Despite being an uncommon cause of meningoencephalitis, West Nile virus (WNV) recently provoked significant outbreaks throughout Europe. West Nile neuroinvasive disease (WNND) is associated with ...significant morbidity and mortality in older and compromised individuals, while its diagnosis may be demanding for the clinician. Here discussed are three cases of WNND with a focus on the diagnostic challenges they presented due to atypical clinical presentation and laboratory findings. The laboratory findings here discussed, in particular CSF parameters, are only partially consistent with those described in the literature, which highlights the need for further research. While serology and NAATs on blood and urine appear the most reliable techniques in the diagnostic work-up of WNND, utility of NAATs on CSF specimens is limited by the kinetics of WNV viremia in biological fluids. This report underlines that WNND should always be included in the differential diagnosis of meningoencephalitis during WNV transmission period.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•We describe the importance of patients’s characteristics and comorbidities in the outcome of COVID-19 disease.•We point out two different waves of epidemics in Lombardy, the first one in younger and ...the second in older patients.•Careful assessment of local setting in which COVID-19 spreads is needed to forsee fatality rates and hospital engagement.
We aimed to document data on the epidemiology and factors associated with clinical course leading to death of patients hospitalised with COVID-19.
Prospective observational cohort study on patients hospitalised with COVID-19 disease in February-24th/May-17th 2020 in Milan, Italy. Uni-multivariable Cox regression analyses were performed. Death’s percentage by two-weeks’ intervals according to age and disease severity was analysed.
A total of 174/539 (32.3%) patients died in hospital over 8228 person-day follow-up; the 14-day Kaplan–Meier probability of death was 29.5% (95%CI: 25.5–34.0). Older age, burden of comorbidities, COVID-19 disease severity, inflammatory markers at admission were independent predictors of increased risk, while several drug-combinations were predictors of reduced risk of in-hospital death. The highest fatality rate, 36.5%, occurred during the 2nd–3rd week of March, when 55.4% of patients presented with severe disease, while a second peak, by the end of April, was related to the admission of older patients (55% ≥80 years) with less severe disease, 30% coming from long-term care facilities.
The unusual fatality rate in our setting is likely to be related to age and the clinical conditions of our patients. These findings may be useful to better allocate resources of the national healthcare system, in case of re-intensification of COVID-19 epidemics.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Mortality rate from COVID-19 in Italy is among the world's highest. We aimed to ascertain whether there was any reduction of in-hospital mortality in patients hospitalised for COVID-19 in the ...second-wave period (October 2020-January 2021) compared to the first one (February-May 2020); further, we verified whether there were clusters of hospitalised patients who particularly benefitted from reduced mortality rate.
Data collected related to in-patients' demographics, clinical, laboratory, therapies and outcome. Primary end-point was time to in-hospital death. Factors associated were evaluated by uni- and multivariable analyses. A flow diagram was created to determine the rate of in-hospital death according to individual and disease characteristics.
A total of 1561 patients were included. The 14-day cumulative incidence of in-hospital death by competing risk regression was of 24.8% (95% CI: 21.3-28.5) and 15.9% (95% CI: 13.7-18.2) in the first and second wave. We observed that the highest relative reduction of death from first to second wave (more than 47%) occurred mainly in the clusters of patients younger than 70 years.
