Comparing the accuracy of point-of-care with laboratory (capillary, venous, and arterial) blood glucose levels in critically ill patients with and without shock.

OBJECTIVES: To compare the accuracy of point-of-care capillary and venous/arterial samples to laboratory testing of venous/arterial samples in critically sick shocked and non-shocked patients. This is a prospective case-control study including capillary, venous, and arterial blood samples from 268 critically ill patients. The King Fahd Military Medical Complex in Dhahran, Saudi Arabia, was the site of this investigation. RESULTS: We were able to obtain data on 268 patients for this investigation. POCT and lab findings of venous and central blood did not differ significantly (P = 0.389 and 0.208), while POCT indicated somewhat higher results with venous glucose concentrations of 10.18 and 10.05 (POCT and lab tests respectively) and 9.18 and 9.54 (POCT and lab tests respectively). In addition, the mean differences between POC and laboratory analyses of venous, arterial, and central glucose were 0.13, - 1.75, and - 0.36 mmol/L for venous, arterial, and central glucose, respectively. Except for arterial blood glucose, we did not observe a significant difference between POCT and routine laboratory analysis of glucose concentrations in critically ill patients. Compared to laboratory blood analysis, the use of POCT is marginally accurate, with no difference between shocked and non-shocked patients.

Routine Elastin Staining in Surgically Resected Colorectal Cancer: Impact on Venous Invasion Detection and its Association With Oncologic Outcomes.

Venous invasion (VI) is a powerful yet underreported prognostic factor in colorectal cancer (CRC). Its detection can be improved with an elastin stain. We evaluated the impact of routine elastin staining on VI detection in resected CRC and its relationship with oncologic outcomes. Pathology reports from the year before (n=145) and the year following (n=128) the implementation of routine elastin staining at our institution were reviewed for established prognostic factors, including VI. A second review, using elastin stains, documented the presence/absence, location, number, and size of VI foci. The relationship between VI and oncologic outcomes was evaluated for original and review assessments. VI detection rates increased from 21% to 45% following implementation of routine elastin staining (odds ratio [OR]=3.1; 95% confidence interval [CI]: 1.8-5.3; P<0.0001). The second review revealed a lower VI miss rate postimplementation than preimplementation (22% vs. 48%, respectively; P=0.007); this difference was even greater for extramural VI-positive cases (9% vs. 38%, respectively; P=0.0003). Missed VI cases postimplementation had fewer VI foci per missed case (P=0.02) and a trend towards less extramural VI than those missed preimplementation. VI assessed with an elastin stain was significantly associated with recurrence-free survival (P=0.003), and cancer-specific survival (P=0.01) in contrast to VI assessed on hematoxylin and eosin alone (P=0.053 and 0.1, respectively). The association between VI and hematogenous metastasis was far stronger for elastin-detected VI (OR=11.5; 95% CI: 3.4-37.1; P<0.0001) than for hematoxylin and eosin-detected VI (OR=3.7; 95% CI: 1.4-9.9; P=0.01). Routine elastin staining enhances VI detection and its ability to stratify risk in CRC and should be considered for evaluation of CRC resection specimens.

Determination of finerenone - a novel, selective, nonsteroidal mineralocorticoid receptor antagonist - in human plasma by high-performance liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study in venous and capillary human plasma.

