Search for Gamma-Ray Spectral Lines from Dark Matter Annihilation up to 100 TeV toward the Galactic Center with MAGIC.

Linelike features in TeV γ rays constitute a "smoking gun" for TeV-scale particle dark matter and new physics. Probing the Galactic Center region with ground-based Cherenkov telescopes enables the search for TeV spectral features in immediate association with a dense dark matter reservoir at a sensitivity out of reach for satellite γ-ray detectors, and direct detection and collider experiments. We report on 223 hours of observations of the Galactic Center region with the MAGIC stereoscopic telescope system reaching γ-ray energies up to 100 TeV. We improved the sensitivity to spectral lines at high energies using large-zenith-angle observations and a novel background modeling method within a maximum-likelihood analysis in the energy domain. No linelike spectral feature is found in our analysis. Therefore, we constrain the cross section for dark matter annihilation into two photons to ⟨σv⟩≲5×10^{-28} cm^{3} s^{-1} at 1 TeV and ⟨σv⟩≲1×10^{-25} cm^{3} s^{-1} at 100 TeV, achieving the best limits to date for a dark matter mass above 20 TeV and a cuspy dark matter profile at the Galactic Center. Finally, we use the derived limits for both cuspy and cored dark matter profiles to constrain supersymmetric wino models.

Bounds on Lorentz Invariance Violation from MAGIC Observation of GRB 190114C.

On January 14, 2019, the Major Atmospheric Gamma Imaging Cherenkov telescopes detected GRB 190114C above 0.2 TeV, recording the most energetic photons ever observed from a gamma-ray burst. We use this unique observation to probe an energy dependence of the speed of light in vacuo for photons as predicted by several quantum gravity models. Based on a set of assumptions on the possible intrinsic spectral and temporal evolution, we obtain competitive lower limits on the quadratic leading order of speed of light modification.

From the bench to practice - Field integration of community-based services for older citizens with different levels of functional limitation across European Regions.

The meeting of the European Innovation Partnership on Active and Healthy Ageing (EIPonAHA) action group A3 together with members of the Reference site collaborative network (RSCN) in December 2019 in Rome focused on integration of evidence-based approaches on health and care delivery for older citizens at different levels of needs with expertise coming from stakeholder across Europe. It was the final aim of the group to co-create culturally sensitive pathways and facilitate co-ownership for further implementation of the pathways in different care systems across Europe. The study design is a mixed method approach. Based on data analysis from a cohort of community-dwelling over-65 citizens in the framework of a longitudinal observational study in Rome, which included health, social and functional capacity data, three personas profiles were developed: the pre-frail, the frail and the very frail personas. Based on these data, experts were asked to co-create care pathways due to evidence and eminence during a workshop and included into a final report. All working groups agreed on a common understanding that integration of care means person-centered integration of health and social care, longitudinally provided across primary and secondary health care including citizens' individual social, economic and human resources. Elements for consideration during care for pre-frail people are loneliness and social isolation, which, lead to limitation of physical autonomy in the light of reduced access to social support. Frail people need adaption of environmental structures and, again, social resource allocation to maintain at home. Very frail are generally vulnerable patients with complex needs. Most of them remain at home because of a strong individual social support and integrated health care delivery. The approach described in this publication may represent a first approach to scaling-up care delivery in a person-centered approach.

Associations between the presence of specific antibodies to the West Nile Virus infection and candidate genes in Romanian horses from the Danube delta.

The West Nile virus (WNV) is a mosquito-borne flavivirus causing meningoencephalitis in humans and animals. Due to their particular susceptibility to WNV infection, horses serve as a sentinel species. In a population of Romanian semi-feral horses living in the Danube delta region, we have analyzed the distribution of candidate polymorphic genetic markers between anti WNV-IgG seropositive and seronegative horses. Thirty-six SNPs located in 28 immunity-related genes and 26 microsatellites located in the MHC and LY49 complex genomic regions were genotyped in 57 seropositive and 32 seronegative horses. The most significant association (pcorr < 0.0002) was found for genotypes composed of markers of the SLC11A1 and TLR4 genes. Markers of five other candidate genes (ADAM17, CXCR3, IL12A, MAVS, TNFA), along with 5 MHC class I and LY49-linked microsatellites were also associated with the WNV antibody status in this model horse population. The OAS1 gene, previously associated with WNV-induced clinical disease, was not associated with the presence of anti-WNV antibodies.

