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Aims.: Maternal mental disorders have been associated with the risk of attention-deficit/hyperactivity disorder (ADHD) in children. Within the context of a mother–child cohort, we examined whether maternal anxiety, depression and sleep disorders are associated with pre-school ADHD symptoms. Methods.: The study included 3634 singletons from the Italian NINFEA (Nascita e INFanzia: gli Effetti dell'Ambiente') cohort. Maternal doctor-diagnosed anxiety, depression and sleep disorders before and during pregnancy were assessed from the questionnaires completed during pregnancy and 6 months after delivery. Mothers rated child ADHD symptoms at 4 years of age, according to the Diagnostic and Statistical Manual of Mental Disorders. Hyperactive–impulsive (ADHD-H), inattentive (ADHD-I) and total ADHD scores were analysed in the models adjusted for child's gender, first-born status, maternal age, education, alcohol consumption and smoking during pregnancy. Results.: The total ADHD score at age 4 was associated with maternal lifetime anxiety (17.1% percentage difference in score compared with never; 95% CI 7.3–27.9%), sleep disorders (35.7%; 95% CI 10.7–66.5%) and depression (17.5%; 95% CI 3.2–33.8%). Similar positive associations were observed also for ADHD-H and ADHD-I traits, with slightly attenuated associations between maternal sleep disorders and child ADHD-I score, and maternal depression and both ADHD scores. All the estimates were enhanced when the disorders were active during pregnancy and attenuated for disorders active only during the pre-pregnancy period. Conclusions.: Maternal anxiety, depression and sleep disorders are associated with a relative increase in the number of ADHD-H, ADHD-I and total ADHD symptoms in preschoolers. [ABSTRACT FROM AUTHOR]

Background: Previous studies on the association between maternal age and risk of childhood leukemia found inconsistent results. Objectives: We aimed to assess whether there is an association between maternal age and risk of childhood leukemia and whether such an association is modified by maternal year of birth. Methods: By linking nationwide Swedish registers, we analyzed leukemia incidence among all children between 1 and 5 years of age born between 1960 and 1999. We estimated incidence time trends by child year of birth (overall and stratified by maternal age) and incidence rate ratios (RRs) for maternal age groups stratified by maternal birth cohort. We tested the interaction between maternal age and child year of birth through the likelihood ratio test between nested Poisson regression models. Results: We observed 1,562 leukemia cases. The overall annual percent change (APC) was 1.00 [95% confidence interval (CI) , 0.51 to 1.49]. Stratifying by maternal age classes, APCs decreased from 1.66 (0.68 to 2.65) for mothers < 24 years to 0.23 (-0.93 to 1.40) for mothers > 35 years at delivery. RRs for children born to the oldest with respect to the youngest mothers were 2.42 (1.31 to 4.67) , 1.68 (1.00 to 2.72) , 1.34 (0.87 to 2.01) , and 0.87 (0.46-1.54) for mothers born in 1930-1934, 1940-1944, 1950-1954, and 1960-1964, respectively. Conclusions: Childhood leukemia risk increased with maternal age for mothers born in the past, whereas maternal age had no effect on this risk for mothers born more recently. This finding may explain the inconsistency of previous studies and suggests that leukemia risk may be related to an environmental factor to which women's exposure has changed over time. [ABSTRACT FROM AUTHOR]

