5-En-androstene-3 beta,17 beta-diol inhibits the growth of MCF-7 breast cancer cells when oestrogen receptors are blocked by oestradiol.

Adrenal androgens show a dual and apparently opposite effect on the growth of oestrogen-responsive breast cancer: they stimulate growth on their own, but counteract the growth-stimulatory effect of oestrogens. Focusing on the inhibitory action we have studied the effects of 5-en-androstene-3 beta,17 beta-diol (ADIOL) on the growth of oestrogen-responsive MCF-7 breast cancer cells in the presence of oestrogens (oestradiol and diethylstilboestrol), antiestrogens (tamoxifen) and antiandrogens (hydroxyflutamide). The inhibition of oestrogen-stimulated growth, attained with nanomolar concentrations of ADIOL, was not modified by increasing concentrations of diethylstilboestrol up to 100 nM. This inhibition was counteracted by antiandrogens, which were unable to block the ADIOL stimulatory effect in steroid-free medium. On the other hand, in the presence of tamoxifen ADIOL showed an additive antiproliferative activity also in steroid-free medium, rather than the usual stimulatory effect. These results suggest that ADIOL stimulates breast cancer cell growth via oestrogen receptors, but inhibits oestrogen-stimulated growth via androgen receptors

Role of glucose-6-phosphate dehydrogenase inhibition in the antiproliferative effects of dehydroepiandrosterone on human breast cancer cells.

Epidemiological and experimental studies suggest that dehydroepiandrosterone (DHEA) exerts a protective effect against breast cancer. It has been proposed that the non-competitive inhibition of glucose-6-phosphate dehydrogenase (G6PD) contributes to DHEA antitumor action. We evaluated the effects of DHEA on G6PD activity and on the in vitro proliferation of two human breast cancer cell lines, MCF-7 (steroid receptor positive) and MDA-MB-231 (steroid receptor negative), in a serum-free assay. DHEA inhibition of G6PD was only found to occur at concentrations above 10 microM; at these high concentrations, the growth curve was parallel to the enzyme inhibition curve in both cell lines. In contrast, at concentrations in the in vivo breast tissue concentration range, neither cell growth nor enzyme activity was inhibited. The results failed to confirm DHEA's putative anti-tumor action on breast cancer through G6PD inhibition, as the enzyme blockade only becomes apparent at pharmacological concentrations of the steroid

Alert sign and symptoms for the early diagnosis of pulmonary tuberculosis: analysis of patients followed by a tertiary pediatric hospital

Background Intercepting earlier suspected TB (Tuberculosis) cases clinically is necessary to reduce TB incidence, so we described signs and symptoms of retrospective cases of pulmonary TB and tried to evaluate which could be early warning signs. Methods We conducted a retrospective descriptive study of pulmonary TB cases in children in years 2005-2017; in years 2018-2020 we conducted a cohort prospective study enrolling patients < 18 years accessed to Emergency Department (ED) with signs/symptoms suggestive of pulmonary TB. Results In the retrospective analysis, 226 patients with pulmonary TB were studied. The most frequently described items were contact history (53.5%) and having parents from countries at risk (60.2%). Cough was referred in 49.5% of patients at onset, fever in 46%; these symptoms were persistent (lasting >= 10 days) in about 20%. Lymphadenopathy is described in 15.9%. The prospective study enrolled 85 patients of whom 14 (16.5%) were confirmed to be TB patients and 71 (83.5%) were non-TB cases. Lymphadenopathy and contact history were the most correlated variables. Fever and cough lasting >= 10 days were less frequently described in TB cases compared to non-TB patients (p < 0.05). Conclusions In low TB endemic countries, pulmonary TB at onset is characterized by different symptoms, i.e. persistent fever and cough are less described, while more relevant are contact history and lymphadenopathy. It was not possible to create a score because signs/symptoms usually suggestive of pulmonary TB (considered in the questionnaire) were not significant risk factors in our reality, a low TB country

The impact of pertussis in infants: insights from a hospital-based enhanced surveillance system, Lazio region, Italy, 2016 to 2019