A straightforward and rapid high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay allowing the sensitive and selective quantitation of finerenone (BAY 94-8862) in lithium heparin human plasma is described. Finerenone is a novel, selective, nonsteroidal mineralocorticoid receptor antagonist that is in phase III clinical trials for the treatment of chronic kidney disease. Finerenone quantitation is performed after addition of its stable isotope-labelled internal standard (ISTD) by protein precipitation with acidified acetonitrile followed by HPLC-MS/MS separation and detection. The determination of finerenone concentrations was validated for a plasma volume of 0.100 mL and subsequently also for a lower plasma volume of 0.010 mL, collected e.g. in paediatric studies. The analytical range was from 0.100 µg/L (lower limit of quantification) to 200 µg/L (upper limit of quantification). Inter-day accuracy was 99.7-105.0% for the plasma volume of 0.100 mL and 101.1-104.5% for the plasma volume of 0.010 mL. Inter-day precision was ≤ 7.0%, independent of the extracted plasma volume. A moderate, concentration-independent matrix effect on ionisation was observed for both finerenone and its ISTD of 0.535-0.617, which is fully compensated by the ISTD (ISTD-normalised matrix factors were 0.98-1.03). The assay was successfully applied with both validated plasma volumes to a clinical phase I study in which the pharmacokinetics of 20 mg finerenone were compared in capillary plasma (0.010 mL) and venous plasma (0.100 mL) in a concentration range from the lower limit of quantification to 310 µg/L (capillary plasma) and 252 µg/L (venous plasma). The area under the plasma concentration versus time curve was similar in both matrices, while maximum concentrations were 37% higher in capillary plasma. In conclusion, capillary sampling should not bias pharmacokinetic exposure estimates compared with venous plasma values, if limited to sampling times in the distribution and elimination phases of finerenone.

Feasibility and Performance of Elastin Trichrome as a Primary Stain in Colorectal Cancer Resection Specimens: Results of an Interobserver Variability Study.

Venous invasion (VI) is a powerful prognostic factor in colorectal cancer (CRC) that is widely underreported. The ability of elastin stains to improve VI detection is now recognized in several international CRC pathology protocols. However, concerns related to the cost and time required to perform and evaluate these stains in addition to routine hematoxylin and eosin (H&E) stains remains a barrier to their wider use. We therefore sought to determine whether an elastin trichrome (ET) stain could be used as a "stand-alone" stain in CRC resections, by comparing the sensitivity, accuracy, and reproducibility of detection of CAP-mandated prognostic factors using ET and H&E stains. Representative H&E- and ET-stained slides from 50 CRC resections, including a representative mix of stages and prognostic factors, were used to generate 2 study sets. Each case was represented by H&E slides in 1 study set and by corresponding ET slides from the same blocks in the other study set. Ten observers (3 academic gastrointestinal [GI] pathologists, 4 community pathologists, 3 fellows) evaluated each study set for CAP-mandated prognostic factors. ET outperformed H&E in the assessment of VI with respect to detection rates (50% vs. 28.6%; P<0.0001), accuracy (82% vs. 59%, P<0.0001), and reproducibility (k=0.554 vs. 0.394). No significant differences between ET and H&E were observed for other features evaluated. In a poststudy survey, most observers considered the ease and speed of assessment at least equivalent for ET and H&E for most prognostic factors, and felt that ET would be feasible as a stand-alone stain in practice. If validated by others, our findings support the use of ET, rather than H&E, as the primary stain for the evaluation of CRC resections.

A metabolic investigation of arterialized venous flaps in rabbits using mass spectrometry-based metabolomics.

An arterialized venous flap (AVF) is an ideal choice of flap to repair wounds. However, the survival of these flaps remains the source of some concern. This study used metabolomic analysis to investigate the mechanisms underlying survival in AVF flaps in order to guide the clinical application of these flaps. Thirty-six male Japanese rabbits were randomly divided into a sham group and an AVF group. They were used for histology and hemodynamic investigations. Three days after surgery, tissue samples were analyzed by mass spectroscopy-based metabolomics. The results of the study revealed a reduction in blood flow, infiltration of inflammatory cells, and necrosis of flaps in the AVF group. In addition, notable changes were evident in the levels of several metabolites in the AVF group, including lactic acid, acetoacetic acid, inositol phosphate, arachidonic acid, and other metabolites. Our results indicate that the AVF group experienced changes in several biological pathways, including energy metabolism, cell membrane stability, and inflammatory response. There is a significant metabolic difference between AVFs and physiological flaps. The dysregulation in certain metabolites may be related to the specific hemodynamics and insufficient energy metabolism of the AVFs.

