The primary study objective was to investigate three decades from 1985 to 2014 of changes in pregnancies among HIV-infected women. The secondary objective was to assess risk factors associated with ...preterm delivery and severe small-for-gestational-age (SGA) infants in HIV-infected women. A retrospective review of deliveries among pregnant HIV-infected women at the University of Genoa and IRCCS San Martino-IST in Genoa between 1985 and 2014 was performed. Univariate and multivariable analyses were used to study the variables associated with neonatal outcomes. Overall, 262 deliveries were included in the study. An increase in median age (26 years in 1985–1994 vs. 34 years in 2005–2014), in the proportion of foreigners (none in 1985–1994 vs. 27/70 (38·6%) in 2005–2014), and a decrease in intravenous drug use (75·2% (91/121) in 1985–1994 vs. 12·9% (9/70) in 2005–2014) among pregnant HIV-infected women was observed. Progressively, HIV infections were diagnosed sooner (prior to pregnancy in 80% (56/70) of women in the last decade). An increase in combined antiretroviral therapy (cART) prescription during pregnancy (50% (27/54) in 1995–2004 vs. 92·2% (59/64) in 2005–2014) and in HIV-RNA <50 copies/ml at delivery (19·2% (5/26) in 1995–2004 vs. 82·3% (53/64) in 2005–2014) was observed. The rate of elective caesarean section from 1985 to 1994 was 9·1%, which increased to 92·3% from 2004 to 2015. Twelve (10·1%) mother-to-child transmissions (MTCT) occurred in the first decade, and six (8·3%) cases occurred in the second decade, the last of which was in 2000. Preterm delivery (<37 weeks gestation) was 5% (6/121) from 1985 to 1994 and increased to 17·1% (12/70) from 2005 to 2014. In univariate and multivariable logistic regression analyses, advancing maternal age and previous pregnancies were associated with preterm delivery (odds ratio (OR) 2·7; 95% confidence intervals (CI) 1–7·8 and OR 2·6; 95% CI 1·1–6·7, respectively). In the logistic regression analysis, use of heroin or methadone was found to be the only risk factor for severe SGA (OR 3·1; 95% CI 1·4–6·8). In conclusion, significant changes in demographic, clinical and therapeutic characteristics of HIV-infected pregnant women have occurred over the last 30 years. Since 2000, MTCT has decreased to zero. An increased risk of preterm delivery was found to be associated with advancing maternal age and previous pregnancies but not with cART. The use of heroin or methadone has been confirmed as a risk factor associated with severe SGA.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
A retrospective study was conducted to assess the role of initial serum (1,3)-β-d-glucan (BDG) values in predicting mortality in proven candidaemia. The study was conducted in two large teaching ...hospitals in Italy and Brazil. From January 2009 to June 2014, all patients with proven candidaemia who underwent a BDG test within 96 hours before or after the first positive blood culture were included in the study. The primary end point was 28-day mortality, with the role of initial BDG being assessed by univariate and multivariate analyses. A total of 104 patients met the inclusion criteria. Overall, the crude 28-day mortality was 30% (31/104). In the final multivariate model, an initial BDG of >287 pg/mL (odds ratio (OR) 4.40, 95% confidence interval (CI) 1.56–12.39, p 0.005), haemodialysis (OR 4.33, 95% CI 1.24–15.17, p 0.022) and a Pitt score of ≥2 (OR 4.10, 95% CI 1.24–13.54, p 0.021) were significant predictors of 28-day mortality. The >287 pg/mL cutoff predicted 28-day mortality with 65% sensitivity and 70% specificity. Centre of enrolment (p for interaction 0.012), haemodialysis (p for interaction 0.062) and timing of BDG test of more than 24 hours before or after the positive culture (p for interaction 0.143) appeared to interact with BDG's ability to predict mortality. Although not statistically significant, the last two of these interactions might partially explain why BDG's ability to predict mortality was present only in the Italian cohort.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Objectives
To investigate the long-term safety and efficacy of a treatment switch to dual ART with atazanavir/ritonavir + lamivudine versus continuing a standard regimen with ...atazanavir/ritonavir + 2NRTI in virologically suppressed patients.
Methods
ATLAS-M is a 96 week open-label, randomized, non-inferiority (margin −12%) trial enrolling HIV-infected adults on atazanavir/ritonavir + 2NRTI, with stable HIV-RNA <50 copies/mL and CD4 counts >200 cells/mm3. At baseline, patients were randomized 1:1 to switch to atazanavir/ritonavir + lamivudine or to continue the previous regimen. Here, we report the 96 week efficacy and safety data. The study was registered with ClinicalTrials.gov, number NCT01599364.
