Role of the kallikrein–kinin system in the maturation of cardiovascular phenotype

Recent studies indicate that during early phases of life the kallikrein–kinin system (KKS) plays a role in kidney development. In the rat kidney, the spatial and temporal pattern of expression of the genes encoding for kallikrein or bradykinin (BK) B₂-receptors parallels postnatal nephrogenesis and blood flow redistribution from the inner to the outer renal cortex. Animal models with genetic dysfunction of the renal KKS show alterations in the functional maturation of the kidney, and ultimately develop salt-sensitive hypertension. Kininogen-deficient Brown Norway Katholiek rats have undetectable urinary kinin levels and show an exaggerated blood pressure sensitivity to chronic excess of salt or mineralocorticoids. Another rat model with genetic reduction in urinary kallikrein excretion is characterized by an altered pressure–natriuresis relationship, with this defect being corrected by infusion of purified rat tissue kallikrein. Knockout mice lacking the BK B₂-receptor gene show elevated blood pressure and heart rate under basal conditions and enhanced blood pressure sensitivity to salt. In rats, prenatal blockade of the BK B₂-receptor by icatibant leads to a cardiovascular phenotype similar to that of animals with genetic defects of the KKS. Delayed renal maturation is observed when high salt intake is associated with icatibant. Collectively, these findings indicate a relevant role of the KKS in the physiologic maturation of renal and cardiovascular phenotypes. Genetic or environmental factors, able to potentiate the activity of the renal KKS, could protect against the development of arterial hypertension.     

Accuracy performance of the Medtronic NexSensor™ for 6 days in an inpatient setting using abdomen and buttocks insertion sites

Background

Users of continuous glucose monitoring are concerned with product accuracy and choice of insertion site. The Medtronic NexSensor™ was evaluated for accuracy during 6 days of wear when inserted in the abdomen and buttocks areas.

Methods

Adults (ages 18–75) with type 1 diabetes wore two sensors simultaneously for 6 days, one each inserted in the abdomen and buttocks. Subjects underwent a frequent blood sampling study for 12 hours, during which time reference blood glucose values were obtained every 15 minutes and compared to sensor values.

Results

Sixty-three subjects were enrolled, and 61 subjects completed the study. The mean agreement rate between sensor and blood glucose values was 75.5% [95% confidence interval (CI), 69.5, 81.4] at the abdomen site, 73.8% (95% CI, 68.8, 78.8) at the buttocks site, and 75.6% (95% CI, 70.8, 80.4) when sensor and reference data were combined between sites. Over 90% of paired sensor-reference values on Clarke error grids were within the A and B ranges. The mean absolute relative differences were 17.1% at the abdomen site, 16.5% at the buttocks site, and 16.8% when sites were combined.

Conclusion

The NexSensor was accurate for inpatient, frequent-sample testing for 6 days when inserted into the abdomen and buttocks. The results of this study also provide evidence that both the abdomen and buttocks are suitable as sensor insertion sites.     

Hydrogen sulfide system in the pathogenesis of renovascular hypertension in rats

Objective To investigate the role of hydrogen sulfide (H2S) synthases/H2S pathway in the pathogenesis of renovascular hypertension.Methods Wistar rats were subdivided into 4 groups:(1) 2-kidney,1-clip (2K-1C group,n=7),(2) control (n=7),(3)sham (n=7),and (4) 2K-1C plus sodium hydrosulfide (NariS) (NariS-treated group,n=7).The systolic blood pressure (SBP) was measured by a tail-cuff method using a pulse transducer once a week.Four weeks later,all rats were killed and the concentration of plasma hydrogen sulfide (H2S),the activity of the H2S syntha.ses in the kidneys on both sides,the plasma angiotensin Ⅱ concentration,and the left-to-whole heart weight ratio were measured.Results The SBP was significantly increased in the 2K-IC group (185.4± 14.0mmHg) comparing with those in the sham group (112.9±6.5mmHg,,or the NariS-treated group(134.8±9.5mmHg) (both P＜0.01).At 4 weeks,the angiotensin Ⅱ concentration in the plasma was increased in the 2K-1C and NariS-treated group,comparing with the control and the sham group (306.92±7.03 pg/ml and 240.73±13.22 pg/ml vs 122.6±25.49 pg/ml and 125.95±10.55 pg/ml,respectively,both P＜0.05).The plasma H2S concentration and the activity of H2S synthases in the left kidney were decreased in the 2K-1C group comparing with those in the sham and the control groups.There was no difference of the activity of the H2S synthases in the right kidneys among the 4 groups.The left-to-whole heart weight ratio was increased in the 2K-1C and the NariS-treated group camparing with that in the sham and natural control groups.Conclusions Dysfunction of the H2S synthases/H2S pathway was involved in the 2K-1C-induced renovascular hypertension in rat.Exogenous administration of H2S donor can attenuate the development of hypertension.These findings suggest that the H2S synthases/H2S pathway participates in the pathogenesis of renovascular hypertension.     

