Combination therapy with an ACE inhibitor and an angiotensin receptor blocker for diabetic nephropathy - a meta-analysis

WSTĘP. Inhibitory konwertazy angiotensyny (ACEI) i blokery receptora angiotensyny (ARB) zapobiegają progresji nefropatii cukrzycowej (DN). Wyniki badań sugerują, że połączenie układu renina-angiotensyna-aldosteron (RAAS) i czynników hamujących działa addytywnie w procesie leczenia DN. Ponieważ badania te obejmowały niewielkie grupy chorych, autorzy niniejszej pracy przeprowadzili metaanalizę prób dotyczących leczenia skojarzonego DN. METODY. Badania do metaanalizy wybrano na podstawie baz danych MEDLINE, EMBASE, CINAHL i Cochrane. Włączono wszystkie próby dotyczące skojarzonego leczenia za pomocą ACEI i ARB. Głównym punktem końcowym było dobowe wydalanie białka z moczem, a dodatkowe punkty końcowe obejmowały: wartości ciśnienia tętniczego, stężenia potasu we krwi i współczynnika przesączania kłębuszkowego (GFR). WYNIKI. W 10 włączonych do analizy badaniach 156 chorych otrzymało ACEI i ARB, a 159 jedynie ACEI. Większość badań trwało 8-12 tygodni. U osób leczonych ACEI i ARB uzyskano zmniejszenie proteinurii (p = 0,01), co wiązało się ze znaczną statystyczną heterogenicznością (p = 0,005). Terapia ACEI i ARB była związana ze zmniejszeniem GFR [3,87 ml/min (7,32-0,42); p = 0,03] i tendencją do wzrostu stężenia kreatyniny w surowicy (6,86 umol/l 95% CI -0,76-13,73; p = 0,09). Stężenie potasu zwiększyło się o 0,2 (0,08-0,32) mmol/l (p < 0,01) u chorych leczonych ACEI i ARB. Skurczowe i rozkurczowe ciśnienie krwi obniżyło się odpowiednio o 5,2 mm Hg (2,1-8,4) (p < 0,01) i 5,3 mm Hg (2,2-8,4) (p < 0,01). WNIOSKI. Wyniki metaanalizy sugerują, że łączne stosowanie ACEI + ARB w większym stopniu zmniejsza 24-godzinne wydalanie białka z moczem niż przyjmowanie jedynie ACEI. Korzystne efekty terapii skojarzonej są wynikiem niewielkiego wpływu leków na GFR, stężenie kreatyniny i potasu w surowicy oraz ciśnienie tętnicze. Rezultaty te należy interpretować ostrożnie, ponieważ większość analizowanych badań charakteryzowała się krótkim czasem obserwacji, a w kilku długoterminowych próbach (12 miesięcy) nie wykazano korzystnego wpływu leczenia.AIMS. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) prevent the progression of diabetic nephropathy (DN). Studies suggest that combination renin-angiotensin-aldosterone system (RAAS)-inhibiting therapy provides additive benefit in DN. However, these studies are small in size. We performed a meta-analysis of studies investigating combination therapy for DN. METHODS. Studies were identified through a search of MEDLINE, EMBASE, CINAHL and the Cochrane Database. All trials involving combined ACEI and ARB for slowing progression of DN were included. The primary end point was 24- Blood pressure, serum potassium and glomerular filtration rate (GFR) were secondary end points. RESULTS. In the 10 included trials, 156 patients received ACEI + ARB and 159 received ACEI only. Most studies were 8&#8211;12 weeks in duration. Proteinuria was reduced with ACEI + ARB (p = 0.01). This was associated with significant statistical heterogeneity (p = 0.005). ACEI + ARB was associated with a reduction in GFR [3.87 ml/min (7.32-0.42); p = 0.03] and a trend towards an increase in serum creatinine (6.86 umol/l 95% CI: -0.76-13.73; p = 0.09). Potassium was increased by 0.2 (0.08-0.32) mmol/l (p < 0.01) with ACEI + ARB. Systolic and diastolic blood pressure were reduced by 5.2 (2.1-8.4) mm Hg (p < 0.01) and 5.3 (2.2-8.4) mm Hg (p < 0.01), respectively. CONCLUSIONS. This meta-analysis suggests that ACEI + + ARB reduces 24-h proteinuria to a greater extent than ACEI alone. This benefit is associated with small effects on GFR, serum creatinine, potassium and blood pressure. These results should be interpreted cautiously as most of the included studies were of short duration and the few long-term studies (12 months) have not demonstrated benefi

