Ospedale Maggiore Policlinico Research Articles

Prognostic Significance of NLR and PLR in COVID-19: A Multi-Cohort Validation Study.

Recent studies have highlighted the prognostic value of easily accessible inflammatory markers, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) for predicting severe outcomes in patients affected by Coronavirus disease 2019 (COVID-19). Our study validates NLR and PLR cut-off values from a prior cohort at IRCCS Policlinico San Matteo (OSM) of Pavia, Italy, across two new cohorts from different hospitals. This aims to enhance the generalizability of these prognostic indicators. In this retrospective cohort study, conducted at Milan's Ospedale Luigi Sacco (OLS) and IRCCS Ospedale Maggiore Policlinico (OMP) hospitals, we assess the predictive capacity of NLR and PLR for three main outcomes-non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP) usage, invasive ventilation (IV), and death-in patients with COVID-19 at admission. For each outcome, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were computed separately for male and female cohorts. Distinct NLR and PLR cut-off values were used for men (7.00, 7.29, 7.00 for NLR; 239.22, 248.00, 250.39 for PLR) and women (6.36, 7.00, 6.28 for NLR; 233.00, 246.45, 241.54 for PLR), retrieved from the first cohort at OSM. A total of 3599 patients were included in our study, 1842 from OLS and 1757 from OMP. OLS and OMP sensitivity values for both NLR and PLR (NLR: 24-67%, PLR: 40-64%) were inferior to specificity values (NLR: 64-76%, PLR: 55-72%). Additionally, PPVs generally remained lower (< 63%), while NPVs consistently surpassed 68% for PLR and 72% for NLR. Finally, both PLR and NLR exhibited consistently higher NPVs for more severe outcomes (> 82%) compared to NPVs for CPAP/NIV. Consistent findings across diverse patient populations validate the reliability and applicability of NLR and PLR cut-off values. High NPVs emphasize their role in identifying individuals less likely to experience severe outcomes. These markers not only aid in risk stratification but also guide resource allocation in emergencies or limited-resource situations.

Validation of Indirect Calorimetry in Children Undergoing Single-Limb Non-Invasive Ventilation: A Proof of Concept, Cross-Over Study.

The accurate assessment of resting energy expenditure (REE) is essential for personalized nutrition, particularly in critically ill children. Indirect calorimetry (IC) is the gold standard for measuring REE. This methodology is based on the measurement of oxygen consumption (VO2) and carbon dioxide production (VCO2). These parameters are integrated into the Weir equation to calculate REE. Additionally, IC facilitates the determination of the respiratory quotient (RQ), offering valuable insights into a patient's carbohydrate and lipid consumption. IC validation is limited to spontaneously breathing and mechanically ventilated patients, but it is not validated in patients undergoing non-invasive ventilation (NIV). This study investigates the application of IC during NIV-CPAP (continuous positive airway pressure) and NIV-PS (pressure support). This study was conducted in the Pediatric Intensive Care Unit of IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, between 2019 and 2021. Children < 6 years weaning from NIV were enrolled. IC was performed during spontaneous breathing (SB), NIV-CPAP, and NIV-PS in each patient. A Bland-Altman analysis was employed to compare REE, VO2, VCO2, and RQ measured by IC. Fourteen patients (median age 7 (4; 18) months, median weight 7.7 (5.5; 9.7) kg) were enrolled. The REE, VO2, VCO2, and RQ did not differ significantly between the groups. The Limits of Agreement (LoA) and bias of REE indicated good agreement between SB and NIV-CPAP (LoA +28.2, -19.4 kcal/kg/day; bias +4.4 kcal/kg/day), and between SB and NIV-PS (LoA -22.2, +23.1 kcal/kg/day; bias 0.4 kcal/kg/day). These preliminary findings support the accuracy of IC in children undergoing NIV. Further validation in a larger cohort is warranted.

Correlation Between Colposcopic Patterns and Histological Grade of Vaginal Intraepithelial Neoplasia: A Retrospective Cohort Study.