Background: Routine surveillance systems for pertussis often suffer from under-recognition and under-reporting. Aim: Our aim was to describe the epidemiology and the clinical features of pertussis in children younger than 1 year in an Italian region, detected through an enhanced hospital surveillance system. Methods: From 2016 to 2019, we monitored the incidence and the clinical characteristics of hospitalised pertussis cases younger than 1 year in two paediatric hospitals involved in the PERTINENT project. Results: We detected 141 pertussis cases, corresponding to an estimated incidence of 105.8 per 100.000 in 2016, 91.7 per 100.000 in 2017, 64.5 per 100.000 in 2018 and 40.9 per 100.000 in 2019, based on the hospitals' catchment area, roughly corresponding to the Lazio region. A total of 101 cases (77.1%) had a household member with cough or other respiratory symptoms. The most frequent combination of symptoms was paroxysmal cough with apnoea in the absence of fever. Almost 40% had been prescribed an antibiotic treatment before hospitalisation, and the median time from symptom onset to contact with the hospital was 8 days. Thirty-one (22.0%) had complications. Conclusion: An enhanced surveillance system showed a high incidence of pertussis among infants in the Lazio region, where the impact of this disease may still be underestimated. Increasing the coverage of pertussis immunisation among pregnant women and improving the capacity for early detection in primary care may contribute to reducing the impact of pertussis among infants

Clostridium difficile infection in children: epidemiology and risk of recurrence in a low-prevalence country

Clostridium difficile infection (CDI) is increasingly found in children worldwide, but limited data are available from children living in southern Europe. A 6-year retrospective study was performed to investigate the epidemiology, clinical features, treatment, and risk of recurrence in Italy. Data of children with community- and hospital-acquired CDI (CA-CDI and HA-CDI, respectively) seen at seven pediatric referral centers in Italy were recorded retrospectively. Annual infection rates/10,000 hospital admissions were calculated. Logistic regression was used to investigate risk factors for recurrence. A total of 177 CDI episodes was reported in 148 children (83 males, median age 55.3 months), with a cumulative infection rate of 2.25/10,000 admissions, with no significant variability over time. The majority of children (60.8 %) had CA-CDI. Children with HA-CDI (39.2 %) had a longer duration of symptoms and hospitalization (p = 0.003) and a more common previous use of antibiotics (p = 0.0001). Metronidazole was used in 70.7 % of cases (87/123) and vancomycin in 29.3 % (36/123), with similar success rates. Recurrence occurred in 16 children (10.8 %), and 3 (2 %) of them presented a further treatment failure. The use of metronidazole was associated with a 5-fold increase in the risk of recurrence [odds ratio (OR) 5.18, 95 % confidence interval (CI) 1.1-23.8, p = 0.03]. Short bowel syndrome was the only underlying condition associated with treatment failure (OR 5.29, 95 % CI 1.17-23.8, p = 0.03). The incidence of pediatric CDI in Italy is low and substantially stable. In this setting, there is a limited risk of recurrence, which mainly concerns children treated with oral metronidazole and those with short bowel syndrome

One Year of Lung Ultrasound in Children with SARS-CoV-2 Admitted to a Tertiary Referral Children's Hospital: A Retrospective Study during 2020-2021

During the COVID-19 pandemic, the lung ultrasound (LU) turned out to be a pivotal tool to study the lung involvement in the adult population, but the same was not well evaluated in children. We detected the LU patterns through an integrated approach with clinical-laboratory features in children hospitalized for COVID-19 in relation to the temporal trend of the Italian epidemic. We conducted a retrospective study which took place at a pediatric tertiary hospital from 15 March 2020 to 15 March 2021. We compared the characteristics of the initial phase of the first COVID-19 year-in the spring and summer (15 March-30 September 2020)-and those of the second phase-in the autumn and winter (1 October 2020-15 March 2021). Twenty-eight patients were studied both in the first and in the second phase of the first COVID-19 year. The disease severity score (DSS) was significantly greater in the second phase (p = 0.015). In the second phase of the first COVID-19 year, we detected a more significant occurrence of the following LU features than in the first phase: the irregular pleural line (85.71% vs. 60.71%; p = 0.035), the B-lines (89.29% vs. 60%; p = 0.003) and the several but non-coalescent B-lines (89.29% vs. 60%; p = 0.003). The LU score correlated significantly with the DSS, with a moderate relationship (r = 0.51, p < 0.001). The combined clinical, laboratory and ultrasound approaches might be essential in the evaluation of pulmonary involvement in children affected by COVID-19 during different periods of the pandemic