Artemisinin drug resistance and monitoring: a narrative review

Artemisinin drug resistance is one of the major reasons for malaria treatment failures in the sub-Saharan African countries where artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated malaria. The occurrence of single nucleotide polymorphisms (SNPs) is found to correlate with antimalarial drug resistance. With artemisinin, the SNPs occurs at the Kelch 13-propeller gene locus on chromosome 13. The artemisinin drug resistance surveillance strategy involves continuous monitoring of Kelch 13-propeller biomarker to detect emergence of mutations which could herald drug resistance in the region. In this narrative review paper, we examined existing literature to bridge the knowledge gap and accentuate the importance of routine surveillance for artemisinin resistance in sub-Saharan Africa. We conducted our search on PubMed database and Google Scholar to identify peer-reviewed articles, reports, and abstracts on artemisinin drug resistance using the following keywords; 'artemisinin drug resistance', 'antimalarial drug resistance', 'artemisinin-based combination therapy', 'Kelch 13-propeller', 'K13- propeller gene', and 'K13 molecular marker'. The review provided pertinent information on artemisinin derivatives, artemisinin-based combination therapy, molecular action of artemisinin, definition of artemisinin resistance, genetic basis of artemisinin drug resistance and discovery of Kelch 13, and the importance of artemisinin resistance surveillance. Molecular surveillance can provide healthcare policy makers a forecast of impending threats to malaria treatment. This is more so when drugs are in combination therapy, for instance, molecular surveillance can give a hint that one drug is failing despite the fact that in combination, it is still apparently clinically effective.

Angio-Based Index of Microcirculatory Resistance for the Assessment of the Coronary Resistance: A Proof of Concept Study.

BACKGROUND: The study of coronary microcirculation has gained increasing consideration and importance in cath lab. Despite the increase of evidence, its use still remains very limited. QFR is a novel angio-based approach for the evaluation of coronary stenosis. The aim of our study was to use the QFR assessment in stable patients to recreate the IMR formula and to correlate the result of the two techniques. METHODS: From June 1, 2019, to February 29, 2019, 200 patients with CCS and indication of coronary artery angiography and referred to the cath lab of the University Hospital of Ferrara (Italy) were enrolled. After baseline coronary angiogram, quantitative flow ratio, fractional flow reserve, and index of microcirculatory resistance evaluation were performed. RESULTS: Pearson correlation (r) between angio-based index of microcirculatory resistance (A-IMR) and IMR 0.32 with R 2 = 0.098, P=0.03: McNemar test showed a difference between the two tests of 6.82% with 95% CI from -12.05% to 22.89%, which is not significant (P=0.60). Bland and Altman plot showed a mean difference of 23.3 (from -26.5 to 73.1). Sensitivity, specificity, NPV, and PPV were 70%, 83.3%, 75%, and 70% for A-IMR value >44.2. The area under the ROC curve for A-IMR was 0.76 (95% CI 0.61-0.88, P=0.0003). CONCLUSION: We have validated for the first time the formula of the A-IMR, a tool for the calculation of microvascular resistance which does not require the use of pressure guides and the induction of hyperemia.

Effects of Foam Microbubbles on Electrical Resistivity and Capillary Pressure of Partially Saturated Porous Media.

Laboratory measurements of capillary pressure (Pc) and the electrical resistivity index (RI) of reservoir rocks are used to calibrate well logging tools and to determine reservoir fluid distribution. Significant studies on the methods and factors affecting these measurements in rocks containing oil, gas, and water are adequately reported in the literature. However, with the advent of chemical enhanced oil recovery (EOR) methods, surfactants are mixed with injection fluids to generate foam to enhance the gas injection process. Foam is a complex and non-Newtonian fluid whose behavior in porous media is different from conventional reservoir fluids. As a result, the effect of foam on Pc and the reliability of using known rock models such as the Archie equation to fit experimental resistivity data in rocks containing foam are yet to be ascertained. In this study, we investigated the effect of foam on the behavior of both Pc and RI curves in sandstone and carbonate rocks using both porous plate and two-pole resistivity methods at ambient temperature. Our results consistently showed that for a given water saturation (Sw), the RI of a rock increases in the presence of foam than without foam. We found that, below a critical Sw, the resistivity of a rock containing foam continues to rise rapidly. We argue, based on knowledge of foam behavior in porous media, that this critical Sw represents the regime where the foam texture begins to become finer, and it is dependent on the properties of the rock and the foam. Nonetheless, the Archie model fits the experimental data of the rocks but with resulting saturation exponents that are higher than conventional gas-water rock systems. The degree of variation in the saturation exponents between the two fluid systems also depends on the rock and fluid properties. A theory is presented to explain this phenomenon. We also found that foam affects the saturation exponent in a similar way as oil-wet rocks in the sense that they decrease the cross-sectional area of water available in the pores for current flow. Foam appears to have competing and opposite effects caused by the presence of clay, micropores, and conducting minerals, which tend to lower the saturation exponent at low Sw. Finally, the Pc curve is consistently lower in foam than without foam for the same Sw.