APACHE system is better than Ranson system in the prediction of severity of acute pancreatitis

BACKGROUND: It has been suggested that addition of obesity score to the APACHE-Ⅱ system can lead to more accurate prediction of severity of acute pancreatitis. However there is scanty information on the usefulness of the combined APACHE-O scoring system in Asian patients. This study aimed to compare the accuracy of Ranson, APACHE-Ⅱ and APACHE-O systems in assessing severity of acute pancreatitis in a local Chinese population. METHODS: One hundred and one consecutive patients with acute pancreatitis were prospectively studied. Body mass index (BMI) was measured on admission. Ranson score, APACHE-Ⅱ and APACHE-O scores were recorded on admission and at 48 hours. By adopting the cut-off levels and definitions advocated in the Atlanta consensus for severe disease, the diagnostic accuracy of the three scoring systems was compared by the area under the curve (AUC) under the receiver operator characteristic curve. RESULTS: Of the 101 patients, 12 (11.9%) patients suffered from severe pancreatitis. Obesity was uncommon and only two patients (2.0%) had BMI >30. Eighty-two (81.2%) patients were normal weight (BMI≤25) whereas 17 (16.8%) were overweight ( BMI 25-30 ). Overweight or obesity (BMI >25) was not associated with severe pancreatitis (P= 0.40). The AUC for admission scores of Ranson, APACHE-Ⅱ, and APACHE-O systems was 0. 549, 0. 904 and 0. 904, respectively. The AUC for 48-hour scores of Ranson, APACHE-Ⅱ and APACHE-O systems was 0.808, 0.955 and 0.951, respectively. CONCLUSIONS: The APACHE-Ⅱ scoring system is more accurate than the Ranson scoring system of the prediction of severity in acute pancreatitis. Addition of obesity score does not significantly improve the predictive accuracy of the APACHE-Ⅱ system in our local population with a low prevalence of obesity.     

Increased proportion of time in hybrid closed-loop “Auto Mode” is associated with improved glycaemic control for adolescent and young patients with adult type 1 diabetes using the MiniMed 670G insulin pump

The Medtronic MiniMed 670G system delivers insulin to patients with type 1 diabetes mellitus (T1DM) using either its hybrid closed-loop (HCL) “Auto Mode” feature or an open-loop mode. In this retrospective, cross-sectional analysis, we quantified the association between time in Auto Mode and both haemoglobin A1c (HbA1c) and time in range (TIR, sensor glucose 70–180 mg/dL) among 96 paediatric and young adult patients with T1DM. The median percentage time in Auto Mode was 38.5% (interquartile range 0%–64%). The percentage time in Auto Mode significantly correlated with HbA1c after adjustment for covariables (β = −0.008, P = 0.014). Each daily 3.4-h increase in Auto Mode time was associated with a 0.1% decrease in HbA1c. Auto Mode time was also correlated with TIR after adjustment for covariables (β = 0.14, P = 0.02): for each daily 8.6-h increase in Auto Mode time, TIR increased by 5%. While Auto Mode use was low, increased time in Auto Mode was associated with a significantly lower HbA1c and increased TIR. These findings emphasize the importance of identifying strategies to improve the ease of use of HCL systems.     

