Cystic fibrosis in Europe: improved lung function and longevity - reasons for cautious optimism, but challenges remain.

BACKGROUND: Prognosis and disease severity in cystic fibrosis (CF) are linked to declining lung function. To characterise lung function by the number of adults in countries with different levels of Gross National Income (GNI), data from the European Cystic Fibrosis Society Patient Registry were utilised. METHODS: Annual data including age, forced expiratory volume in 1 s (FEV1), anthropometry, genotype, respiratory cultures and CF-related diabetes (CFRD) were retrieved between 2011 and 2021. All countries were stratified into GNI per capita to reflect differences within Europe. RESULTS: A consistent improvement in FEV1 % pred and survival was observed among the 47 621 people with CF (pwCF), including subjects with chronic Pseudomonas aeruginosa infection, CFRD and/or undernutrition. Mean values of FEV1 % pred changed from 85% to 94.2% for children and from 63.6% to 74.7% for adults. FEV1 % pred further increased among those carrying the F508del mutation in 2021, when elexacaftor/tezacaftor/ivacaftor was available. The number of adult pwCF increased from 13 312 in 2011 to 21 168 in 2021, showing a 60% increase. PwCF living in European lower income countries did not demonstrate a significant annual increase in FEV1 % pred or in the number of adults. CONCLUSION: This pan-European analysis demonstrates a consistent improvement in FEV1 % pred, number of adult pwCF and survival over the last decade only in European higher and middle income countries. Urgent action is needed in the lower income countries where such improvement was not observed. The notable improvement observed in pwCF carrying the F508del mutation emphasises the need to develop treatments for all CF mutations.

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

BACKGROUND: Median survival for cystic fibrosis (CF) patients in Europe is unknown and is likely to be influenced by socioeconomic factors. Using the European CF 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 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, CF transmembrane conductance regulator (CFTR) genotype and transplant status. RESULTS: 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 (95% CI 50.0-53.4) years. After adjusting for potential confounders age at diagnosis, sex, CFTR genotype and transplant status, there remained strong evidence of an association between socioeconomic factors and mortality (p<0.001). Countries in the highest third of healthcare spending had a 46% lower hazard of mortality (HR 0.54, 95% CI 0.45-0.64) than countries in the lowest third of healthcare spending. CONCLUSIONS: Median survival for patients with CF in Europe is comparable to that reported in other jurisdictions and differs by socioeconomic factors.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

Following publication of the original article [1], the authors reported that the affiliation of author Annalisa Orenti was omitted.

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

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/m2, 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.

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.

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.

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

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.

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

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.

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

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.

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

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.

Pneumococcal colonization in older adults.

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.

Autoimmunity and Cytokine Imbalance in Inherited Epidermolysis Bullosa.

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)-1ß, IL-2, IL-6, IL-10, tumor necrosis factor-ß, 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.