype existed in patients with unprovoked with acute PE, suggesting the need to evaluate them for APS.MethodsWe retrospectively reviewed patients with PE and APS (n=24) and those with unprovoked PE with aPL negative (n=44), evaluated 2006–2016 at the Asan Medical Center. We compared patient demographics, clinical manifestations, laboratory findings, and radiological findings between the groups.ResultsOn multivariate logistic regression analysis, two models of independent risk factors for APS-PE were suggested. Model I included hemoptysis (odds ratio [OR], 12.897; 95% confidence interval [CI], 1.025–162.343), low PE severity index (OR, 0.948; 95% CI, 0.917–0.979), and activated partial thromboplastin time (aPTT; OR, 1.166; 95% CI, 1.040–1.307). Model II included age (OR, 0.930; 95% CI, 0.893–0.969) and aPTT (OR, 1.104; 95% CI, 1.000–1.217).ConclusionWe conclude that patients with first unprovoked PE with hemoptysis and are age <40; have a low pulmonary embolism severity index, especially in risk class I–II; and/or prolonged aPTT (above 75th percentile of the reference interval), should be suspected of having APS, and undergo laboratory testing for aPL.

Ultrasound assessment of carotid arteries: Current concepts, methodologies, diagnostic criteria, and technological advancements.

Following cardiac disease and cancer, stroke continues to be the third leading cause of death and disability due to chronic disease in the developed world. Appropriate screening tools are integral to early detection and prevention of major cardiovascular events. In a carotid artery, the presence of increased intima-media thickness, plaque, or stenosis is associated with increased risk of a transient ischemic attack or a stroke. Carotid artery ultrasound remains a long-standing and reliable tool in the current armamentarium of diagnostic modalities used to assess vascular morbidity at an early stage. The procedure has, over the last two decades, undergone considerable upgrades in technology, approach, and utility. This review examines in detail the current state and usage of this integrally important means of extracranial cerebrovascular assessment.

Evaluation of Anticoagulant Use during Pregnancy in Mothers with Antiphospholipid Syndrome: An Observational Cross-Sectional Study

Introduction: Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by vascular thrombosis and/or pregnancy morbidity with persistent elevated concentration of antiphospholipid antibody. The use of anticoagulant in pregnant women with APS has reduced implantation failure, reduced rate of placental insufficiency, increased rate of delivery of live infant, and reduced rate of abortion. However, compared to its beneficial effects, anticoagulant therapy during pregnancy can be challenging because of the burden of the treatment (self-injecting anticoagulant for 9 months, cost of the treatment) and potential anticoagulant side effects. The purpose of this study was to evaluate the outcome of pregnant women with APS with anticoagulant.Method: We searched through medical records of pregnant women who visited hematology oncology clinic of Cikini CCI Hospital from year 2000 to 2017. Pregnant women with positive antiphospholipid antibodies who were treated with anticoagulant and followed up until presence of outcome were included in the study. Main outcome was any delivery of live infant above 22 weeks gestational age. Activated partial thromboplastin time (aPTT), d dimer level, birth weight and length were also documented.Results: We identified 92 pregnancies in 88 mothers diagnosed with antiphospholipid syndrome who were prescribed anticoagulant. From 92 pregnancies, 67 (73%) and 25 (27%) patients were prescribed low molecular weight heparin (LMWH) and unfractionated heparin (UFH), respectively, with combination of low dose antiplatelet agent. APTT and d dimer level of every patients were monitored monthly. 80% of the pregnancies successfully resulted in live births. The proportion of successful delivery of healthy infant in patients treated with UFH (21 out of 25; 84%) was greater than LMWH (53 out of 67; 79%) but not statistically different (p = 0,708) (Figure 1). Birth weight and length between groups were similar.Conclusion: UFH may be used as safe and cost-effective alternative treatment to LMWH in pregnant women with APS. Despite the use of anticoagulant and antiplatelet agents, 20% of patients still had adverse pregnancy outcome. DisclosuresNo relevant conflicts of interest to declare.

Retinal Vasculature Reactivity During Flicker Light Provocation, Cardiac Stress and Stroke Risk in Africans: The SABPA Study.