Vaginal intraepithelial neoplasia (VaIN) is a rare human papillomavirus (HPV)- related premalignant condition. VaIN lesions are diagnosed histologically through colposcopy-guided biopsies of suspicious areas, conduced by gynecologists with expertise in lower genital tract diseases. The present study aimed to evaluate the accuracy of colposcopy in the diagnosis of VaIN of any grade. We conducted a retrospective analysis on a cohort of 149 women diagnosed with low grade (LG)-VaIN (VaIN1) and high grade (HG)-VaIN (VaIN2-3) between 2010 and 2022 at the "Regional Referral Center for Prevention, Diagnosis and Treatment of HPV-related Genital Disorders", Ospedale Maggiore Policlinico, Milan, Italy. All women had been referred to our center for an abnormal Pap smear or as part of routine follow-up of other HPV-related diseases and had undergone a vaginal biopsy under colposcopic guidance. The distribution of the histological grades of VaIN lesions was the following: 62 women (41.6%) were diagnosed with VaIN1, 51 (34.2%) with VaIN2, and 36 (24.2%) with VaIN3. Grade II (major) abnormal colposcopic patterns were recorded in 71 cases (47.7%) and were more commonly observed in women with VaIN3 (80.6%). However, we found a poor and not statistically significant association between colposcopic and histological grade of VaIN. The sensitivity, specificity, positive predictive value, and negative predictive value of colposcopy for histologically confirmed VaIN were 56.3%, 64.5%, 69% and 51.2%, respectively. The overall diagnostic accuracy of colposcopy was 59.7%. Colposcopy-guided biopsy plays an important role in the diagnosis of VaIN and in the distinction between low and high-grade lesions. Our data show that major colposcopic abnormalities moderately correlate with HG-VaIN and that grade I colposcopic findings do not exclude HG-VaIN, especially VaIN2. Targeted biopsies of suspicious vaginal areas must be performed in all women with an abnormal Pap smear.

PM2 .5, PM10 and bronchiolitis severity: A cohort study.

A few studies suggest that particulate matter (PM) exposure might play a role in bronchiolitis. However, available data are mostly focused on the risk of hospitalization and come from retrospective studies that provided conflicting results. This prospective study investigated the association between PM (PM_2.5 and PM₁₀ ) exposure and the severity of bronchiolitis. This prospective cohort study was conducted between November 2019 and February 2020 at the pediatric emergency department of the Fondazione IRCCS Ca' Ospedale Maggiore Policlinico, Milan, Italy. Infants &lt;1year of age with bronchiolitis were eligible. The bronchiolitis severity score was assessed in each infant and a nasal swab was collected to detect respiratory viruses. The daily PM₁₀ and PM_2.5 exposure in the 29 preceding days were considered. Adjusted regression models were employed to evaluate the association between the severity score and PM₁₀ and PM_2.5 exposure. A positive association between the PM_2.5 levels and the severity score was found at day-2 (β 0.0214, 95% CI 0.0011-0.0417, p=.0386), day-5 (β 0.0313, 95% CI 0.0054-0.0572, p=.0179), day-14 (β 0.0284, 95% CI 0.0078-0.0490, p=.0069), day-15 (β 0.0496, 95% CI 0.0242-0.0750, p=.0001) and day-16 (β 0.0327, 95% CI 0.0080-0.0574, p=.0093).Similar figures were observed considering the PM₁₀ exposure and limiting the analyses to infants with respiratory syncytial virus. This study shows for the first time a direct association between PM_2.5 and PM₁₀ levels and the severity of bronchiolitis.

P.168 Observational study: The quality of life in patients with alpha-sarcoglycan, beta-sarcoglycan and gamma-sarcoglycan gene mutation

