The role of immune suppression in COVID-19 hospitalization: clinical and epidemiological trends over three years of SARS-CoV-2 epidemic

Specific immune suppression types have been associated with a greater risk of severe COVID-19 disease and death. We analyzed data from patients >17 years that were hospitalized for COVID-19 at the “Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico” in Milan (Lombardy, Northern Italy). The study included 1727 SARS-CoV-2-positive patients (1,131 males, median age of 65 years) hospitalized between February 2020 and November 2022. Of these, 321 (18.6%, CI: 16.8–20.4%) had at least one condition defining immune suppression. Immune suppressed subjects were more likely to have other co-morbidities (80.4% vs. 69.8%, p < 0.001) and be vaccinated (37% vs. 12.7%, p < 0.001). We evaluated the contribution of immune suppression to hospitalization during the various stages of the epidemic and investigated whether immune suppression contributed to severe outcomes and death, also considering the vaccination status of the patients. The proportion of immune suppressed patients among all hospitalizations (initially stable at <20%) started to increase around December 2021, and remained high (30–50%). This change coincided with an increase in the proportions of older patients and patients with co-morbidities and with a decrease in the proportion of patients with severe outcomes. Vaccinated patients showed a lower proportion of severe outcomes; among non-vaccinated patients, severe outcomes were more common in immune suppressed individuals. Immune suppression was a significant predictor of severe outcomes, after adjusting for age, sex, co-morbidities, period of hospitalization, and vaccination status (OR: 1.64; 95% CI: 1.23–2.19), while vaccination was a protective factor (OR: 0.31; 95% IC: 0.20–0.47). However, after November 2021, differences in disease outcomes between vaccinated and non-vaccinated groups (for both immune suppressed and immune competent subjects) disappeared. Since December 2021, the spread of the less virulent Omicron variant and an overall higher level of induced and/or natural immunity likely contributed to the observed shift in hospitalized patient characteristics. Nonetheless, vaccination against SARS-CoV-2, likely in combination with naturally acquired immunity, effectively reduced severe outcomes in both immune competent (73.9% vs. 48.2%, p < 0.001) and immune suppressed (66.4% vs. 35.2%, p < 0.001) patients, confirming previous observations about the value of the vaccine in preventing serious disease

"Virtù ascosta e negletta". La Calabria nella Modernità

Il titolo del volume riprende un verso della canzone Agli Italiani di Campanella. La considerazione su una virtù nascosta e trascurata dagli altri, ma anche da se stessa, è rivolta all’Italia, ma essa riguarda tanto più da vicino la patria del filosofo, quella Calabria in cui era nato e alla quale si sentì avvinto da un legame talora critico e doloroso, ma sempre profondissimo. Alla luce di tale ambivalenza, il volume prende le mosse da taluni aspetti del pensiero campanelliano – sul piano filosofico, politico, scientifico, letterario – per poi soffermarsi su momenti della vicenda storica e culturale della Calabria: dalla stagione umanistica e della prima modernità, che vide fiorire l’Accademia Cosentina e la filosofia nuova di Telesio, l’opera storiografica di Gabriele Barrio e la partecipazione al dibattito sulla nuova scienza, fino a momenti dei secoli successivi, in cui immagini stereotipate dei luoghi e dei loro abitanti convivono con nuovi interessi e feconde ricerch

New insights into the Shwachman-Diamond Syndrome-related haematological disorder: Hyper-activation of mTOR and STAT3 in leukocytes

Shwachman-Diamond syndrome (SDS) is an inherited disease caused by mutations of a gene encoding for SBDS protein. So far little is known about SBDS exact function. SDS patients present several hematological disorders, including neutropenia and myelodysplastic syndrome (MDS), with increased risk of leukemic evolution. So far, the molecular mechanisms that underlie neutropenia, MDS and AML in SDS patients have been poorly investigated. STAT3 is a key regulator of several cellular processes including survival, differentiation and malignant transformation. Moreover, STAT3 has been reported to regulate neutrophil granulogenesis and to induce several kinds of leukemia and lymphoma. STAT3 activation is known to be regulated by mTOR, which in turn plays an important role in cellular growth and tumorigenesis. Here we show for the first time, to the best of our knowledge, that both EBV-immortalized B cells and primary leukocytes obtained from SDS patients present a constitutive hyper-activation of mTOR and STAT3 pathways. Interestingly, loss of SBDS expression is associated with this process. Importantly, rapamycin, a well-known mTOR inhibitor, is able to reduce STAT3 phosphorylation to basal levels in our experimental model. A novel therapeutic hypothesis targeting mTOR/STAT3 should represent a significant step forward into the SDS clinical practice

AID-GM: An Advanced System Supporting Continuous Monitoring of T1DM Patients

In this paper, we present AID-GM, a web application for the analysis and summarization of continuous blood glucose monitoring data in patients with Type 1 Diabetes. AID-GM allows patients and their care providers to share data and analyze them thanks to a set of advanced and personalized intelligent data analysis tools. Such tools enable the extraction of complex multivariate temporal patterns from data. We present a preliminary evaluation of the functionalities of the tool, both on a set of healthy volunteers, and on real patients' data in the pediatric context

Topical eye treatment with p-blocker abolishes sweat secretion triggered by intradermal isoprenaline plus aminophylline: a clinical observation