Targeted gene expression analysis of human deep veins.

OBJECTIVE: Endothelial-derived molecules involved in thrombosis and hemostasis have been investigated mainly in arteries and in experimental animals. The actual presence and integral function of these molecules in the human deep venous system have received less attention. Our aim was to evaluate the expression of certain prothrombotic and antithrombotic genes in the normal human deep veins of the lower extremities. METHODS: Macroscopically intact and competent valve-containing segments of human deep veins were prospectively collected from patients who had undergone above-knee amputation. Vein samples were separated into four zones: zone 1, postvalve (downstream, proximal) vein wall; zone 2, the valve cusp; zone 3, prevalve (upstream, distal) vein wall; and zone 4, vein wall within the valve cusp (cusp removed). Real-time quantitative polymerase chain reaction for principal genes involved in coagulation, fibrinolysis, and inflammation was performed to quantify messenger RNA. Selected protein gene products were measured by the western blot assay. One additional valve-containing segment underwent mass spectrometry analysis to investigate global differences in the proteome between the study zones. RESULTS: Seventeen valve-containing vein segments were analyzed. Significant upregulation of antithrombotic (protein C receptor [PROCR], thrombomodulin [THBD], tissue factor pathway inhibitor [TFPI]), prothrombotic (con Willebrand factor [VWF]), and proinflammatory (selectin P [SELP], intercellular adhesion molecule 1 [ICAM1]) genes was found in the valve cusp compared with the vein wall (P < .05). PROCR and THBD demonstrated the highest level of upregulation in the valve cusp. PROCR, serpin peptidase inhibitor, clade E, member 1 (SERPINE1), and SELP were upregulated in the valve cusp at the protein level (P < .05). Messenger RNA composition in the vein wall within the valve cusp was similar to the prevalve and postvalve vein wall for all genes, except for two times overexpressed ICAM1 (P < .05). Substantial differences within the proteome between the study zones were observed with mass spectrometry. CONCLUSIONS: The biological properties of the valve cusp, vein wall within the valve cusp, and vein wall beyond the valve cusp are different. The endothelium of the valve cusps of a normal competent deep venous valve may be naturally less thrombogenic compared with the vein wall. The endothelium of the valve cusp may have a higher potential to interact with white blood cells compared with the vein wall. Mass spectrometry demonstrates substantial differences in the proteome between the vein wall and the valve cusps that were not anticipated before. (J Vasc Surg Venous Lymphat Disord 2021;9:770-80.) CLINICAL RELEVANCE: Deep vein thrombosis (DVT) is a major cause of mortality, morbidity, and impaired quality of life. Multiple risk factors have been identified, although their relative weight and pathophysiologic interactions remain obscure. Many patients with multiple risk factors for DVT never develop this condition. Conversely, in numerous cases DVT cannot be attributed to any known clinical risk factor. The molecular mechanisms that initiate DVT are unclear. An improved understanding of the normal biology of human deep veins will serve as an important foundation for new hypotheses of the pathogenesis of DVT. The latter may suggest new projects on novel therapeutic strategies.

Approach to the Patient with Primary Aldosteronism: Utility and Limitations of Adrenal Vein Sampling.