Association of Hyperhomocysteinemia with Increased Coronary Microcirculatory Resistance and Poor Short-Term Prognosis of Patients with Acute Myocardial Infarction after Elective Percutaneous Coronary Intervention.

BACKGROUND: This study aims to investigate the coronary microcirculatory resistance and prognosis of patients with acute myocardial infarction (AMI) concomitant with hyperhomocysteinemia (HHcy) after an elective percutaneous coronary intervention (PCI). METHODS: A total of 101 patients that underwent elective PCI between May 2015 and July 2018 due to AMI were consecutively enrolled in this study. Patients were divided into a HHcy group (53) and a normal Hcy group (control; 48) based on their plasma homocysteine concentration. The characteristics of coronary angiography, the index of microcirculatory resistance (IMR) of infarct-related vessels (IRV), changes in left ventricular end diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) before and after PCI, and the incidence of major adverse cardiovascular events (MACE) three months after PCI were compared between these groups. RESULTS: Compared to the results from the Hcy group, the HHcy group had a higher IMR. The HHcy group had significantly higher LVEDd and a lower LVEF than the Hcy group 3 months after PCI. Additionally, the incidence of MACE at three months after PCI was higher in the HHcy group than in the Hcy group. Pearson correlation analysis revealed a positive correlation with IMR in the HHcy group. Furthermore, there was a difference in the LVEDd measured at one day after PCI and at three months after PCI in the HHcy group. CONCLUSION: AMI patients concomitant with HHcy that undergo elective PCI are prone to coronary microcirculatory dysfunction and have a poor cardiac function and poor prognosis at three months after PCI.

Clinical and coronary haemodynamic determinants of recurrent chest pain in patients without obstructive coronary artery disease - A pilot study.

BACKGROUND: Coronary haemodynamic testing frequently identifies abnormal pathophysiological parameters in patients with angina and non-obstructed coronaries on angiography (NoCAD) but the clinical utility of these measures has received limited attention. OBJECTIVE: This study aims to identify the clinical and coronary haemodynamic determinants of recurrent chest pain at one month in patients with NoCAD. METHODS: Patients with angina, NoCAD (<50% stenosis) and normal LV systolic function underwent invasive coronary haemodynamic testing involving: (1) angiographic TIMI frame and opacification rate, (2) microvascular functional measures including coronary flow reserve (CFR) and hyperaemic microvascular resistance (HMR), (3) coronary endothelial function assessment with low dose intracoronary acetylcholine (IC-ACh) infusions (0.18 µg/min & 1.8 µg/min over 2 min), and (4) Provocative spasm testing with high dose IC-ACh boluses (25, 50 and 100 µg). Clinical and health status were assessed at baseline and one month. RESULTS: In the 49 NoCAD patients (78% female, mean age of 54 ±â€¯11) undergoing comprehensive coronary haemodynamic testing, 33 (67%) continued to experience chest pain at one month. Determinants of recurrent chest pain on univariate analysis included baseline chest pain status or a HMR > 1.9. Multivariate logistic regression analysis identified frequent angina at baseline (OR: 68.9 [4.1, 1165.0], p = 0.003), previous unstable angina admission (OR: 43.9 [3.5, 547.9], p = 0.003) and a HMR > 1.9 (OR: 15.6 [2.1, 114.0], p = 0.007) as independent predictors of recurrent chest pain. CONCLUSION: In this small pilot study, an abnormal HMR was the only coronary haemodynamic parameter that was a determinant of ongoing angina at short-term follow-up.