Progress in care and supporting therapies did affect population over 70 years to a lesser extent. Preventive and vaccination campaigns should focus on individuals whose risk of death from COVID-19 remains high.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
With the aim of describing the burden and epidemiology of community-acquired/healthcare-associated and hospital-acquired bloodstream infections (CA/HCA-BSIs and HA-BSIs) in patients hospitalised with ...COVID-19, and evaluating the risk factors for BSIs and their relative impact on mortality, an observational cohort study was performed on patients hospitalised with COVID-19 at San Paolo Hospital in Milan, Italy from 24 February to 30 November 2020. Among 1351 consecutive patients hospitalised with COVID-19, 18 (1.3%) had CA/HCA-BSI and 51 (3.8%) HA-BSI for a total of 82 episodes of BSI. The overall incidence of HA-BSI was 3.3/1000 patient-days (95% CI 2.4–4.2). Patients with HA-BSI had a longer hospital stay compared to CA/HCA-BSI and no-BSI groups (27 (IQR 21–35) vs. 12 (7–29) vs. 9 (5–17) median-days, p < 0.001) but a similar in-hospital mortality (31% vs. 33% vs. 25%, p = 0.421). BSI was not associated with an increased risk of mortality (CA/HCA-BSI vs. non-BSI aOR 1.27 95% CI 0.41–3.90, p = 0.681; HA-BSI vs. non-BSI aOR 1.29 95% CI 0.65–2.54, p = 0.463). Upon multivariate analysis, NIMV/CPAP (aOR 2.09, 95% CI 1.06–4.12, p = 0.034), IMV (aOR 5.13, 95% CI 2.08–12.65, p < 0.001) and corticosteroid treatment (aOR 2.11, 95% CI 1.06–4.19, p = 0.032) were confirmed as independent factors associated with HA-BSI. Development of HA-BSI did not significantly affect mortality. Patients treated with corticosteroid therapy had double the risk of developing BSI.
Whether vaccination confers a protective effect against progression after hospital admission for COVID-19 remains to be elucidated. Observational study including all the patients admitted to San ...Paolo Hospital in Milan for COVID-19 in 2021. Previous vaccination was categorized as: none, one dose, full vaccination (two or three doses >14 days before symptoms onset). Data were collected at hospital admission, including demographic and clinical variables, age-unadjusted Charlson Comorbidity index (CCI). The highest intensity of ventilation during hospitalization was registered. The endpoints were in-hospital death (primary) and mechanical ventilation/death (secondary). Survival analysis was conducted by means of Kaplan-Meier curves and Cox regression models. Effect measure modification by age was formally tested. We included 956 patients: 151 (16%) fully vaccinated (18 also third dose), 62 (7%) one dose vaccinated, 743 (78%) unvaccinated. People fully vaccinated were older and suffering from more comorbidities than unvaccinated. By 28 days, the risk of death was of 35.9% (95%CI: 30.1−41.7) in unvaccinated, 41.5% (24.5−58.5) in one dose and 28.4% (18.2−38.5) in fully vaccinated (p = 0.63). After controlling for age, ethnicity, CCI and month of admission, fully vaccinated participants showed a risk reduction of 50% for both in-hospital death, AHR 0.50 (95%CI: 0.30−0.84) and for mechanical ventilation or death, AHR 0.49 (95%CI: 0.35−0.69) compared to unvaccinated, regardless of age (interaction p > 0.56). Fully vaccinated individuals in whom vaccine failed to keep them out of hospital, appeared to be protected against critical disease or death when compared to non-vaccinated. These data support universal COVID-19 vaccination.
A long period of isolation was observed in patients hospitalized for COVID-19 in Milan over March-September 2020 (45; IQR: 37–54 days). A significantly shorter period would have been observed by the ...application of May-WHO (22, IQR: 17–30 days,
P
< 0.001) and October-Italian (26, IQR: 21–34 days,
P
< 0.001) Guidelines. The adoption of the new symptom-based criteria is likely to lead to a significant reduction in the length of the isolation period with potential social, economic and psychological benefits, particularly in the younger population with mild/moderate disease and no comorbidities. In our opinion, the release from isolation after 21 days from symptoms onset, even without a PCR diagnostic test, in most cases seems the most adequate strategy that could balance precautions to prevent SARS CoV-2 transmission and unnecessary prolonged isolation or overuse of diagnostic testing.