Several studies over the past 3 decades document a higher prevalence of primary aldosteronism (PA) among hypertensive patients than generally presumed. PA exists as a spectrum from mild to severe aldosterone excess. Although a variety of PA subtypes exist, the 2 most common are aldosterone-producing adenomas (APAs) and bilateral hyperaldosteronism (BHA). The distinction is important, because APA-and other subtypes, with aldosterone production mostly from 1 adrenal-can be cured surgically, and BHA should be treated medically with mineralocorticoid-receptor antagonists (MRAs). The major shortcomings in the tailored management of patients with possible PA are the low rates of screening for case identification and the expensive and technically challenging imaging and interventional procedures required to distinguish APA from BHA, especially adrenal vein sampling (AVS). When AVS identifies an APA and allows the patient to be cured surgically, the procedure is of great value. In contrast, the patient with BHA is treated with MRA whether AVS is performed or not. Consequently, it is prudent to gauge how likely it is to benefit from imaging and AVS in each case prior to embarking on these studies. The explosion of information about PA in the past decade, including predictors of APA and of surgical benefit, are useful in limiting the evaluation for some patients with a positive PA screening test. This article will review our suggestions for approaching these patients in a pragmatic style, recognizing the limitations to even the best resources and facilities.

Determination of piperaquine concentration in human plasma and the correlation of capillary versus venous plasma concentrations.

BACKGROUND: A considerable challenge in quantification of the antimalarial piperaquine in plasma is carryover of analyte signal between assays. Current intensive pharmacokinetic studies often rely on the merging of venous and capillary sampling. Drug levels in capillary plasma may be different from those in venous plasma, Thus, correlation between capillary and venous drug levels needs to be established. METHODS: Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was used to develop the method. Piperaquine was measured in 205 pairs of capillary and venous plasma samples collected simultaneously at ≥24hr post dose in children, pregnant women and non-pregnant women receiving dihydroartemisinin-piperaquine as malaria chemoprevention. Standard three-dose regimen over three days applied to all participants with three 40mg dihydroartemisinin/320mg PQ tablets per dose for adults and weight-based dose for children. Correlation analysis was performed using the program Stata® SE12.1. Linear regression models were built using concentrations or logarithm transformed concentrations and the final models were selected based on maximal coefficient of determination (R2) and visual check. RESULTS: An LC-MS/MS method was developed and validated, utilizing methanol as a protein precipitation agent, a Gemini C18 column (50x2.0mm, 5µm) eluted with basic mobile phase solvents (ammonium hydroxide as the additive), and ESI+ as the ion source. This method had a calibration range of 10-1000 ng/mL and carryover was negligible. Correlation analysis revealed a linear relationship: Ccap = 1.04×Cven+4.20 (R2 = 0.832) without transformation of data, and lnCcap = 1.01×lnCven+0.0125, (R2 = 0.945) with natural logarithm transformation. The mean ratio (±SD) of Ccap/Cven was 1.13±0.42, and median (IQR) was 1.08 (0.917, 1.33). CONCLUSIONS: Capillary and venous plasma PQ measures are nearly identical overall, but not readily exchangeable due to large variation. Further correlation study accounting for disposition phases may be necessary.

MED12 exon 2 mutation is uncommon in intravenous leiomyomatosis: clinicopathologic features and molecular study.

Intravenous leiomyomatosis (IVL) is a rare neoplasm that is characterized by smooth muscle cell proliferation within venous vessels. The aim of this study is to investigate the clinicopathological features, immunophenotypes, and MED12 gene mutations in IVL. Nine cases of IVL from the Affiliated Hospital of Qingdao University were collected, and the clinicopathological features were reviewed. The immunohistochemical expressions of p16, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), alpha thalassemia/mental retardation syndrome X-linked (ATRX), retinoblastoma 1 (RB1), fumarate hydratase (FH), and p53, were evaluated. The mutation status of MED12 gene exon 2 was detected by Sanger sequencing. All the 9 patients were women ranging from 32 to 58 years, and uterine leiomyomas were identified in 5 patients. Immunohistochemical staining showed that all IVL and leiomyoma samples were positive for estrogen receptor and progesterone receptor, but negative for CD34. IVL displayed similar immunostaining patterns with their uterine counterparts with focal p16 immunostaining. FH, PTEN, ATRX, and RB1 were variably positive, and p53 and Ki-67 positive rates were less than 5% in all cases. Two novel genetic variations at MED12 exon 2, a synonymous mutation c.141C>T (p.Asn47=), and an in-frame deletion mutation c.133_147del15 (p.Phe45_Pro49del) were identified in two IVL cases. One missense mutation c.131G>A (p.Gly44Asp) was identified in one uterine leiomyoma. The remaining 11 tumor samples (7 IVL cases and 4 uterine leiomyomas) showed no mutations at MED12 exon 2. Our results showed two novel MED12 mutations in IVL. The MED12 mutations are different between IVL and uterine leiomyoma. These findings indicate that IVL is a unique entity and different from uterine leiomyoma.