Structural and functional similarities exist between the retinal, cerebral and, as previously suggested, the coronary microvasculature. Retinal microvascular structure and functionality (in response to flicker-light-induced-provocation (FLIP)) may relate to coronary artery disease risk and possible stroke risk. We investigated associations between retinal vessel structure, functionality and cardiac stress markers (cardiac troponin T [cTnT], amino-terminal B-type natriuretic peptide [NT-proBNP]) to translate these retina-heart relationships to stroke risk. We included 317 African and Caucasian teachers' (aged 23-68years), who participated in the Sympathetic Activity and Ambulatory Blood Pressure in Africans (SABPA) study. Fasting plasma and serum samples for cTnT and NT-proBNP were collected. Retinal vascular calibres were quantified from fundus images and dynamic retinal vessel calibre responses during FLIP. The University of California stroke risk score was applied to assess sub-clinical 10-year stroke risk. cTnT levels were similar in Africans and Caucasians, whereas NT-proBNP levels were lower in Africans. In Africans, a reduced arteriolar calibre and attenuated arteriolar dilation during FLIP was associated with higher cTnT (p < 0.01). Their larger retinal-venular calibre (p < 0.02) and attenuated arteriolar dilation during FLIP (p < 0.05) were associated with lower NT-proBNP. Again, exclusively in Africans, increased cardiac stress, wider venular calibres and retinal arteriovenous nicking predicted an increased 10-year stroke risk with odds ratios of 1.57 (95% CI, 1.34; 1.68, p = 0.031), 1.51 (95% CI, 1.26; 1.59, p = 0.002), 1.10 (95% CI, 0.94; 2.85, p = 0.002) and 1.06 (95% CI 0.83; 1.56, p = 0.052), respectively. None of these associations were evident in the Caucasian group. Investigating the retinal vasculature may serve as a tool to approximate sub-clinical coronary and cerebral microvasculature damage or dysfunction. These cardiac stress-retinal associations additionally predicted a greater stroke risk in the SABPA African cohort. Observable changes in the retinal vasculature may serve as markers for the identification and prediction of cardio-systemic and cerebral vascular morbidities and risks, thereby establishing a brain-heart link. Graphical Abstract Proposed series of events during which sustained high pressure and increased cardiac stress may alter retinal reactivity and link to increased stroke risk.

Angiotensinogen M235T Gene Polymorphism is a Genetic Determinant of Cerebrovascular and Cardiopulmonary Morbidity in Adolescents with Sickle Cell Disease

BackgroundCerebrovascular stroke is a common critical complication of sickle cell disease (SCD). Angiotensinogen (AGT) M235T gene polymorphism is associated with risk of ischemic stroke and cardiovascular disease. AimWe investigated the potential association between angiotensinogen M235T gene polymorphism and susceptibility to cerebrovascular and cardiopulmonary complications in adolescents with SCD. MethodsForty-six patients with SCD in steady state were studied stressing on history of stroke, hydroxyurea/chelation therapy, hematological profile, and echocardiographic findings. Polymerase chain reaction-based restriction fragment length polymorphism analysis was used to detect AGT M235T gene polymorphism. Fifty sex- and age-matched healthy controls were enrolled for assessment of M235T gene polymorphism pattern. ResultsThe distribution of AGT M235T gene polymorphism was similar between SCD patients and healthy controls. The frequency of T allele of AGT M235T gene polymorphism (TT and MT genotypes) was significantly higher among patients with history of manifest stroke (P < .001). Patients with TT and MT genotypes had higher incidence of cardiopulmonary complications (P = .041) as well as higher percentage of HbS (P < .001) and lower hemoglobin level (P = .008) compared with those with MM genotype. Serum ferritin, liver iron concentration, and cardiac T2* were not related to T alleles or genotypes. Logistic regression analysis revealed that M235T genotype was a significant independent factor related to the occurrence of stroke among patients with SCD (Odds Ratio 14.05, 95% confidence interval 3.82-28.91; P = .001). ConclusionAGT M235T gene polymorphism may represent a genetic modifier to vascular morbidities in Egyptian patients with SCD.

