Publications by authors named "Annalisa Orenti"

33 Publications

Hospital discharge: testing the "Blaylock Risk Assessment Screening Score" in a surgical department.

Acta Biomed 2021 07 29;92(S2):e2021039. Epub 2021 Jul 29.

ASST Vimercate.

Background and aim of the work Standardizing patients' assessment to identify individuals at greater risk in encountering difficulties at discharge may help to assist healthcare professionals in clinical decision making and address the gaps in quality that negatively affect continuity of care. We analyzed the predictive validity and the test-retest reliability of the BRASS index in surgical inpatients. Moreover, we evaluated the association between other variables and length of stay or location at discharge. Methods A prospective observational study was conducted. Four hundred twenty-eight patients (≥18 years old) hospitalized in the surgical department of Vimercate hospital were recruited. Data were collected using BRASS index within 48 hours from admission and before discharge. Results We found a high specificity for BRASS in identifying patients discharged to their home with assistance or to residential care. The hospital stay for medium and high-risk patients was significantly longer than those in the low-risk group. There was no statistically significant difference of the BRASS scores during hospitalization. Type of admission, pressure ulcers, ASA score, multidrug-resistant bacterial infections, medical complications and Intensive Unit Care stay showed a significant correlation with longer hospitalization and increased probability to be discharged to their home with assistance or to residential care. Conclusions The BRASS Index may support healthcare professionals to identify surgical inpatients requiring a discharge planning and needs to be completed just once at admission. The inclusion of other patient-specific factors in the assessment process could be valuable for targeting the at-risk population.
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http://dx.doi.org/10.23750/abm.v92iS2.10761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383228PMC
July 2021

Incidence of SARS-CoV-2 in people with cystic fibrosis in Europe between February and June 2020.

J Cyst Fibros 2021 07 18;20(4):566-577. Epub 2021 Apr 18.

Centre for Cystic Fibrosis, Hospital de Santa Maria, Lisbon, Portugal.

Background: Viral infections can cause significant morbidity in cystic fibrosis (CF). The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic could therefore have a serious impact on the health of people with CF (pwCF).

Methods: We used the 38-country European Cystic Fibrosis Society Patient Registry (ECFSPR) to collect case data about pwCF and SARS-CoV-2 infection.

Results: Up to 30 June 2020, 16 countries reported 130 SARS-CoV-2 cases in people with CF, yielding an incidence of 2.70/1000 pwCF. Incidence was higher in lung-transplanted patients (n=23) versus non-transplanted patients (n=107) (8.43 versus 2.36 cases/1000). Incidence was higher in pwCF versus the age-matched general population in the age groups <15, 15-24, and 25-49 years (p<0.001), with similar trends for pwCF with and without lung transplant. Compared to the general population, pwCF (regardless of transplantation status) had significantly higher rates of admission to hospital for all age groups with available data, and higher rates of intensive care, although not statistically significant. Most pwCF recovered (96.2%), however 5 died, of whom 3 were lung transplant recipients. The case fatality rate for pwCF (3.85%, 95% CI: 1.26-8.75) was non-significantly lower than that of the general population (7.46%; p=0.133).

Conclusions: SARS-CoV-2 infection can result in severe illness and death for pwCF, even for younger patients and especially for lung transplant recipients. PwCF should continue to shield from infection and should be prioritized for vaccination.
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http://dx.doi.org/10.1016/j.jcf.2021.03.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053246PMC
July 2021

Home physiotherapists assisting follow-up treatment in cystic fibrosis: a multicenter observational study.

Monaldi Arch Chest Dis 2021 Apr 15;91(2). Epub 2021 Apr 15.

Cystic Fibrosis Centre, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan; 3Department of Clinical Sciences and Community Health, Laboratory of Medical Statistics, Epidemiology and Biometry G. A. Maccacaro, University of Milan .

Inhaled therapies are relatively simple and easy to be managed however ineffective use of aerosols when self-administered may occur. We described variation of the number of clinic visits, lung function and number of antibiotic courses performed over 12 months in participants with cystic fibrosis (CF), when supervised or not by physiotherapists (PTs) at home. Participants in 8 Italian CF centers with a prescription of dry-powder antibiotic choose whether to be supervised at home (PT-FU) or not (non-PT-FU), in adjunct to routine clinic visits. PTs assisted participants with their inhaled therapies regimen and reviewed the airway clearance program in use.  Mixed-effect regression models were fitted to evaluate the variation of selected endpoints over time. A total of 163 participants were included.  Lung function declined over time in both groups, at higher extent in the non-PT-FU group at 6 months (-1.8, 95%CI: -4.4 to 0.7 % predicted), without reaching statistical significance, whereas in the PT-FU group only, nearly one visit less was recorded (p=0.027). Regardless the type of supervision adopted, the number of antibiotic courses did not change compared to the previous year. We counted 19/90 (21.1%) drop-out in the PT-FU, double compared to the group followed up at the clinics (p=0.065). Participants under a course of an inhaled antibiotic therapy showed a 1-year decline in lung function, whereas only the group receiving home supervision counted nearly one visit less at the CF center, whose clinical relevance should be further discussed.
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http://dx.doi.org/10.4081/monaldi.2021.1619DOI Listing
April 2021

Ensuring tight control in patients with rheumatoid arthritis treated with targeted therapies during the COVID-19 pandemic using a telehealth strategy.

Ann Rheum Dis 2021 09 13;80(9):1243-1245. Epub 2021 Apr 13.

Dept. of Clinical Sciences & Community Health, Research Center for Adult and Pediatric Rheumatic Diseases, Università degli Studi di Milano, Milano, Italy.

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http://dx.doi.org/10.1136/annrheumdis-2021-220142DOI Listing
September 2021

Acute pulmonary embolism in patients presenting pulmonary deterioration after hospitalisation for non-critical COVID-19.

Intern Med J 2021 08;51(8):1236-1242

Department of Clinical Sciences and Community Health, Laboratory of Medical Statistics Epidemiology and Biometry 'G. A. Maccacaro', University of Milan, Milan, Italy.

Background: Emerging evidence suggests an association between COVID-19 and acute pulmonary embolism (APE).

Aims: To assess the prevalence of APE in patients hospitalised for non-critical COVID-19 who presented clinical deterioration, and to investigate the association of clinical and biochemical variables with a confirmed diagnosis of APE in these subjects.

Methods: All consecutive patients admitted to the internal medicine department of a general hospital with a diagnosis of non-critical COVID-19, who performed a computer tomography pulmonary angiography (CTPA) for respiratory deterioration in April 2020, were included in this retrospective cohort study.