TEMPORAL STABILITY OF IN VITRO VENOUS BLOOD GAS, pH, AND LACTATE VALUES OF COWNOSE RAYS (RHINOPTERA BONASUS) AND RED-EARED SLIDER TURTLES (PSEUDEMYS SCRIPTA ELEGANS).

This study assessed the in vitro temporal changes that occur in blood pH and lactate concentrations for an elasmobranch species and a chelonian species, as well as blood gases (partial pressures of carbon dioxide [pCO2] and oxygen [pO2]) for a chelonian species, with a portable clinical point-of-care analyzer. Blood samples were collected from 10 cownose rays (Rhinoptera bonasus) and 10 red-eared sliders (Pseudemys scripta elegans), stored on ice, and serially analyzed at six time points up to 90 min postcollection. Results indicate that analysis should be conducted as soon as possible after blood collection for these species, with immediate analysis being preferred. However, if analysis must be delayed, syringes may be capped, placed on ice, and analyzed at a later time. Analysis within 90 min provided clinically acceptable results for pH and lactate in both species and for pCO2 in red-eared sliders, whereas substantial artifactual increases of pO2 were seen in red-eared sliders.

Assessing Acid-Base Status in Circulatory Failure: Relationship Between Arterial and Peripheral Venous Blood Gas Measurements in Hypovolemic Shock.

BACKGROUND AND OBJECTIVES: In severe circulatory failure agreement between arterial and mixed venous or central venous values is poor; venous values are more reflective of tissue acid-base imbalance. No prior study has examined the relationship between peripheral venous blood gas (VBG) values and arterial blood gas (ABG) values in hemodynamic compromise. The objective of this study was to examine the correlation between hemodynamic parameters, specifically systolic blood pressure (SBP) and the arterial-peripheral venous (A-PV) difference for all commonly used acid-base parameters (pH, Pco 2, and bicarbonate). DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Data were obtained prospectively from adult patients with trauma. When an ABG was obtained for clinical purposes, a VBG was drawn as soon as possible. Patients were excluded if the ABG and VBG were drawn >10 minutes apart. RESULTS: The correlations between A-PV pH, A-PV Pco 2, and A-PV bicarbonate and SBP were not statistically significant (P = .55, .17, and .09, respectively). Although patients with hypotension had a lower mean arterial and peripheral venous pH and bicarbonate compared to hemodynamically stable patients, mean A-PV differences for pH and Pco 2 were not statistically different (P = .24 and .16, respectively) between hypotensive and normotensive groups. CONCLUSIONS: In hypovolemic shock, the peripheral VBG does not demonstrate a higher CO2 concentration and lower pH compared to arterial blood. Therefore, the peripheral VBG is not a surrogate for the tissue acid-base status in hypovolemic shock, likely due to peripheral vasoconstriction and central shunting of blood to essential organs. This contrasts with the selective venous respiratory acidosis previously demonstrated in central venous and mixed venous measurements in circulatory failure, which is more reflective of acid-base imbalance at the tissue level than arterial blood. Further work needs to be done to better define the relationship between ABG and both central and peripheral VBG values in various types of shock.

Vascularization of the arteriovenous fistula wall and association with maturation outcomes.