We explored the association between female gender and long COVID syndrome, defined as persistence of physical and/or psychological symptoms for more than 4 weeks after recovery from acute COVID-19 ...disease. The secondary aim was to identify predictors of long COVID syndrome by multivariable logistic regression analysis.
This was a single-centre prospective cohort study conducted at San Paolo Hospital in Milan, Italy. We enrolled adult patients who were evaluated at the post-COVID outpatient service of our Infectious Diseases Unit between 15 April 2020 and 15 December 2020. Participants were individuals who had clinically recovered from COVID-19 and in whom virological clearance had occurred. Previous infection by SARS-CoV-2 was microbiologically documented by positivity using a reverse-transcriptase polymerase chain reaction (RT-PCR) assay of nasopharyngeal swab. All enrolled patients underwent blood tests and a comprehensive medical examination at follow-up. Individuals were interviewed about resolved and persisting symptoms and were asked to fill in two questionnaires to allow assessment of the Hospital Anxiety and Depression symptoms (HADS) score and of the Impact of Event Scale–Revised (IES-R) score.
A total of 377 patients were enrolled in the study. The median time from symtpom onset to virological clerance was 44 (37–53) days. A diagnosis of long COVID syndrome was made in 260/377 (69%) patients. The most common reported symptoms were fatigue (149/377, 39.5%), exertional dyspnoea (109/377, 28.9%), musculoskeletal pain (80/377, 21.2%) and “brain fog” (76/377, 20.2%). Anxiety symptoms were ascertained in 71/377 (18.8%) individuals, whereas 40/377 (10.6%) patients presented symptoms of depression. Post-traumatic stress disorder (defined by a pathological IES-R score) was diagnosed in one-third of patients (85/275, 31%). Female gender was independently associated with long COVID syndrome at multivariable analysis (AOR 3.3 vs. males, 95% CI 1.8–6.2, p < 0.0001). Advanced age (adjusted (A)OR 1.03 for 10 years older, 95% CI 1.01–1.05, p 0.01) and active smoking (AOR 0.19 for former smokers vs. active smokers, 95% CI 0.06–0.62, p 0.002) were also associated with a higher risk of long COVID, while no association was found between severity of disease and long COVID (AOR 0.67 for continuous positive airway pressure (CPAP)/non-invasive mechanical ventilation (NIMV)/orotracheal intubation (OTI) vs. no 02 therapy, 95% CI 0.29–1.55, p 0.85).
Factors that were found to be associated with a higher risk of developing “long COVID” syndrome were female gender, older age and active smoking, but not severity of the acute disease. Individuals affected by SARS-CoV-2 infection with the aforementioned features should be early identified and involved in follow-up programmes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Ovarian dysfunction and lower circulating anti-Müllerian hormone (AMH) feature women living with HIV (WLWH). Because treated human immunodeficiency virus (HIV) infection is characterized by a ...pro-inflammatory/oxidative phenotype resulting in residual comorbidity, we sought to investigate possible associations between plasma AMH and markers of inflammation, immune activation/senescence/exhaustion, oxidative stress as well as comorbidities in a cohort of combined anti-retroviral therapy (cART)-treated WLWH versus age-matched HIV-uninfected, healthy women.Eighty WLWH on effective cART aged 25 to 50 years and 66 age-matched healthy women were enrolled. We measured: plasma AMH, IL-6, reactive oxygen species modulator 1 (ROMO1) (ELISA); plasma tumor necrosis factor α, IL-10, soluble vascular cell adhesion molecule 1, osteopontin (Luminex); CD4/CD8 activation (CD38/CD69), apoptosis (CD95), exhaustion (PD1), maturation (CD45RA/CD45R0/CD127/CCR7), recent thymic emigrants (CD31/CD103) (flow cytometry). Mann Whitney and chi-squared tests were used. Univariate and multivariate logistic regression analyses were used to assess factors associated with low AMH (≤1 ng/mL).Compared to healthy women, WLWH were more frequently non-Caucasian, drug/alcohol abusers, with history of late menarche, lower hormonal contraceptive use, with higher gravidity and lower parity. WLWH showed significantly lower AMH (P = .004) as well as higher ROMO1 (P = .0003) and tumor necrosis factor α (P < .0001). The multivariate analyses revealed ROMO1 (adjusted odds ratio AOR: 1.42, P = .03) and HIV infection (AOR: 8.1, P = .0001) as independently associated with low AMH. The logistic regression model with both HIV status and ROMO1 (a marker of oxidative stress) confirmed HIV as the only predictor of low AMH (AOR: 17, P = .0003).Despite effective cART, WLWH showed lower AMH compared to age-matched peers, indicating pre-mature ovarian ageing. Both HIV and oxidative stress are independently associated with low AMH, emphasizing the impact of HIV-associated oxidative stress on reproductive aging.