LGMDR3, LGMDR4, LGMDR5 are recessive autosomal diseases, there are no specific treatments, except for some physical therapies that prevent worsening of muscle contractures and therapies associated with cardiac and respiratory problems. In 2013 the volunteer organization named Family Group of Beta-sarcoglycanopathy (GFB ODV; www.lgmd2e.org) was established to stimulate and support basic and clinical research on these diseases. Since 2012, families of the GFB ODV funded a research project of gene therapy for LGMDR4, under the supervision of Prof. J. Mendell, at the Ohio State University (Columbus, Ohio, USA). The first clinical trial, conducted by Sarepta Therapeutics, is currently underway. In 2018 GFB Odv promoted a natural history study on Italian patients "Clinical Determinants of disease progression in patients with beta-sarcoglycan gene mutations", led by Prof. Yvan Torrente, of the University of Milan, Ospedale Maggiore Policlinico in Milan, Italy. Since 2021 GFB Odv has started an ongoing observational study on the quality of life in patients with beta-sarcoglycan, alpha-sarcoglycan, and gamma-sarcoglycan gene mutation, again in collaboration with Prof. Yvan Torrente. The study is aimed at international GFB patients. At this time 139 patients from 45 countries have joined the Project: in particular, 68 with LGMDR4, 32 with LGMDR5, 39 with LGMDR3. 201 questionnaires have already been filled out. The ACTIVLIM, ABILHAND, EK, PEDSQL and PROMIS scales are used in the study, both in paper and electronic format. The study will run for 3 years and the scales will be given to patients every 6 months.

Minor Recurrent Aphthous Ulcer Management with Hyaluronic Acid Gel in an Italian Cohort: A Double-Blind Randomized Clinical Trial

Background. Recurrent aphthous ulcer is a common mucosal disease and encompasses diverse interventions for its management of symptoms like pain and discomfort. Since new therapies keep evolving with better outcomes as compared to traditional interventions, one such therapy using hyaluronic acid has been recently explored using clinical studies based on advances in dental therapeutics. Therefore, we designed this clinical study which is double blinded and randomized using minor recurrent aphthous cases. Objective. To evaluate the efficacy of hyaluronic acid topical oral gel in the treatment of minor RAS ulcers, with regard to pain relief and reduction in ulcer size. Design. A double-blind randomized controlled clinical trial was designed to conduct an experimental research at IRCCS Fondazione Ca’ Granda, Ospedale Maggiore Policlinico, Milan. The participants were recruited from the unit of oral maxillofacial surgery and randomly assigned to test (hyaluronic acid gel) and control groups (placebo gel). 1 : 1 computer-generated random sequence was prepared, and opaque closed envelopes were used for allocation concealment. Participants and clinical investigators were blinded. The outcome measures included ulcer size (mm) and the visual analogue scale for pain and healing as a secondary outcome measure (efficacy index). Results. The mean baseline score for ulcer size for the test group was1.85±1and the placebo group was1.85±1.2. At day 7, the test group was1±1.5and the placebo group was2±1.5(p&lt;0.001). There was significant reduction in ulcer size as compared to the placebo group. In addition, there was significant improvement in pain levels (p&lt;0.01) in the test group as compared to the control group. Conclusion. In conclusion, there was significant decrease in the size of the ulcer in the test group as compared to the placebo group. Hyaluronic acid seems to have promising effects on the ulcer size and pain relief associated with minor aphthous ulcers. Trial Registration. The protocol of this clinical trial was registered with the Clinical Trial Registry of ISRCTN with study ID ISRCTN16509838, registered 30 June 2020. It can be accessed on this URL: 10.1186/ISRCTN16509838

Conservative Treatment for Cervical Adenocarcinoma In Situ: Long-Term Results.

This study aimed to evaluate the effectiveness of conservative treatment for cervical adenocarcinoma in situ (AIS). This is a retrospective study on women with histologically confirmed AIS on cervical loop electrosurgical excision procedure specimen, treated conservatively between 2008 and 2020 in our center, Ospedale Maggiore Policlinico, Milan. The main outcome investigated was the risk of recurrence defined as a subsequent finding of recurrent AIS or invasive adenocarcinoma in a long-term follow-up. The disease-free survival curve was computed using the Kaplan-Meyer method. All patients underwent colposcopy with endocervical curettage and cytology every 6 months for the first 2 years after initial surgery and then annual cytology. Thirty women, aged 26 to 51 years, with histologically proven AIS on excisional specimen with negative margins, negative apex, and negative endocervical curettage were included. The median follow-up was 5.4 years. One woman had a recurrence of AIS after 8 years of follow-up and underwent total hysterectomy. No invasive cervical disease was detected during surveillance. Women with cervical AIS can be managed conservatively by an excisional procedure, provided that the margins are free and a close and long-term follow-up is guaranteed.