Chronic exposure to tumor necrosis factor alpha induces retinal pigment epithelium cell dedifferentiation.

BACKGROUND: The retinal pigment epithelium (RPE) is a monolayer of pigmented cells with important barrier and immuno-suppressive functions in the eye. We have previously shown that acute stimulation of RPE cells by tumor necrosis factor alpha (TNFα) downregulates the expression of OTX2 (Orthodenticle homeobox 2) and dependent RPE genes. We here investigated the long-term effects of TNFα on RPE cell morphology and key functions in vitro. METHODS: Primary porcine RPE cells were exposed to TNFα (at 0.8, 4, or 20 ng/ml per day) for 10 days. RPE cell morphology, phagocytosis, barrier- and immunosuppressive-functions were assessed. RESULTS: Chronic (10 days) exposure of primary RPE cells to TNFα increases RPE cell size and polynucleation, decreases visual cycle gene expression, impedes RPE tight-junction organization and transepithelial resistance, and decreases the immunosuppressive capacities of the RPE. TNFα-induced morphological- and transepithelial-resistance changes were prevented by concomitant Transforming Growth Factor ß inhibition. CONCLUSIONS: Our results indicate that chronic TNFα-exposure is sufficient to alter RPE morphology and impede cardinal features that define the differentiated state of RPE cells with striking similarities to the alterations that are observed with age in neurodegenerative diseases such as age-related macular degeneration.

Dissociation of local and global skeletal muscle oxygen transport metrics in type 2 diabetes.

AIMS: Exercise capacity is impaired in type 2 diabetes, and this impairment predicts excess morbidity and mortality. This defect appears to involve excess skeletal muscle deoxygenation, but the underlying mechanisms remain unclear. We hypothesized that reduced blood flow, reduced local recruitment of blood volume/hematocrit, or both contribute to excess skeletal muscle deoxygenation in type 2 diabetes. METHODS: In patients with (n=23) and without (n=18) type 2 diabetes, we recorded maximal reactive hyperemic leg blood flow, peak oxygen utilization during cycling ergometer exercise (VO2peak), and near-infrared spectroscopy-derived measures of exercise-induced changes in skeletal muscle oxygenation and blood volume/hematocrit. RESULTS: We observed a significant increase (p<0.05) in skeletal muscle deoxygenation in type 2 diabetes despite similar blood flow and recruitment of local blood volume/hematocrit. Within the control group skeletal muscle deoxygenation, local recruitment of microvascular blood volume/hematocrit, blood flow, and VO2peak are all mutually correlated. None of these correlations were preserved in type 2 diabetes. CONCLUSIONS: These results suggest that in type 2 diabetes 1) skeletal muscle oxygenation is impaired, 2) this impairment may occur independently of bulk blood flow or local recruitment of blood volume/hematocrit, and 3) local and global metrics of oxygen transport are dissociated.

Possible type 1 diabetes risk prediction: Using ultrasound imaging to assess pancreas inflammation in the inducible autoimmune diabetes BBDR model.

BACKGROUND/AIMS: Studies of human cadaveric pancreas specimens indicate that pancreas inflammation plays an important role in type 1 diabetes pathogenesis. Due to the inaccessibility of pancreas in living patients, imaging technology to visualize pancreas inflammation is much in need. In this study, we investigated the feasibility of utilizing ultrasound imaging to assess pancreas inflammation longitudinally in living rats during the progression leading to type 1 diabetes onset. METHODS: The virus-inducible BBDR type 1 diabetes rat model was used to systematically investigate pancreas changes that occur prior to and during development of autoimmunity. The nearly 100% diabetes incidence upon virus induction and the highly consistent time course of this rat model make longitudinal imaging examination possible. A combination of histology, immunoblotting, flow cytometry, and ultrasound imaging technology was used to identify stage-specific pancreas changes. RESULTS: Our histology data indicated that exocrine pancreas tissue of the diabetes-induced rats underwent dramatic changes, including blood vessel dilation and increased CD8+ cell infiltration, at a very early stage of disease initiation. Ultrasound imaging data revealed significant acute and persistent pancreas inflammation in the diabetes-induced rats. The pancreas micro-vasculature was significantly dilated one day after diabetes induction, and large blood vessel (superior mesenteric artery in this study) dilation and inflammation occurred several days later, but still prior to any observable autoimmune cell infiltration of the pancreatic islets. CONCLUSIONS: Our data demonstrate that ultrasound imaging technology can detect pancreas inflammation in living rats during the development of type 1 diabetes. Due to ultrasound's established use as a non-invasive diagnostic tool, it may prove useful in a clinical setting for type 1 diabetes risk prediction prior to autoimmunity and to assess the effectiveness of potential therapeutics.

