During the Coronavirus disease 2019 (COVID-19) pandemic, advanced health systems have come under pressure by the unprecedented high volume of patients needing urgent care. The impact on mortality of ...this "patients' burden" has not been determined.
Through retrieval of administrative data from a large referral hospital of Northern Italy, we determined Aalen-Johansen cumulative incidence curves to describe the in-hospital mortality, stratified by fixed covariates. Age- and sex-adjusted Cox models were used to quantify the effect on mortality of variables deemed to reflect the stress on the hospital system, namely the time-dependent number of daily admissions and of total hospitalized patients, and the calendar period. Of the 1225 subjects hospitalized for COVID-19 between February 20 and May 13, 283 died (30-day mortality rate 24%) after a median follow-up of 14 days (interquartile range 5-19). Hospitalizations increased progressively until a peak of 465 subjects on March 26, then declined. The risk of death, adjusted for age and sex, increased for a higher number of daily admissions (adjusted hazard ratio AHR per an incremental daily admission of 10 patients: 1.13, 95% Confidence Intervals CI 1.05-1.22, p = 0.0014), and for a higher total number of hospitalized patients (AHR per an increase of 50 patients in the total number of hospitalized subjects: 1.11, 95%CI 1.04-1.17, p = 0.0004), while was lower for the calendar period after the peak (AHR 0.56, 95%CI 0.43-0.72, p<0.0001). A validation was conducted on a dataset from another hospital where 500 subjects were hospitalized for COVID-19 in the same period. Figures were consistent in terms of impact of daily admissions, daily census, and calendar period on in-hospital mortality.
The pressure of a high volume of severely ill patients suffering from COVID-19 has a measurable independent impact on in-hospital mortality.
A new nitroxide-based biradical having a long electron spin–lattice relaxation time (T 1e) has been developed as an exogenous polarization source for DNP solid-state NMR experiments. The performance ...of this new biradical is demonstrated on hybrid silica-based mesostructured materials impregnated with 1,1,2,2-tetrachloroethane radical containing solutions, as well as in frozen bulk solutions, yielding DNP enhancement factors (ε) of over 100 at a magnetic field of 9.4 T and sample temperatures of ∼100 K. The effects of radical concentration on the DNP enhancement factors and on the overall sensitivity enhancements (Σ†) are reported. The relatively high DNP efficiency of the biradical is attributed to an increased T 1e, which enables more effective saturation of the electron resonance. This new biradical is shown to outperform the polarizing agents used so far in DNP surface-enhanced NMR spectroscopy of materials, yielding a 113-fold increase in overall sensitivity for silicon-29 CPMAS spectra as compared to conventional NMR experiments at room temperature. This results in a reduction in experimental times by a factor >12 700, making the acquisition of 13C and 15N one- and two-dimensional NMR spectra at natural isotopic abundance rapid (hours). It has been used here to monitor a series of chemical reactions carried out on the surface functionalities of a hybrid organic–silica material.
The risk of developing AIDS is elevated not only among those with a late HIV diagnosis but also among those lost to care (LTC). The aims were to address the risk of becoming LTC and of clinical ...progression in LTC patients who re-enter care. Patients were defined as LTC if they had no visit for ≥ 18 months. Of these, persons with subsequent visits were defined as re-engaged in care (RIC). Factors associated with becoming LTC and RIC were investigated. The risk of disease progression was estimated by comparing RIC with patients continuously followed. Over 11,285 individuals included, 3962 became LTC, and of these, 1062 were RIC. Older age, presentation with AIDS and with higher HIV-RNA were associated with a reduced risk of LTC. In contrast, lower education level, irregular job, being an immigrant and injecting-drug user were associated with an increased LTC probability. Moreover, RIC with HIV-RNA > 200 copies/mL at the re-entry had a higher risk of clinical progression, while those with HIV-RNA ≤ 200 copies/mL had a higher risk of only non-AIDS progression. Patients re-entering care after being LTC appeared to be at higher risk of clinical progression than those continuously in care. Active strategies for re-engagement in care should be promoted.
Chronic airway infection is a key aspect of the pathogenesis of bronchiectasis. A growing interest has been raised on non-tuberculous mycobacteria (NTM) infection. We aimed at describing the clinical ...characteristics, diagnostic process, therapeutic options and outcomes of bronchiectasis patients with pulmonary NTM (pNTM) disease. This was a prospective, observational study enrolling 261 adult bronchiectasis patients during the stable state at the San Gerardo Hospital, Monza, Italy, from 2012 to 2015. Three groups were identified: pNTM disease; chronic
infection; chronic infection due to bacteria other than
. NTM were isolated in 32 (12%) patients, and among them, a diagnosis of pNTM disease was reached in 23 cases. When compared to chronic
infection, patients with pNTM were more likely to have cylindrical bronchiectasis and a "tree-in-bud" pattern, a history of weight loss, a lower disease severity and a lower number of pulmonary exacerbations. Among pNTM patients who started treatment, 68% showed a radiological improvement, and 37% achieved culture conversion without recurrence, while 21% showed NTM isolation recurrence. NTM isolation seems to be a frequent event in bronchiectasis patients, and few parameters might help to suspect NTM infection. Treatment indications and monitoring still remain an important area for future research.