Paradoxical Effect of Chest Wall Compression on Respiratory System Compliance: A Multicenter Case Series of Patients With ARDS, With Multimodal Assessment

Paradoxical Effect of Chest Wall Compression on Respiratory System Compliance: A Multicenter Case Series of Patients With ARDS, With Multimodal Assessment

INSIDE Project: Individual Air Pollution Exposure, Extracellular Vesicles Signaling and Hypertensive Disorder Development in Pregnancy.

Hypertensive disorders are common complications during pregnancy (HDP) with substantial public health impact. Acute and chronic particulate matter (PM) exposure during pregnancy increases the risk of HDP, although the underlying molecular mechanisms remain unclear. Extracellular vesicles (EVs) may be the ideal candidates for mediating the effects of PM exposure in pregnancy as they are released in response to environmental stimuli. The INSIDE project aims to investigate this mechanism in pregnancy outcomes. The study population is enrolled at the Fetal Medicine Unit of Fondazione IRCCS Ca’Granda—Ospedale Maggiore Policlinico at 10–14 weeks of gestation. Exposure to PM10 and PM2.5 is assessed using the flexible air quality regional model (FARM) and Bayesian geostatistical models. Each woman provides a blood sample for EV analysis and circulating biomarker assessment. Moreover, a subgroup of recruited women (n = 85) is asked to participate in a cardiovascular screening program including a standard clinical evaluation, a non-invasive assessment of right ventricular function, and pulmonary circulation at rest and during exercise. These subjects are also asked to wear a personal particulate sampler, to measure PM10, PM2.5, and PM1. The INSIDE study is expected to identify the health impacts of PM exposure on pregnancy outcomes.

PF737 SURVIVAL RATES AND CAUSES OF DEATH IN ELDERLY PATIENTS WITH SICKLE CELL DISEASE

Background: Sickle cell disease (SCD) is endemic in the native Italian population, mainly localized in Southern regions with prevalent βthal/HbS genotype. In the last decade, the number of affected SCD subjects has increased globally throughout Italy, partly due to the migratory phenomena from North and Central Africa, the Balkans, Central and South American countries, and the Far East, leading to a change in the national distribution of SCD. Aims: The main aim of the study was to define survival and causes of death in elderly SCD patients with ß+/ßS, ß°/ßS, and ßS/ßS genotype. Methods: This is an observational longitudinal systemic multicenter study (registered at: https://clinicaltrials.gov/ct2/show/NCT03397017). Data were collected from 2015 to 2018 through a standard web-based application (available at: www.SITE-italia.org) encrypted by the Central Server. The study was approved by the Ethics Committee of the Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy. Results: Six hundred and ninety-seven patients from six Italian hemoglobinopathy comprehensive care centers were evaluated: 203 ß+/ßS, 206 ß°/ßS, 288 ßS/ßS, equally distributed by gender. Median age was 41 years [interquartile range (IQR): 30–52 years] for Caucasians and 17 years (IQR: 8–31 years) for Africans (p < 0.001). Ninety percent of African patients presented ßS/ßS genotype. Distribution of genotypes in Caucasians was: 189 ß+/ßS (38%), 197 ß°/ßS (40%), 111 ßS/ßS (22%), with no significant differences in age among the three subgroups. Fifty-eight patients died during the study: 19 ß+/ßS, 23 ß°/ßS, 16 ßS/ßS (Caucasians accounted for 100%, 96% and 81%, respectively). Causes of death were: 20 acute chest syndrome (ACS), 18 liver failure, 7 stroke, 4 solid cancer, 2 kidney failure, 1 sepsis, 1 pulmonary hypertension, 5 other causes. As shown in Fig. 1A, no difference in the causes of death was observed among genotypes. One hundred and eighty-nine patients were splenectomized: 62 ß+/ßS, 103 ß°/ßS, 24 ßS/ßS (Caucasians accounted for 100%, 100% and 80%, respectively). There was a significant difference in age at splenectomy in ß+/ßS compared to ß°/ßS and ßS/ßS (p < 0.001). ßS/ßS Africans were younger than Caucasians; therefore, to avoid age-related bias, survival analysis was limited to the Caucasian population. No differences were found in survival according to different genotypes (p = 0.7, Figure 1B) or splenectomy (p = 0.5). Figure 1. Caucasian sickle cell disease (SCD) patients. (A) Causes of death (n = 54 patients). Acute Chest Syndrome (ACS). (B) Survival curves by genotypeSummary/Conclusion: The Italian SCD population is characterized by a cohort of elderly Caucasians with a long-term follow up (median follow up 37 years; 95%CI: 36–39 years, calculated by the “reverse Kaplan-Meier” technique) and a younger cohort of patients of African descent. The major finding of our study is that genotype or splenectomy does not affect the overall survival of SCD patients. ACS was the first cause of death; unexpectedly, liver failure was the second cause of death in elderly SCD patients, most likely due to chronic sickle cell-related liver damage. The analysis of others factors triggering chronic hepatopathy is under evaluation in this large population of elderly SCD subjects.