The capillary bed offers the largest hemodynamic resistance to the cortical blood supply.

The cortical angioarchitecture is a key factor in controlling cerebral blood flow and oxygen metabolism. Difficulties in imaging the complex microanatomy of the cortex have so far restricted insight about blood flow distribution in the microcirculation. A new methodology combining advanced microscopy data with large scale hemodynamic simulations enabled us to quantify the effect of the angioarchitecture on the cerebral microcirculation. High-resolution images of the mouse primary somatosensory cortex were input into with a comprehensive computational model of cerebral perfusion and oxygen supply ranging from the pial vessels to individual brain cells. Simulations of blood flow, hematocrit and oxygen tension show that the wide variation of hemodynamic states in the tortuous, randomly organized capillary bed is responsible for relatively uniform cortical tissue perfusion and oxygenation. Computational analysis of microcirculatory blood flow and pressure drops further indicates that the capillary bed, including capillaries adjacent to feeding arterioles (d < 10 µm), are the largest contributors to hydraulic resistance.

Changes in pulsatility and resistance indices of cerebral arteriovenous malformation feeder arteries after embolization and surgery.

OBJECTIVES: Embolization reduces flow in cerebral arteriovenous malformations (AVMs) before surgical resection, but changes in pulsatility and resistance indices (PI, RI) are unknown. Here, we measure PI, RI in AVM arterial feeders before and after embolization/surgery. METHODS: Records of patients who underwent AVM embolization and surgical resection at our institution between 2007 and 2014 and had PI, RI, and flows obtained using quantitative magnetic resonance angiography were retrospectively reviewed. PI = [(systolic - diastolic flow velocity)/mean flow velocity] and RI = [(systolic - diastolic flow velocity)/systolic flow velocity]. Hemodynamic parameters were compared between the feeder and contralateral artery before and after embolization/surgery. RESULTS: 38 patients were included (6 embolization only, 24 embolization and surgery, 8 surgery only). After embolization, flow volume rates within feeders decreased significantly (p < 0.001) to match flows in their contralateral counterparts (p = 0.78). On the other hand, mean, systolic, and diastolic flow velocities (p = 0.60, 0.32, 0.34, respectively) as well as PI, RI (p = 0.99, 0.68) did not change significantly after embolization. However, after surgery mean, systolic, and diastolic flow velocities within feeders decreased significantly (p = 0.001, 0.002, 0.001, respectively) and PI, RI normalized to match the indices of their contralateral counterparts (p = 0.46, 0.46). CONCLUSION: Following partial AVM embolization, PI, RI are unchanged and flow velocities in feeder arteries also remain unchanged likely due to redistribution of flow through residual nidus. Thus, staged management of AVMs is unlikely to increase outflow resistance and offers a safe treatment strategy.

Lung function, transfusion, pulmonary capillary blood volume and sickle cell disease.

Lung function abnormalities occur in children with sickle cell disease (SCD) and may be associated with elevated pulmonary blood volume. To investigate that association, we determined whether blood transfusion in SCD children acutely increased pulmonary capillary blood volume (PCBV) and increased respiratory system resistance (Rrs5). Measurements of Rrs5 and spirometry were made before and after blood transfusion in 18 children, median age 14.2 (6.6-18.5) years. Diffusing capacity for carbon monoxide and nitric oxide were assessed to calculate the PCBV. Post transfusion, the median Rrs5 had increased from 127.4 to 141.3% predicted (p<0.0001) and pulmonary capillary blood volume from 39.7 to 64.1 ml/m2 (p<0.0001); forced expiratory volume in one second (p=0.0056) and vital capacity (p=0.0008) decreased. The increase in Rrs5 correlated with the increase in PCBV (r=0.50, p=0.0493). Increased pulmonary capillary blood volume may at least partially explain the lung function abnormalities in SCD children.