Results
Overall, 266 subjects were enrolled (133 in each arm). At 96 weeks, in the ITT population, patients free of treatment failure totalled 103 (77.4%) with atazanavir/ritonavir + lamivudine and 87 (65.4%) with triple therapy (difference +12.0%, 95% CI +1.2/+22.8, P = 0.030), demonstrating the superiority of dual therapy. Two (1.5%) and 9 (6.8%) virological failures occurred in the dual-therapy arm and the triple-therapy arm, respectively, without development of resistance to any study drug. Clinical adverse events occurred at similar rates in both arms. A higher frequency of grade 3–4 hyperbilirubinemia (66.9% versus 50.4%, P = 0.006) and hypertriglyceridaemia (6.8% versus 1.5%, P = 0.031) occurred with dual therapy, although this never led to treatment discontinuation. A significant improvement in renal function and lumbar spine bone mineral density occurred in the dual-therapy arm. The evolution of CD4, HIV-DNA levels and neurocognitive performance was similar in both arms.
Conclusions
In this randomized study, a treatment switch to atazanavir/ritonavir + lamivudine was superior over the continuation of atazanavir/ritonavir + 2NRTI in virologically suppressed patients, with a sustained benefit in terms of improved renal function and bone mineral density.
A retrospective study was conducted to assess the role of initial serum (1,3)- beta -d-glucan (BDG) values in predicting mortality in proven candidaemia. The study was conducted in two large teaching ...hospitals in Italy and Brazil. From January 2009 to June 2014, all patients with proven candidaemia who underwent a BDG test within 96 hours before or after the first positive blood culture were included in the study. The primary end point was 28-day mortality, with the role of initial BDG being assessed by univariate and multivariate analyses. A total of 104 patients met the inclusion criteria. Overall, the crude 28-day mortality was 30% (31/104). In the final multivariate model, an initial BDG of >287 pg/mL (odds ratio (OR) 4.40, 95% confidence interval (CI) 1.56-12.39, p 0.005), haemodialysis (OR 4.33, 95% CI 1.24-15.17, p 0.022) and a Pitt score of greater than or equal to 2 (OR 4.10, 95% CI 1.24-13.54, p 0.021) were significant predictors of 28-day mortality. The >287 pg/mL cutoff predicted 28-day mortality with 65% sensitivity and 70% specificity. Centre of enrolment (p for interaction 0.012), haemodialysis (p for interaction 0.062) and timing of BDG test of more than 24 hours before or after the positive culture (p for interaction 0.143) appeared to interact with BDG's ability to predict mortality. Although not statistically significant, the last two of these interactions might partially explain why BDG's ability to predict mortality was present only in the Italian cohort.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To estimate the sensitivity and specificity of posterior elevation in discriminating keratoconus and subclinical keratoconus from normal corneas.
Prospective case-control study.
Seventy-five patients ...with keratoconus, 25 with subclinical keratoconus, and 64 refractive surgery candidates with normal corneas.
In one eye of each patient, posterior corneal elevation was measured in the central 5 mm using the Pentacam rotating Scheimpflug camera (Oculus, Wetzlar, Germany). Posterior corneal elevation in keratoconus and subclinical keratoconus were compared with that in normal corneas in separate analyses. Receiver operating characteristic (ROC) curves were used to determine the test's overall predictive accuracy (area under the curve) and to identify optimal posterior corneal elevation cutoff points to maximize sensitivity and specificity in discriminating keratoconus and subclinical keratoconus from normal corneas. Logistic regression was used to support cutoff points identified through ROC curve analysis, and to check for model validity; model goodness-of-fit was estimated using r(2), and its internal validation was by bootstrapping analysis.
Posterior corneal elevation in keratoconus, subclinical keratoconus, and normal corneas.
Mean posterior corneal elevation was statistically higher in keratoconus (100.7+/-49.2 microm; P<0.001), and subclinical keratoconus (39.9+/-15.0 microm; P = 0.01) versus normal corneas (19.8+/-6.37 microm). ROC curve analyses showed high overall predictive accuracy of posterior elevation for both keratoconus and subclinical keratoconus (area under the curve 0.99 and 0.93, respectively). Optimal cutoff points were 35 microm for keratoconus and 29 microm for subclinical keratoconus. These values were associated with sensitivity and specificity of 97.3% and 96.9%, respectively, for keratoconus, and 68% and 90.8% for subclinical keratoconus. Similar cutoff points were obtained with logistic regression analysis (38 microm for keratoconus and 32 microm for subclinical keratoconus). The models showed good fit to the data, including after internal validation.