BACKGROUND AND OBJECTIVES: The venous vasa vasorum is the mesh of microvessels that provide oxygen and nutrients to the walls of large veins. Whether changes to the vasa vasorum have any effects on human arteriovenous fistula outcomes remains undetermined. In this study, we challenged the hypothesis that inadequate vascularization of the arteriovenous fistula wall is associated with maturation failure. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: This case-control pilot study includes pre-access veins and arteriovenous fistula venous samples (i.e. tissue pairs) from 30 patients undergoing two-stage arteriovenous fistula creation (15 matured and 15 failed to mature). Using anti-CD31 immunohistochemistry, we quantified vasa vasorum density and luminal area (vasa vasorum area) in the intima, media, and adventitia of pre-access veins and fistulas. We evaluated the association of pre-existing and postoperative arteriovenous fistula vascularization with maturation failure and with postoperative morphometry. RESULTS: Vascularization of veins and arteriovenous fistulas was predominantly observed in the outer media and adventitia. Only the size of the microvasculature (vasa vasorum area), but not the number of vessels (vasa vasorum density), increased after arteriovenous fistula creation in the adventitia (median vasa vasorum area 1366 µm2/mm2 (interquartile range 495-2582) in veins versus 3077 µm2/mm2 (1812-5323) in arteriovenous fistulas, p < 0.001), while no changes were observed in the intima and media. Postoperative intimal thickness correlated with lower vascularization of the media (r 0.53, p = 0.003 for vasa vasorum density and r 0.37, p = 0.045 for vasa vasorum area). However, there were no significant differences in pre-existing, postoperative, or longitudinal change in vascularization between arteriovenous fistulas with distinct maturation outcomes. CONCLUSION: The lack of change in intimal and medial vascularization after arteriovenous fistula creation argues against higher oxygen demand in the inner walls of the fistula during the vein to arteriovenous fistula transformation. Postoperative intimal hyperplasia in the arteriovenous fistula wall appears to thrive under hypoxic conditions. Vasa vasorum density and area by themselves are not predictive of maturation outcomes.

Three-dimensional visualization of cleared human pancreas cancer reveals that sustained epithelial-to-mesenchymal transition is not required for venous invasion.

Venous invasion is three times more common in pancreatic cancer than it is in other major cancers of the gastrointestinal tract, and venous invasion may explain why pancreatic cancer is so deadly. To characterize the patterns of venous invasion in pancreatic cancer, 52 thick slabs (up to 5 mm) of tissue were harvested from 52 surgically resected human ductal adenocarcinomas, cleared with a modified iDISCO method, and labeled with fluorescent-conjugated antibodies to cytokeratin 19, desmin, CD31, p53 and/or e-cadherin. Labeled three-dimensional (3D) pancreas cancer tissues were visualized with confocal laser scanning or light sheet microscopy. Multiple foci of venous and even arterial invasion were visualized. Venous invasion was detected more often in 3D (88%, 30/34 cases) than in conventional 2D slide evaluation (75%, 25/34 cases, P < 0.001). 3D visualization revealed pancreatic cancer cells crossing the walls of veins at multiple points, often at points where preexisting capillary structures bridge the blood vessels. The neoplastic cells often retained a ductal morphology (cohesive cells forming tubes) as they progressed from a stromal to intravenous location. Although immunolabeling with antibodies to e-cadherin revealed focal loss of expression at the leading edges of the cancers, the neoplastic cells within veins expressed e-cadherin and formed well-oriented glands. We conclude that venous invasion is almost universal in pancreatic cancer, suggesting that even surgically resectable PDAC has access to the venous spaces and thus the ability to disseminate widely. Furthermore, we observe that sustained epithelial-mesenchymal transition is not required for venous invasion in pancreatic cancer.

Arterio-venous metabolomics exploration reveals major changes across liver and intestine in the obese Yucatan minipig.

