Inhalation therapy in the next decade : Determinants of adherence to treatment in asthma and COPD

Peer reviewedPublisher PD

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Changes in extracellular Ca2+ can affect the pattern of discharge in rat thalamic neurons

The aim of this study was to investigate some of the cellular mechanisms involved in the effects caused by changes in extracellular Ca2+ concentration ([Ca2+]o).Current and voltage-clamp experiments were carried out on acutely isolated thalamic neurons of rats.Increasing [Ca2+]o alone induced a transition of the discharge from single spike to burst mode in isolated current-clamped neurons.Increasing [Ca2+]o caused the voltage-dependent characteristics of the low voltage-activated (LVA) transient Ca2+ currents to shift towards positive values on the voltage axis. Changing [Ca2+]o from 0.5 to 5 mM caused the inactivation curve to shift by 21 mV.Extracellular Ca2+ blocked a steady cationic current. This current reversed at −35 mV, was scarcely affected by Mg2+ and was completely blocked by the non-selective cation channel inhibitor gadolinium (10 μM). The effect of [Ca2+]o was mimicked by 500 μM spermine, a polyamine which acts as an agonist for the Ca2+-sensing receptor, and was modulated by intracellular GTP-γ-S.At the resting potential, both the voltage shift and the block of the inward current removed the inactivation of LVA calcium channels and, together with the increase in the Ca2+ driving force, favoured a rise in the low threshold Ca2+ spikes, causing the thalamic firing to change to the oscillatory mode.Our data indicate that [Ca2+]o is involved in multiple mechanisms of control of the thalamic relay and pacemaker activity. These findings shed light on the correlation between hypercalcaemia, low frequency EEG activity and symptoms such as sleepiness and lethargy described in many clinical papers

An Enterococcus faecium Isolated from Bovine Feces in Italy Shares optrA- and poxtA-Carrying Plasmids with Enterococci from Switzerland

Abstract: To investigate the occurrence of oxazolidinone resistance genes, 18 florfenicol-resistant enterococci were isolated from 66 fecal samples collected from several cattle farms in central Italy. The PCR screening indicated that only a bovine florfenicol-resistant isolate, Enterococcus faecium 249031-C, was positive for the presence of optrA and poxtA genes. The strain was tested for its susceptibility to florfenicol, chloramphenicol, linezolid, tedizolid, tetracycline, erythromycin, and vancomycin. Whole Genome Sequencing analysis showed that E. faecium 249031-C, belonging to the ST22 lineage, harbored two plasmids: the optrA-carrying p249031-S (179 kb) and the poxtA-carrying p1818-c (23 kb). p249031-S, containing a new optrA-carrying Tn7695 transposon, was closely related to the plasmid pF88_1 of E. faecium F88, whereas p1818-c had already been detected in a human E. faecium, both enterococci were from Switzerland. The linezolid resistance genes were cotransferred to the E. faecium 64/3 recipient. Circular forms from both optrA- and poxtA-carrying genetic contexts were obtained. The occurrence of oxazolidinone resistance genes in a bovine E. faecium isolate and their localization on conjugative and mobilizable plasmids pose a risk for public health

Reference equations for spirometry from a general population sample in central Italy

SummaryAim of this study was to derive new lung function reference equations and compare the predicted values with those from three sets of existing reference equations: one derived from a Northern Italy population and the two others widely used in European (ECCS) and American (NHANES III) clinical practice.Reference equations for flow-volume curve indexes and VC were derived on 497 normal subjects, aged 8–74, from the epidemiological survey in Pisa, Central Italy (1991–1993). By applying natural cubic splines, one single smooth and continuous equation for the entire age range was provided for each index, separately by gender.Along with age and height, reference values also depended on BMI. Differences among the four reference equations for FEV1, FVC, VC were quantified for average subjects. The magnitude largely varied over the age range in both genders, reaching up to half litre of air volume at specific ages. Age-gender-specific prevalence rates of airway obstruction, as defined by the ERS criterion, largely varied by applying the considered equations, the differences ranging from −3% to 28%.The observed discrepancies confirm that reference equations should be derived from a population most similar to that for which the equations are to be used and based on measurements obtained by the same instrument and testing procedures, in order to minimize technical variability in lung function both for clinical and epidemiological purposes

Synthesis and Antitumor Activity of a New Class of Pyrazolo[4,3-e]pyrrolo[1,2-a][1,4]diazepinone Analogs of Pyrrolo[1,4][2,1-c]benzodiazepines

A new class of pyrrolo[l,4lbenzodiazepine (PBD) analogues featuring a pyrazolo[4,3-e]pyrrolo- [l72-al[l,4]diazepinone ring system has been designed and synthesized. These compounds, 2a-0, are characterized by the substitution of the aromatic A ring, characteristic of the PBDs, with a disubstituted pyrazole ring bearing alkyl and benzyl substituents at N6 or N7 and alkyl or carbomethoxy substituents at c8. Biological evaluation revealed an appreciable in vitro cytotoxic activity for compounds 2a,b,f-i

Mortalità per malattie respiratorie in Italia (1990-2010). Parte I: Metodi e tassi grezzi nazionali e per regione

Negli anni ’70 e ’80, in Italia, si evidenziava un leggero ma costante decremento della mortalità per malattie dell’apparato respiratorio (MAR, tumori esclusi) e un incremento della mortalità per broncopneumopatia cronica ostruttiva. Scopo del presente lavoro è valutare l’andamento della mortalità per MAR, e in particolare per malattie respiratorie croniche (MRC), negli anni ’90 e nel primo decennio del nuovo millennio. I risultati sono presentati in due report distinti. Nel presente report (Parte I) si osserva che nel periodo 1990-2010, in Italia, si è avuto un progressivo aumento di decessi per MAR e MRC. I tassi grezzi di mortalità per MAR, dopo andamento altalenante fino all’inizio del nuovo millennio, tendono a lieve incremento. A livello di macro-aree geografiche, i tassi sono più elevati al Nord e meno elevati al Sud e, nel periodo in esame, tendono a calare in maniera evidente nelle Isole ed a crescere in maniera altrettanto evidente nel Centro. I tassi grezzi si sono mantenuti abbastanza stabili sia nel Nord sia nel Sud. In generale, i tassi grezzi di mortalità per MRC, in calo fino all’inizio del nuovo millennio, tendono poi a lieve incremento. Contrariamente a quanto accade per le MAR, i tassi di mortalità per MRC risultano più elevati nel Sud (specialmente) e nelle Isole che nel Centro e nel Nord. Nell’ultimo ventennio si registra un lieve decremento del tasso di mortalità per MRC in tutte le macroaree geografiche, eccetto che nel Centro. Per una corretta valutazione dell’andamento della mortalità in Italia è necessario considerare anche l’effetto confondente dell’età. Tassi standardizzati, oltre ad un confronto con l’Europa, e conclusioni sono riportati nel nostro secondo report sulla mortalità in Italia (Parte II)