DNA mixtures interpretation - A proof-of-concept multi-software comparison highlighting different probabilistic methods' performances on challenging samples.

The present study investigated the capabilities and performances of semi-continuous and fully-continuous probabilistic approaches to DNA mixtures interpretation, particularly when dealing with Low-Template DNA mixtures. Five statistical interpretation software, such as Lab Retriever and LRmix Studio - involving semi-continuous algorithms - and DNA•VIEW®, EuroForMix and STRmixTM- employing fully-continuous formulae - were employed to calculate likelihood ratio, comparing the prosecution and the defense hypotheses relative to a series of on-purpose prepared DNA mixtures that respectively contained 2 and 3 known contributors. National Institute of Standards and Technologies (NIST) certified templates were used for samples set up, which contained different DNA amounts for each contributor. 2-person mixtures have been prepared with proportions equal to 1:1, 19:1 and 1:19 in terms of DNA concentration. Conversely, three person mixtures were constituted by proportions equal to 20:9:1, 8:1:1, 6:3:1 and 1:1:1 in terms of DNA concentration. Furthermore, 8 equally-proportioned 3-person mixtures were prepared by means of scalar dilutions starting from an overall amount of 0.500 ng, then ranging up to DNA samples with concentrations equal to 0.004 ng (i.e. Low-Template DNA). DNA mixtures were set up in triplicate and amplified with 7 DNA amplification kits (i.e. GlobalFiler PCR Amplification Kit, NGM SElect PCR Amplification Kit, MiniFiler PCR Amplification Kit, Power Plex Fusion, PowerPlex 6C Matrix System, Power Plex ESI 17 Fast and Power Plex ESX 17 Fast) in order to evaluate whether the selection of a certain kit might represent a bias factor, capable of altering the whole interpretation process. A multi-software approach helped us to highlight any trend in the likelihood ratio results provided by semi- and fully-continuous software. As a matter of fact, fully-continuous computations provided different (higher) results in terms of degrees of magnitude of the likelihood ratio values with respect to those from the semi-continuous approach, regardless of the amplification kit that was utilized.

Redescription of the adult stages of Ixodes (Afrixodes) rasus Neumann 1899, with notes on its phylogenetic position within the genus Ixodes.

The tick subgenus Afrixodes Morel 1966 (Ixodidae) is distributed in sub-Saharan Africa. It consists of about 60 species which are described based on a few specimens and/or only some developmental stages, mostly adults. Because of this, the diagnosis of the African species of Ixodes is in many aspects complicated. Ixodes rasus Neumann 1899 is a common species, widely distributed in tropical and subtropical moist broadleaved forests in central Africa, whose morphology remains poorly described. We redescribe the adults of the species and provide molecular data for 16S rDNA based on three questing females and one male collected in the Central African Republic. Both sexes have an anal groove rounded and closed. The female has syncoxae on coxae I to III, a dental formula of 2/2, and long, curved auriculae. The male has moderate syncoxae on coxae I-III, coxae I-II carry one single internal spur each: coxae III and IV unarmed. The cornua are absent in the male, and the auriculae are small lobes. The male pregenital plate is longer than broad, with an anterior margin widely rounded; the median plate is large and clearly divergent posteriorly, with adanal plates fused posteriorly to the anus, and a dental formula of 4/4 (one row of 5/5). The molecular features of 16S rDNA place I. rasus near I. aulacodi (the only other Afrixodes species for which 16S rDNA is available) and near I. turdus and I. frontalis; two species of ticks of the Palearctic region, which commonly infest birds. The paucity of data regarding the subgenus Afrixodes makes it necessary to provide reliable and comparable re-descriptions of several species, as well as description of the immature stages for many of the currently known taxa.