Objectives: Two new versions of the sweat test have recently been developed with claimed advantages of being sensitive enough to quantify residual CFTR function and to measure efficacy of basic therapies. Methods: Rates of water evaporation (kg water/hr/m2 ) and of volume of sweat per gland (nL/min) were measured in a healthy female, 61 yrs, following the reported test protocols. Results: Cholinergic stimulation gave normal results (maximal evaporimetric response 5 min after intradermal injection of carbachol: 95.1 kg water/hr/m2 and gland secretion rate obtained 10 min after methacholine injection: 1.8 nL/min). However, the β-adrenergic (isoprenaline plus aminophylline) stimulation, induced in the presence of atropine to block cholinergic stimulation, was abolished (β-adrenergic/cholinergic ratio: 0 and 5.8% of the normal values for evaporimetry and bubble test, respectively), eliciting a diagnosis of CF. The results were confirmed by repeating each test at least twice. Sweat chloride after pilocarpine iontophoresis using a coulometric method was 24 mmol/L. PCR-based screening showed no CFTR mutation. History of current medications possibly interfering with the pharmacological agents used during the tests revealed long-term (>12 yrs) treatment of a well-controlled primary angle closure glaucoma consisting on a daily topical use of β-blocker carteol 2% (1 drop/left eye). No apparent symptom of β-blocker intoxication is present (heart rate: 66 beats/min, regular sinus rhythm, no symptom of asthma). Conclusion: Much attention should be paid to the use of medications that may interfere with the pharmacological steps of the β-secretion tests. The clinical observation confirms the proof-of-concept that the second phase of both tests directly evaluates β-adrenergic sweat production that is very sensitive to β-blocker treatment, even at topical eye use, leading to false positive test results

Kinetic enantioselectivity of a protonated bis(diamido)-bridged basket resorcin[4]arene towards alanine peptides

Efficient enantiodiscrimination of some alanine-containing di- ani tri-peptides by using chiral protonated bis(diamido)-bridged basket resorcin[4]arenes depends on several factors, including the basicity of the amino acid residues at the C- and N-termini of the peptide

<i>N</i>-Acetyl-<span style="font-variant: small-caps">l</span>-phenylalanine Racemization during TBTU Amidation: An In-Depth Study for the Synthesis of Anti-Inflammatory 2-(<i>N</i>-Acetyl)-<span style="font-variant: small-caps">l</span>-phenylalanylamido-2-deoxy-<span style="font-variant: small-caps">d</span>-glucose (NAPA)

A thorough study on the amidation conditions of N-acetyl-l-phenylalanine using TBTU and various bases is reported for the synthesis of 2-(N-acetyl)-l-phenylalanylamido-2-deoxy-d-glucose (NAPA), a promising drug for the treatment of joints diseases. TBTU-mediated diastereoselective amidation reaction with 1,3,4,6-tetra-O-acetyl-β-d-glucosamine always gave racemization of N-acetyl-l-phenylalanine. The stereochemical retention under amidation conditions was studied in detail in the presence of difference bases and via other control experiments, evidencing the possibility to reduce racemization using pyridine as base

Patient-Generated Health Data Integration and Advanced Analytics for Diabetes Management: The AID-GM Platform

Diabetes is a high-prevalence disease that leads to an alteration in the patient&rsquo;s blood glucose (BG) values. Several factors influence the subject&rsquo;s BG profile over the day, including meals, physical activity, and sleep. Wearable devices are available for monitoring the patient&rsquo;s BG value around the clock, while activity trackers can be used to record his/her sleep and physical activity. However, few tools are available to jointly analyze the collected data, and only a minority of them provide functionalities for performing advanced and personalized analyses. In this paper, we present AID-GM, a web application that enables the patient to share with his/her diabetologist both the raw BG data collected by a flash glucose monitoring device, and the information collected by activity trackers, including physical activity, heart rate, and sleep. AID-GM provides several data views for summarizing the subject&rsquo;s metabolic control over time, and for complementing the BG profile with the information given by the activity tracker. AID-GM also allows the identification of complex temporal patterns in the collected heterogeneous data. In this paper, we also present the results of a real-world pilot study aimed to assess the usability of the proposed system. The study involved 30 pediatric patients receiving care at the Fondazione IRCCS Policlinico San Matteo Hospital in Pavia, Italy

Dysbiosis in Children With Neurological Impairment and Long-Term Enteral Nutrition

Severe neurological impairment (NI) is often accompanied by the need for artificial nutritional support, normally provided enterally (enteral nutrition [EN]) to ensure growth, counteract morbidity and mortality, and improve quality of life. On the other hand, long-term EN (LTEN) may contribute to the establishment, or exacerbation, of gastrointestinal disorders that may lead to malnutrition, which in turn is associated with alterations in gut microbiota (GM) composition and functional capacities. To the best of our knowledge, we investigated, for the first time in this study, the consequences of LTEN in a pediatric population in this pathological context. Using amplicon sequencing, we compared the fecal microbiota of a pediatric population suffering from severe NI and under LTEN to that of sex- and age-matched controls. The two groups presented evident differences in GM composition and a consistent differential clustering. In general, the taxonomic picture in NI children under LTEN seemed to mirror a profound dysbiotic condition, in which anti-inflammatory taxa appear severely depleted (among others, the Clostridiales families of Lachnospiraceae and Ruminococcaceae, and, within the latter, Faecalibacterium spp. and Gemmiger spp.), while known pathobionts (Gammaproteobacteria and Klebsiella) or emerging pathogens (e.g., Synergistales, Cloacibacillus, and Fusobacterium) were significantly enriched. Our data suggest that LTEN has a significant impact on the GM taxonomic composition in NI children. Even if other factors are probably at work, such as the bidirectional interaction between gastrointestinal impairment/immaturity and the central nervous system (CNS), the assumption of drugs, and physical inactivity, these data define possible routes and targets to try to alleviate this dysbiosis, with a view to better management of these patients and an improvement in their quality of life