The Great pretender: the first case of septic shock due to Capnocytophaga canimorsus in Sardinia. A Case report and review of the literature

Capnocytophaga canimorsus (C. canimorsus) is an emerging pathogen in critical care. C. canimorsus is a Gram-negative bacillus, commonly isolated as a commensal microorganism of the oral flora of healthy dogs and cats. A 63-year-old woman came to the emergency department with fever, chills, and malaise 2 days after a minor dog bite. After admission to the medicine ward, she developed respiratory failure and livedo reticularis. In the intensive care unit (ICU), she presented full-blown septic shock with thrombocytopenia, coagulopathy, severe acute kidney injury, and liver injury. We describe the first case of septic shock with Multiple Organ Dysfunction Syndrome related to Capnocytophaga canimorsus infection in Sardinia and its treatment in a tertiary hospital ICU. We also review recent literature on the relevance of C. canimorsus in human disease and critical illness

<i>Angiostrongylus chabaudi</i> Biocca, 1957: a new parasite for domestic cats?

Background Natural infection with a species of Angiostrongylus has been reported only once in wildcats from central Italy by Biocca in 1957. The causative species of this infection was identified as Angiostrongylus chabaudi. Following this report, this parasite had never been found in either wild or domestic cats. Findings The lungs and the pulmonary arteries of an adult female cat (Felis silvestris catus), roadkilled in Sardinia, Italy, were macroscopically examined and dissected under a light microscope for the presence of parasites. A slender nematode was detected and its morphometrical features were consistent with those of A. chabaudi. Morphological data were supplemented by sequencing of the partial cytochrome oxidase c subunit 1 (cox1) gene, as well as the internal transcribed spacer 2 (ITS2) of the rDNA. Nucleotide sequences displayed 99% homology with the ITS2 sequence [GenBank KM216825.1] of a specimen of Angiostrongylus sp. recovered recently from the pulmonary artery of a wildcat in Germany and 91% with cox1 sequence [GenBank GU138118.1] of Angiostrongylus vasorum. Conclusion The results of the present study indicate, for the first time, that A. chabaudi may also infect domestic cats, and thus should be considered in the diagnosis of metastrongyloid species infecting their cardio-pulmonary system.</br

Nationwide consensus on the clinical management of treatment-resistant depression in Italy: a Delphi panel

Background: Treatment-resistant depression (TRD) is defined by the European Medicines Agency as a lack of clinically meaningful improvement after treatment, with at least two different antidepressants. Individual, familiar, and socio-economic burden of TRD is huge. Given the lack of clear guidelines, the large variability of TRD approaches across different countries and the availability of new medications to meet the need of effective and rapid acting therapeutic strategies, it is important to understand the consensus regarding the clinical characteristics and treatment pathways of patients with TRD in Italian routine clinical practice, particularly in view of the recent availability of esketamine nasal spray. Methods: A Delphi questionnaire with 17 statements (with a 7 points Likert scale for agreement) was administered via a customized web-based platform to Italian psychiatrists with at least 5 years of experience and specific expertise in the field of depression. In the second-round physicians were asked to answer the same statements considering the interquartile range of each question as an index of their colleagues' responses. Stata 16.1 software was used for the analyses. Results: Sixty panellists, representative of the Italian territory, answered the questionnaire at the first round. For 8/17 statements more than 75% of panellists reached agreement and a high consensus as they assigned similar scores; for 4 statements the panellists assigned similar scores but in the middle of the Likert scale showing a moderate agreement with the statement, while for 5 statements there was indecision in the agreement and low consensus with the statement. Conclusions: This Delphi Panel showed that there is a wide heterogeneity in Italy in the management of TRD patients, and a compelling need of standardised strategies and treatments specifically approved for TRD. A high level of consensus and agreement was obtained about the importance of adding lithium and/or antipsychotics as augmentation therapies and in the meantime about the need for long-term maintenance therapy. A high level of consensus and agreement was equally reached for the identification of esketamine nasal spray as the best option for TRD patients and for the possibility to administrate without difficulties esketamine in a community outpatient setting, highlighting the benefit of an appropriate educational support for patients

Two subsets of stem-like CD8+ memory T cell progenitors with distinct fate commitments in humans

T cell memory relies on the generation of antigen-specific progenitors with stem-like properties. However, the identity of these progenitors has remained unclear, precluding a full understanding of the differentiation trajectories that underpin the heterogeneity of antigen-experienced T cells. We used a systematic approach guided by single-cell RNA-sequencing data to map the organizational structure of the human CD8+ memory T cell pool under physiological conditions. We identified two previously unrecognized subsets of clonally, epigenetically, functionally, phenotypically and transcriptionally distinct stem-like CD8+ memory T cells. Progenitors lacking the inhibitory receptors programmed death-1 (PD-1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) were committed to a functional lineage, whereas progenitors expressing PD-1 and TIGIT were committed to a dysfunctional, exhausted-like lineage. Collectively, these data reveal the existence of parallel differentiation programs in the human CD8+ memory T cell pool, with potentially broad implications for the development of immunotherapies and vaccines

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Plasminogen purification from serum through affinity membranes

The use of plasmin in some eye treatment and, in particular, as a facilitator for eye surgery to prevent retinal detachment is beneficial for the patient and entails less surgical risks than conventional vitrectomy. Plasmin is obtained by activation of plasminogen using a variety of enzymes, including tissue plasminogen activator, urokinase and streptokinase. The isolation of plasminogen from blood is normally performed with bead-based affinity chromatography however, affinity membranes are ideally suited for this application since they can be easily packed in small units providing a fast and economic process. In this work, we prepared affinity membranes for plasminogen purification using L-lysine as affinity ligand. To this aim regenerated cellulose membranes were used as a support for ligand immobilization. The efficiency of L-lysine coupling was inspected by applying different binding protocols and the immobilization yield was studied as a function of the reaction conditions. The membranes have been characterized in batch and in complete chromatographic cycles using bovine and human serum as test probes. The results obtained indicate that the L-lysine affinity membranes are a promising alternative for the purification of plasminogen