A national study of the prevalence and risk factors associated with peripheral arterial disease from China: The China Hypertension Survey, 2012–2015

BackgroundPeripheral arterial disease (PAD) is the third leading cause of atherosclerotic vascular morbidity after coronary heart disease and stroke. Epidemiology data of PAD is very limited in low-income and middle-income countries. A national wide survey was conducted from October 2012 to December 2015 to assess the prevalence of PAD in China. MethodsData from the China Hypertension Survey (CHS). In total, 56,000 people aged 35 years or older were enrolled in this sub-survey for PAD, and 30,025 participants were eligible for analysis. Ankle-brachial index was measured using an automated ABI device (WatchBP Office device Microlife, China). PAD was defined by ABI and Edinburgh Claudication Questionnaire. Results and conclusionsOverall, 6.6% (estimated 45.3 million) of the Chinese adult population age 35 years or older had PAD. The weighted prevalence of PAD increased significantly after aged ≥75 years. There were no significant differences in PAD prevalence between urban and rural residents, as well as between males and females. Among individuals with PAD, only 4.9% (95% CI: 0%–10.1%) were aware of their condition, 1.9% (95% CI: 0%–4.0%) received revascularization, and 0.2% (95% CI: 0%–0.4%) achieved ABI >0.9. Older age, Han population, current smokers, education level, hypertension, CAD, diabetes, dyslipidemia, and rural residences all were significantly associated with an increased risk of PAD. In China, there is an increasing prevalence of PAD, but the awareness, treatment, and control were very low. Special attention should be paid to prevent and control PAD in China.Clinical trial registration number: ChiCTR-ECS-14004641.

Prospective study on prescribing pattern of antihypertensive drugs at a tertiary care hospital

Background: Hypertension is the leading non-communicable disease risk attributing to cardio vascular morbidity and mortality. Various reasons are socio-economic, behavioural, sedentary life style, nutritional, age, obesity and poor health maintenance. A wide range of antihypertensive drugs belonging to different pharmacological classes are available alone or in combinations. Present study was done to evaluate the prescribing pattern of antihypertensive drugs at a tertiary care hospital.Methods: A prospective, observational, non-interventional, hospital-based study was carried out in hypertensive patients attending outpatient department of General Medicine at Medical College Hospital attached to Vijayanagar Institute of Medical Sciences, Ballari. Data was collected from outpatient slip of patients in a predesigned case record form, which was analysed using descriptive statistics.Results: Among 200 patients analysed 95 (47.5%) were males and 105 (52.5%) were females, with maximum number of patients falling in the age group 61-70years. Among antihypertensives prescribed, amlodipine (78.5%) was most frequently prescribed drug. Frequently used drugs for monotherapy - amlodipine (37.5%), for two drug therapy - amlodipine + atenolol (25.5%), and for three drug therapy - amlodipine + atenolol + telmisartan (2.5%). WHO prescribing indicators: Average number of drugs per encounter is 2.38 (±1.19). Percentage of drugs prescribed by generic name is 76.47%. Percentage of drugs prescribed from essential drug list is 97.89%.Conclusions: Present study shows current trends in prescription of antihypertensives in tertiary care hospital and their rational use. Study emphasizes need for preventive and educative measures about hypertension in population.

PEGylated Domain I of Beta-2-Glycoprotein I Inhibits the Binding, Coagulopathic, and Thrombogenic Properties of IgG From Patients With the Antiphospholipid Syndrome.

APS is an autoimmune disease in which antiphospholipid antibodies (aPL) cause vascular thrombosis and pregnancy morbidity. In patients with APS, aPL exert pathogenic actions by binding serum beta-2-glycoprotein I (β2GPI) via its N-terminal domain I (DI). We previously showed that bacterially-expressed recombinant DI inhibits biological actions of IgG derived from serum of patients with APS (APS-IgG). DI is too small (7 kDa) to be a viable therapeutic agent. Addition of polyethylene glycol (PEGylation) to small molecules enhances the serum half-life, reduces proteolytic targeting and can decrease immunogenicity. It is a common method of tailoring pharmacokinetic parameters and has been used in the production of many therapies in the clinic. However, PEGylation of molecules may reduce their biological activity, and the size of the PEG group can alter the balance between activity and half-life extension. Here we achieve production of site-specific PEGylation of recombinant DI (PEG-DI) and describe the activities in vitro and in vivo of three variants with different size PEG groups. All variants were able to inhibit APS-IgG from: binding to whole β2GPI in ELISA, altering the clotting properties of human plasma and promoting thrombosis and tissue factor expression in mice. These findings provide an important step on the path to developing DI into a first-in-class therapeutic in APS.