Spinal direct current stimulation (tsDCS) in hereditary spastic paraplegias (HSP): A sham-controlled crossover study

Objective: Hereditary spastic paraplegia (HSP) represents a heterogeneous group of neurodegenerative diseases characterized by progressive spasticity and lower limb weakness. We assessed the effects of transcutaneous spinal direct current stimulation (tsDCS) in HSP. Design: A double-blind, randomized, crossover and sham-controlled study. Setting: Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan. Participants: eleven patients with HSP (six men, mean age ± SD: 37.3 ± 8.1 years), eight affected by spastin/SPG4,1 by atlastin1/SPG3a, 1 by paraplegin/SPG7 and 1 by ZFYVE26/SPG15. Interventions: tsDCS (anodal or sham, 2.0 mA, 20’, five days) delivered over the thoracic spinal cord (T10-T12). Outcome measures: Motor-evoked potentials (MEPs), the H-reflex (Hr), F-waves, the Ashworth scale for clinical spasticity, the Five Minutes Walking test and the Spastic Paraplegia Rating Scale (SPRS) were assessed. Patients were evaluated before tsDCS (T 0), at the end of the stimulation (T 1), after one week (T 2), one month (T 3) and two months (T 4). Results: The score of the Ashworth scale improved in the anodal compared with sham group, up to two months following the end of stimulation (T1, P = .0137; T4, P = .0244), whereas the Five Minutes Walking test and SPRS did not differ between the two groups. Among neurophysiological measures, both anodal and sham tsDCS left Hr, F-waves and MEPs unchanged over time. Conclusions: Anodal tsDCS significantly decreases spasticity and might be a complementary strategy for the treatment of spasticity in HSP.

Prevalence and risk factors of overweight and obesity after liver transplantation: retrospective study at three years after transplantation

Weight gain is frequently observed among liver transplanted patients. This condition is often associated to the development of other post LT morbidities which might influence the long-term post-transplant survival. However, the risk factors asso- ciated have not yet been identified. The aim of this study was to assess the prevalence of over- weight and obesity, to notice Body Mass Index changes and associated risk factors, within three years after LT. All the patients consecutively transplanted at the Liver Transplantation Unit of Fondazione IRCCS "Cà-Granda Ospedale Maggiore Policlinico", Milan between January 2005 and June 2014 were retrospectively evaluated for inclusion. Clinical, Biochemical and pharmaco- logical data were collected at hospital discharge and at 1st,2nd and 3rd years post-LT. 145 patients, 95(66%) male, 53 years (44-59 yr), 48(33%) HBV+HDV positive and 30(21%)alcohol abusers pre LT, were enrolled. At hospital discharge patients' BMI was 21.9 Kg/m2 (IQR: 20.1-24.1 Kg/m2) and the prevalence of overweight was 14%. The same para- meters after 1,2 and 3 years of follow-up were 25.6 Kg/m2 and 40%, 25.5 Kg/m2 and 41%, 25.4 Kg/m2 and 37%. The main weight gain was 9.8 Kg during the 1st year after LT while only 0.9 Kg and 0.5 Kg during the 2nd and 3rd year, respectively, No correlation between weight gain and any clinical, biochemical and pharmacological parameters considered was observed. The weight gain and the development of obesity are predominant during the first year after LT; this is probably due to an improper diet and lack of physical activity.