Results: Study populations: 41 subjects, median (interquartile range) age: 71.7 (63-76) years, CPTA confirmed APE = 8 (19.51%, 95% confidence interval (CI): 8.82-34.87%). Among patients with and without APE, no significant differences were found with regards symptoms, comorbidities, treatment, Wells score and outcomes. The optimal cut-off value of d-dimer for predicting APE was 2454 ng/mL, sensitivity (95% CI): 63 (24-91), specificity: 73 (54-87), positive predictive value: 36 (13-65), negative predictive value: 89 (71-98) and AUC: 0.62 (0.38-0.85). The standard and age-adjusted d-dimer cut-offs, and the Wells score ≥2 did not associate with confirmed APE, albeit a cut-off value of d-dimer = 2454 ng/mL showed an relative risk: 3.21; 95% CI: 0.92-13.97; P = 0.073. Heparin at anticoagulant doses was used in 70.73% of patients before performing CTPA.

Conclusion: Among patients presenting pulmonary deterioration after hospitalisation for non-critical COVID-19, the prevalence of APE is high. Traditional diagnostic tools to identify high APE pre-test probability patients do not seem to be clinically useful. These results support the use of a high index of suspicion for performing CTPA to exclude or confirm APE as the most appropriate diagnostic approach in this clinical setting.
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http://dx.doi.org/10.1111/imj.15307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251288PMC
August 2021

Survival estimates in European cystic fibrosis patients and the impact of socioeconomic factors: a retrospective registry Cohort study.

Eur Respir J 2021 Mar 7. Epub 2021 Mar 7.

Department of Pediatrics, Justus-Liebig-University Giessen, Giessen, Germany.

Background: Median survival for cystic fibrosis (CF) patients in Europe is unknown and is likely to be influenced by socioeconomic factors. Using the European Cystic Fibrosis Society Patient Registry (ECFSPR), median survival estimates were obtained for CF patients across Europe and the impact of socioeconomic status on survival was examined.

Methods: CF subjects known to be alive and in the ECFSPR between 2010 and 2014 were included. Survival curves were estimated using the Kaplan-Meier (KM) method. Differences in the survival curves were assessed using the log rank test. Cox regression was used to estimate the association between socioeconomic factors and the age-specific hazard of death, with adjustment for sex, age at diagnosis, genotype and transplant status.

Findings: The final analysis included 13 countries with 31 987 subjects (135 833 person years of follow-up) and 1435 deaths. Median survival age for these patients in the ECFSPR was 51.7 years (95% C.I. 50.0-53.4). After adjusting for potential confounders age at diagnosis, sex, genotype and transplant status, there remained strong evidence of an association between socioeconomic factors and mortality (p<0.001). Countries with higher health care spending had a 46% lower hazard of mortality (HR: 0.54, 95% CI: 0.45-0.64) than countries with lowest health care spending.

Interpretation: Median survival for patients with CF in Europe is comparable to that reported in other jurisdictions and differs by socioeconomic factors.
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http://dx.doi.org/10.1183/13993003.02288-2020DOI Listing
March 2021

Predictors of medium- and long-term mortality in elderly patients with acute pulmonary embolism.

Heliyon 2020 Sep 14;6(9):e04857. Epub 2020 Sep 14.

Department of Clinical Sciences and Community Health, Laboratory of Medical Statistics, Epidemiology and Biometry G. A. Maccacaro, University of Milan, Milan, Italy.

Introduction: Data on medium- and long-term prognostic factors for death in elderly patients with acute Pulmonary Embolism (APE) are lacking. The present study aimed to assess sPESI score and the Charlson Comorbidity Index (CCI) as medium- and long-term predictors of mortality in elderly patients with haemodinamically stable APE.

Methods: All consecutive patients aged≥65 years old, evaluated at the emergency department (ED) of our hospital from 2010 through 2014, with a final diagnosis of APE, were included in this retrospective cohort study.

Results: Study population:162 patients, female:36.5%, median age:79 years old, 74% presented a sPESI score>0, and 61% a CCI≥ 1. All causes mortality: 19.8%, 23.5%, 26.5%, 32.1% and 48.2% at 3, 6 months, 1, 2 and 5 years after APE. Univariate regression analysis: CCI≥1 was associated with a higher mortality at 3, 6 months, 1, 2 and 5 years. Multivariate Cox analysis: CCI≥1 associated with increased mortality at 3 months (HR:4.29; IC95%:1.46-12.59), 6 months (HR:5.33; IC95%:1.84-15.44), 1 year (HR:4.87; IC95%:1.87-12.70), 2 years (HR:3.78; IC95%:1.74-8.25), and 5 years (HR:2.30; IC95%:1.33-3.99). sPESI score≥1 was not found to be related to an increased medium-or long-term mortality. Negative predictive values (IC95%) of CCI≥1 were 93.65% (87.61-99.69), 93.65% (87.61-99.69), 92.06% (85.37-98.76), 87.3% (79.05-95.55) and 71.61% (60.13-83.1) for mortality at 3, 6 months, 1, 2 and 5 years.

Conclusion: In elderly patients with a confirmed normotensive APE, unlike sPESI score, CCI showed to be an independent prognostic factor for medium- and long-term mortality. In these patients, after the acute phase following a PE event, the assessment of the comorbidities burden represents the most appropriate approach for predicting medium- and long-term mortality.
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http://dx.doi.org/10.1016/j.heliyon.2020.e04857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494465PMC
September 2020

The burden of air pollution and temperature on Raynaud's phenomenon secondary to systemic sclerosis.

Epidemiol Prev 2020 Jul-Aug;44(4):218-227

Division of Clinical Rheumatology, Azienda Socio Sanitaria Territoriale Pini-CTO, Milan (Italy).

Objectives: to evaluate the effect of air pollution (ozone - O3 and particulate matter <=10 μm and <=2.5 μm - PM10 and PM2.5) on the severity of Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc).

Design: cross-sectional, observational, and single centre study.

Setting And Participants: all consecutive SSc patients residing in Lombardy (Northern Italy) were enrolled. PM10, PM2.5, and O3 concentrations were calculated for each patient at municipality resolution in the week before the evaluation. Similar considerations were made for meteorological variables (temperature and humidity).

Main Outcome Measures: patients were asked to assess RP severity during the week before the evaluation according to a visual analogue scale (VAS). Ordinal logistic regression models were fitted to evaluate the short-term effect of temperature and air pollution with respect to RP. A univariate linear regression model was created to consider the association between temperature and pollutants.

Results: in this study, 87 SSc patients were enrolled. Temperature was confirmed to strongly influence RP severity. PM10 and PM.5 were found to significantly worsen RP severity for the first four days before the evaluation, including the day of the visit, and as mean up to six days before the evaluation. O3 seemed to exert a protective effect on RP severity that was significant for the first four days before the evaluation, including the day of the visit, and as mean up to seven days before the evaluation.