Background
Pancreatic texture is one of the key predictors of postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD). Currently, the “gold standard” for assessment of pancreatic ...texture is surgeon’s subjective evaluation through manual palpation.
Aim
To evaluate a new “durometer” that is able to assess quantitatively the pancreatic stiffness by measuring its elastic module (i.e., the resistance offered by the pancreatic stump when elastically deformed expressed in mPa).
Methods
Measurements were obtained from the pancreatic remnant during 138 consecutive PDs performed at the Department of General and Pancreatic Surgery—The Pancreas Institute, University of Verona Hospital Trust. Values were correlated to clinical features and, in particular, with the senior surgeon’s evaluation of pancreatic texture (hard/soft). Sixteen beating-heart donors were used as a control group to assess the stiffness of a non-pathologic pancreas. Univariate analysis was performed for the assessment of POPF predictors.
Results
Durometry allowed segregating between non-pathologic, soft and hard pancreas according to surgeon’s evaluation (mean values 111 vs. 196 vs. 366 mPa,
p
< 0.01). There were no significant differences in stiffness with regard to histology, BMI, and neoadjuvant therapy. Larger tumors (>20 mm) and male sex were associated with greater stiffness on univariate analysis. Pancreatic texture, pancreatic duct size, BMI, prior neoadjuvant therapy, and histology were predictors of POPF. Patients who developed POPF showed a lesser stiffness (178 vs. 261 mPa,
p
= 0.05).
Conclusion
Assessment of pancreatic stiffness using a durometer correlated with the surgeon’s evaluation of pancreatic texture. Measurement of pancreatic parenchymal stiffness is reliable and correlates with the development of POPF.
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EMUNI, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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The aim of this work was to profile, by using an HPLC-MS/MS method, cranberry compounds and metabolites found in human urine after ingestion of a highly standardized cranberry extract ...(Anthocran®). Two different strategies were adopted for the data analysis: a targeted and an untargeted approach. These strategies allowed the identification of 42 analytes including cranberry components, known metabolites and metabolites hitherto unreported in the literature, including six valerolactones/valeric acid derivatives whose presence in urine after cranberry consumption has never been described before. Absolute concentrations of 26 over 42 metabolites were obtained by using pure available standards. Urine collected at different time points after the last dosage of Anthocran® were tested on the reference strain C. albicans SC5314, a biofilm-forming strain. Fractions collected after 12 h were found to significantly reduce the adhesion and biofilm formation compared to the control (p < 0.05). A similar effect was then obtained by using Anthocran™ Phytosome™, the lecithin formulation containing 1/3 of standardized cranberry extract and formulated to enhance the absorption of the cranberry components. The urinary profile of cranberry components and metabolites in the urine fractions collected at 1 h, 6 h and 12 h after the last capsule intake were then reproduced by using the pure standards at the concentration ranges found in the urine fraction, and tested on C. albicans. Only the mixture mimicking the urinary fraction collected at 12 h and containing as main components, quercetin and 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone was found effective thus confirming the ex-vivo results.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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