Pneumocystis pneumonia in HIV-negative immunocompromised patients in Internal Medicine ward

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection typically observed in AIDS patients, for whom it represents a leading cause of death. However, its incidence among HIV-negative immunocompromised patients is progressively increasing, with a significantly higher mortality compared to that of AIDS-patients. We performed a retrospective observational study on HIV-negative patients with PJP. We aimed to determine their epidemiological features and their biohumoral and therapeutic variables, searching for a correlation between them and our patients' outcome. We included all patients admitted to our Internal Medicine ward from January 2010 to June 2015, who were immunocompromised at the time of admission and had microbiologically confirmed PJP (association between compatible clinical-radiological findings and qualitative polymerase chain reaction positivity on bronchoalveolar lavage). Their immune impairment was assessed considering both their medical history and their complete white blood cells (WBC), differential WBC and their CD4 cell count. Transfer to Intensive Care Unit (ICU) or death was considered as an unfavorable clinical outcome, while hospital discharge or transfer to a non-ICU ward was considered as a favorable outcome. We included a total of 18 patients in our statistical analysis. We used Student's t-test and Fischer's χ-square test to compare, respectively, normally distributed continuous variables and non-continuous variables. Our patients' mean age was 65±13.9 years. All of them had cancer, mostly hematological malignancies (13/18), notably non-Hodgkin lymphoma (NHL; 8/13). They were all being or had been recently treated with chemotherapy (10/18) and/or high-dose glucocorticoids, with full dose or during tapering (13/18). Statistical analysis of blood tests results showed a significant difference between mean serum lactate dehydrogenase (LDH) concentration in the group of patients with favorable vs unfavorable outcome. Also, mean serum immunoglobulins G (IgG) concentration and certain arterial blood gas findings (mean arterial paO2/FiO2, mean blood Ph and mean paCO2) at the time of admission were significantly different in the two groups of patients. 12/18 patient's outcome turned out unfavorable. Trimethoprim + sulfamethoxazole (TMP+SMX) treatment was given to all our patients, with a mean duration of 13.39±9.36 days. Patients with a favorable outcome had received TMP+SMX treatment significantly earlier than those with an unfavorable outcome. Hematological malignancies, according to literature, confer the strongest predisposition to PJP. Both chemotherapy and high-dose Glucocorticoid treatment are well known predisposing factors. A remarkable elevation of serum LDH represents both a typical clinical feature and a well-known negative prognostic factor in PJP. Low IgG levels have never been reported as a negative prognostic factor, but their role in enhancing macrophage killing of pneumocystis may account for the worst observed prognosis in the group of patients with lower mean levels. Therefore, in order to reduce the heavy mortality rate associated with PJP, an early beginning of specific treatment is of utmost importance, and even if this is certainly true for many infectious diseases, the time gap is particularly limited in the setting of this type of pneumonia. Hence, PJP should be ruled out as soon as possible and, in case of a strong clinical- radiological suspicion, therapy should be started immediately, even while waiting for microbiological confirmation (especially in critically-ill patients)

Exploring Cosmic Origins with CORE: Cosmological Parameters

We forecast the main cosmological parameter constraints achievable with theCORE space mission which is dedicated to mapping the polarisation of the CosmicMicrowave Background (CMB). CORE was recently submitted in response to ESA'sfifth call for medium-sized mission proposals (M5). Here we report the resultsfrom our pre-submission study of the impact of various instrumental options, inparticular the telescope size and sensitivity level, and review the great,transformative potential of the mission as proposed. Specifically, we assessthe impact on a broad range of fundamental parameters of our Universe as afunction of the expected CMB characteristics, with other papers in the seriesfocusing on controlling astrophysical and instrumental residual systematics. Inthis paper, we assume that only a few central CORE frequency channels areusable for our purpose, all others being devoted to the cleaning ofastrophysical contaminants. On the theoretical side, we assume LCDM as ourgeneral framework and quantify the improvement provided by CORE over thecurrent constraints from the Planck 2015 release. We also study the jointsensitivity of CORE and of future Baryon Acoustic Oscillation and Large ScaleStructure experiments like DESI and Euclid. Specific constraints on the physicsof inflation are presented in another paper of the series. In addition to thesix parameters of the base LCDM, which describe the matter content of aspatially flat universe with adiabatic and scalar primordial fluctuations frominflation, we derive the precision achievable on parameters like thosedescribing curvature, neutrino physics, extra light relics, primordial heliumabundance, dark matter annihilation, recombination physics, variation offundamental constants, dark energy, modified gravity, reionization and cosmicbirefringence. (ABRIDGED