Conclusions: since the overwhelming effect of temperature on RP, final conclusions about the exact contribution of pollutants on RP severity cannot be drawn because of the strong inter-correlation between air pollution and temperature.
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http://dx.doi.org/10.19191/EP20.4.P228.052DOI Listing
June 2021

[The assessment of planned discharges: agreement between BRASS index and clinical judgement].

Assist Inferm Ric 2019 Oct-Dec;38(4):183-191

. The assessment of planned discharges: agreement between BRASS index and clinical judgement.

Introduction: The BRASS (Blaylock Risk Assessment Screening Score) index is a risk screening tool for identification of patients at risk of difficult discharge.

Objective: To assess the agreement of discharge options between the BRASS classification and the nurses' clinical judgement.

Methods: Consecutive patients admitted to surgical wards of a large Italian hospital from November 2016 to June 2017 were assessed with the BRASS index within 48 hours from admission and 24 hours before discharge. After discharge a group of expert nurses, blind to the BRASS score and patient effective destination, planned the patients' discharge reviewing the clinical records. Patients were classified as needing ordinary discharge, with support or to hospital.

Results: The 90% of the 428 included patients remained in the same BRASS risk class; the agreement between BRASS score (K Cohen) at admission and clinical judgement was 0.474 and 0.533 at discharge. Of the 96 subject at need of discharge with support or to hospital, 60 were classified in the same class by the BRASS Index. Factors that impacted on the different classification were patients' age, presence of devices and availability and appropriateness of social support.

Conclusions: Most patients remained in the same BRASS class. There is moderate agreement between BRASS index and clinical judgement, specifically for patients at medium/high risk of difficult discharge. Our data confirm the need for including new items in the Brass scale.
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http://dx.doi.org/10.1702/3273.32395DOI Listing
May 2020

Short and long-term mortality in elderly patients with suspected not confirmed pulmonary embolism.

Eur J Intern Med 2020 03 8;73:36-42. Epub 2019 Nov 8.

Department of Clinical Sciences and Community Health, Laboratory of Medical Statistics, Epidemiology and Biometry G. A. Maccacaro, University of Milan, Milan, Italy.

Introduction: Most patients evaluated for suspected pulmonary embolism(PE) conclude the Emergency Department(ED) work-up with a diagnosis of PE not confirmed(PE excluded;PE-E). We aimed to investigate the clinical features, short and long-term mortality, and prognostic factors for death in elderly with PE-E, and to compare these figures with those of patients with PE confirmed(PE-C).

Methods: Consecutive patients ≥65 years old evaluated in the ED for clinically suspected hemodynamically stable acute PE were included in this retrospective cohort study.

Results: Study population: 657 patients with suspected PE, PE-C:162(24.65%). When compared with PE-C, patients with PE-E presented a higher prevalence of chronic cardiopulmonary disease (17.37% vs 8.02%, p = 0.003), a lower prevalence of pulse rate >110 (13.13% vs 25.93%; p<0.001), of arterial oxygen saturation <90% (16.16% vs. 25.93%; p = 0.007) and of hospitalized patients (52.93% vs 98.15%; p < 0.001). Thirty-day, 90-day, 1-year, 2-year and 5-year overall mortality was 8.83%, 15.98%, 23.59%, 29.68%, and 51.09%, respectively, differences between PE-E and PE-C non statistically significant. Among patients with PE-E, multivariate analysis showed that simplified Pulmonary Embolism Severity Index score>0 was associated with higher short and long-term mortality (30-day:HR:5.31,p = 0.029; 5 year:HR:2.18, p < 0.001), meanwhile comorbidity (Charlson Comorbidity Index>0) only with higher long-term mortality (30-day: HR:1.60, p = 0.342; 5 year: HR:1.41, p = 0.038).

Conclusion: In real world haemodinamically stable elderly patients evaluated in the ED for suspected PE, short and long-term mortality was markedly high regardless whether PE was confirmed or excluded. At the time to set management and follow up strategies, elderly patients with PE excluded should not be considered a low-risk population.
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http://dx.doi.org/10.1016/j.ejim.2019.10.024DOI Listing
March 2020

Changing epidemiology of the respiratory bacteriology of patients with cystic fibrosis-data from the European cystic fibrosis society patient registry.

J Cyst Fibros 2020 05 3;19(3):376-383. Epub 2019 Sep 3.

Pediatric Pulmonology, Department of Pediatrics, University of Leuven, Leuven, Belgium. Electronic address:

Background: Monitoring changes in the epidemiology of cystic fibrosis (CF) pathogens is essential for clinical research, quality improvement, and clinical management.

Methods: We analyzed data reported to the European Cystic Fibrosis Society Patient Registry (ECFSPR) from 2011 to 2016 to determine the overall and the age-specific annual prevalence and incidence of selected CF pathogens and their trends during these years. The ECFSPR collects data on three chronic infections: Pseudomonas aeruginosa (PsA), Burkholderia cepacia complex Species (BCC) and Staphylococcus aureus (SA), as well as on the occurrence of non-tuberculous mycobacteria (NTM) and Stenotrophomonas maltophilia (SM). The same analyses were performed for different country groups, according to their gross national income (GNI).

Results: The pathogens with the highest prevalence were SA and PsA, with prevalence, in 2016, equal to 38.3% and 29.8% respectively, followed by SM (8.1%). The pathogens with the lowest prevalence were NTM (3.3%) and BCC (3.1%). The overall prevalence and incidence significantly decreased for PsA; they also decreased for BCC, while they increased significantly for SA. The overall prevalence of NTM and SM increased significantly. The most considerable prevalence changes were observed for PsA, which decreased across all income country groups and all age strata (with the exception of 0-1 years) The prevalence and incidence of pathogens differed significantly according to GNI.

Conclusions: The epidemiology of CF pathogens in Europe has changed; epidemiologic data differ significantly among countries with different socio-economic status. The causes of these observations are multifactorial and include improvements in clinical care and infection control.
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http://dx.doi.org/10.1016/j.jcf.2019.08.006DOI Listing
May 2020

Minimal increases of serum alpha-foetoprotein herald HCC detection in Caucasian HBV cirrhotic patients under long-term oral therapy.

Liver Int 2019 10 12;39(10):1964-1974. Epub 2019 Aug 12.

CRC 'A. M. and A. Migliavacca' Center for the Study of Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.

Background & Aims: In Caucasian patients with compensated cirrhosis caused by hepatitis B virus (HBV), the risk of hepatocellular carcinoma (HCC) developing persist despite long-term nucleos(t)ide analogs (NUC) treatment. In the surveillance of this population with persistently normal transaminases because of NUCs, the added value of serum alpha-foetoprotein (AFP) monitoring is poorly defined.