Posterior corneal elevation very effectively discriminates keratoconus from normal corneas. Its efficacy is lower for subclinical keratoconus, and thus data concerning posterior elevation should not be used alone to stratify patients with this condition.
P2X7 Variants in Pathophysiology Pegoraro, Anna; Grignolo, Marianna; Ruo, Luigia ...
International journal of molecular sciences,
06/2024, Volume:
25, Issue:
12
Journal Article
Peer reviewed
Open access
P2X7 receptor activation by extracellular adenosine triphosphate (eATP) modulates different intracellular pathways, including pro-inflammatory and tumor-promoting cascades. ATP is released by cells ...and necrotic tissues during stressful conditions and accumulates mainly in the inflammatory and tumoral microenvironments. As a consequence, both the P2X7 blockade and agonism have been proposed as therapeutic strategies in phlogosis and cancer. Nevertheless, most studies have been carried out on the WT fully functional receptor variant. In recent years, the discovery of P2X7 variants derived by alternative splicing mechanisms or single-nucleotide substitutions gave rise to the investigation of these new P2X7 variants’ roles in different processes and diseases. Here, we provide an overview of the literature covering the function of human P2X7 splice variants and polymorphisms in diverse pathophysiological contexts, paying particular attention to their role in oncological and neuroinflammatory conditions.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The built heritage of the 20
th
century concerns society in general: it is the background to everyday life and the stage of ‘past experience’. Therefore, recent past buildings should not be ...considered merely for their aesthetic features; they also have to do with physical well-being, social rituals and representations, as well as with associated concepts such as values and emotions. But conservation of 20
th
-century heritage is not straightforward. It requires specific strategies as well as critical and operational tools, which are not part of the cultural background of the actors of the transformation of our cities (architects, engineers, heritage officials, etc.) and do not yet feature in current design teaching curricula in most universities. To fill these gaps, in 2008 four Swiss architectural schools (USI, EPFL, ETHZ, SUPSI) launched a research project titled ‘Critical Encyclopaedia for reuse and restoration of 20
th
-century architecture’ (2009–2013). The article presents one of the outcomes of this research: the work developed by the section titled ‘Historical and Critical Tools for Conservation’, which will be published shortly. It provides readers with the cultural, theoretical and critical frame of reference required to understand recent architectural heritage in its widest sense: as a historical, symbolic and aesthetic resource, but also as being endowed with social, economic and ecological value. By examining theories and doctrines which have developed over time and thanks to the exemplary nature and variety of the selected cases, it provides a historical appraisal of how intervention in the field of recent heritage has evolved over the past 60 years. Furthermore the oeuvre presents intervention tools in action: by analysing a vast array of case studies which address the main areas of conservation practice (historical and critical research, analysis of materials and technical features, identification of compatible new uses, regulatory compliance), it provides a methodology to develop concrete and appropriate criteria for any specific case.
Purpose To assess repeatability, reproducibility, and agreement of rotating Scheimpflug camera (Pentacam Oculus, Wetzlar, Germany) and ultrasound pachymetry in measuring central thickness of ...keratoconic corneas. Design Method-comparison study. Methods In 33 patients with keratoconus (one eye per patient), two examiners each used both pachymetric methods to measure central corneal thickness (CCT); in the same session, measurements then were repeated by examiner 1 (A.M.). The difference between two examiners, and between first and second measurements by examiner 1, with both methods and the difference between the two pachymetric methods in measuring central thickness of keratoconic corneas were noted. Results With the rotating Scheimpflug camera, interexaminer correlation was higher (intra-class correlation coefficient ICC, 0.98 vs 0.76) and inter-examiner variability was lower (95% limits of agreement 95% LoA, −14.8 to 13.8 μm vs −18.0 to +49.5 μm) than with ultrasound pachymetry. Both methods showed close first- to second-measurement correlation (ICC, > 90), but the rotating Scheimpflug camera had lower variability (95% LoA, −14.5 to 14.2 μm vs −27.4 to 26.0 μm). Mean CCT was 478.9 ± 34.6 μm with the rotating Scheimpflug camera and 486.6 ± 30 μm with ultrasound pachymetry. Although the mean difference was small (−7.8 μm), the 95% LoA (−43.8 to 28.2 μm) showed that the difference between the two methods can be considerable. Conclusions In keratoconic corneas, the rotating Scheimpflug camera provides measurements of central thickness that are more reproducible and repeatable than those obtained with ultrasound pachymetry. The rotating Scheimpflug camera seems to be suitable for disease staging and follow-up, when corneal thickness measurements may be repeated over time by different examiners.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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