Lowering Pulmonary Wedge Pressure after Heart Transplant: Pulmonary Compliance and Resistance Effect / Redução da Pressão Capilar Pulmonar após Transplante Cardíaco: Complacência Pulmonar e Efeito Resistência

AbstractBackground:Right ventricular (RV) afterload is an important risk factor for post-heart transplantation (HTx) mortality, and it results from the interaction between pulmonary vascular resistance (PVR) and pulmonary compliance (CPA). Their product, the RC time, is believed to be constant. An exception is observed in pulmonary hypertension because of elevated left ventricular (LV) filling pressures.Objective:Using HTx as a model for chronic lowering of LV filling pressures, our aim was to assess the variations in RV afterload components after transplantation.Methods:We retrospectively studied 159 patients with right heart catheterization before and after HTx. The effect of Htx on hemodynamic variables was assessed.Results:Most of the patients were male (76%), and the mean age was 53 ± 12 years. HTx had a significant effect on the hemodynamics, with normalization of the LV and RV filling pressures and a significant increase in cardiac output and heart rate (HR). The PVR decreased by 56% and CPA increased by 86%. The RC time did not change significantly, instead of increasing secondary to pulmonary wedge pressure (PWP) normalization after HTx as expected. The expected increase in RC time with PWP lowering was offset by the increase in HR (because of autonomic denervation of the heart). This effect was independent from the decrease of PWP.Conclusion:The RC time remained unchanged after HTx, notwithstanding the fact that pulmonary capillary wedge pressure significantly decreased. An increased HR may have an important effect on RC time and RV afterload. Studying these interactions may be of value to the assessment of HTx candidates and explaining early RV failure after HTx.

ResumoFundamento:A pós-carga do ventrículo direito (VD) é um fator de risco importante para avaliar a mortalidade decorrente de transplante cardíaco (HTx) e resulta da interação entre a resistência vascular pulmonar (RVP) e a complacência pulmonar (CPA). Acredita-se que o produto da interação, o RC-time, seja constante. Entretanto, é exceção a hipertensão pulmonar devido às elevadas pressões de preenchimento do ventrículo esquerdo (VE).Objetivos:Ao utilizar o HTx como modelo para redução crônica das pressões de preenchimento do VE, nosso objetivo foi avaliar as variações nos componentes pós-carga do VD após o transplante.Métodos:Foram estudados, retrospectivamente, 159 pacientes com cateterismo cardíaco direito realizado antes e após o HTx. O impacto do HTx nas variáveis hemodinâmicas foi avaliado.Resultados:A maioria dos pacientes foi do sexo masculino (76%) e a média de idade foi 53 ± 12 anos. O HTx teve um efeito significativo na hemodinâmica, com normalização do VE e das pressões de preenchimento de VD e no aumento significativo do débito cardíaco e da freqüência cardíaca (FC). A RVP diminuiu 56% e a CPA aumentou 86%. Em vez de aumentar como era esperado, o RC-time não alterou significativamente e teve papel secundário em relação à normalização da pressão capilar pulmonar (PECP) após o HTx. O aumento esperado no RC timecom PWP reduzido foi atenuado pelo aumento da FC (devido à denervação autonômica do coração). Esse efeito ocorreu independentemente da diminuição da PCPConclusões:O RC-time permaneceu inalterado após HTx, entretanto a PECP diminuiu significativamente. O aumento da FC pode ter impacto importante no RC-time e na pós-carga do VD. O estudo dessas interações pode ser de grande valor para avaliar os candidatos HTx e explicar a falência do VD ocorrida logo após o HTx.

Lowering pulmonary wedge pressure after heart transplant: pulmonary compliance and resistance effect.