Methods: Two hundred and fifty-eight Caucasian HCC-free patients with HBV-compensated cirrhosis who started tenofovir or entecavir while having normal serum AFP levels (≤7 ng/mL) at baseline or within the first year of treatment underwent HCC surveillance by semiannual ultrasound evaluation and serum AFP determination.

Results: During 96 (18-120) months of antiviral therapy, 3947 AFP values were collected, median AFP level was 2 ng/mL. Thirty-five patients developed an HCC at an overall 8-year crude cumulative incidence of 14% (annual incidence of 2%). HCC incidence increased in parallel with increasing AFP thresholds: 24%, 36%, 64% and 92% for AFP levels after exceeding 2, 4, 6 and 7 ng/mL for the first-time. Of the 12 patients who experienced an AFP rise > 7 ng/mL, 11 developed an HCC and one had liver metastases of lung cancer. Overall, an AFP > 7 ng/mL had 99.6% specificity, 31.4% sensitivity, 91.7% PPV, 90.2% NPV, LR+ 70.1 and LR- 0.69 for HCC; this excellent specificity was maintained up to 18 months before HCC detection.

Conclusions: In Caucasian patients with HBV-compensated cirrhosis on long-term NUC, an increase in AFP over 7 ng/mL shows excellent specificity, heralding HCC development within 1 year.
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http://dx.doi.org/10.1111/liv.14197DOI Listing
October 2019

Investigation on Dabigatran Etexilate and Worsening of Renal Function in Patients with Atrial fibrillation: The IDEA Study.

Clin Drug Investig 2019 Apr;39(4):355-362

Department of Clinical Sciences and Community Health, Laboratory of Medical Statistics, Epidemiology, and Biometry G. A. Maccacaro, University of Milan, via Vanzetti 5, 20133, Milan, Italy.

Background And Objectives: Warfarin-related nephropathy is an unexplained acute kidney injury, and may occur in patients with supratherapeutic INR, in the absence of overt bleeding. Similar findings have been observed in rats treated with dabigatran etexilate. We conducted a prospective study in dabigatran etexilate-treated patients to assess the incidence of dabigatran-related nephropathy and to investigate the possible correlation between dabigatran plasma concentration (DPC) and worsening renal function.

Method: One hundred and seven patients treated long term with dabigatran etexilate for non-valvular atrial fibrillation (NVAF) were followed up for 90 days. DPC, serum creatinine (SCr) and serum cystatin C were prospectively measured. Ninety five patients had complete follow-up data and were evaluable for primary endpoint.

Results: Eleven patients had supratherapeutic DPC, defined as DPC higher than 200 ng/ml at study enrolment, but at the end of follow-up no patient showed a persistent increase in SCr. No patients experienced acute kidney injury.

Conclusions: Our study shows that no persistent renal detrimental effect is associated with dabigatran treatment. An increase in SCr during dabigatran treatment is reversible and it seems to be unrelated to dabigatran itself.
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http://dx.doi.org/10.1007/s40261-018-0742-1DOI Listing
April 2019

Total ankle replacement: is pre-operative varus deformity a predictor of poor survival rate and clinical and radiological outcomes?

Int Orthop 2019 01 15;43(1):243-249. Epub 2018 Oct 15.

Ortopedia e Traumatologia - Centro di Chirurgia dell'Anca e Traumatologia, I.R.C.C.S Policlinico San Donato, San Donato Milanese, Milan, Italy.

Purpose: The objective of this study was to compare survival rate and clinical and radiological outcomes of a cementless mobile-bearing total ankle replacement (TAR) between two groups of patients, affected by end-stage ankle arthritis, with or without a pre-operative varus deformity.

Methods: A total of 81 patients (81 ankles) were included in the study and divided in two groups. Group A, "varus" group, includes 11 patients with pre-operative varus deformity of more than 10 ° and group B, "neutral" group, includes 70 patients, with a varus/valgus deformity of less than 10 °. American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, visual analogue scale (VAS), and Short Form (SF)-12 score were used to compare clinical outcomes. Radiological parameters, complications, and survival rate at last follow-up were also recorded.

Results: In both groups, all clinical and radiological parameters improved after surgery (p < 0.05) without statistically significant difference. Complications were similar between two groups. Overall in three cases, an implant revision was necessary: 1 in group A (9%) at 3.1 years follow-up and 2 (3%) in group B at 3.8 years, without statistically significant difference (p > 0.001).

Conclusions: Severe varus malalignment should not be considered a contraindication for a mobile-bearing TAR. Nevertheless, TAR in severe deformity should be performed only by experienced surgeons.
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http://dx.doi.org/10.1007/s00264-018-4189-zDOI Listing
January 2019

Correction to: Observational study on the prognostic value of testosterone and adiposity in postmenopausal estrogen receptor positive breast cancer patients.

BMC Cancer 2018 09 10;18(1):876. Epub 2018 Sep 10.

Laboratory of Medical Statistics and Epidemiology,"Giulio A. Maccacaro", Department of Clinical Sciences and Community Health, University of Milan, Via Vanzetti 5, 20133, Milan, Italy.

Following publication of the original article [1], the authors reported that the affiliation of author Annalisa Orenti was omitted.
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http://dx.doi.org/10.1186/s12885-018-4799-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130063PMC
September 2018

Comorbidity burden conditions the prognostic performance of D-dimer in elderly patients with acute pulmonary embolism.

Am J Emerg Med 2019 05 18;37(5):799-804. Epub 2018 Jul 18.

Department of Clinical Sciences and Community Health, Laboratory of Medical Statistics, Epidemiology and Biometry G. A. Maccacaro, University of Milan, Milan, Italy.

Introduction: The prognostic accuracy of D-dimer for risk assessment in acute Pulmonary Embolism (APE) patients may be hampered by comorbidities. We investigated the impact of comorbidity burden (CB) by using the Charlson Comorbidity Index (CCI), on the prognostic ability of D-dimer to predict 30 and 90-day mortality in hemodynamically stable elderly patients with APE.

Methods: All patients aged >65 years with normotensive APE, consecutively evaluated in the Emergency Department since 2010 through 2014 were included in this retrospective cohort study. Area under the curve (AUC) and ½ Net Reclassification Improvement (NRI) were calculated.