Background: Consolidative thoracic radiotherapy (TRT) has been commonly used in the management of extensive-stage small cell lung cancer (ES-SCLC). Nevertheless, phase III trials exploring first-line chemoimmunotherapy have excluded this treatment approach. However, there is a strong biological rationale to support the use of radiotherapy (RT) as a boost to sustain anti-tumor immune responses. Currently, the benefit of TRT after chemoimmunotherapy remains unclear. The present report describes the real-world experiences of 120 patients with ES-SCLC treated with different chemoimmunotherapy combinations. Preclinical data supporting the hypothesis of anti-tumor immune responses induced by RT are also presented., Methods: A total of 120 ES-SCLC patients treated with chemoimmunotherapy since 2019 in the South of Italy were retrospectively analyzed. None of the patients included in the analysis experienced disease progression after undergoing first-line chemoimmunotherapy. Of these, 59 patients underwent TRT after a multidisciplinary decision by the treatment team. Patient characteristics, chemoimmunotherapy schedule, and timing of TRT onset were assessed. Safety served as the primary endpoint, while efficacy measured in terms of overall survival (OS) and progression-free survival (PFS) was used as the secondary endpoint. Immune pathway activation induced by RT in SCLC cells was explored to investigate the biological rationale for combining RT and immunotherapy., Results: Preclinical data supported the activation of innate immune pathways, including the STimulator of INterferon pathway (STING), gamma-interferon-inducible protein (IFI-16), and mitochondrial antiviral-signaling protein (MAVS) related to DNA and RNA release. Clinical data showed that TRT was associated with a good safety profile. Of the 59 patients treated with TRT, only 10% experienced radiation toxicity, while no ≥ G3 radiation-induced adverse events occurred. The median time for TRT onset after cycles of chemoimmunotherapy was 62 days. Total radiation dose and fraction dose of TRT include from 30 Gy in 10 fractions, up to definitive dose in selected patients. Consolidative TRT was associated with a significantly longer PFS than systemic therapy alone (one-year PFS of 61% vs. 31%, p<0.001), with a trend toward improved OS (one-year OS of 80% vs. 61%, p=0.027)., Conclusion: Multi-center data from establishments in the South of Italy provide a general confidence in using TRT as a consolidative strategy after chemoimmunotherapy. Considering the limits of a restrospective analysis, these preliminary results support the feasibility of the approach and encourage a prospective evaluation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Longo, Della Corte, Russo, Spinnato, Ambrosio, Ronga, Marchese, Del Giudice, Sergi, Casaluce, Gilli, Montrone, Gristina, Sforza, Reale, Di Liello, Servetto, Lipari, Longhitano, Vizzini, Manzo, Cristofano, Paolelli, Nardone, De Summa, Perrone, Bisceglia, Derosa, Nardone, Viscardi, Galetta and Vitiello.)

Background: Since February 2021 active screening of COVID-19-associated pulmonary aspergillosis (CAPA) has been implemented in our institution., Objectives: To evaluate CAPA incidence in our centre and evaluate performance of our screening protocol., Methods: We screened once per week, collecting endotracheal aspirates for fungal culture and galactomannan (GM) and serum for 1,3-ß-D-glucan (BG). In case of positivity (GM more than 4.5, platelia assay, and/or BG >7 pg/ml, wako and/or positive fungal culture), second-level investigations were performed to pursue CAPA diagnosis according to ECMM/ISHAM criteria: bronchoalveolar lavage (BAL) fungal culture and GM, chest computed tomography (CT), serum GM., Results: A total of 102 patients were screened (median age 64 years, range 39-79; 28 (27.4%) females). Twenty-two patients were diagnosed with CAPA (21%). 12 patients were positive for serum BG, 17 patients were positive for endotracheal aspirates GM and 27 patients were positive for endotracheal aspirates fungal culture. Thirty-two BALs were performed, and 26 patients underwent CT chest. Following the second level investigations 61% of the patients with positive screening tests were diagnosed with CAPA. Serum BG above 20 pg/ml or positive serum GM were always associated with typical CT chest signs of aspergillosis. Compared with 1 single positive test, having 2 positive screening test was significantly more associated with CAPA diagnosis (p = .0004)., Conclusions: Active CAPA screening with serum 1,3-ß-D-glucan and endotracheal aspirates galactomannan and fungal cultures and consequent second level investigations led to high number of CAPA diagnosis. Combining more positive fungal biomarkers was more predictive of CAPA diagnosis., (© 2022 Wiley-VCH GmbH.)

Citrobacter koseri is a facultative anaerobic, motile, non-spore-forming Gram-negative bacillus, which belongs to the family of Enterobacteriaceae. Severe infections due to Citrobacter spp. have been reported in the urinary tract, respiratory airways, intra-abdominal organs, skin and soft tissue, eye, bone, bloodstream, and central nervous system. In newborns, C. koseri is a well-known cause of meningitis, cerebral abscesses, brain adhesions, encephalitis, and pneumocephalus. Infection can be acquired through vertical maternal transmission or horizontal hospital settings; however, in many cases, the source is unknown. Preterm premature rupture of membranes (PPROM), caused by C. koseri , has rarely been described. Herein, we describe a case of PPROM at 16 weeks and 3 days of gestation, leading to anhydramnios. The parents opted for legal termination of the pregnancy, as the prognosis was very poor. C. koseri was isolated postmortem from a placental subamniotic swab and parenchymal sample, as well as fetal blood and lung. To the best of our knowledge, this is the first case of early second-trimester PPROM in which C. koseri infection was demonstrated.