Efficacy of short-term psychodynamic psychotherapy vs treatment as usual in a sample of patients with anxiety and depressive disorders

The aim of this study is to evaluate the clinical efficacy of short-term psychodynamic psychotherapy (STPP) in comparison with treatment as usual (TAU) in treatment of patients suffering from anxiety and depressive disorders. Sixty patients were recruited from the Psychotherapy Service, University of Milan, Department of Psychiatry, at Milan's IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico with the diagnosis of depressive or anxiety disorders according to DSM-IV-TR criteria. These subjects were randomly assigned in a 1:1 ratio to an intervention group (STPP) or control group (TAU) for 12 months (T1). Each patient was clinically evaluated at the moment of recruitment (T0) and after 12 months using a battery composed of these scales: Clinical Global Impression Scale (CGI), Symptom Checklist-90-Revised (SCL-90-R), Inventory of Interpersonal Problems (IIP). Statistical analysis highlighted significant improvements (p<0.05) for the group treated with STPP in every clinical scale. Instead control group revealed significant changes (p<0.05) only for SCL-90 scale scores. We noticed a clinical improvement in both groups without particular differences, but the IIP scores went through a significant higher enhancement only in STPP group. Our results suggest that STPP is so effective as TAU in treatment of anxiety and depressive disorders. Moreover STPP leads to a better recover of relational functioning.

P0206 : Prevention of bleeding following invasive procedures in cirrhotic patients: A single center experience

Background: Risk of bleeding in cirrhosis has predominantly been associated with coagulopathy and thrombocytopenia due to impaired liver function and splenomegaly. The evaluation of the actual bleeding risk in cirrhotic patientsundergoing invasiveprocedures is a critical point to optimizemanagement in termsof platelet (Plt) or plasma prophylactic transfusions. Methods: During 2013, 480 cirrhotic patients underwent diagnostic or therapeutic invasive procedures at our Liver Unit (Fondazione IRCCS Ca Granda, Ospedale Maggiore Policlinico, Milan, Italy). Plt transfusion was performed when Plt count less than 50,000/mmc while fresh frozen plasma was infused when international normalized ratio (INR) >1.5, except those undergoing paracentesis. Low-molecular-weight-heparin was discontinued 24h before any procedure while antiaggregant therapy was interrupted five days before any procedure except oesophageal varices band ligation and paracentesis. Major hemorrhagic events were those requiring hospitalisation or blood transfusion; minor events was a haemoglobin decline >1.5 g/dl post procedure without clinical relevance. Results: 174 Transarterial Chemo-Embolization (TACE), 16 Radio-Frequency Termal Alblation (RFTA), 214 paracentesis, 59 oesophageal varices banding, 6 trans-jugular liver biopsy (LB) and 11 Percutaneous Ethanol Injection (PEI) were performed. Overall, 61 procedures met the criteria for plasma or Plt infusion and major bleeding complications occurred in 3 patients (0,6%). In 2 patients, anemia-related paracentesis was treated by blood transfusions whereas one patient following variceal band ligation had to be hospitalized for severe anemia. Major complications rate was 1.6% in Plt/plasma infusion exposed patients versus 0.47% in unexposed (p=0.28).Minor eventswith a>1.5 g/dl haemoglobindecline occurred in 17 patients (15 paracentesis and 2 band ligations), rate was 3.2% in Plt/plasma infusion exposed patients versus 3.5% in unexposed (p=0.9). Conclusion: Pre-treatment platelet transfusion in cirrhotic patients with Plt count 1.5, was associated with a negligible risk of bleeding and appeared as a safe, cost/effective strategy.

Cross-Informant Agreement on Preadolescent's Emotional and Behavioral Problems in a Non-Clinical Cohort of Northern Italy Subjects: A Pilot Study