Results: Study population: 162 patients, median age: 79.2 years. The optimal cut-off value of CCI score for predicting mortality was ≤1 (Low CB) and >1 (High CB), AUC = 0.786. Higher levels of D-dimer were associated with an increased risk death at 30 (HR = 1.039, 95%CI:1.000-1.080, p = 0.049) and 90 days (HR = 1.039, 95%CI:1.009-1.070, p = 0.012). When added to simplified Pulmonary Embolism Severity Index (sPESI) score, D-dimer increased significantly the AUC for predicting 30-day mortality in Low CB (AUC = 0.778, 95%CI:0.620-0.937, ½NRI = 0.535, p = 0.015), but not in High CB patients (AUC = 0.634, 95%CI:0.460-0.807, ½ NRI = 0.248, p = 0.294). Similarly, for 90-day mortality D-dimer increased significantly the AUC in Low CB (AUC = 0.786, 95%CI:0.643-0.929, ½NRI = 0.424, p-value = 0.025), but not in High CB patients (AUC = 0.659, 95%CI:0.541-0.778, ½NRI = 0.354, p-value = 0.165).

Conclusion: In elderly patients with normotensive APE, comorbidities condition the prognostic performance of D-dimer, which was found to be a better predictor of death in subjects with low CB. These results support multimarker strategies for risk assessment in this population.
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http://dx.doi.org/10.1016/j.ajem.2018.07.034DOI Listing
May 2019

Evidence of macro- and micro-angiopathy in scleroderma: An integrated approach combining 22-MHz power Doppler ultrasonography and video-capillaroscopy.

Microvasc Res 2019 03 6;122:125-130. Epub 2018 Jul 6.

Division of Rheumatology, ASST Pini-CTO, Milano, Italy; Dept of Clinical Sciences & Community Health, Università degli Studi di Milano, Milano, Italy. Electronic address:

Objective: We aimed to study in SSc patients macrovascular involvement by using power Doppler ultrasound (PDUS) and microvascular one by PDUS and nailfold video-capillaroscopy (NVC) and to examine the association between history of digital ulcers (HDU) and imaging (PDUS and NVC) parameters.

Methods: NVC and PDUS were systematically performed in 106 consecutive SSc patients at the 3rd and 4th finger of the dominant hand after exclusion of ulnar artery occlusion (UAO). 22 MHz PDUS measurements included nailbed and fingertip qualitatively graded, and resistivity index (RI) of ulnar and radial proper digital arteries. Capillary number/mm was calculated by NVC on the same digits examined by PDUS.

Results: Vascularization at fingertip and nailbed showed a good correlation between them and to capillary number. RI, representative of macrovascular involvement, did not correlate to microvascular involvement as assessed by PDUS and NVC. RI and capillary number at NVC showed significant correlation to HDU while fingertip and nailbed vascularization as assessed by PDUS did not. As such, PDUS and NVC provide different and potentially complementary information on SSc-related peripheral macro- and micro-vascular involvement.

Conclusion: Macro- and micro-vascular involvement in SSc patients are different processes and are not present at the same time in every patient. Thus, both these aspects should be carefully evaluated in SSc patients.
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http://dx.doi.org/10.1016/j.mvr.2018.07.001DOI Listing
March 2019

Observational study on the prognostic value of testosterone and adiposity in postmenopausal estrogen receptor positive breast cancer patients.

BMC Cancer 2018 Jun 13;18(1):651. Epub 2018 Jun 13.

Laboratory of Medical Statistics and Epidemiology,"Giulio A. Maccacaro", Department of Clinical Sciences and Community Health, University of Milan, Via Vanzetti 5, 20133, Milan, Italy.

Background: Despite the clear endocrine-metabolic relationship between androgenic activity and adiposity, the role of androgens in breast cancer prognosis according to patient's adiposity is scarcely explored. Here, we aimed at investigating the prognostic value of circulating testosterone in association with patient's body mass index (BMI).

Methods: Circulating testosterone and BMI were evaluated at breast cancer diagnosis in 460 estrogen receptor (ER)-positive postmenopausal patients. Local relapse, distant metastasi(e)s and contralateral breast cancer were considered recurrence events. The Kruskal-Wallis test was performed to evaluate if testosterone levels differed within subgroups of categorical tumour characteristics. The Cox proportional hazard regression model was fitted to estimate the impact of standard prognostic factors on relapse-specific hazard ratio (HR). After backward selection, a model including continuous testosterone level, BMI categories (< 25, normal-weight; =25-30, overweight; ≥30 kg/m, obese), tumour size and lymph nodes number was fitted. Furthermore, Cox models provided the relapse-specific HRs for median, third quartile and 95th percentile compared to the first quartile of testosterone levels, stratified by BMI categories.

Results: During a median follow up of 6.3 years, 45 patients relapsed. Testosterone levels significantly increased across BMI categories (p = 0.001). Both circulating testosterone and BMI were positively associated with disease free survival (p = 0.005 and p = 0.021, respectively). A significant interaction was found between testosterone and BMI (p = 0.006). For normal-weight women, testosterone concentration around median (0.403 ng/mL) or third quartile (0.532 ng/mL) showed a high significant HR of relapse (5.52; 95% CI:1.65-18.49 and 4.55; 95% CI:1.09-18.98, respectively). Overweight patients showed increased HR at increasing testosterone levels, reaching a significant high HR (4.68; 95% CI:1.39-15.70) for testosterone values of 0.782 ng/mL (95th percentile). For obese patients HR decreased (not significantly) at increased testosterone concentrations, explaining the interaction between testosterone levels and BMI categories.

Conclusions: In ER-positive postmenopausal breast cancer patients, high testosterone levels are associated with worse prognosis in normal-weight and overweight women, whereas in obese seems to be associated with a better outcome. Although the results require further validation, they suggest that assessment of circulating testosterone and BMI could help to identify postmenopausal ER-positive patients at higher risk of relapse and potentially open new therapeutic strategies.
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http://dx.doi.org/10.1186/s12885-018-4558-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5998599PMC
June 2018

Acute and chronic effects of two different intravenous iloprost regimens in systemic sclerosis: a pragmatic non-randomized trial.

Rheumatology (Oxford) 2018 Aug;57(8):1408-1416

Division of Rheumatology, ASST Pini-CTO, Università degli Studi di Milano, Milan, Italy.

Objectives: I.v. iloprost (ILO) may be used in the treatment of refractory RP and digital ulcers. We aim to evaluate the acute and chronic effects of two different ILO regimens by power Doppler US (PDUS) and nailfold videocapillaroscopy.

Methods: In this 3-month single-centre pragmatic non-randomized trial, 96 SSc patients were included and stratified according to ILO treatment as: no ILO (group A), ILO once monthly (group B) and ILO for five consecutive days (group C). Resistivity index (RI), finger pulp blood flow and periungual vascularization by PDUS, and sum of capillaries apex width in 1 mm by nailfold videocapillaroscopy were evaluated. Results were adjusted for the average outdoor temperature at the place of residence.