HCV INFECTION AND ERYTHROPOIETIN IN HAEMODIALYSIS PATIENTS

Background: Renal anemia is associated with increased cardio vascular morbidity and mortality and decreased quality of life. It may worsen the preexisting heart disease and consequently may accelerate the progression of renal dysfunction in a vicious circle.Renal anemia related mainly to decreased production of erythropoietin (EPO) by the kidney, decreased it’s response by bone marrow and disturbed iron status. Aim of the Study: Was to evaluate the relationship between HCV infection and erythrropoietin in patients on regular HD. Patients and Methods: This study included 50 hemodialysis patients (25 patients +ve HCV and 25 -ve HCV), 16 were male and 34 were female, and their ages ranged from 20 to 67 years, with a mean ± SD of 50.5 ± 12.7 years, 15 apparently healthy individuals with normal kidney function and not anemic were included in the study as a control Group. Results: The patients were divided into two groups as the following: Group I consisted of 25 hemodialysis patients were positive for HCV antibody, which was confirmed by PCR, and their ages ranged from 27 to 67 years, with a mean of 47.28 ± 11.91 years. Group II consisted of 25 hemodialysis patients were negative for HCV antibody; their ages ranged from 20 to 65 years, with a mean age of 46.32 ± 11.50 years. In contrast, 15 patients served as age-matched and gender-matched; their ages ranged from 20 to 55 years, with a mean age of 44.13 ± 10.76 years, and were used as controls. Conclusion: Serum levels of erythropoietin correlate with chronic hepatitis C infection, which was associated with an increased number of RBCs and higher values of hemoglobin and hematocrit, which Result in lowering of the necessary erythropoietin dose and iron therapy.

Cold shock Y-box binding protein-1 acetylation status in monocytes is associated with systemic inflammation and vascular damage

Background and aimsIn dialysis patients, vascular morbidities are highly prevalent and linked to leukocyte extravasation, especially of polarized monocytes. Experimental data demonstrate that phenotypic changes in monocytes require Y-box binding protein-1 (YB-1) upregulation. MethodsWe determined YB-1 expression in circulating and vessel-invading monocytes from healthy controls and dialysis patients to correlate results with intima plaque formation and systemic inflammation. ResultsCompared to healthy subjects, dialysis patients have fewer classical and more intermediate and non-classical monocytes. Post-translationally modified YB-1 (lysine 301/304 acetylation) is detected at high levels in the nucleus of adherent and invading CD14+CD68+ monocytes from umbilical cord and atherosclerosis-prone vessels. The content of non-acetylated YB-1 is significantly decreased (p < 0.001), whereas acetylated YB-1 is correspondingly increased (p < 0.001) throughout all monocyte subpopulations, such that the overall content remains unchanged. ConclusionsIn dialysis patients the YB-1 acetylation status is higher with prevailing diabetes and intima plaque formation. Pro-inflammatory mediators TNFα, IL-6, uPAR, CCL2, M-CSF, progranulin, ANP, and midkine, as well as anti-inflammatory IL-10 are significantly increased in dialysis patients, emphasizing a systemic inflammatory milieu. Strong positive correlations of monocytic YB-1 content are seen with ANP, IP-10, IL-6, and IL-10 serum levels. This is the first study demonstrating an association of cold shock protein YB-1 expression with inflammation in hemodialysis patients.

Lower limb perfusion during robotic-assisted laparoscopic radical prostatectomy evaluated by near-infrared spectroscopy: an observational prospective study

BackgroundDecreased perfusion in the lower extremities is one of the several adverse effects of placing patients in a lithotomy or Trendelenburg position during surgery. This study aimed to evaluate the effects of patient positioning in lower limb perfusion patients undergoing robotic-assisted laparoscopic radical prostatectomy (RARP) using near-infrared spectroscopy (NIRS).MethodsThis observation study comprised 30 consenting males with American Society of Anaesthesiologists physical status classes I and II (age range, ≥20 to < 80 years). Regional saturation of oxygen measurements was obtained using an INVOS™ oximeter (Somanetics, Troy, MI, USA). A NIRS sensor was positioned on the surface of the skin at the mid-diaphyseal region of the calf muscles (the gastrocnemius and soleus), over the posterior compartment, in the right lower leg. Regional saturation of oxygen (rSO2) was sampled during the following time points: before and 5 min after induction of anaesthesia (T0,T1); 5 min after establishment of pneumoperitoneum in a 0° lithotomy position (T2); 5 min after a 25° Trendelenburg position (T3); 30, 60, 90 and 120 min after pneumoperitoneum in a Trendelenburg position (T4, T5, T6 and T7, respectively); after desufflation in a supine position (T8); and after tracheal extubation (T9).ResultsLower limb perfusion evaluated by NIRS was increased after induction of anaesthesia and maintained during steep Trendelenburg positions in RARP patients with no risk for lower limb compartment syndrome (LLCS) (T0:65 ± 7.2%, T1:69 ± 6.1%, T2:70±:6.1%, T3:68 ± 6.7%, T4:66 ± 7.5%, T5:67 ± 6.9%, T6:68 ± 7.2%, T8:73 ± 7.2%, T9:71 ± 7.9%, respectively).ConclusionsLower limb perfusion evaluated by NIRS was maintained during the RARP procedure. Correct patient positioning and careful assessment of risk factors such as vascular morbidity could be important for the prevention of LLCS during RARP.