Background: The emotional-behavioral repertoire has been extensively studied in children and adolescents, devoting less effort to preadolescence. Objective: To investigate the emotional-behavioral repertoire compared to different sources of information – parents versus children – on a pilot non-clinical sample of Italian preadolescents. Methods: Thirty pre-adolescents aged 11 to 14 years old (16 females, 14 males) are consecutively referred to the Service of Psychotherapy, Ospedale Maggiore Policlinico, Milan for an evaluation of their mental health status. Pre-adolescents and their parents were respectively asked to fill in the Youth Self- Report (YSR) and the Child Behavior Check List (CBCL). Results: Significant differences between mothers and fathers emerged at Syndrome Scales (SSs): Anxious/ Depressed (p=0.026), Social Problems (p=0.035); at DSM-oriented Scales (DOSs) in Emotional Problems (p=0.012) and at the scales in Internalization (p=0.019). There are also significant differences on the total score (p=0.035). Comparing answers reported by pre-adolescents versus those reported by their parents, the number of scales with significant differences increases (SSs. Anxious/Depressed: p=0.032; Somatic Complaints: p=0.004; Thought Problems: p=0.010; DOSs. Anxiety Problems: p=0.044; Somatic Problems: p=.006; Internalization: p=0.016), with influences also the total score (p=0.049). Discreet correlations in all the global scales and in total scores between pre-adolescents and mothers, but not fathers, were found. Conclusions: Parents show differences in their perception of children’s emotional- behavioral problems, especially of internalizing behaviors. These results suggest the specific importance of an extended family analysis at this stage of development.

A new recombinant factor VIII: from genetics to clinical use.

Advances in recombinant technology and knowledge about coagulation factor VIII (FVIII) are building a platform for new therapeutic options in patients with hemophilia A. The development of turoctocog alfa, a novel, high-purity, third-generation, B-domain truncated recombinant FVIII, has been produced and formulated without the use of animal-derived or human serum-derived components, in the wake of understanding of the new biochemical characteristics of FVIII, namely its protein structure, and glycosylation and sulfating patterns. Culture conditions and a five-step purification process have been developed to optimize the safety of turoctocog alfa. The results of two pilot clinical trials using turoctocog alfa confirmed high safety levels, with no patient developing inhibitors during the period of observation. The purpose of this review is to describe briefly the molecular and biological properties of turoctocog alfa, together with details of its clinical development, with emphasis on the needs of patients with hemophilia A.

ESX1 mRNA expression in seminal fluid is an indicator of residual spermatogenesis in non-obstructive azoospermic men.

Is the presence of ESX1 mRNA in seminal fluid (SF) an indicator of residual spermatogenesis in men with non-obstructive azoospermic (NOA)? ESX1 mRNA in SF is a suitable molecular marker for predicting the presence of residual spermatogenesis in testis. ESX1 is an X-linked homeobox gene whose expression in testis is restricted to germ cells. We previously reported, in the testicular biopsies from azoospermic men, a positive correlation between the presence of ESX1 mRNA and residual spermatogenesis. We investigated ESX1 mRNA expression in 70 testicular fragments (TF) and 56 (SF) of 70 NOA men. As controls, we analyzed 8 TF from men with obstructive azoospermic (OA) and 9 SF from normozoospermic men. For all patients we considered the histological classification of testis biopsies and the recovery of spermatozoa by surgical procedures. Relative ESX1 mRNA expression was evaluated by quantitative RT-PCR using the ΔΔCt method. The results were compared with the recovery of spermatozoa at surgery. In TF from NOA patients we found that: (i) ESX1 mRNA level was significantly decreased as the severity of spermatogenic defects increased (P < 0.0001, one-way analysis of variance); (ii) the presence of ESX1 mRNA can predict the success of sperm retrieval (sensitivity: 80%). In SF from NOA patients we found that: (i) ESX1 mRNA was present in 78.5% of NOA men; (ii) the presence of ESX1 mRNA could predict the success of sperm retrieval (sensitivity: 84%). Spermatozoa were recovered at surgery in 5 out of 12 patients whose SF was negative for ESX1 mRNA expression. We think that discrepancies between molecular and clinical results could be reduced by analyzing more than one ejaculate from each man. The data confirm that the ESX1 transcript in the semen of men with NOA is a suitable molecular marker for predicting the presence of residual foci of spermatogenesis in the testis. The implication of these results is that some patients 'with azoospermia', although having a severe impairment of spermatogenesis, could still maintain residual foci of spermatogenesis in limited areas of the testes, not always recovered by surgery. This work was supported by the Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: Ricerca Corrente [grant number RC2014/519-02] to M.M. and from ASM onlus 2010-2011 to M.M. The authors declare that they have no conflict of interest.