Results: An acute ILO effect was observed for only finger pulp blood flow in groups B and C (P < 0.001 and P < 0.005, respectively). An acute effect was observed for RI and periungual vascularization only in group B. A progressive increase was observed for other parameters without statistical difference. ILO effects were not observed any longer before the following infusion. Some parameters (finger pulp blood flow in group B and RI in group C) showed a statistically higher increase the lower the outdoor temperature was.

Conclusion: ILO had an acute effect as assessed by PDUS, especially in group B. By contrast, an ILO chronic effect was not detectable before the following infusion in both treatment groups. More studies are needed to define how often ILO should be administered.
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http://dx.doi.org/10.1093/rheumatology/key113DOI Listing
August 2018

Serum levels of testosterone and SHBG in association with body mass index improve the predictive capability of consolidate tumor biomarkers in pre- and postmenopausal breast cancer patients.

Jpn J Clin Oncol 2018 Apr;48(4):308-316

Senology Center, Casa di Cura Ambrosiana, Fondazione Sacra Famiglia, Cesano Boscone, Milan, Italy.

Objective: To investigate the contribution of serum levels of testosterone (TS) and sex hormone binding globulin (SHBG) in association with body mass index (BMI) as a surrogate marker of obesity, to the predictive capability of tumor size (T), lymph node (N) and estrogen receptor (ER) status and proliferative activity (TLI).

Methods: We investigated 120 women with primary breast cancer and median follow-up of 138 months. Serum levels of TS and SHBG and patient's BMI were evaluated before surgery. The contribution of TS, SHBG, their ratio (TS/SHBG) and BMI to the predictive capability of tumor-specific biomarkers was investigated by Harrell's c statistic.

Results: TS alone did not affect prognosis, whereas SHBG was protective in postmenopausal patients, in which BMI was associated with a progressive increase in the relapse-specific hazard ratio (HR). When in combination, TS, SHBG and BMI, affected prognosis in different ways depending on menopausal status. The best predictive capability (c = 0.78) was observed in postmenopausal patients when at the basic model (N + TLI) were added TS, BMI, TS * BMI interaction, with or without SHBG. In premenopause subgroup, the best predictive capability (c = 0.67) was provided by the basic model (N + TLI) plus TS and SHBG or their ratio, BMI and TS * BMI or TS/SHBG * BMI interaction.

Conclusions: Patient-associated features such as BMI and serum levels of TS and SHBG can improve the predictive capability of consolidate tumor-specific biomarkers in both pre- and postmenopause, thus providing a relevant contribution to the decision-making process.
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http://dx.doi.org/10.1093/jjco/hyy012DOI Listing
April 2018

An international SUrvey on non-iNvaSive tecHniques to assess the mIcrocirculation in patients with RayNaud's phEnomenon (SUNSHINE survey).

Rheumatol Int 2017 Nov 11;37(11):1879-1890. Epub 2017 Sep 11.

Centre for Musculoskeletal Research, The University of Manchester, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.

To canvas opinion concerning the role of non-invasive techniques in the assessment of patients with Raynaud's phenomenon (Rp) in clinical and research settings: four nailfold capillaroscopy methods [videocapillaroscopy (NVC), dermoscopy, stereomicroscopy, digital USB microscopy], four laser Doppler methods (laser Doppler flowmetry, imaging, anemometry/velocimetry, laser speckle contrast analysis), thermographic imaging, and upper limb arterial Doppler ultrasound. Emails with a link to the survey were sent to physicians from the European Scleroderma Trials and Research group (EUSTAR), the EULAR Study Group on Microcirculation in Rheumatic Diseases (SG_MC/RD) and members of the pediatric rheumatology Email board. The main descriptive analysis related to physicians looking after adult patients, with some analysis also of opinions from paediatric rheumatologists. 106 'adult physicians' responded (a response rate of 25.8%), of whom 68.9% were European, and 81.1% practising for more than 10 years. Nineteen paediatricians responded. The most widely available technique was NVC (72.7%). Nailfold capillaroscopy was most frequently performed by the physician him/herself, using different types of equipment relating to availability. Most rheumatologists reported high levels of appropriateness for NVC in both clinical and research settings for global assessment and differential diagnosis of Rp. Other techniques were less used. Of all the different techniques, nailfold capillaroscopy was the one most used in both clinical and research settings by adult physicians, the majority of whom use NVC in their everyday practice. The low proportion of clinicians using other techniques suggests that these are currently mainly research tools, available only in specialist centres.
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http://dx.doi.org/10.1007/s00296-017-3808-0DOI Listing
November 2017

Comorbidity assessment as predictor of short and long-term mortality in elderly patients with hemodynamically stable acute pulmonary embolism.

J Thromb Thrombolysis 2017 Oct;44(3):316-323

Laboratory of Medical Statistics, Epidemiology and Biometry G. A. Maccacaro, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.

Elderly patients presenting with acute pulmonary embolism (PE) frequently have significant underlying comorbidities which may condition the prognosis. The current study aimed to determine the ability of Charlson comorbidity index (CCI) score to predict short and long-term mortality in elderly patients with hemodynamically stable acute PE. All hemodynamically stable patients aged >65 years with acute PE, evaluated in the Emergency Department since 2010 through 2014, were included in this retrospective cohort study. CCI, simplified pulmonary embolism severity index (sPESI) scores and vital status were recorded. Were included 162 patients with confirmed PE, out of 657 suspected cases (24.7%). Median age: 79.2 years, 74.1% presented an sPESI > 1 and 61.1% a CCI > 1. The overall 30, 90-day and 2-year mortality was 11.7% (95%CI 6.6-16.6), 19.8% (95%CI 13.4-25.7) and 31.8% (95%CI 24.1-38.8). For 30-day mortality sPESI showed an AUC 0.642 (95%CI 0.511-0.772) and adding CCI as covariate did not increase its prognostic performance. For 90-day mortality, in an adjusted model including sPESI and CCI, CCI showed a HR 1.282 (95%CI 1.151-1.429, p-value < 0.001), and sPESI a HR = NS(p-value = 0.267). For 2-year mortality, in an adjusted model including sPESI and CCI, CCI showed a HR 1.295 (95%CI 1.180-1.421, p-value < 0.001) and sPESI a HR = NS(p-value = 0.353). In elderly patients with hemodynamically stable PE, the CCI score was found to be an independent predictor of mortality. CCI shows a significantly better ability to predict 90-day and 2-year mortality than sPESI. The assessment of comorbidity burden by using the CCI score may be proposed as an useful tool to predict mortality in these patients.
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http://dx.doi.org/10.1007/s11239-017-1540-yDOI Listing
October 2017

Serotypes not Included in 13-Valent Pneumococcal Vaccine as Causes of Acute Otitis Media with Spontaneous Tympanic Membrane Perforation in a Geographic Area with High Vaccination Coverage.

