Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Arrhythmogenic mechanisms in the isolated perfused hypokalaemic murine heart

AIM: Hypokalaemia is associated with a lethal form of ventricular tachycardia (VT), torsade de pointes, through pathophysiological mechanisms requiring clarification. METHODS: Left ventricular endocardial and epicardial monophasic action potentials were compared in isolated mouse hearts paced from the right ventricular epicardium perfused with hypokalaemic (3 and 4 mm [K(+)](o)) solutions. Corresponding K(+) currents were compared in whole-cell patch-clamped epicardial and endocardial myocytes. RESULTS: Hypokalaemia prolonged epicardial action potential durations (APD) from mean APD(90)s of 37.2 ± 1.7 ms (n = 7) to 58.4 ± 4.1 ms (n =7) and 66.7 ± 2.1 ms (n = 11) at 5.2, 4 and 3 mm [K(+)](o) respectively. Endocardial APD(90)s correspondingly increased from 51.6 ± 1.9 ms (n = 7) to 62.8 ± 2.8 ms (n = 7) and 62.9 ± 5.9 ms (n = 11) giving reductions in endocardial–epicardial differences, ΔAPD(90), from 14.4 ± 2.6 to 4.4 ± 5.0 and −3.4 ± 6.0 ms respectively. Early afterdepolarizations (EADs) occurred in epicardia in three of seven spontaneously beating hearts at 4 mm [K(+)](o) with triggered beats followed by episodes of non-sustained VT in nine of 11 preparations at 3 mm. Programmed electrical stimulation never induced arrhythmic events in preparations perfused with normokalemic solutions yet induced VT in two of seven and nine of 11 preparations at 4 and 3 mm [K(+)](o) respectively. Early outward K(+) current correspondingly fell from 73.46 ± 8.45 to 61.16±6.14 pA/pF in isolated epicardial but not endocardial myocytes (n = 9) (3 mm [K(+)](o)). CONCLUSIONS: Hypokalaemic mouse hearts recapitulate the clinical arrhythmogenic phenotype, demonstrating EADs and triggered beats that might initiate VT on the one hand and reduced transmural dispersion of repolarization reflected in ΔAPD(90) suggesting arrhythmogenic substrate on the other

The Effect of Preventive Conservation Measures on the Technical Condition of A Religious Building Located in the Mining Area

The article presents the case study of a historical religious building located in the area of “Bogdanka” S.A. Coal Mine. As the building lacked adequate resistance to the expected effects of mining, the Mine undertook efforts so that it was fully protected against mining impacts before the commencement of mining operations. A preventive conservation system was used, consisting of an external stiffening reinforced concrete plate at the ground level and a system of steel tie rods established at the level of vault supports. The article assesses the effect of undertaken preventive conservation measures on the current technical condition of the building. The basis for the assessment was the extent of damage to the building confirmed after the occurrence of impacts from the performed mining operations combined with the analysis of ground deformation.W artykule przedstawiono przypadek zabytkowego budynku sakralnego, usytuowanego na terenie górniczym Kopalni LW „Bogdanka” S.A. Z powodu braku odpowiedniej odporności na prognozowane wpływy górnicze, staraniem Kopalni budynek ten został kompleksowo zabezpieczony profilaktycznie przeciw wpływom górniczym jeszcze przed rozpoczęciem eksploatacji. Zastosowano system zabezpieczeń profilaktycznych złożony z zewnętrznej żelbetowej tarczy usztywniającej w poziomie terenu oraz układu stalowych ściągów, założonych w poziomie oparcia sklepień. W artykule dokonano oceny wpływu podjętych działań profilaktycznych na aktualny stan techniczny budynku. Podstawą oceny był zakres uszkodzeń budynku stwierdzony po ujawnieniu się wpływów od dokonanej eksploatacji górniczej, w powiązaniu z analizą deformacji terenu