Use of R ™ stent in the percutaneous coronary intervention of coronary bifurcation lesions

BACKGROUND: Percutaneous Coronary Intervention (PCI) of coronary bifurcation lesion is technically quite demanding. It has been associated with a lower procedural success, higher rates of complication and restenosis. Side-branch occlusion and plaque shifting or 'snow plow' effect are not uncommon. Stenting of the main vessel may cause 'stent jail' of the side-branch. Modern stent design may allow passage of a balloon or stent into the side-branch through the struts of the stent placed in the main vessel. A newly developed 316 stainless steel tubular stent, the R? stent is uniquely designed to provide flexibility, radial strength on deployment and conformability. Its large cell size facilitates PCI of bifurcation lesion. AIM: To assess the feasibility of R ? stent in the treatment of symptomatic patients with bifurcation coronary lesions. The main objective was to assess the ease of deployment, side-branch access and overall success of the R ? stent in this group of patients without any major adverse events. METHODS: Between December 1998 and September 2000 the R ? stent was used as a main stent in 28 consecutive patients with coronary bifurcation lesions, 46% of which had unstable angina. The mean age was 59 &#45 10 and 89% were male. Adjunctive medical therapy included clopidrogel, aspirin and intraprocedure heparin. Abciximab (ReoPro) was given to 9 patients. RESULTS: Successful stent deployment was achieved in all patients. Thirty-four R Stents and 16 other stents were used. Two patients had post-procedure rise in cardiac enzymes. There were no major adverse events at 30 days. LAD/D1 with LAD/diagonal was the target lesion in the majority of patients. Stenting of the side-branch was done in 18 and balloon dilatation in 9 patients. At 3-23 months (mean 11.8) follow-up, repeat angiography was done in 18 patients with restenosis in 4, two of them had repeat PCI and one had coronary artery bypass graft (CABG). CONCLUSION: Coronary bifurcation lesions are not uncommon. Current advances in stent technology offer a safe and effective revascularisation strategy for such complex lesions. The R ? stent appears to be a suitable device that provides good wall coverage, radial strength, conformability and easy side-branch access.     

Real-world experience of tocilizumab in rheumatoid arthritis: sub-analysis of data from the Italian biologics’ register GISEA

To assess the long-term effectiveness and safety of tocilizumab, abatacept, and tumor necrosis factor-α inhibitors (TNFi), in the Italian real-world setting of rheumatoid arthritis (RA). The records of adult RA patients from the Italian biologics’ registry Gruppo Italiano Studio Early Arthritis (GISEA) were analyzed. Demographic and clinical data were obtained at entry. The disease remission rate (28-joint disease activity score calculated using the erythrocyte sedimentation rate [DAS28-ESR] ≤ 2.6) and frequency of adverse events (AEs) were evaluated at 2 years. From 1999 to 2014, 7539 patients were treated with biologics (61.3% in first- and 22.6% in second-line), 68% of cases received TNFi, 9.1% tocilizumab, and 8.6% abatacept. Treatment groups showed a similar DAS28 at entry. As first-line, tocilizumab induced a significantly higher remission rate than abatacept or TNFi at 6 (51 vs 23.3 and 26.2%, respectively; p < 0.0001) and 24 months (52.3 vs 33.3 and 34.4%, respectively; p < 0.01). A similar pattern was observed in later lines. The most common AEs reported were infections, reactions to biologics (more frequent among TNFi-treated patients), increased transaminase (more frequent among TCZ-treated patients), and cardiovascular events. In clinical practice, TCZ induced a rapid and long-lasting remission and in a higher percentage of patients compared to abatacept and TNFi, with a good safety profile.     

Use of drug-carrier system in the treatment of Plasmodium berghei infected-mice.

359 mice infected with Plesmodium berghei were divided into 36 groups and treated with serialdosages of chloroquine entrapped in liposome.This drug-carrier system was compared with free chloro-quinn in another serial dosages.Five experiments were accomplished with various controls in each.Thetotal dosage for each mouse was divided into 2-3 parts i.p.cn Day 3,4 or Day 3,4,7.The percentagecf prolongation of the average life span(PALS)of mice was calculated according to the fourmula:     

iMAP™ imaging of tumorous lesions surrounding the coronary arteries in a patient with an elevated serum level of immunoglobulin G4