Pediatr Infect Dis J 2017 05;36(5):521-523

From the *Department of Pathophysiology and Transplantation, Pediatric Highly Intensive Care Unit, Università degli Studi di Milan, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; †Primary Care Pediatrician, Milan, Italy; and ‡Department of Clinical Sciences and Community Health, Unit of Medical Statistics, Biometry and Bioinformatics "G.A. Maccacaro," Università degli Studi di Milan, Milan, Italy.

In 177 children living in an area with high 13-valent pneumococcal conjugate vaccine 13 coverage, who had acute otitis media complicated with spontaneous tympanic membrane perforation, Streptococcus pneumoniae was identified in the middle ear fluid of 48 (27.1%) subjects, with 37 (77.1%) cases caused by nonpneumococcal conjugate vaccine 13 serotypes.
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http://dx.doi.org/10.1097/INF.0000000000001485DOI Listing
May 2017

Autoimmunity and Cytokine Imbalance in Inherited Epidermolysis Bullosa.

Int J Mol Sci 2016 Sep 24;17(10). Epub 2016 Sep 24.

Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy.

In order to evaluate the serum anti-skin autoantibodies and cytokine concentrations in patients with different epidermolysis bullosa (EB) types and severity, 42 EB patients and 38 controls were enrolled. Serum anti-skin antibodies were significantly higher in the patients than in the controls (p = 0.008, p < 0.001, p < 0.001, p < 0.001 and p < 0.001 for desmoglein 1 (DSG1) desmoglein 3 (DSG3), bullous pemphigoid 180 (BP180), BP230 and type VII collagen (COL7), respectively). The same trend was observed for interleukin (IL)-1β, IL-2, IL-6, IL-10, tumor necrosis factor-β, and interferon-γ (p < 0.001, p < 0.001, p < 0.001, p = 0.008, p < 0.001 and p = 0.002, respectively). Increases in anti-skin antibodies and cytokine concentrations were higher in patients with recessive dystrophic EB than in those with different types of EB, in generalized cases than in localized ones, and in patients with higher Birmingham Epidermolysis Bullosa Severity (BEBS) scores than in those with a lower score. The BEBS score was directly correlated with BP180, BP230, COL7 (p = 0.015, p = 0.008 and p < 0.001, respectively) and IL-6 (p = 0.03), whereas IL-6 appeared significantly associated with DSG1, DSG3, BP180, BP230 and COL7 (p = 0.015, p = 0.023, p = 0.023, p = 0.015 and p = 0.005, respectively). This study showed that autoimmunity and inflammatory responses are frequently activated in EB, mainly in severe forms, suggesting the use of immunosuppressive drugs or biologicals that are active against pro-inflammatory cytokines to reduce clinical signs and symptoms of disease.
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http://dx.doi.org/10.3390/ijms17101625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085658PMC
September 2016

Prognostic value of D-dimer in elderly patients with Pulmonary Embolism.

J Thromb Thrombolysis 2016 Oct;42(3):386-92

Research and Study Center of the Italian Society of Angiology and Vascular Pathology (Società Italiana di Angiologia E Patologia Vascolare, SIAPAV), Milan, Italy.

In a general population with acute Pulmonary Embolism (PE) elevated D-dimer concentrations associate with increased mortality. The aim of the study was to assess the ability of D-dimer to predict 30 and 90-days mortality in elderly patients with acute PE. Hemodynamically stable patients aged ≥65 years old with confirmed PE were included in this retrospective cohort study. A pulmonary computerized tomography angiography scan, D-dimer concentrations, simplified Pulmonary Embolism Severity Index (sPESI) variables and vital status were available for all patients. The study included 154 confirmed cases of PE (23.5 % of suspected), median age 79.1 years. D-dimer was higher in patients dead than in those alive at 30 (median 14,547 vs. 8340 ng/mL, p = 0.05) and 90 days (13,604 vs. 7973 ng/mL, p = 0.013). When adding D-dimer to sPESI, the discriminant capacity to predict mortality within 30 and 90 days was increased by 0.080 and 0.089, respectively. The contribution of D-dimer to the discriminating ability was NRI = 0.286 (95 % CI -0.198 to 0.770, p value: 0.247) at 30 days and NRI = 0.605 (95 % CI 0.223-0.988, p-value: 0.002) at 90 days.D-dimer concentration was associated with 30 and 90-days mortality and showed a higher discriminant capacity than sPESI alone to predict 90-days mortality. Adding D-dimer concentrations to sPESI score seems to improve its prognostic ability, supporting multivariable risk models as the best approach to estimate prognosis in elderly patients with PE.
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http://dx.doi.org/10.1007/s11239-016-1394-8DOI Listing
October 2016

Fever and Pain Management in Childhood: Healthcare Providers' and Parents' Adherence to Current Recommendations.

Int J Environ Res Public Health 2016 05 13;13(5). Epub 2016 May 13.

Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 9, Milano 20122, Italy.

In order to evaluate the adherence of healthcare providers and parents to the current recommendations concerning fever and pain management, randomized samples of 500 healthcare providers caring for children and 500 families were asked to complete an anonymous questionnaire. The 378 health care providers (HCPs) responding to the survey (75.6%) included 144 primary care pediatricians (38.1%), 98 hospital pediatricians (25.9%), 62 pediatric residents (16.4%), and 71 pediatric nurses (19.6%); the 464 responding parents (92.8%) included 175 whose youngest (or only) child was ≤5 years old (37.7%), 175 whose youngest (or only) child was aged 6-10 years (37.7%), and 114 whose youngest (or only) child was aged 11-14 years (24.6%). There were gaps in the knowledge of both healthcare providers and parents. Global adherence to the guidelines was lower among the pediatric nurses than the other healthcare providers (odds ratio 0.875; 95% confidence interval 0.795-0.964). Among the parents, those of children aged 6-10 and 11-14 years old, those who were older, and those without a degree answered the questions correctly significantly less frequently than the others. These findings suggest that there is an urgent need to improve the dissemination of the current recommendations concerning fever and pain management among healthcare providers and parents in order to avoid mistaken and sometimes risky attitudes, common therapeutic errors, and the unnecessary overloading of emergency department resources. Pediatric nurses and parents with older children, those who are older, and those with a lower educational level should be the priority targets of educational programmes.
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http://dx.doi.org/10.3390/ijerph13050499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881124PMC
May 2016

Antibody response to respiratory syncytial virus infection in children <18 months old.

Hum Vaccin Immunother 2016 07 22;12(7):1700-6. Epub 2016 Feb 22.

a Paediatric Highly Intensive Care Unit , Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Milan , Italy.