Quantum test of the equivalence principle for atoms in coherent superposition of internal energy states.

The Einstein equivalence principle (EEP) has a central role in the understanding of gravity and space-time. In its weak form, or weak equivalence principle (WEP), it directly implies equivalence between inertial and gravitational mass. Verifying this principle in a regime where the relevant properties of the test body must be described by quantum theory has profound implications. Here we report on a novel WEP test for atoms: a Bragg atom interferometer in a gravity gradiometer configuration compares the free fall of rubidium atoms prepared in two hyperfine states and in their coherent superposition. The use of the superposition state allows testing genuine quantum aspects of EEP with no classical analogue, which have remained completely unexplored so far. In addition, we measure the Eötvös ratio of atoms in two hyperfine levels with relative uncertainty in the low 10-9, improving previous results by almost two orders of magnitude.

Diversity of Flea (Siphonaptera) Parasites on Red Foxes (Vulpes vulpes) in Romania.

Red foxes (Vulpes vulpes (L.)) are widespread across Europe, tolerant of synanthropic ecosystems, and susceptible to diseases potentially shared with humans and other animals. We describe flea fauna on red foxes in Romania, a large, ecologically diverse country, in part because fleas may serve as an indicator of the risk of spillover of vector-borne disease. We found 912 individual fleas of seven species on the 305 foxes assessed, for an infestation prevalence of 49.5%. Mean flea load per fox was 5.8 (range 0-44 fleas), and flea detections were most abundant in fall and early spring. Fleas included generalists (Ctenocephalides canis (Curtis), 32.6% of all fleas), Ct. felis (Bouché, 0.1%), and Pulex irritans L. (29.9%), the fox specialist Chaetopsylla globiceps (Taschenberg, 32.5%), mesocarnivore fleas Paraceras melis Walker (3.2%) and Ch. trichosa Kohaut (1.5%), and the small mammal flea Ctenophthalmus assimilis (Taschenberg, 0.1%), which is rarely or never reported from carnivores. There were significantly more female than male Ch. globiceps, Ct. canis, and Pu. irritans, and these three species were the most broadly distributed geographically. Diversity indices suggested reduced diversity in mountainous areas above 700 m. When compared to other flea studies on foxes in Europe, Romania had flea diversity near the median of reports, which was unexpected given Romania's high ecological diversity. Notably absent prey specialists, compared to other studies, include Archaeopsylla erinacei (Bouché) and Spilopsyllus cuniculi (Dale). Further studies of possible disease agents in fox fleas could help elucidate possible risks of vector-borne disease in foxes, domestic animals, and humans as well.

A comparative test of ixodid tick identification by a network of European researchers.

This study reports the results of a comparative test of identification of ticks occurring in Western Europe and Northern Africa. A total of 14 laboratories were voluntarily enrolled in the test. Each participant received between 22 and 25 specimens of adult and nymphal ticks of 11 species: Dermacentor marginatus, D. reticulatus, Haemaphysalis punctata, Hyalomma lusitanicum, Hy. marginatum, Ixodes ricinus, I. hexagonus, Rhipicephalus annulatus, R. bursa, R. rossicus, and/or R. sanguineus s.l. Ticks were morphologically identified by three of the co-authors and the identification confirmed by a fourth co-author who used molecular methods based on several genes. Then ticks were randomly selected and blindly distributed among participants, together with a questionnaire. Only specimens collected while questing and, if possible, in the same survey, were circulated. Because of the random nature of the test, a participant could receive several specimens of the same species. Species in the different genera had variable misidentification rates (MR) of 7% (Dermacentor), 14% (Ixodes), 19% (Haemaphysalis), 36% (Hyalomma), and 54% (Rhipicephalus). Within genera, the MR was also variable ranging from 5.4% for I. ricinus or 7.4% for D. marginatus or D. reticulatus to 100% for R. rossicus. The test provided a total misidentification rate of 29.6% of the species of ticks. There are no significant differences in MR according to the sex of the tick. Participants were requested to perform a second round of identifications on the same set of ticks, using only purposely prepared keys (without illustrations), circulated to the enrolled participants, including 2 species of the genus Dermacentor, 8 of Haemaphysalis, 10 of Hyalomma, 23 of Ixodes, and 6 of Rhipicephalus. The average MR in the second round was 28%: 0% (Dermacentor), 33% (Haemaphysalis), 30% (Hyalomma) 18% (Ixodes), and 50% (Rhipicephalus). Species which are not reported in the countries of a participating laboratory had always highest MR, i.e. purely Mediterranean species had highest MR by laboratories in Central and Northern Europe. Participants expressed their concerns about a correct identification for almost 50% of the ticks of the genera Hyalomma and Rhipicephalus. The results revealed less than total confidence in identifying the most prominent species of ticks in the Western Palearctic, and underpin the need for reference libraries for specialists involved in this task. Results also showed that a combination of certain genes may adequately identify the target species of ticks.