Rapid identification of causative microorganisms of microbial keratitis (MK) and knowledge of the most common local pathogens are prerequisites for rational antimicrobial therapy. We retrospectively reviewed the characteristics of MK diagnosed at the IRCCS Arcispedale Santa Maria Nuova of Reggio Emilia (Italy) in a 5-years period, where the Ophthalmologist Unit is a reference center for corneal infections. During the study period, 183 MK were evaluated through corneal scrapings cultures. The positivity rate was 54,1%. A total of 107 microorganisms have been isolated: Acanthamoeba species was the etiologic agent in 19 cases. Pseudomonas aeruginosa and Staphylococcus aureus were more frequently isolated in bacterial keratitis, while Fusarium spp., Candida albicans, and Alternaria alternata were predominant among the fungal isolates. Strict cooperation between ophthalmologists and clinical microbiologists is advisable to allow the best diagnostic approach for MK., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Klebsiella pneumoniae is a Gram-negative, rod-shaped bacterium, responsible for hospital and community acquired pneumonia, urinary tract and wound infections, and bloodstream dissemination. K. pneumoniae infection in pregnancy, leading to acute chorioamnionitis (AC), preterm premature rupture of membranes (PPROM) and early pregnancy loss in the second trimester, has been rarely reported. Herein, we present a case of K. pneumoniae AC that caused intrauterine fetal demise (IUFD) at 19 weeks + 5 days. The 36-year-old mother was admitted at 18 weeks + 1 day of gestation for threatened abortion. IUFD occurred 11 days after. Fetal postmortem showed severe AC and funisitis, neutrophils within alveoli and intestinal lumen, associated with rod-like bacteria. Fetal blood and lung cultures grew K. pneumoniae , β-lactamase-non-producing strain. Antibiogram revealed sensitivity for piperacillin/tazobactam. Three days after IUFD, the mother presented with fever (37.8 °C) which persisted for one week. Maternal blood and urine cultures were negative. According to fetal microbiological results, available 6 days after IUFD, initial treatment with amoxicillin/clavulanic acid was replaced with piperacillin/tazobactam with full patient recovery. Therefore, in the event of PPROM and IUFD, fetal microbiological investigations should always be performed to isolate the proper etiologic agent and start the correct medical treatment.

Treatment options for patients with metastatic synovial sarcoma are limited. Over recent years, trabectedin has emerged as an effective agent for patients with advanced soft tissue sarcomas resistant to anthracyclines and ifosfamide. The aim of this retrospective analysis was to study the efficacy of trabectedin in the subgroup of synovial sarcomas. A retrospective analysis was carried out on patients with advanced synovial sarcoma treated with trabectedin at four European reference sarcoma centers and within the Italian Rare Cancer Network between 2000 and 2013. Radiological response, progression-free, and overall survival, as well as serious and unexpected adverse events were retrospectively assessed. Sixty-one patients with metastatic synovial sarcoma were identified. The median number of previous chemotherapy regimens was 2 (range 1-6). Nine patients had a partial response, in addition to two minor responses, and 19 patients had stable disease, for an overall response rate of 15% and a tumor control rate of 50%. The median progression-free survival was 3 months, with 23% of patients free from progression at 6 months. The median progression-free survival in responding patients was 7 months. Trabectedin is a therapeutic option for palliative treatment of a subset of patients with metastatic synovial sarcoma.

Adult height is associated with testicular cancer risk. We studied to what extent this association is explained by parental height, childhood height and age at puberty. We conducted a case-control study on germ-cell testicular cancer patients diagnosed in 1997-2008 and resident in the Province of Turin. Information was collected using mailed questionnaires in 2008-2011. Specifically, we asked for adult height (in cm), height at age 9 and 13 (compared to peers) and age at puberty (compared to peers). We also asked for paternal and maternal height (in cm) as indicators of genetic components of adult height. The analysis included 255 cases and 459 controls. Odds ratios (ORs) of testicular cancer were estimated for the different anthropometric variables. Adult height was associated with testicular cancer risk [OR: 1.16, 95% confidence interval (CI): 1.03-1.31 per 5-cm increase]. The risk of testicular cancer was only slightly increased for being taller vs. shorter than peers at age 9 (OR: 1.55, 95% CI: 0.91-2.64) or age 13 (OR: 1.26, 95% CI: 0.78-2.01), and parental height was not associated with testicular cancer risk. The OR for adult height was 1.32 (95% CI: 1.12-1.56) after adjustment for parental height. Among participants with small average parental height (<167 cm or less), the OR of testicular cancer for tall (>180 cm) vs. short (<174 cm) subjects was 3.47 (95% CI: 1.60-7.51). These results suggest that the association between height and testicular cancer is likely to be explained by environmental factors affecting growth in early life, childhood and adolescence., (© 2013 UICC.)