•Heavily treatment-experienced people living with HIV (PLWH) often have few antiretroviral drugs available.•As of the end of 2021, heavily treatment-experienced (HTE) patients account for 0.01% of ...PLWH in the Italian Cohort Naïve Antiretrovirals (ICONA) cohort.•Lower clusters of differentiation 4 counts and hepatitis C virus positivity increase the risk of becoming HTE.•Some HTE individuals currently exhibit ongoing immune-virological failure.•This special group of HTE PLWH is a potential candidate for new antiviral drugs.
Heavily treatment-experienced (HTE) people living with HIV (PLWH) pose unique challenges due to limited antiretroviral treatment (ART) options. Our study aimed to investigate the prevalence and features of HTE individuals followed up in the Italian Cohort Naïve Antiretrovirals (ICONA) cohort as of December 31, 2021.
HTE were defined based on meeting specific conditions concerning their current ART and their ART history up to December 31, 2021. Descriptive statistics were performed by HTE status. Regression analyses explored factors associated with becoming HTE based on pre-ART patients' characteristics. Cluster dendrogram analysis provided insights into subgroups with inadequate responses based on clusters of differentiation (CD4) counts and viral load (VL) trajectories.
Among the 8758 PLWH actively followed in our cohort, 163 individuals (1.9%), mainly female, younger, Italian, and infected through heterosexual contact, met the HTE criteria. A lower CD4 count at ART initiation (odds ratio OR 1.60 per 100 cells/mmc lower CD4, 95% confidence interval CI 1.06-2.41, P = 0.03) and hepatitis C virus antibody positivity (OR 1.90, 95% CI 1.16-3.11, P = 0.01) were associated with higher HTE risk. Thirty PLWH exhibited ongoing immune-virological failure (18% of the HTE subgroup and 0.003% of the total population). Thirty PLWH exhibited ongoing immune-virological failure (i.e., with a current CD4 count <200 cells/mmc or VL>200 copies/mL). A cluster analysis identified 13 (43%) with a current CD4 count <200 cells/mmc. Also, notably, 19/30 (63%) had major acquired resistance-associated mutations to at least one antiretroviral drug class.
HTE is rare in our cohort and tends to co-exist with major resistance mutations. A focused investigation into treatment history and immuno-virological response is warranted, particularly given the availability of new antiretroviral drugs.
Prompt diagnosis of active tuberculosis (TB) has paramount importance to reduce TB morbidity and mortality and to prevent the spread of Mycobacterium tuberculosis. Few studies so far have assessed ...the diagnostic delay of TB and its risk factors in low-incidence countries.
We present a cross-sectional multicentre observational study enrolling all consecutive patients diagnosed with TB in seven referral centres in Italy. Information on demographic and clinical characteristics, health-seeking trajectories and patients' knowledge and awareness of TB were collected. Diagnostic delay was assessed as patient-related (time between symptoms onset and presentation to care) and healthcare-related (time between presentation to care and TB diagnosis). Factors associated with patient-related and healthcare-related delays in the highest tertile were explored using uni- and multivariate logistic regression analyses.
We enrolled 137 patients, between June 2011 and May 2012. The median diagnostic delay was 66 days (Interquartile Range IQR 31-146). Patient-related and healthcare-related delay were 14.5 days (IQR 0-54) and 31 days (IQR: 7.25-85), respectively. Using multivariable analysis, patients living in Italy for < 5 years were more likely to have longer patient-related delay (> 3 weeks) than those living in Italy for > 5 years (Odds Ratio OR 3.47; 95% Confidence Interval CI 1.09-11.01). The most common self-reported reasons to delay presentation to care were the mild nature of symptoms (82%) and a good self-perceived health (76%). About a quarter (26%) of patients had wrong beliefs and little knowledge of TB, although this was not associated with longer diagnostic delay. Regarding healthcare-related delay, multivariate analysis showed that extra-pulmonary TB (OR 4.3; 95% CI 1.4-13.8) and first contact with general practitioner (OR 5.1; 95% CI 1.8-14.5) were both independently associated with higher risk of healthcare-related delay > 10 weeks.