Neonatal Anaplasma platys infection in puppies: Further evidence for possible vertical transmission.

Anaplasma platys, the aetiological agent of infectious canine cyclic thrombocytopaenia, infects platelets of dogs, usually causing mild or asymptomatic disease. Although A. platys is transmitted by ticks, as for other Anaplasma species, alternative modes of transmission may be involved. The aim of the present study was to evaluate the occurrence of A. platys infection in litters of puppies, which could suggest possible vertical transmission. Twelve litters, together with the respective bitches, were included in the study for the detection of A. platys DNA by PCR, followed by sequencing. Five puppies, from 2/4 litters <28 days of age, tested positive for A. platys DNA. No puppies from eight litters 1-3 months of age tested positive for A. platys DNA. The identical sequences (16S rRNA and gltA partial gene), the absence of ticks on puppies at the time of collection and the young age of the five infected puppies suggest vertical transmission of A. platys. This mode of transmission might contribute to the maintenance and spread of the pathogen in canine populations.

Canceling the Gravity Gradient Phase Shift in Atom Interferometry.

Gravity gradients represent a major obstacle in high-precision measurements by atom interferometry. Controlling their effects to the required stability and accuracy imposes very stringent requirements on the relative positioning of freely falling atomic clouds, as in the case of precise tests of Einstein's equivalence principle. We demonstrate a new method to exactly compensate the effects introduced by gravity gradients in a Raman-pulse atom interferometer. By shifting the frequency of the Raman lasers during the central π pulse, it is possible to cancel the initial position- and velocity-dependent phase shift produced by gravity gradients. We apply this technique to simultaneous interferometers positioned along the vertical direction and demonstrate a new method for measuring local gravity gradients that does not require precise knowledge of the relative position between the atomic clouds. Based on this method, we also propose an improved scheme to determine the Newtonian gravitational constant G towards the 10 ppm relative uncertainty.

Occurrence of ticks in the subcutaneous tissue of red foxes, Vulpes vulpes in Czech Republic and Romania.

An extensive survey of parasites in red foxes (Vulpes vulpes) was independently conducted in Romania and the Czech Republic. Carcasses were examined by necropsy, and small, dark nodules apparently containing ticks were noticed in the subcutaneous tissue of several foxes. Histopathological examination was performed using hematoxylin and eosin (HE) staining. Of the 91 foxes examined from the Czech Republic, 14 (15.4%) were harboring ticks in the subcutaneous tissue. In the majority of these cases, 1-3 nodules/fox were found, with a maximum of 31 nodules/fox. In Romania a single examined fox had subcutaneous ticks. All ticks collected from subcutaneous tissue were partially engorged adults. Based on morphological features, Ixodes ricinus, I. hexagonus, I. crenulatus and Dermacentor reticulatus were identified. The histopathological examination revealed chronic granulomatous panniculitis with peripheral fibrosis and intralesional presence of the ticks. Only few data are available regarding ticks localized in the subcutaneous tissue of any host. All the ticks were dead or already decomposed and it is evident that subcutaneous location does not represent an evolutionary advantage, as the detachment and finishing the life cycle is impossible.