Planck Intermediate Results. XXXVI. Optical identification and redshifts of Planck SZ sources with telescopes at the Canary Islands Observatories

We present the results of approximately three years of observations of Planck Sunyaev-Zeldovich (SZ) sources with telescopes at the Canary Islands observatories as part of the general optical follow-up programme undertaken by the Planck collaboration. In total, 78 SZ sources are discussed. Deep-imaging observations were obtained for most of these sources; spectroscopic observations in either in long-slit or multi-object modes were obtained for many. We effectively used 37.5 clear nights. We found optical counterparts for 73 of the 78 candidates. This sample includes 53 spectroscopic redshift determinations, 20 of them obtained with a multi-object spectroscopic mode. The sample contains new redshifts for 27 Planck clusters that were not included in the first Planck SZ source catalogue (PSZ1).Comment: 15 pages, 14 figures, accepted for publication in A&

VizieR Online Data Catalog: Planck Sunyaev-Zeldovich sources (PSZ2) (Planck+, 2016)

Three pipelines are used to detect SZ clusters: two independent implementations of the Matched Multi-Filter (MMF1 and MMF3), and PowellSnakes (PwS). The main catalogue is constructed as the union of the catalogues from the three detection methods. The completeness and reliability of the catalogues have been assessed through internal and external validation as described in section 4 of the paper. (5 data files)

The modal condition of Sensitivity in Robert Nozick’s epistemology: themes and problems

openIl contributo più celebre di Robert Nozick all’epistemologia consiste nella clausola modale di Sensibilità, che si serve dei controfattuali nel distinguere casi di conoscenza da casi di semplice credenza vera. Nel presente lavoro propongo un’analisi di questa teoria, valutandone punti di forza e criticità e selezionando alcuni contributi notevoli nel panorama contemporaneo. Partendo da una sua contestualizzazione nel dibattito precedente, esporrò la teoria ricostruendo le argomentazioni dello stesso Nozick. Successivamente mi soffermerò sul rapporto fra Sensibilità e scetticismo, nel quale emerge il rifiuto del principio di chiusura, un tema controverso che sfida il senso comune. Infine mi dedicherò all’esposizione di ulteriori criticità della teoria, facendo appello ad alcuni controesempi e confrontandola con la nozione di Sicurezza, una forte alternativa proposta da Duncan Pritchard.Robert Nozick's most renowned contribution to epistemology lies in the modal principle of Sensitivity, which employs counterfactuals to distinguish cases of knowledge from cases of mere true belief. In this present work, I offer an analysis of this theory, evaluating its strengths and critical issues and highlighting significant contributions in the contemporary debate. Beginning with its contextualization in the previous debate, I will present the theory by reconstructing Nozick's arguments. Subsequently, I will explain the relationship between Sensitivity and skepticism, where the rejection of the closure principle emerges as a controversial theme, challenging common sense. Finally, I will address additional problems of the theory, invoking some counterexamples and comparing it to the notion of Safety, a robust alternative proposed by Duncan Pritchard

Laboratory and Metabolomic Fingerprint in Heart Failure with Preserved Ejection Fraction: From Clinical Classification to Biomarker Signature

Heart failure with preserved ejection fraction (HFpEF) remains a poorly characterized syndrome with many unknown aspects related to different patient profiles, various associated risk factors and a wide range of aetiologies. It comprises several pathophysiological pathways, such as endothelial dysfunction, myocardial fibrosis, extracellular matrix deposition and intense inflammatory system activation. Until now, HFpEF has only been described with regard to clinical features and its most commonly associated risk factors, disregarding all biological mechanisms responsible for cardiovascular deteriorations. Recently, innovations in laboratory and metabolomic findings have shown that HFpEF appears to be strictly related to specific cells and molecular mechanisms’ dysregulation. Indeed, some biomarkers are efficient in early identification of these processes, adding new insights into diagnosis and risk stratification. Moreover, recent advances in intermediate metabolites provide relevant information on intrinsic cellular and energetic substrate alterations. Therefore, a systematic combination of clinical imaging and laboratory findings may lead to a ‘precision medicine’ approach providing prognostic and therapeutic advantages. The current review reports traditional and emerging biomarkers in HFpEF and it purposes a new diagnostic approach based on integrative information achieved from risk factor burden, hemodynamic dysfunction and biomarkers’ signature partnership

Risk Factors and Cellular Differences in Heart Failure: The Key Role of Sex Hormones