Aim: We investigated the pathogenic role of biofilm and the therapeutic efficacy of anidulafungin in experimental infections of the wax moth Galleria mellonella by Candida albicans clinical strains., Materials & Methods: On the basis of the in vitro propensity to form biofilm, five biofilm-producer (BP) and four nonproducer (NP) C. albicans clinical strains were used in this study. For each strain, we assessed the virulence by infecting G. mellonella larvae and observing survival. Anidulafungin was administered 2 h after yeast inoculum at 0.6 µg, according to the therapeutic dose recommended for humans., Results: Biofilm-forming ability highly influenced the larva-killing rate. A significant (p < 0.0001) survival decrease was observed in the BP group, with 80% of the infected larvae dying within 72 h. NP isolates did not reach the same killing rate, even at the end of experiments (216 h). Larval survival was enhanced (p < 0.0001) by anidulafungin administration in both groups. Survival rate at 72 h was similar in both groups (BP 78.5% and NP 87.5%); whereas there were still differences at the end of the experiments, with a higher survival in the NP group (75 vs 48%)., Conclusion: Our data confirm the pathogenic role of biofilm in C. albicans infections. Its importance was further enhanced by a lack of contribution from extracellular enzymes, detected in both NP and BP strains. In addition, we demonstrated anidulafungin efficacy in treating biofilm-related invasive candidiasis.

Background: Several studies have reported a reduction in acute coronary events (ACEs) in the general population after the enforcement of smoking regulations, although there is uncertainty concerning the magnitude of the effect of such interventions. We conducted a country-wide evaluation of the health effects of the introduction of a smoking ban in public places, using data on hospital admissions for ACEs from the Italian population after the implementation of a national smoking regulation in January 2005., Methods and Findings: Rates of admission for ACEs in the 20 Italian regions from January 2002 to November 2006 were analysed using mixed-effect regression models that allowed for long-term trends and seasonality. Standard methods for interrupted time-series were adopted to assess the immediate and gradual effects of the smoking ban. Effect modification by age was investigated, with the assumption that exposure to passive smoking in public places would be greater among young people. In total, 936,519 hospital admissions for ACEs occurred in the Italian population during the study period. A 4% reduction in hospital admissions for ACEs among persons aged less than 70 years was evident after the introduction of the ban (Rate Ratio [RR], 0.96; 95% Confidence Interval [CI], 0.95-0.98). No effect was found among persons aged at least 70 years (RR 1.00; 95% CI 0.99-1.02). Effect modification by age was further suggested by analyses using narrower age categories., Conclusions: Smoke-free policies can constitute a simple and inexpensive intervention for the prevention of cardiovascular diseases and thus should be included in prevention programmes.

Background: Detection and quantification of human papillomavirus (HPV) may help in predicting the evolution of HPV infection and progression of associated lesions., Objectives: We propose a novel protocol using consensus primers GP5+/6+ in a SYBR Green quantitative real-time (Q-RT) polymerase chain reaction (PCR). The strategy permits screening for HPV infection and viral load quantification simultaneously., Study Design: DNA from 153 archived cervical samples, previously tested for HPV detection by GP5+/6+ PCR and typed by EIA-RLB (enzyme immunoassay-reverse line blot) or sequence analysis, was analysed using SYBR Green Q-RT PCR. Melting temperature assay (T(m)) and cycle threshold (C(t)) were used to evaluate HPV positivity and viral load. The T(m) in the range of 77-82 degrees C was considered to be positive for HPV-DNA. HPV results generated through GP5+/6+ conventional PCR were considered the gold standard against which sensitivity and specificity of our assay were measured., Results: Out of 104 HPV positive samples, 100 (96.2%) were also determined as positive by SYBR Green Q-RT PCR; of the 49 HPV-negative samples, all were determined as negative. There was an excellent positivity agreement (kappa=0.94) between the SYBR Green Q-RT and the previous methods employed. The specificity and sensitivity were 100% and 96.2%, respectively. Comparison of SYBR Green Q-RT and TaqMan oligo-probe technologies gave an excellent concordance (rho(c)=0.95) which validated the proposed strategy., Conclusions: We propose a sensitive and easy-to-perform technique for HPV screening and viral load quantification simultaneously.