Identification of a novel agrin-dependent pathway in cell signaling and adhesion within the erythroid niche.

Establishment of cell-cell adhesion is crucial in embryonic development as well as within the stem cell niches of an adult. Adhesion between macrophages and erythroblasts is required for the formation of erythroblastic islands, specialized niches where erythroblasts proliferate and differentiate to produce red blood cells throughout life. The Eph family is the largest known family of receptor tyrosine kinases (RTKs) and controls cell adhesion, migration, invasion and morphology by modulating integrin and adhesion molecule activity and by modifying the actin cytoskeleton. Here, we identify the proteoglycan agrin as a novel regulator of Eph receptor signaling and characterize a novel mechanism controlling cell-cell adhesion and red cell development within the erythroid niche. We demonstrate that agrin induces clustering and activation of EphB1 receptors on developing erythroblasts, leading to the activation of α5ß1 integrins. In agreement, agrin knockout mice display severe anemia owing to defective adhesion to macrophages and impaired maturation of erythroid cells. These results position agrin-EphB1 as a novel key signaling couple regulating cell adhesion and erythropoiesis.

Mouse mesenchymal stem cells inhibit high endothelial cell activation and lymphocyte homing to lymph nodes by releasing TIMP-1.

Mesenchymal stem cells (MSC) represent a promising therapeutic approach in many diseases in view of their potent immunomodulatory properties, which are only partially understood. Here, we show that the endothelium is a specific and key target of MSC during immunity and inflammation. In mice, MSC inhibit activation and proliferation of endothelial cells in remote inflamed lymph nodes (LNs), affect elongation and arborization of high endothelial venules (HEVs) and inhibit T-cell homing. The proteomic analysis of the MSC secretome identified the tissue inhibitor of metalloproteinase-1 (TIMP-1) as a potential effector molecule responsible for the anti-angiogenic properties of MSC. Both in vitro and in vivo, TIMP-1 activity is responsible for the anti-angiogenic effects of MSC, and increasing TIMP-1 concentrations delivered by an Adeno Associated Virus (AAV) vector recapitulates the effects of MSC transplantation on draining LNs. Thus, this study discovers a new and highly efficient general mechanism through which MSC tune down immunity and inflammation, identifies TIMP-1 as a novel biomarker of MSC-based therapy and opens the gate to new therapeutic approaches of inflammatory diseases.

A novel and personalized rehabilitation program for obese kidney transplant recipients.

INTRODUCTION: Physical rehabilitation programs for kidney transplant recipients are not routinely personalized to patients' physical and emotional health, which could result in a potentially limited health impact, shorter-term participation, and an overall low success rate. MATERIALS AND METHODS: We conducted an internal review board-approved randomized prospective study involving a 12-month supervised multidisciplinary rehabilitation program (GH method) initiated after kidney transplantation in obese recipients (body mass index >30). The new method incorporates 3 major components: physical exercise, behavioral interventions, and nutritional guidance. We compared 9 patients who underwent supervised rehabilitation with 8 patients who underwent standard care. Patients were followed up after the start of the intervention, and multiple assessments were performed. RESULTS: The adherence to training and follow-up was 100% in the intervention group, compared with 25% at 12 months in the control group. There was a trend for a higher glomerular filtration rate in the intervention group compared with the control group (55.5 ± 18.6 mL/min/1.73 m(2) vs 38.8 ± 18.9 mL/min/1.73 m(2), P = .06). The quality of life (SF-36) mean score improved more in the intervention group compared with the control group (583 ± 13 vs 436 ± 22, P = .008). There was a significantly higher employment rate in the intervention group, 77.7% at 12 months compared with 12.5% in the control group (P = .02). CONCLUSIONS: Our preliminary results suggest that this comprehensive approach to physical rehabilitation can improve adherence, kidney function, quality of life, and employment rate for obese patients after kidney transplantation.

High rate of unemployment after kidney transplantation: analysis of the United network for organ sharing database.

INTRODUCTION: Despite an increased quality of life after transplant, in the United States, recipients participate less in employment compared to the general population. Employment after kidney transplantation is an important marker of clinically significant individual health recovery. Furthermore, it has been shown that employment status in the post-transplant period has a strong and independent association with patient and graft survival. MATERIALS AND METHODS: Using the United Network for Organ Sharing (UNOS) database, we identified all adults (between 18 and 64 years of age) who underwent kidney transplantation between 2004 and 2011. Patients with a stable renal allograft function and with full 1-, 3-, and 5-year follow-up were included. For recipients of multiple transplants, the most recent transplant was considered the target transplant. The data collected included employment rate after kidney transplantation in recipients employed and unemployed before transplant. The employment data were stratified for insurance payer (private, Medicaid, and Medicare). The results of categorical variables are reported as percentages. Comparisons between groups for categorical data were performed using the χ(2) test with Yates continuity correction or Fisher test when appropriate. RESULTS: The UNOS database available for this study included a total of 100,521 patients. The employment rate at the time of transplant was 23.1% (n = 23,225) under private insurance and 10% (n = 10,032) under public insurance (Medicaid and Medicare, P < .01, compared to private insurance). Over a total of 29,809 recipients analyzed, alive and with stable renal allograft function who were working at time of transplantation, the employment rate was 47% (n = 14,010), 44% (n = 13,115), and 43% (n = 12,817) at 1, 3, and 5 years after transplant under private insurance and 16% (n = 4769), 14% (n = 4173), and 12% (n = 3567), respectively, under public insurance (P < .01, compared to private insurance). Over a total of 46,363 recipients alive and with stable renal function who were not working at time of transplant, the employment rate was 5.3% (n = 2457), 5.6% (n = 2596), and 6.2% (n = 2874) at 1, 3, and 5 years after transplant under private insurance and 6.5% (n = 3013), 7.8% (n = 3616), and 7.5% (n = 3477), respectively, under public insurance (P < .01, compared to private insurance). CONCLUSION: The employment rates at the time of transplant in the United States are generally low, although privately insured patients are significantly more likely than patient with public insurance to have employment. Only a portion of these patients returns to work after transplantation. For the patients unemployed at the time of transplantation, the chance to find a job afterward is quite low even in privately insured patients. A concerted effort should be made by the transplant community to improve the ability of successful kidney transplant recipients to return to work or find a new employment. It had been shown that employment status in the post-transplant period has a strong and independent association with the graft and recipient survival.

External vs. endonasal dacryocystorhinostomy: has the current view changed?

In past years, external dacryocystorhinostomy has been considered the gold standard in terms of functional outcome for treatment for nasolacrimal duct obstruction. In comparison, interest in the use of the recently developed endonasal dacyocystorhinostomy procedure has been rekindled because of advances in instrumentation. For the past 10 years, differences in the outcomes between the two techniques have been reduced; thus, currently, the choice of the type of surgery is associated with the experience of the surgeon, resources available in the healthcare system and patient preferences.

Competing risks and prognostic stages of cirrhosis: a 25-year inception cohort study of 494 patients.

BACKGROUND: Morphological, haemodynamic and clinical stages of cirrhosis have been proposed, although no definite staging system is yet accepted for clinical practice. AIM: To investigate whether clinical complications of cirrhosis may define different prognostic disease stages. METHODS: Analysis of the database from a prospective inception cohort of 494 patients. Decompensation was defined by ascites, bleeding, jaundice or encephalopathy. Explored potential prognostic stages: 1, compensated cirrhosis without oesophago-gastric varices; 2, compensated cirrhosis with varices; 3, bleeding without other complications; 4, first nonbleeding decompensation; 5, any second decompensating event. Patient flow across stages was assessed by a competing risks analysis. RESULTS: Major patient characteristics were: 199 females, 295 males, 404 HCV+, 377 compensated, 117 decompensated cirrhosis. The mean follow-up was 145 ± 109 months without dropouts. Major events: 380 deaths, 326 oesophago-gastric varices, 283 ascites, 158 bleeding, 146 encephalopathy, 113 jaundice, 126 hepatocellular carcinoma and 19 liver transplantation. Patients entering each prognostic stage along the disease course were: 202, stage 1; 216, stage 2; 75 stage 3; 206 stage 4; 213 stage 5. Five-year transition rate towards a different stage, for stages 1-4 was 34.5%, 42%, 65% and 78%, respectively (P < 0.0001); 5-year mortality for stages 1-5 was 1.5%, 10%, 20%, 30% and 88% respectively (P < 0.0001). An exploratory analysis showed that this patient stratification may configure a prognostic system independent of the Child-Pugh score, Model for End Stage Liver Disease and comorbidity. CONCLUSION: The development of oesophago-gastric varices and decompensating events in cirrhosis identify five prognostic stages with significantly increasing mortality risks.

Impact of drug-eluting stent generation on patient- and stent-related adverse events of diabetic patients treated by percutaneous coronary intervention.

AIM: Aim of the present study was to assess stent- and patient-related outcomes of the first- vs. second-generation drug-eluting stents (DES) in diabetics, according to the insulin requirement status. METHODS: Data were obtained from a prospective, single-center registry of 816 consecutive patients with diabetes mellitus (23% insulin-requiring) who underwent percutaneous coronary intervention (PCI) between April 2003 and May 2012 with first- (N.=534) or second-generation DES (N.=282) at our Institution, with at least 12 months of follow-up. We assessed the occurrence of stent-related outcome, including cardiac death, target vessel-related myocardial infarction and target lesion revascularization, versus patient-related outcome, including any cause death, any myocardial infarction and any coronary revascularization. RESULTS: Patients treated with second-generation DES were older and had more complex lesions than patients treated with first-generation DES. Both among patients treated with first-generation DES and those treated with second generation DES, patient-related events were almost double than stent-related events. No interactions were observed between the DES generation type and insulin requirement status. CONCLUSION: In this observational study, first- and second-generation DES were equally safe and efficacious in diabetic patients undergoing PCI, regardless of insulin requirements. The greater number of patient-related than stent-related events in patients with complex clinical and lesion characteristics emphasizes that the optimization of secondary prevention is at least as important as the selection of which new generation DES to implant in a specific lesion.

Systematic review with meta-analysis: the haemodynamic effects of carvedilol compared with propranolol for portal hypertension in cirrhosis.

BACKGROUND: Propranolol is recommended for prophylaxis of variceal bleeding in cirrhosis. Carvedilol is a nonselective beta-blocker with a mild anti-alfa-1-adrenergic activity. Several studies have compared carvedilol and propranolol, yielding inconsistent results. AIM: To perform a systematic review and meta-analysis of the randomised clinical trials comparing carvedilol with propranolol for hepatic vein pressure gradient reduction. METHODS: Studies were searched on the MEDLINE, EMBASE and Cochrane library databases up to November 2013. The weighted mean difference in percent hepatic vein pressure gradient reduction and the relative risk of failure to achieve a hemodynamic response (reduction ≥20% of baseline or to ≤12 mmHg) with each drug were used as measures of treatment efficacy. RESULTS: Five studies (175 patients) were included. Indication to treatment was primary prophylaxis of variceal bleeding in 76% of patients. There were overall three acute (60-90 min after drug administration) and three long-term (after 7-90 days of therapy) comparisons. The summary mean weighted difference in % of reduction in hepatic vein pressure gradient was: acute -7.70 (CI -12.40, -3.00), long-term -6.81 (CI -11.35, -2.26), overall -7.24 (CI -10.50, -3.97), favouring carvedilol. The summary relative risk of failure to achieve a hemodynamic response with carvedilol was 0.66 (CI 0.44, 1.00). Adverse events were nonsignificantly more frequent and serious with carvedilol. However, quality of trials was mostly unsatisfactory. CONCLUSIONS: Carvedilol reduces portal hypertension significantly more than propranolol. However, available data do not allow a satisfactory comparison of adverse events. These results suggest a potential for a cautious clinical use.