BACKGROUND: Right ventricular (RV) afterload is an important risk factor for post-heart transplantation (HTx) mortality, and it results from the interaction between pulmonary vascular resistance (PVR) and pulmonary compliance (CPA). Their product, the RC time, is believed to be constant. An exception is observed in pulmonary hypertension because of elevated left ventricular (LV) filling pressures. OBJECTIVE: Using HTx as a model for chronic lowering of LV filling pressures, our aim was to assess the variations in RV afterload components after transplantation. METHODS: We retrospectively studied 159 patients with right heart catheterization before and after HTx. The effect of Htx on hemodynamic variables was assessed. RESULTS: Most of the patients were male (76%), and the mean age was 53 ± 12 years. HTx had a significant effect on the hemodynamics, with normalization of the LV and RV filling pressures and a significant increase in cardiac output and heart rate (HR). The PVR decreased by 56% and CPA increased by 86%. The RC time did not change significantly, instead of increasing secondary to pulmonary wedge pressure (PWP) normalization after HTx as expected. The expected increase in RC time with PWP lowering was offset by the increase in HR (because of autonomic denervation of the heart). This effect was independent from the decrease of PWP. CONCLUSION: The RC time remained unchanged after HTx, notwithstanding the fact that pulmonary capillary wedge pressure significantly decreased. An increased HR may have an important effect on RC time and RV afterload. Studying these interactions may be of value to the assessment of HTx candidates and explaining early RV failure after HTx.

Black tea protects against hypertension-associated endothelial dysfunction through alleviation of endoplasmic reticulum stress.

Hypertensive patients have been found to be associated with elevated levels of homocysteine, known as hyperhomocysteinemia. Homocysteine (Hcy) can induce endoplasmic reticulum (ER) stress in endothelial cells. This study aims to investigate whether black tea (BT) protects against hypertension-associated endothelial dysfunction through alleviation of ER stress. Rat aortae and cultured rat aortic endothelial cells were treated with Hcy, BT extract, and theaflavin-3,3'-digallate (TF3). Male Sprague Dawley rats were infused with angiotensin II (Ang II) to induce hypertension and orally administrated with BT extract at 15 mg/kg/day for 2 weeks. Hcy impaired endothelium-dependent relaxations of rat aortae and led to ER stress in endothelial cells, which were ameliorated by co-incubation of BT extract and TF3. The blood pressure of Ang II-infused rats and plasma Hcy level were normalized by BT consumption. Impaired endothelium-dependent relaxations in renal arteries, carotid arteries and aortae, and flow-mediated dilatations in third-order mesenteric resistance arteries were improved. Elevations of ER stress markers and ROS level, plus down-regulation of Hcy metabolic enzymes in aortae from Ang II-infused rats were prevented by BT treatment. Our data reveal the novel cardiovascular benefits of BT in ameliorating vascular dysfunctions, providing insight into developing BT into beneficial dietary supplements in hypertensive patients.

[Raynaud's phenomenon and other circulatory disorders of the fingers]. / Das Raynaud-Phänomen und andere Durchblutungsstörungen der Finger.

Raynaud's phenomenon (RP) is defined as attacks of blanking, subsequent cyanosis and rubeosis of fingers due to vasospasms in response to cold or emotional stimuli. Primary RP has no known underlying cause and occurs mainly in young and otherwise healthy women. Secondary RP goes along with various causes such as connective tissue diseases, toxic substances, drugs, physical trauma or organic finger artery occlusions, and occurs at any age and in both genders. Related affections are acrocyanosis and finger artery occlusions either due to arteriosclerosis or vasculitis. Also spontaneous finger hematoma may provoke an episode of RP. Therapeutically strict cold protection and avoidance of possible noxa is recommended besides the treatment of underlying diseases. No standard vasoactive drug has proven ideal for RP due to side effects. In cases with rest pain or ulcerations the same principles are applied as in ischemic diseases with no possibility for revascularization.