Portal and superior mesenteric vein resection in radical pancreatectomy for pancreatic cancer

Radical resection remains essential for prolonging survival and increasing the possibility of cure in pancreatic cancer. However, few patients are resectable at the time of diagnosis, with a portion of patients presenting with portal and superior mesenteric vein invasion and regarded as resectable or locally advanced disease. Venous resection in pancreatectomy enables achievement of tumor-free margins in patients with venous invasion. This review provides an overview of preoperative evaluation, resection and reconstruction types, vascular grafts selection, morbidity, mortality and survival in radical pancreatectomy with portal and superior mesenteric vein resection. Key words: Pancreatic neoplasms; Vascular resection; Portal vein; Superior mesenteric vein

Gene expression profiling identifies distinct molecular signatures in thrombotic and obstetric antiphospholipid syndrome

Antiphospholipid antibodies (aPL) cause vascular thrombosis (VT) and/or pregnancy morbidity (PM). Differential mechanisms however, underlying the pathogenesis of these different manifestations of antiphospholipid syndrome (APS) are not fully understood. Therefore, we compared the effects of aPL from patients with thrombotic or obstetric APS on monocytes to identify different molecular pathways involved in the pathogenesis of APS subtypes. VT or PM IgG induced similar numbers of differentially expressed (DE) genes in monocytes. However, gene ontology (GO) analysis of DE genes revealed disease-specific genome signatures. Compared to PM, VT-IgG showed specific up regulation of genes associated with cell response to stress, regulation of MAPK signalling pathway and cell communication. In contrast, PM-IgG regulated genes involved in cell adhesion, extracellular matrix and embryonic and skeletal development. A novel gene expression analysis based on differential variability (DV) was also applied. This analysis identified similar GO categories compared to DE analysis but also uncovered novel pathways modulated solely by PM or VT-IgG. Gene expression analysis distinguished a differential effect of VT or PM-IgG upon monocytes supporting the hypothesis that they trigger distinctive physiological mechanisms. This finding contributes to our understanding of the pathology of APS and may lead to the development of different targeted therapies for VT or PM APS.

Mild to Moderate Intrapulmonary Shunting in Pediatric Liver Transplantation: Is Screening Necessary?

BackgroundDespite reported associations between intrapulmonary vascular shunting (IPVS) and morbidity and mortality in pediatric liver transplantation (LT), there are no guidelines for screening. ObjectiveTo investigate IPVS before and after pediatric LT. MethodsRetrospective records review of all pediatric LT (n = 370) from 2005 to 2015 at a single institute in Japan. All children with cirrhosis and clinical suspicion of IPVS without cardiac or pulmonary conditions were included. 99mTechnetium labelled macroaggregated albumin (99mTcMAA) scans were performed before and after LT. The severity of IPVS was graded using shunt ratios. ResultsTwenty-four children fulfilled inclusion criteria and underwent Tc99MAA scans. All revealed mild (<20%) to moderate (20%-40%) grades of IPVS. Following LT, the mean shunt ratio regressed from 20.69 ± 6.26% to 15.1 ± 3.4% (P = .06). The median (range) follow-up was 17 (4–85) months. Mortality was zero. The incidence of portal vein thrombosis (4.2%) biliary strictures (12.5%) and graft loss (4.1%) in the study group was not statistically significant compared to the remainder of the 370 transplants (3.2%, 9.4% and 3%, respectively). Sub-group analysis revealed hepatopulmonary syndrome (HPS) in 2 out of 24 children. The mean shunt ratios before and after LT were 39.2 ± 0.77% and 16.2 ± 8.5%, respectively (P = .08). There was 1 complication (intra-abdominal abscess). ConclusionsHPS is less likely in mild to moderate IPVS. LT may achieve comparable results when performed in the presence of mild to moderate IPVS.