Blood circulation mainly aims at distributing the nutrients required for tissue metabolism and collecting safely the by-products of all tissues to be further metabolized or eliminated. The simultaneous study of arterial (A) and venous (V) specific metabolites therefore has appeared to be a more relevant approach to understand and study the metabolism of a given organ. We propose to implement this approach by applying a metabolomics (NMR) strategy on paired AV blood across the intestine and liver on high fat/high sugar (HFHS)-fed minipigs. Our objective was to unravel kinetically and sequentially the metabolic adaptations to early obesity/insulin resistance onset specifically on these two tissues. After two months of HFHS feeding our study of AV ratios of the metabolome highlighted three major features. First, the hepatic metabolism switched from carbohydrate to lipid utilization. Second, the energy demand of the intestine increased, resulting in an enhanced uptake of glutamine, glutamate, and the recruitment of novel energy substrates (choline and creatine). Third, the uptake of methionine and threonine was considered to be driven by an increased intestine turnover to cope with the new high-density diet. Finally, the unique combination of experimental data and modelling predictions suggested that HFHS feeding was associated with changes in tryptophan metabolism and fatty acid ß-oxidation, which may play an important role in lipid hepatic accumulation and insulin sensitivity.

Histopathological and proteomic analyses identify integrin-ß1 as a potential mediator of phlebosclerosis in uremic patients.

BACKGROUND: Patients with uremia have an excessive mortality from cardiovascular disease (CVD). Arterial remodeling is mainly responsible for uremia-induced CVD and has been well studied, yet venous remodeling is poorly understood. Here we investigate the histopathology and proteomic profiles of venous remodeling in uremic patients. METHODS: Forearm cephalic veins were isolated from nine uremic patients during surgeries for arteriovenous fistula, and from nine healthy controls when applying surgical debridement. Hematoxylin-eosin, Masson's trichrome, von Kossa, and immunohistochemistry (IHC) against proliferating cell nuclear antigen were stained for histopathology. Isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis was executed to explore the proteome of the veins. The core regulatory protein was validated by western blot, IHC, and immunofluorescence. RESULTS: Phlebosclerosis, characterized by intimal rarefaction and medial thickening with disordered proliferation of vascular smooth muscle cells (VSMCs), was the prominent pathological manifestation of peripheral veins in uremic patients, while inflammatory cell infiltration, atherosclerosis or calcification were not obviously detected. iTRAQ analysis showed that 350 proteins were significantly changed in phlebosclerosis of uremic patients compared with healthy controls, of which integrin-ß1 (ITGß1) exhibited the strongest regulatory ability by intermolecular interaction network analysis. The enhanced ITGß1 expression was mainly co-expressed with the disordered proliferation of VSMCs while a little with vascular endothelial cells in the forearm cephalic veins of uremic patients. CONCLUSIONS: Phlebosclerosis is the prominent pathological manifestation in peripheral veins of uremic patients. This pathological alteration mainly attributes to the disordered proliferation of VSMCs, which is potentially mediated by ITGß1.

VENOUS AND ARTERIAL ACID-BASE ANALYSIS OF MAGELLANIC PENGUINS (SPHENISCUS MAGELLANICUS), AWAKE AND ANESTHETIZED BY ISOFLURANE.

This study aimed to compare the venous acid-base status of healthy awake versus anesthetized Magellanic penguins (Spheniscus magellanicus). Ten nonanesthetized penguins were manually restrained, and a venous blood sample was collected. Six of these penguins were anesthetized by 2% isoflurane and, after an anesthetic stabilization period, both venous and arterial blood samples were simultaneously withdrawn. Using an i-STAT analyzer, partial pressure of carbon dioxide (PCO2), partial pressure of oxygen (PO2), pH, standard bicarbonate concentration (HCO3-), total carbon dioxide (ctCO2), oxygen saturation (SO2), base excess (BE), Na+, and K+ levels were measured in venous blood samples of awake (Gawake) penguins and in venous (Gven) and arterial blood (Gart) samples of anesthetized penguins. There were no significant differences between groups in pH, BE, or Na+. Venous carbon dioxide pressure, HCO3-, and venous ctCO2 were higher in Gven than Gawake penguins, whereas PCO2 was higher in Gven than Gart penguins. PO2 and SO2 were higher in the Gart group than in the other groups. Both venous and arterial blood samples may be used to evaluate the acid-base profile of Magellanic penguins.