Le phénomène de Raynaud(PR) est défini comme des attaques de blancheur suivie d'une cyanose et d'une rougeur des doigts dues à un vasospasme en réponse au froid ou à un stimulus émotionnel. Le PR primaire n'a pas de cause connue et atteint surtout des jeunes femmes qui sont par ailleurs en bonne santé. Le PR secondaire se rencontre avec des causes variées comme la sclérodermie, des substances toxiques, des médicaments, des traumatismes physiques ou des occlusions artérielles au niveau des doigts. Cette forme de PR peut survenir à tout âge, tant chez l'homme que chez la femme. Des affections relatées au PR sont l'acrocyanose et les occlusions des artères digitales dues à l'artériosclérose ou une vasculite. Enfin, un hématome spontané au niveau d'un doigt peut provoquer un PR. Une protection stricte contre le froid et l'évitement autant que possible des facteurs favorisants est recommandé, ceci en plus du traitement de la maladie sous-jacente. Il n'y a pas de médicament vasoactif standard idéal pour traiter le PR, particulièrement en raison de leurs effets secondaires. En cas de douleur au repos ou en présence d'ulcérations les mêmes principes de traitement sont appliqués que lors d'affections ischémiques, avec cependant l'impossibilité d'effectuer une revascularisation.

Capillary refill time is a predictor of short-term mortality for adult patients admitted to a medical department: an observational cohort study.

BACKGROUND: Capillary refill time (CRT) has been advocated as a tool for rapid assessment of circulatory status. The correlation between neither CRT and mortality nor CRT and markers of circulatory status has been assessed. We performed a prospective observational cohort study to assess the relationship between CRT (using two existing definitions and as a continuous variable) and short-term mortality. METHODS: We included all acutely admitted adult patients to a medical admission unit. We measured CRT, blood pressure, pulse, temperature and peripheral oxygen saturation. We presented the data descriptively. Difference between continuous data was analysed using Wilcoxon Rank Sum Test and categorical data using χ(2) test. The primary endpoint was 1-day all-cause mortality. RESULTS: 3046 patients were enrolled and CRT was measured on 1935. In univariate analyses, we found increasing all-cause 1-day mortality with all definitions of CRT. Performing multivariable analysis, controlling for age, sex, mean blood pressure, pulse, temperature and peripheral oxygen saturation, we found increasing CRT as a continuous variable and according to the Schriger and Baraff definition to be associated with increased mortality. Both the Trauma score and Schriger and Baraff definitions had high negative predictive values. The calculations on the Schriger and Baraff definition were based on limited power. CONCLUSIONS: We found a significant association between CRT measured as a continuous variable and short-term mortality. Using the definition of Schriger and Baraff also seems appropriate, but this is based on calculations of limited power.

Systemic sclerosis patients with and without pulmonary arterial hypertension: a nailfold capillaroscopy study.

OBJECTIVE: Pulmonary arterial hypertension (PAH) is a complication of SSc due to increased vascular resistance, and abnormal vascularity is a well-known feature of the disease as shown by nailfold videocapillaroscopy (NVC). This study investigated for specific NVC changes in SSc patients with and without PAH to assess any useful difference. METHODS: Twenty-four SSc patients, 12 with PAH and 12 without, entered the study. Evidence of PAH was defined as increased systolic pulmonary artery pressure (PAP) (≥35 mmHg), indirectly assessed by echocardiography and confirmed by right heart catheterization (mPAP > 25 mmHg). NVC was performed, and a semi-quantitative rating scale, a rating system for avascular areas and a specific NVC pattern evaluation, namely early, active and late, were used. RESULTS: An NVC score >1 was more frequently found in patients with PAH than those without, 11 cases (92%) vs 5 cases (42%) (P = 0.03); an avascular areas grade >1 was present in 10 (83%) and 2 (17%) cases, respectively (P = 0.003); and a more severe NC pattern (active/late) was described in 11 (92%) and 5 (42%) patients, respectively (P = 0.03). When we compared the mPAP with NVC parameters, we found significant correlations between mPAP values and the NVC score (P < 0.005) and with the avascular areas score (P < 0.001). CONCLUSION: Our results underline the relevance of early microvascular assessment in patients at risk of developing a severe complication such as PAH that can amplify the systemic microvascular impairment in SSc. More severe NVC abnormalities should lead to strict cardiopulmonary surveillance and a complete NVC study is indicated.

[Optimization approach to arterial hemodynamics in elastic capillaries].

The article considers a number of ways of optimizing arterial hemodynamics including finding of the best value of capillary resistance or coefficient of elasticity.