Patients with heart failure are conventionally stratified into phenotypic groups based on their ejection fraction. The aim of this stratification is to improve disease management with a more targeted therapeutic approach. A further subdivision based on patient gender is justified. It is recognized that women are underrepresented in randomized controlled clinical trials, resulting in limited clinical and molecular differentiation between males and females. However, many observational studies show that the onset, development, and clinical course of the disease may substantially differ between the two sexes. According to the emerging concept of precision medicine, investigators should further explore the mechanisms responsible for the onset of heart failure due to sex differences. Indeed, the synergistic or opposing effects of sex hormones on the cardiovascular system and underlying heart failure mechanisms have not yet been clarified. Sex hormones, risk factors impact, and cardiovascular adaptations may be relevant for a better understanding of the intrinsic pathophysiological mechanisms in the two sexes. Despite the differences, treatment for HF is similar across the whole population, regardless of sex and gender. In our review, we describe the main differences in terms of cardiovascular dysfunction, risk factors, and cellular signaling modifications related to the hormonal pattern

Thromboembolic Complications in Covid-19: From Clinical Scenario to Laboratory Evidence

SARS-Cov-2 infection, a pandemic disease since March 2020, is associated with a high percentage of cardiovascular complications mainly of a thromboembolic (TE) nature. Although clinical patterns have been described for the assessment of patients with increased risk, many TE complications occur in patients with apparently moderate risk. Notably, a recent statement from the European Society of Cardiology (ESC) atherosclerosis and vascular biology working group pointed out the key role of vascular endothelium for the recruitment of inflammatory and thrombotic pathways responsible for both disseminated intravascular coagulation and cardiovascular complications. Therefore, a better understanding of the pathophysiological process linking infection to increased TE risk is needed in order to understand the pathways of this dangerous liaison and possibly interrupt it with appropriate treatment. In this review, we describe the histological lesions and the related blood coagulation mechanisms involved in COVID-19, we define the laboratory parameters and clinical risk factors associated with TE events, and propose a prophylactic anticoagulation treatment in relation to the risk category. Finally, we highlight the concept that a solid risk assessment based on prospective multi-center data would be the challenge for a more precise risk stratification and more appropriate treatment

Effects of Metolazone Administration on Congestion, Diuretic Response and Renal Function in Patients with Advanced Heart Failure

Background: Advanced heart failure (HF) is a condition often requiring elevated doses of loop diuretics. Therefore, these patients often experience poor diuretic response. Both conditions have a detrimental impact on prognosis and hospitalization. Aims: This retrospective, multicenter study evaluates the effect of the addition of oral metolazone on diuretic response (DR), clinical congestion, NTproBNP values, and renal function over hospitalization phase. Follow-up analysis for a 6-month follow-up period was performed. Methods: We enrolled 132 patients with acute decompensated heart failure (ADHF) in advanced NYHA class with reduced ejection fraction (EF < 40%) taking a mean furosemide amount of 250 ± 120 mg/day. Sixty-five patients received traditional loop diuretic treatment plus metolazone (Group M). The mean dose ranged from 7.5 to 15 mg for one week. Sixty-seven patients continued the furosemide (Group F). Congestion score was evaluated according to the ESC recommendations. DR was assessed by the formula diuresis/40 mg of furosemide. Results: Patients in Group M and patients in Group F showed a similar prevalence of baseline clinical congestion (3.1 ± 0.7 in Group F vs. 3 ± 0.8 in Group M) and chronic kidney disease (CKD) (51% in Group M vs. 57% in Group F; p = 0.38). Patients in Group M experienced a better congestion score at discharge compared to patients in Group F (C score: 1 ± 1 in Group M vs. 3 ± 1 in Group F p > 0.05). Clinical congestion resolution was also associated with weight reduction (−6 ± 2 in Group M vs. −3 ± 1 kg in Group F, p < 0.05). Better DR response was observed in Group M compared to F (940 ± 149 mL/40 mgFUROSEMIDE/die vs. 541 ± 314 mL/40 mgFUROSEMIDE/die; p < 0.01), whereas median ΔNTproBNP remained similar between the two groups (−4819 ± 8718 in Group M vs. −3954 ± 5560 pg/mL in Group F NS). These data were associated with better daily diuresis during hospitalization in Group M (2820 ± 900 vs. 2050 ± 1120 mL p < 0.05). No differences were found in terms of WRF development and electrolyte unbalance at discharge, although Group M had a significant saline solution administration during hospitalization. Follow-up analysis did not differ between the group but a reduced trend for recurrent hospitalization was observed in the M group (26% vs. 38%). Conclusions: Metolazone administration could be helpful in patients taking an elevated loop diuretics dose. Use of thiazide therapy is associated with better decongestion and DR. Current findings could suggest positive insights due to the reduced amount of loop diuretics in patients with advanced HF