A 76-year-old woman with multiple coronary risk factors was admitted to our hospital because of episodes of new-onset chest pain that had begun 3 days previously. She underwent percutaneous coronary intervention (PCI) for severe stenoses in the two high lateral (HL) branches. Intravascular ultrasound (IVUS) revealed massive stenotic lesions in the HL branches and tumorous nonstenotic lesions in the left anterior descending coronary artery (LAD) and the left circumflex coronary artery (LCx). iMAP?, optical coherence tomography (OCT), and coronary computed tomography angiography (CCTA) were performed. iMAP depicted fibrosis in the vessel (green areas) and nonfibrotic tissue change suggestive of inflammation outside the vessel (yellow/red areas). OCT revealed high-intensity homogenous intimal hyperplasia with superficial calcification, and CCTA showed massive periarterial soft lesions in the HL, LAD, and LCx. The serum IgG4 level was high at 252–427 mg/dL (8 measurements) (reference range, 4.8–105.0 mg/dL). We suspected IgG4-related coronary periarteritis on the basis of the comprehensive diagnostic criteria as a possible diagnosis. The clinical course was good after initial and subsequent PCIs for both the HL stenoses and the progressing LCx stenosis, and there was no recurrence of angina pectoris thereafter. Steroids were not administered because the massive lesions did not enlarge during the 16 months of follow-up. iMAP was able to evaluate the tissue characteristics of tumorous lesions in the stenosed HL branches and the nonstenotic LAD and LCx in a patient with an elevated level of IgG4.     

ORIGINAL ARTICLE: Evaluation of the CellaVision™ DM automated microscope in pediatrics

The DM is an automated microscope, which performs WBC differential counts and monitors red cell morphology. The user either validates the cell recognition if the DM has correctly identified the WBCs or reclassifies the WBCs in the good category in case of a DM mis-assignment. Morphological anomalies of leukocytes, red blood cells or platelets are analyzed and registered. We studied 521 newborns and infants sorted by age and pathology. The results correlated well with those using conventional microscopy except for samples containing blasts, in which the percentage of malignant cells was underestimated. Newborns had the lowest rates of overall accuracy and postclassification agreement. For red cell analysis, 10% of the selected areas were considered unreadable. However, the DM diagnosed faithfully all studied red cell pathologies. The DM was also very useful in analyzing samples of storage diseases. Timesavings ranging from 1 up to 10 min (for vacuolated lymphocyte screening) were observed when performing analysis with the DM. The DM represents a useful diagnostic and training tool. However, conventional microscopy remains essential, in particular when the image quality is poor, such as in the case of lymphoblasts, and in the screening of platelet clusters.     

Use of the Harmonic Scalpel™ in open abdominoperineal surgery for rectal carcinoma

We describe a technique of open abdominoperineal resection with the use of the Harmonic Scalpel in seven patients. Using this instrument we dissected all pelvic vessels, including the middle hemorrhoidal artery, with no subsequent bleeding. In addition, we divided the levator animuscles completely in the abdominal procedure alone.     

Has pay for performance improved the management of diabetes in the United Kingdom?

Over the past decade the UK government has introduced a number of major policy initiatives to improve the quality of health care. One such initiative was the introduction of the Quality and Outcomes Framework (QOF), a pay for performance scheme launched in April 2004, which aims to improve the primary care management of common chronic conditions including diabetes. Some evidence suggest that introduction of QOF has been associated with improvements in the quality indicators for diabetes care included in the framework. However, it is difficult to disentangle the impact of QOF from other quality initiatives as few studies adjusted for underlying trends in quality. There is some evidence that QOF may have reduced inequalities in diabetes care between affluent and deprived areas but women and individuals from ethnic minority groups appear to have benefited least from this initiative. Less is known about the impact of QOF on aspects of diabetes care not reflected in the framework, including self-management and continuity of care.     

EUS-guided trans-esophageal drainage of a mediastinal necrotic fluid collection using the axios electrocautery enhanced delivery system™

Mediastinal collection secondary to necrotic acute pancreatitis, is an extremely rare event caused by the posterior rupture of the pancreatic duct into the retroperitoneal space with the penetration of the pancreatic fluid through the diaphragmatic orifices. Infection of the necrotic collection may occur with a consequent substantial increase of the mortality rate. Due to the rarity of this severe condition, no consensus is known about the management of infected mediastinal necrotic collections. We reported the case of a 61-year-old male who was critically unwell secondary to a large mediastinal necrotic collections after necrotic acute pancreatitis with no improvement after surgery. The patient was successfully treated by EUS-guided trans-esophageal drainage using the AXIOS Electrocautery Enhanced Delivery System?. This procedure proved in this case to be a safe and effective option for the management of infected necrotic mediastinal collections.