Ocena uszkodzeń typowej prefabrykowanej hali magazynowej

This article presents a case of a damaged warehouse building built in the typical reinforced concrete precast technology. Damage and irregularities identified during an inspection were described and their causes were analyzed. Identification of the type and extent of the damage led to the conclusion that the most important are the concrete cracks and losses along the edges of the load-bearing structure column heads at the level of the roof girders support, and not the cracks and displacements of the curtain wall fragments, which the user was most concerned with. The described example is a confirmation of a need to carry out regular evaluations of the technical condition of buildings, so that users can rationally plan renovation works for the further safe use of the structure.W artykule przedstawiono przypadek uszkodzonej hali magazynowej wzniesionej w typowej żelbetowej technologii prefabrykowanej. Opisano stwierdzone podczas inwentaryzacji uszkodzenia i nieprawidłowości oraz przeanalizowano przyczyny ich powstania. Rozpoznanie zakresu uszkodzeń doprowadziło do sformułowania wniosku, że najistotniejsze są pęknięcia i ubytki betonu wzdłuż krawędzi głowic słupów konstrukcji nośnej na poziomie oparcia dźwigarów dachowych, a nie pęknięcia i przemieszczenia fragmentów ścian osłonowych, które wzbudzały niepokój użytkownika. Przedstawiony przykład potwierdza potrzebę wykonywania okresowych ocen stanu technicznego budynków, dzięki którym użytkownicy mogą racjonalnie planować prace remontowe niezbędne do dalszej bezpiecznej eksploatacji obiektu

Wpływ zabezpieczeń profilaktycznych na stan techniczny budynku sakralnego usytuowanego na terenie górniczym

The article presents the case study of a historical religious building located in the area of “Bogdanka” S.A. Coal Mine. As the building lacked adequate resistance to the expected effects of mining, the Mine undertook efforts so that it was fully protected against mining impacts before the commencement of mining operations. A preventive conservation system was used, consisting of an external stiffening reinforced concrete plate at the ground level and a system of steel tie rods established at the level of vault supports. The article assesses the effect of undertaken preventive conservation measures on the current technical condition of the building. The basis for the assessment was the extent of damage to the building confirmed after the occurrence of impacts from the performed mining operations combined with the analysis of ground deformation.W artykule przedstawiono przypadek zabytkowego budynku sakralnego, usytuowanego na terenie górniczym Kopalni LW „Bogdanka” S.A. Z powodu braku odpowiedniej odporności na prognozowane wpływy górnicze, staraniem Kopalni budynek ten został kompleksowo zabezpieczony profilaktycznie przeciw wpływom górniczym jeszcze przed rozpoczęciem eksploatacji. Zastosowano system zabezpieczeń profilaktycznych złożony z zewnętrznej żelbetowej tarczy usztywniającej w poziomie terenu oraz układu stalowych ściągów, założonych w poziomie oparcia sklepień. W artykule dokonano oceny wpływu podjętych działań profilaktycznych na aktualny stan techniczny budynku. Podstawą oceny był zakres uszkodzeń budynku stwierdzony po ujawnieniu się wpływów od dokonanej eksploatacji górniczej, w powiązaniu z analizą deformacji terenu

1561-P: Racial Disparity May Exist in Patients with Diabetes Mellitus Hospitalized with Acute Pancreatitis

Introduction: Acute pancreatitis (AP) is the most common reason for hospitalizations for gastrointestinal disorders in the United States. Diabetes mellitus (DM) is known to increase the risk for AP by almost 3-fold. Single center studies have demonstrated demographic disparities in AP patients with DM. The identification of AP and DM patients at risk may provide clues to etiology and develop population preventative measures to lower AP-related hospitalizations. Our primary aim was to evaluate demographic trends in patients with DM and AP using a large national database. Methods: We extracted data from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample database, from 2012-2014. International Classification of Diseases 9th Version, and used clinical modification codes for adult patients hospitalized with primary diagnosis of AP. Results: There were 1,310,385 primary admissions for AP during the study period. 27.4% were diagnosed with AP-DM. Patients with AP-DM were older in age compared to AP only (p&amp;lt;0.001). Majority of AP only patients were female (50.4%). Majority of patients with AP-DM were male (55.1% without complications and 50.7% with complications). Non-Hispanic Whites (NHW) had the highest prevalence of AP without DM. All other races had greater prevalence of AP-DM, including the largest discrepancy in African-Americans (AA) and Hispanics. For NHW, 67.6% did not have DM, 59.0% and 53.3% had DM without and with complications, respectively. For AA, 14.5% did not have DM, 18.8% and 24.4% had DM without and with complications, respectively. Conclusions: This study is the first to demonstrate a racial disparity in AP patients with DM on a national scale. Patients with AP-DM were likely to be older, male, and AA compared to NHW, which is consistent with previous data. Multiple factors between NHW, AA and Hispanics which include but are not limited to genetic, socioeconomic, and cultural factors may be determinants of this disparity. Disclosure N. Choi: None. M.E. Garcia: None. B.L. Zakhary: None. M.A. Firek: None. D.I. Kim: None. C.S. Jackson: None. A. Firek: None. </jats:sec