Holographic nonlinear hydrodynamics from AdS/CFT with multiple/non-Abelian symmetries

We study viscous hydrodynamics of hot conformal field theory plasma with multiple/non-Abelian symmetries in the framework of AdS/CFT correspondence, using a recently proposed method of directly solving bulk gravity in derivative expansion of local plasma parameters. Our motivation is to better describe the real QCD plasma produced at RHIC, incorporating its U(1)^Nf flavor symmetry as well as SU(2)_I non-Abelian iso-spin symmetry. As concrete examples, we choose to study the STU model for multiple U(1)^3 symmetries, which is a sub-sector of 5D N=4 gauged SUGRA dual to N=4 Super Yang-Mills theory, capturing Cartan U(1)^3 dynamics inside the full R-symmetry. For SU(2), we analyze the minimal 4D N=3 gauged SUGRA whose bosonic action is simply an Einstein-Yang-Mills system, which corresponds to SU(2) R-symmetry dynamics on M2-branes at a Hyper-Kahler cone. By generalizing the bosonic action to arbitrary dimensions and Lie groups, we present our analysis and results for any non-Abelian plasma in arbitrary dimensions.Comment: 37 pages, v3: errors corrected, reference added, JHEP versio

Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody

The henipaviruses, represented by Hendra (HeV) and Nipah (NiV) viruses are highly pathogenic zoonotic paramyxoviruses with uniquely broad host tropisms responsible for repeated outbreaks in Australia, Southeast Asia, India and Bangladesh. The high morbidity and mortality rates associated with infection and lack of licensed antiviral therapies make the henipaviruses a potential biological threat to humans and livestock. Henipavirus entry is initiated by the attachment of the G envelope glycoprotein to host cell membrane receptors. Previously, henipavirus-neutralizing human monoclonal antibodies (hmAb) have been isolated using the HeV-G glycoprotein and a human naïve antibody library. One cross-reactive and receptor-blocking hmAb (m102.4) was recently demonstrated to be an effective post-exposure therapy in two animal models of NiV and HeV infection, has been used in several people on a compassionate use basis, and is currently in development for use in humans. Here, we report the crystal structure of the complex of HeV-G with m102.3, an m102.4 derivative, and describe NiV and HeV escape mutants. This structure provides detailed insight into the mechanism of HeV and NiV neutralization by m102.4, and serves as a blueprint for further optimization of m102.4 as a therapeutic agent and for the development of entry inhibitors and vaccines

Gene expression profiling of mucinous ovarian tumors and comparison with upper and lower gastrointestinal tumors identifies markers associated with adverse outcomes.

PURPOSE: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. EXPERIMENTAL DESIGN: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). RESULTS: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04–7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04–1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01–1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). CONCLUSIONS: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies

Observations of the High Redshift Universe

(Abridged) In these lectures aimed for non-specialists, I review progress in understanding how galaxies form and evolve. Both the star formation history and assembly of stellar mass can be empirically traced from redshifts z~6 to the present, but how the various distant populations inter-relate and how stellar assembly is regulated by feedback and environmental processes remains unclear. I also discuss how these studies are being extended to locate and characterize the earlier sources beyond z~6. Did early star-forming galaxies contribute significantly to the reionization process and over what period did this occur? Neither theory nor observations are well-developed in this frontier topic but the first results presented here provide important guidance on how we will use more powerful future facilities.Comment: To appear in `First Light in Universe', Saas-Fee Advanced Course 36, Swiss Soc. Astrophys. Astron. in press. 115 pages, 64 figures (see http://www.astro.caltech.edu/~rse/saas-fee.pdf for hi-res figs.) For lecture ppt files see http://obswww.unige.ch/saas-fee/preannouncement/course_pres/overview_f.htm

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo