Treatment of Common Femoral Artery Lesions Involving the Superficial and Profunda Femoral Artery Bifurcation: Is the Snow Too Melted to Plow With New Endovascular Devices?

Surgical endarterectomy for common femoral artery bifurcation obstructive atherosclerotic disease repre- sents the "gold standard" therapy, with excellent long-term results and minimal complications. On the other hand, recent advances in endovascular therapy have led to a safer and similar effective results, with a potential reduction in hospital stays, quicker recovery to normal functional status, good short- and long-term clinical outcomes, and consequent lower morbidity and mortality. Percutaneous directional atherectomy and intravascular lithotripsy are game-changer medical devices for the treatment of peripheral arterial disease related to complex and severely calcific atherosclerotic plaque encroaching the common femoral artery bifurcation segment. The application of these devices, technical execution, and clinical experience is reported in two exemplary cases

Immunomodulating Therapies in Acute Myocarditis and Recurrent/Acute Pericarditis

The field of inflammatory disease of the heart or "cardio-immunology " is rapidly evolving due to the wider use of non-invasive diagnostic tools able to detect and monitor myocardial inflammation. In acute myocarditis, recent data on the use of immunomodulating therapies have been reported both in the setting of systemic autoimmune disorders and in the setting of isolated forms, especially in patients with specific histology (e.g., eosinophilic myocarditis) or with an arrhythmicburden. A role for immunosuppressive therapies has been also shown in severe cases of coronavirus disease 2019 (COVID-19), a condition that can be associated with cardiac injury and acute myocarditis. Furthermore, ongoing clinical trials are assessing the role of high dosage methylprednisolone in the context of acute myocarditis complicated by heart failure or fulminant presentation or the role of anakinra to treat patients with acute myocarditis excluding patients with hemodynamically unstable conditions. In addition, the explosion of immune-mediated therapies in oncology has introduced new pathophysiological entities, such as immune-checkpoint inhibitor-associated myocarditis and new basic research models to understand the interaction between the cardiac and immune systems. Here we provide a broad overview of evolving areas in cardio-immunology. We summarize the use of new imaging tools in combination with endomyocardial biopsy and laboratory parameters such as high sensitivity troponin to monitor the response to immunomodulating therapies based on recent evidence and clinical experience. Concerning pericarditis, the normal composition of pericardial fluid has been recently elucidated, allowing to assess the actual presence of inflammation; indeed, normal pericardial fluid is rich in nucleated cells, protein, albumin, LDH, at levels consistent with inflammatory exudates in other biological fluids. Importantly, recent findings showed how innate immunity plays a pivotal role in the pathogenesis of recurrent pericarditis with raised C-reactive protein, with inflammasome and IL-1 overproduction as drivers for systemic inflammatory response. In the era of tailored medicine, anti-IL-1 agents such as anakinra and rilonacept have been demonstrated highly effective in patients with recurrent pericarditis associated with an inflammatory phenotype.Peer reviewe

Bioformulação de Beauveria bassiana (ATCC MYA-4886) e Trichoderma lignorum (ATCC-8751) como biocontrolador de Atta cephalotes

I. The Leaf cutting Ant is associated with losses in the agricultural sector, for the most part in the cultivation of citrus fruit sector, due to its activity defoliator. Control of the species has been handmade, chemical and biologically, the latter with environmental benefits and low risk to human health. This research had as objective develop a formulation biological for the control of the Leaf cutting Ant (Atta cephalotes) using a mixture of spores of two fungi filamentous (Beauveria bassiana and Trichoderma lignorum). M. He was the isolation of Beauveria bassiana (ATCC MYA-4886) and Trichoderma lignorum (ATCC 8751), through cultivation YPDA and was conducted identifying fungal imprint and biochemical tests. Developing five formulations with ratios of 1:1, 6:4, 4:6, 3:7, 2:8 of Beauveria bassiana and Trichoderma lignorum respectively, they underwent the test of viability in nutrient agar, pathogenicity by immersion test and proof of purity; the tests were performed in triplicate. R. The formulations presented viability to 24 h 95% 2, 100% of the formulations were pure after 10 days, formulations 6.4, 1:1, 2:8 infected all of the individuals in 6 days, formulations 4:6 and 3:7-8 days of exposure. C. Formulations 6.4, 1:1, 2:8 of Beauveria bassiana and Trichoderma lignorium, present infectious activity on the Leaf cutting Ant (Atta cephalotes) in laboratory.I. La hormiga arriera está asociada a pérdidas en el sector agrícola, debido a su actividad defoliadora. El control de la especie se ha venido realizado artesanal, química y biológicamente, esta última con beneficios ambientales y de bajo riesgo para la salud humana. El objetivo de esta investigación fue desarrollar una formulación biológica para el control de la hormiga arriera (Atta cephalotes) utilizando una mezcla de esporas de dos hongos filamentosos (Beauveria bassiana y Trichoderma lignorum). M. Se desarrollaron 5 formulaciones empleando las relaciones: 1:1,6:4,4:6,3:7,2:8, de cepas de B. bassiana (ATCC MYA-4886) y T. lignorum (ATCC 8751), realizándoles prueba de viabilidad, patogenicidad y pureza. La colonización de las esporas en tejidos, se evaluó mediante la exposición de ratas Wistar a la formulación y sus componentes, realizando diagnóstico veterinario (disección) y cultivo microbiológico. R. Las formulaciones presentaron viabilidad a 24 h del 95+2 %, el 100% de las formulaciones no se contaminaron después de 10 días, las formulaciones 6.4, 1:1, 2:8 infectaron la totalidad de los individuos en 6 días, las formulaciones 4:6 y 3:7 a los 8 días, no se observó colonización de las cepas en la formulación, ni en tejidos de los biomodelos. C. Las formulaciones 6.4, 1:1, 2:8 de Beauveria bassiana y Trichoderma lignorum, poseen mayor actividad infecciosa sobre la hormiga arriera (Atta cephalotes). I. O formigueiro está associado a perdas no setor agrícola, devido à sua atividade desfolhadora. O controle das espécies tem sido realizado artesanalmente, quimicamente e biologicamente, este último com benefícios ambientais e baixo risco para a saúde humana. O objetivo desta pesquisa foi desenvolver uma formulação biológica para o controle de formigas (Atta cephalotes) usando uma mistura de esporos de dois fungos filamentosos (Beauveria bassiana e Trichoderma lignorum). M. 5 As formulações foram desenvolvidas usando a relação: 1: 1,6: 4,4: 6,3: 7,2: 8 estirpes de B. bassiana (ATCC MAA-4886) e T. lignorum (ATCC 8751), realizándoles Teste de viabilidade, patogenicidade e pureza. A colonização dos esporos nos tecidos foi avaliada pela exposição de ratos Wistar à formulação e seus componentes, realizando diagnóstico veterinário (dissecção) e cultura microbiológica. R. As formulações mostraram viabilidade em 24 h de 95 + 2%, 100% das formulações não foram contaminadas após 10 dias, as formulações 6,4, 1: 1, 2: 8 infectaram todos os indivíduos em 6 dias, as formulações 4: 6 e 3: 7 aos 8 dias, nenhuma colonização das cepas foi observada na formulação, nem nos tecidos dos biomodelos. C. As formulações 6.4, 1: 1, 2: 8 de Beauveria bassiana e Trichoderma lignorum, apresentam maior atividade infecciosa sobre os antirretera (Atta cephalotes)

Distribution of Exonic Variants in Glycogen Synthesis and Catabolism Genes in Late Onset Pompe Disease (LOPD)

Pompe disease (PD) is a monogenic autosomal recessive disorder caused by biallelic pathogenic variants of the GAA gene encoding lysosomal alpha-glucosidase; its loss causes glycogen storage in lysosomes, mainly in the muscular tissue. The genotype-phenotype correlation has been extensively discussed, and caution is recommended when interpreting the clinical significance of any mutation in a single patient. As there is no evidence that environmental factors can modulate the phenotype, the observed clinical variability in PD suggests that genetic variants other than pathogenic GAA mutations influence the mechanisms of muscle damage/repair and the overall clinical picture. Genes encoding proteins involved in glycogen synthesis and catabolism may represent excellent candidates as phenotypic modifiers of PD. The genes analyzed for glycogen synthesis included UGP2, glycogenin (GYG1-muscle, GYG2, and other tissues), glycogen synthase (GYS1-muscle and GYS2-liver), GBE1, EPM2A, NHLRC1, GSK3A, and GSK3B. The only enzyme involved in glycogen catabolism in lysosomes is alpha-glucosidase, which is encoded by GAA, while two cytoplasmic enzymes, phosphorylase (PYGB-brain, PGL-liver, and PYGM-muscle) and glycogen debranching (AGL) are needed to obtain glucose 1-phosphate or free glucose. Here, we report the potentially relevant variants in genes related to glycogen synthesis and catabolism, identified by whole exome sequencing in a group of 30 patients with late-onset Pompe disease (LOPD). In our exploratory analysis, we observed a reduced number of variants in the genes expressed in muscles versus the genes expressed in other tissues, but we did not find a single variant that strongly affected the phenotype. From our work, it also appears that the current clinical scores used in LOPD do not describe muscle impairment with enough qualitative/quantitative details to correlate it with genes that, even with a slightly reduced function due to genetic variants, impact the phenotype

Association of COVID-19 Vaccinations With Intensive Care Unit Admissions and Outcome of Critically Ill Patients With COVID-19 Pneumonia in Lombardy, Italy

IMPORTANCE Data on the association of COVID-19 vaccination with intensive care unit (ICU) admission and outcomes of patients with SARS-CoV-2-related pneumonia are scarce. OBJECTIVE To evaluate whether COVID-19 vaccination is associated with preventing ICU admission for COVID-19 pneumonia and to compare baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study on regional data sets reports: (1) daily number of administered vaccines and (2) data of all consecutive patients admitted to an ICU in Lombardy, Italy, from August 1 to December 15, 2021 (Delta variant predominant). Vaccinated patients received either mRNA vaccines (BNT162b2 or mRNA-1273) or adenoviral vector vaccines (ChAdOx1-S or Ad26.COV2). Incident rate ratios (IRRs) were computed from August 1, 2021, to January 31, 2022; ICU and baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU were analyzed from August 1 to December 15, 2021. EXPOSURES COVID-19 vaccination status (no vaccination, mRNA vaccine, adenoviral vector vaccine). MAIN OUTCOMES AND MEASURES The incidence IRR of ICU admission was evaluated, comparing vaccinated people with unvaccinated, adjusted for age and sex. The baseline characteristics at ICU admission of vaccinated and unvaccinated patients were investigated. The association between vaccination status at ICU admission and mortality at ICU and hospital discharge were also studied, adjusting for possible confounders. RESULTS Among the 10 107 674 inhabitants of Lombardy, Italy, at the time of this study, the median [IQR] agewas 48 [28-64] years and 5 154 914 (51.0%) were female. Of the 7 863 417 individuals who were vaccinated (median [IQR] age: 53 [33-68] years; 4 010 343 [51.4%] female), 6 251 417 (79.5%) received an mRNA vaccine, 550 439 (7.0%) received an adenoviral vector vaccine, and 1 061 561 (13.5%) received a mix of vaccines and 4 497 875 (57.2%) were boosted. Compared with unvaccinated people, IRR of individuals who received an mRNA vaccine within 120 days from the last dosewas 0.03 (95% CI, 0.03-0.04; P <.001), whereas IRR of individuals who received an adenoviral vector vaccine after 120 days was 0.21 (95% CI, 0.19-0.24; P <.001). There were 553 patients admitted to an ICU for COVID-19 pneumonia during the study period: 139 patients (25.1%) were vaccinated and 414 (74.9%) were unvaccinated. Compared with unvaccinated patients, vaccinated patients were older (median [IQR]: 72 [66-76] vs 60 [51-69] years; P <.001), primarily male individuals (110 patients [ 79.1%] vs 252 patients [60.9%]; P <.001), with more comorbidities (median [IQR]: 2 [1-3] vs 0 [0-1] comorbidities; P <.001) and had higher ratio of arterial partial pressure of oxygen (PaO2) and fraction of inspiratory oxygen (FiO(2)) at ICU admission (median [IQR]: 138 [100-180] vs 120 [90-158] mm Hg; P =.007). Factors associated with ICU and hospital mortality were higher age, premorbid heart disease, lower PaO2/FiO(2) at ICU admission, and female sex (this factor only for ICU mortality). ICU and hospital mortality were similar between vaccinated and unvaccinated patients. CONCLUSIONS AND RELEVANCE In this cohort study, mRNA and adenoviral vector vaccines were associated with significantly lower risk of ICU admission for COVID-19 pneumonia. ICU and hospital mortality were not associated with vaccinated status.These findings suggest a substantial reduction of the risk of developing COVID-19-related severe acute respiratory failure requiring ICU admission among vaccinated people

Decreasing hospital burden of COVID-19 during the first wave in Regione Lombardia: an emergency measures context

Abstract: Background: The aim of this study is to quantify the hospital burden of COVID-19 during the first wave and how it changed over calendar time; to interpret the results in light of the emergency measures introduced to manage the strain on secondary healthcare. Methods: This is a cohort study of hospitalised confirmed cases of COVID-19 admitted from February–June 2020 and followed up till 17th July 2020, analysed using a mixture multi-state model. All hospital patients with confirmed COVID-19 disease in Regione Lombardia were involved, admitted from February–June 2020, with non-missing hospital of admission and non-missing admission date. Results: The cohort consists of 40,550 patients hospitalised during the first wave. These patients had a median age of 69 (interquartile range 56–80) and were more likely to be men (60%) than women (40%). The hospital-fatality risk, averaged over all pathways through hospital, was 27.5% (95% CI 27.1–28.0%); and steadily decreased from 34.6% (32.5–36.6%) in February to 7.6% (6.3–10.6%) in June. Among surviving patients, median length of stay in hospital was 11.8 (11.6–12.3) days, compared to 8.1 (7.8–8.5) days in non-survivors. Averaged over final outcomes, median length of stay in hospital decreased from 21.4 (20.5–22.8) days in February to 5.2 (4.7–5.8) days in June. Conclusions: The hospital burden, in terms of both risks of poor outcomes and lengths of stay in hospital, has been demonstrated to have decreased over the months of the first wave, perhaps reflecting improved treatment and management of COVID-19 cases, as well as reduced burden as the first wave waned. The quantified burden allows for planning of hospital beds needed for current and future waves of SARS-CoV-2 i