A comparison between point-of-care testing and venous glucose determination for the diagnosis of diabetes mellitus 6-12 weeks after gestational diabetes.

AIM: To evaluate point-of-care-testing (POCT) for the diagnosis of Type 2 diabetes mellitus 6-12 weeks post-partum in women with gestational diabetes (GDM). METHODS: Post-partum glucose assessment (75-mg oral glucose tolerance test, OGTT) was performed prospectively in 122 women with GDM (1 November 2015 to 1 November 2017) at Tygerberg Hospital, Cape Town, South Africa. Individuals with known pre-existing diabetes were excluded. The accuracy and clinical utility of POCT (capillary finger-prick) were compared with laboratory plasma glucose (hexokinase and glucokinase methods). The OGTT consisted of two time points (fasting and 2 h) during which concurrent glucose samples (POCT and laboratory) were obtained. Bland-Altman plots and paired analysis were used to assess the analytical accuracy of POCT, whereas its diagnostic performance was determined using positive and negative predictive values to calculate specificity and sensitivity. RESULTS: Spearman's ranked correlation analysis indicated a strong association between POCT and laboratory glucose values at both OGTT time points (fasting, r = 0.95, P < 0.0001; 2 h, r = 0.88, P < 0.0001). Thirty-six women were diagnosed with Type 2 diabetes based on gold standard laboratory glucose levels (fasting > 7 mmol/l; 2 h > 11.1 mmol/l). POCT correctly identified Type 2 diabetes in 78% of women (28 of 36) with a positive predictive value of 89.3% and a negative predictive value of 96.7% at the fasting time point. The sensitivity and specificity of POCT to diagnose Type 2 diabetes were 89% (fasting), 85.7% (2 h) and 96.7% (fasting), 98.5% (2 h) respectively. POCT proved less sensitive to diagnose pre-diabetes (69%) but displayed satisfactory specificity (92%) at both time points assessed. CONCLUSION: POCT accurately identifies women with Type 2 diabetes 6-12 weeks after GDM.

Noninvasive, continuous, real-time glucose measurements compared to reference laboratory venous plasma glucose values.

Purpose: Current modalities for glucose monitoring are invasive and inconvenient. The search for a noninvasive technique is still ongoing, without a clinically viable product. The aim of our study was to evaluate the safety and accuracy of a novel non-invasive continuous glucometer - the Wizmi™ device. Methods: Prospective, observational, controlled clinical trial. We included healthy pregnant women designated to undergo a 3-hour oral glucose tolerance test. Each participant underwent synchronous and simultaneous glucose measurement by venous sampling of plasma glucose and non-invasive glucose by Wizmi device. Primary outcome was the accuracy of the Wizmi device as assessed by comparing between paired measurements, i.e. non-invasive glucose measurements by Wizmi versus standard plasma glucose levels, which were taken at the exact same time. Results: Thirty-two women underwent oral glucose tolerance test (OGTT), contributing 224 paired glucose measurements. Of the 224 paired measurements, all were within the clinically appropriate zones of the Clarke error grid analysis zones -208 (93%) in Zone A and 16 (7%) in zone B. Mean absolute relative difference of the Wizmi non-invasive glucose versus plasma glucose laboratory reference was 7.23% or 9.66 mg/dl. Overall, for all 224 paired measurements, across all Wizmi glucose ranges, the agreement was 86.6, 92.0, 97.8 and 99.5% for deviations within ±15, 20, 30, 40% (if glucose >80 mg/dl) or mg/dl (if glucose ≤80 mg/dl). Conclusions: Wizmi device is novel non-invasive continuous glucose monitor, safe to use, with overall high accuracy compared to a gold standard reference of plasma glucose.