In this study, TB was diagnosed with a remarkable delay, mainly attributable to the healthcare services. Delay was higher in patients with extra-pulmonary disease and in those first assessed by general practitioners. We suggest the need to improve knowledge and raise awareness about TB not only in the general population but also among medical providers. Furthermore, specific programs to improve access to care should be designed for recent immigrants, at significantly high risk of patient-related delay.
The study protocol was registered under the US National Institute of Health ClinicalTrials.gov register, reference number: NCT01390987 . Study start date: June 2011.
PTX3 is an important mediator of inflammation and innate immunity. We aimed at assessing its prognostic value in a large cohort of patients hospitalized with COVID-19.
Levels of PTX3 were measured in ...152 patients hospitalized with COVID-19 at San Gerardo Hospital (Monza, Italy) since March 2020. Cox regression was used to identify predictors of time from admission to in-hospital death or mechanical ventilation. Crude incidences of death were compared between patients with PTX3 levels higher or lower than the best cut-off estimated with the Maximally Selected Rank Statistics Method.
Upon admission, 22% of the patients required no oxygen, 46% low-flow oxygen, 30% high-flow nasal cannula or CPAP-helmet and 3% MV. Median level of PTX3 was 21.7 (IQR: 13.5-58.23) ng/ml. In-hospital mortality was 25% (38 deaths); 13 patients (8.6%) underwent MV. PTX3 was associated with risk of death (per 10 ng/ml, HR 1.08; 95%CI 1.04-1.11; P<0.001) and death/MV (HR 1.04; 95%CI 1.01-1.07; P=0.011), independently of other predictors of in-hospital mortality, including age, Charlson Comorbidity Index, D-dimer and C-reactive protein (CRP). Patients with PTX3 levels above the optimal cut-off of 39.32 ng/ml had significantly higher mortality than the others (55% vs 8%, P<0.001). Higher PTX3 plasma levels were found in 14 patients with subsequent thrombotic complications (median IQR: 51.4 24.6-94.4
21 13.4-55.2; P=0.049).
High PTX3 levels in patients hospitalized with COVID-19 are associated with a worse outcome. The evaluation of this marker could be useful in prognostic stratification and identification of patients who could benefit from immunomodulant therapy.
Combined AntiRetroviral Treatments (cARTs) used for HIV infection may result in varied metabolic complications, which in some cases, may be related to patient genetic factors, particularly microRNAs. ...The use of monozygotic twins, differing only for HIV infection, presents a unique and powerful model for the controlled analysis of potential alterations of miRNAs regulation consequent to cART treatment. Profiling of 2578 mature miRNA in the subcutaneous (SC) adipose tissue and plasma of monozygotic twins was investigated by the GeneChip® miRNA 4.1 array. Real-time PCR and ddPCR experiments were performed in order to validate differentially expressed miRNAs. Target genes of deregulated miRNAs were predicted by the miRDB database (prediction score > 70) and enrichment analysis was carried out with g:Profiler. Processes in SC adipose tissue most greatly affected by miRNA up-regulation included (i) macromolecular metabolic processes, (ii) regulation of neurogenesis, and (iii) protein phosphorylation. Furthermore, KEGG analysis revealed miRNA up-regulation involvement in (i) insulin signaling pathways, (ii) neurotrophin signaling pathways, and (iii) pancreatic cancer. By contrast, miRNA up-regulation in plasma was involved in (i) melanoma, (ii) p53 signaling pathways, and (iii) focal adhesion. Our findings suggest a mechanism that may increase the predisposition of HIV+ patients to insulin resistance and cancer.
Silica nanoparticles of 12 nm diameter were surface-doped with ca. 350 (TTF-dppz)Yb(III) surface species, containing bis(propylthio)tetrathiafulvenylidipyrido-3,2-a:2′,3-cphenazine (TTF-dppz) ...as an antenna ligand through a surface organometallic chemistry approach. These nanoparticles absorb and emit in the NIR (λabs = 750 nm, λem = 983 and 1050 nm) with a lifetime (τ1) of 2.8 μs, similarly to the corresponding Yb(III) molecular complex (λabs = 750 nm, λem = 975, 986, 1009, and 1020 nm with τ1 = 6.93 μs). The silica materials were fully characterized using combined spectroscopic techniques (IR, NMR, UV–vis, luminescence and lifetime), molecular models and isostructural diamagnetic yttrium-containing materials for easier characterization by NMR spectroscopy. Having established the surface structures and photophysical properties of these nanoparticles, we transposed this methodology to larger silica particles with a diameter of ca. 100 nm. These larger nanoparticles have similar photophysical properties and contain ca. 30 000 chromophores, making possible one-photon NIR-to-NIR emission optical microscopy imaging of single nanoparticles.
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