Objectives: Decreases in population rates of acute myocardial infarction (AMI) have been repeatedly seen in the first months after the introduction of regulations banning smoking in public places. By decreasing the exposure to passive smoking and its acute cardiovascular effects, smoking regulations may cause an immediate drop in AMI incidence, beginning from the initial days after their introduction. Using simulations, we quantified this expected decrease., Methods: Expected AMI decreases were estimated using several parameters, including prevalence of exposure to passive and active smoking, relative risks of AMI associated with active and passive smoking, decrease in exposure to passive smoking after the introduction of the regulation, and level of susceptibility of active smokers to exposure to passive smoking., Results: After evaluating several possible combinations of these parameters, we found that AMI reductions of 5-15% seem likely. For example, a scenario with a population average of 5 hours per week of overall exposure to passive smoking, a 50% reduction in this exposure after the introduction of the regulation, an acute relative risk (RR) of AMI of 4.5 in the first hour after passive smoking exposure, and similar susceptibility to passive smoking among both active and passive smokers translates into a 8.6% decrease in AMI., Conclusions: Smoking regulations can cause immediate and relevant decreases in AMI through the prevention of exposure to passive smoking.

Setting: Based on the cohort of pulmonary tuberculosis (PTB) cases resident between 2001 and 2005 in the Piedmont region of Italy, this study estimated the effect of selected determinants on the success of standardised short-course chemotherapy (SSCC)., Objective: To identify predictors of unsuccessful treatment of PTB and to generate a nomogram to assist treating physicians and public health authorities with the identification of cases needing close follow-up., Results: Overall, 1564 cases were identified. Among new cases, predictors of successful treatment outcome were sex (women vs. men, aOR 0.48, 95%CI 0.37-0.63), geographic origin (EU vs. non-EU countries, aOR 0.43, 95%CI 0.31-0.60) and treatment setting (out-patient vs. in-patient services and unknown setting, aOR 0.2, 95%CI 0.16-0.26). Predictors of unsuccessful outcome were long-term residency status (homeless vs. residential, aOR 9.91, 95%CI 4.38-22.38) and age (for each year, aOR 1.02, 95%CI 1.01-1.03)., Conclusion: Using a limited number of predictors, the authors designed a nomogram predicting the individual probability of unfavourable SSCC. In principle, this approach is generalisable to other settings and the nomogram can be calibrated on local data to ensure appropriate case management and support targeted treatment follow-up.

The NINFEA cohort is an Italian birth cohort aiming at recruiting pregnant women through the Internet and following-up their children. To understand whether Internet-based recruitment was feasible we started a pilot in July 2005 targeted to pregnant women visiting the hospitals of the city of Turin (900,000 inhabitants), where we advertised the study. For this purpose we constructed a website (www.progettoninfea.it), with on-line questionnaires to be completed during pregnancy and at 6 and 18 months after delivery. Participants' characteristics were compared with those of women giving birth in Turin, which are routinely released as individual anonymous records. We also compared complete with partial respondents. We also carried out a survey of 122 women giving birth in the main Turin obstetric hospital to estimate the proportion of pregnant women with access to the Internet and awareness of the NINFEA cohort. By December 2006, we had recruited 670 women. Participation was associated with being older, a university graduate, primiparous and born in Italy. Complete response (n = 633) was associated with being primiparous and participation after the first trimester. In the survey, 66% (95% confidence interval: 56-74%; n = 80) of the women had access to the Internet and 42% (33-51%; n = 51) were aware of the study; 6.5% (2.9-12.5%; n = 8) had participated in the NINFEA cohort. Our study indicates that recruitment of an Internet-based birth cohort is feasible. As with many other types of birth cohort study, the participants are a self-selected sample. To minimise selection bias analyses should therefore be limited to internal comparisons.