The development of a safe and effective respiratory syncytial virus (RSV) vaccine might be facilitated by knowledge of the natural immune response to this virus. The aims of this study were to evaluate the neutralizing antibody response of a cohort of healthy children <18 months old to RSV infection. During the RSV season, 89 healthy children <18 months old were enrolled and followed up weekly for 12 weeks. At each visit, a nasopharyngeal swab was obtained for RSV detection by real-time polymerase chain reaction (PCR). During the study period, 2 blood samples were drawn and they were used to determine RSV geometric mean neutralizing antibody titres (GMT) against RSV. A total of 35 (39.3%) children had RSV detected during the study period. Among RSV-positive patients, children ≥7 months showed a significantly higher increase in antibody response (p<0.001). A significantly higher number of patients with a ≥4 -fold increase in GMT were ≥7 months old (p = 0.02) and presented lower respiratory tract infections (LRTIs) during the study period (p = 0.01). Viral shedding was longer among children aged ≥7 months (p = 0.06), those with viral load ≥10(6) copies/mL (p = 0.03), and those with LRTIs during the study period (p = 0.03), but it was not associated with the immune response (p = 0.41). In conclusion, natural RSV infection seems to evoke a low immune response in younger children. To be effective in this infant population, which is at highest risk of developing severe LRTIs, vaccines must be able to induce in the first months of life a stronger immune response than that produced by the natural infection.
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http://dx.doi.org/10.1080/21645515.2016.1145847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964805PMC
July 2016

Pneumococcal colonization in older adults.

Immun Ageing 2016 12;13. Epub 2016 Jan 12.

Department of Pathophysiology and Transplantation, Pediatric Highly Intensive Care Unit, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 9, 20122 Milan, Italy.

Background: Little is known about pneumococcal carrier states in older adults. The main aim of this study was to evaluate pneumococcal colonization patterns among older adults in two centres in Milan, Italy, before the widespread use of the 13-valent pneumococcal vaccine (PCV13) in this age group, to investigate demographic and clinical features that are associated with pneumococcal colonization and to estimate the potential coverage offered by PCV13.

Results: Among 417 adults ≥65 years old (171, 41.1 %, ≥75 years), 41 (9.8 %) were pneumococcal carriers. Univariate and multivariate analyses revealed that pneumococcal colonization was significantly less common among individuals with underlying co-morbidities than among those without (odds ratio [OR] 0.453, 95 % confidence interval [CI] 0.235-0.875, p = 0.018; adjusted OR 0.503, 95 % CI 0.255-0.992, p = 0.047). Moreover, among these patients, those with cardiac disease had a significantly lower risk of colonization (OR 0.308, 95 % CI 0.119-0.795, p = 0.015; adjusted OR 0.341, 95 % CI 0.13-0.894, p = 0.029). Only one vaccinated subject who received 23-valent polysaccharide pneumococcal vaccine (PPV23) was colonized. Twenty-five (89.3 %) of the subjects who were <75 years old and 9 (75.0 %) of those who were ≥75 years old were colonized by at least one of the serotypes that is included in PCV13, with serotype 19 F being the most common. Respiratory allergies as well as overall co-morbidities were more common in subjects who were positive for only non-PCV13 serotypes compared with negative subjects and those who were carriers of only PCV13 serotypes.

Conclusions: Although this study included a relatively small number of subjects and has been performed in a limited geographic setting, results showed that pneumococcal colonization in older people is common, and the monitoring of carriers can offer useful information about the circulation of this pathogen among older people and the potential protective effect of pneumococcal vaccines. Because the colonization in most cases involves the strains that are included in PCV13, this vaccine could be useful in the prevention of pneumococcal infections in the overall population of older people. In subjects with respiratory allergies and in those with co-morbidities, the addition of the PPV23 to PCV13 should be recommended. Due to the low vaccination coverage, urgent educational programmes are required to inform older adults and their medical doctors of the risks of pneumococcal infection and the efficacy and safety of the available pneumococcal vaccines.
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http://dx.doi.org/10.1186/s12979-016-0057-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4709868PMC
January 2016

Genetic polymorphisms and the development of invasive bacterial infections in children.

Int J Immunopathol Pharmacol 2016 Mar 18;29(1):99-104. Epub 2015 Dec 18.

Pediatric High Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

To evaluate the associations between single nucleotide polymorphisms (SNPs) of factors involved in the development of invasive bacterial disease (IBD) in children, 47 SNPs of 18 candidate genes were analysed in 49 children with IBD and 100 controls. The G/T genotype of TLR2 rs2149356 and the C genotype of LTA rs2229094 were associated with significantly reduced risk of developing IBD (P=0.04 and P=0.05, respectively), whereas the C/T genotype of RFP175 rs1585110 was associated with a significantly higher risk of developing IBD (P=0.02). These results support the evidence that some genetic variants of factors involved in innate immunity may influence IBD risk in children.
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http://dx.doi.org/10.1177/0394632015622961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806737PMC
March 2016

Genetic Polymorphisms of Functional Candidate Genes and Recurrent Acute Otitis Media With or Without Tympanic Membrane Perforation.

Medicine (Baltimore) 2015 Oct;94(42):e1860

From the Pediatric High Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy (SE, PM, SS, SB, EN, CR, AZ, NP); and Unit of Medical Statistics, Biometry and Bioinformatics "G.A. Maccacaro", Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy (AO, EB).

Evaluation of the genetic contribution to the development of recurrent acute otitis media (rAOM) remains challenging. This study aimed to evaluate the potential association between single nucleotide polymorphisms (SNPs) in selected genes and rAOM and to analyze whether genetic variations might predispose to the development of complicated recurrent cases, such as those with tympanic membrane perforation (TMP).A total of 33 candidate genes and 47 SNPs were genotyped in 200 children with rAOM (116 with a history of TMP) and in 200 healthy controls.INFγ rs 12369470CT was significantly less common in the children with rAOM than in healthy controls (odds ratio [OR] 0.5, 95% confidence interval [CI] 0.25-1, P = 0.04). Although not significant, interleukin (IL)-1β rs 1143627G and toll-like receptor (TLR)-4 rs2737191AG were less frequently detected in the children with rAOM than in controls. The opposite was true for IL-8 rs2227306CT, which was found more frequently in the children with rAOM than in healthy controls. The IL-10 rs1800896TC SNP and the IL-1α rs6746923A and AG SNPs were significantly more and less common, respectively, among children without a history of TMP than among those who suffered from this complication (OR 2.17, 95% CI 1.09-4.41, P = 0.02, and OR 0.42, 95% CI 0.21-0.84, P = 0.01).This study is the first report suggesting an association between variants in genes encoding for factors of innate or adaptive immunity and the occurrence of rAOM with or without TMP, which confirms the role of genetics in conditioning susceptibility to AOM.
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http://dx.doi.org/10.1097/MD.0000000000001860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620788PMC
October 2015
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