Respiratory mechanics during NCPAP and HHHFNC at equal distending pressures

ObjectiveTo compare the effect of heated, humidified, high-flow nasal cannula (HHHFNC) and nasal continuous positive airways pressure (NCPAP) on lung function and mechanics in preterm infants with respiratory distress syndrome...

Skin involvement in cutaneous and systemic vasculitis.

Event Abstract Back to Event Skin involvement in cutaneous and systemic vasculitis. Pamela Vezzoli1*, Angelo V. Marzano2 and Emilio Berti2, 3 1 Ospedale Papa Giovanni XXIII, Dermatology, Italy 2 Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Italy 3 University of Milano - Bicocca, Italy Cutaneous vasculitides are a heterogeneous group of inflammatory disorders affecting skin blood vessels. They may be triggered by several factors, such as infection or drug, or may be related to underlying disease, notably connective tissue or malignancies. However, vasculitis occurs without any demonstrable triggering agents in a relevant number of patients. On the other hand, vasculitic skin lesions may manifest as a component of vasculitis affecting also internal organs; in someone of these patients, skin involvement occurs initially as the sole sign of disease, leading to consider cutaneous vasculitis a diagnosis of exclusion. In this review, we have focused on the most common variants of cutaneous vasculitis, including cutaneous small vessel vasculitis and urticarial vasculitis as well as Henoch-Schönlein purpura, a systemic form in which however skin involvement often predominates. We have also argued on livedoid vasculopathy, a cutaneous entity which, although nonfrankly vasculitic in origin, is frequently associated with connective tissue disease. Finally, we have analyzed the variety of cutaneous manifestations that may develop during the course of the main systemic vasculitides, such as Wegener's granulomatosis, Churg-Strauss syndrome and polyarteritis nodosa. Keywords: Skin Manifestations, Systemic Vasculitis, Cutaneous Vasculitis, Inflammatory Disorders, Livedoid vasculopathy Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Translational immunology and immune intervention Citation: Vezzoli P, Marzano AV and Berti E (2013). Skin involvement in cutaneous and systemic vasculitis.. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00518 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 20 May 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Pamela Vezzoli, Ospedale Papa Giovanni XXIII, Dermatology, Bergamo, Italy, pamela.vezzoli@libero.it Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Pamela Vezzoli Angelo V Marzano Emilio Berti Google Pamela Vezzoli Angelo V Marzano Emilio Berti Google Scholar Pamela Vezzoli Angelo V Marzano Emilio Berti PubMed Pamela Vezzoli Angelo V Marzano Emilio Berti Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Escitalopram tolerability as mono- versus augmentative therapy in patients with affective disorders: a naturalistic study

Background:Escitalopram is a selective serotonin reuptake inhibitor, widely used in the treatment of affective disorders. The purpose of this study was to examine its safety and tolerability, as mono- versus augmentative therapy, in a group of patients with affective disorders.Materials and methods:The sample consisted of 131 patients suffering from different affective disorders, including major depressive disorder, bipolar disorder, and generalized anxiety disorder, who received escitalopram for at least 4 weeks. Data were analyzed on the basis of mono- versus augmentative therapy, as well as age, gender, mean daily dosage, and patterns of combination therapy.Results:Sixty-seven (51.1%) patients were treated with monotherapy (mean dose of 11.76 mg/day) and 64 (48.9%) with augmentative escitalopram (mean dose of 12.81 mg/day). The mean duration of escitalopram treatment was 14 months. The most frequently combined compounds were: other antidepressants (36.5%), mood stabilizers (33.4%), and atypical antipsychotics (30.1%). Side effects were reported in 5.3% of the total sample and the most common were insomnia (2.3%), nausea (2.3%), and dizziness (0.8%). No significant difference, in terms of tolerability, in mono- versus augmentative therapy groups was found. In addition, neither age nor gender was significantly correlated with a greater presence of side effects. Finally, no significant correlation between dosage and side effects was observed.Conclusion:Over a 14-month observation period, escitalopram, either as monotherapy or an augmentative treatment, was found to be well tolerated in a large sample of patients with affective disorders, with an overall low rate of side effects.