Evaluation of COVID-19 impact on DELAYing diagnostic-therapeutic pathways of lung cancer patients in Italy (COVID-DELAY study): fewer cases and higher stages from a real-world scenario.

INTRODUCTION: COVID-19 has disrupted the global health care system since March 2020. Lung cancer (LC) patients (pts) represent a vulnerable population highly affected by the pandemic. This multicenter Italian study aimed to evaluate whether the COVID-19 outbreak had an impact on access to cancer diagnosis and treatment of LC pts compared with pre-pandemic time. METHODS: Consecutive newly diagnosed LC pts referred to 25 Italian Oncology Departments between March and December 2020 were included. Access rate and temporal intervals between date of symptoms onset and diagnostic and therapeutic services were compared with the same period in 2019. Differences between the 2 years were analyzed using the chi-square test for categorical variables and the Mann-Whitney U test for continuous variables. RESULTS: A slight reduction (-6.9%) in newly diagnosed LC cases was observed in 2020 compared with 2019 (1523 versus 1637, P = 0.09). Newly diagnosed LC pts in 2020 were more likely to be diagnosed with stage IV disease (P < 0.01) and to be current smokers (someone who has smoked more than 100 cigarettes, including hand-rolled cigarettes, cigars, cigarillos, in their lifetime and has smoked in the last 28 days) (P < 0.01). The drop in terms of new diagnoses was greater in the lockdown period (percentage drop -12% versus -3.2%) compared with the other months included. More LC pts were referred to a low/medium volume hospital in 2020 compared with 2019 (P = 0.01). No differences emerged in terms of interval between symptoms onset and radiological diagnosis (P = 0.94), symptoms onset and cytohistological diagnosis (P = 0.92), symptoms onset and treatment start (P = 0.40), and treatment start and first radiological revaluation (P = 0.36). CONCLUSIONS: Our study pointed out a reduction of new diagnoses with a shift towards higher stage at diagnosis for LC pts in 2020. Despite this, the measures adopted by Italian Oncology Departments ensured the maintenance of the diagnostic-therapeutic pathways of LC pts.

Removal of selected pharmaceuticals from domestic wastewater in an activated sludge system followed by a horizontal subsurface flow bed - analysis of their respective contributions.

Seventy-three commonly administered pharmaceuticals from twelve different therapeutic classes were investigated at a municipal wastewater treatment plant in northern Italy featuring a conventional activated sludge system (full-scale) and a polishing horizontal subsurface flow bed (pilot plant). Removal of these micro-pollutants by the two systems was assessed in order to evaluate their respective contributions. Mean concentrations and standard deviations were calculated and found to differ for the compounds detected, ranging from few ng/L to over 1,165 ng/L in the secondary effluent and from 11 to 533 in the polished effluent. Eighteen compounds were consistently below the detection limit and the remaining 55 compounds were found at a minimum of one sampling point. Average removal efficiencies of both treatment steps and in treatment train as a whole are evaluated and discussed, highlighting the difficulties in predicting the fate of pharmaceuticals in both an activated sludge system and a horizontal subsurface flow bed. Comparison between the observed average removal efficiencies and those reported in the literature was also carried out for the pharmaceuticals of interest, and the discrepancies that emerged are discussed. The investigated constructed wetland did show efficacy in removing some of these compounds, and it contributed to the overall removal efficiency of each therapeutic class. Indeed, evaluation of the specific mass loadings of each class of PhC detected in the raw wastewaters, secondary and polished effluent evidences that the investigated constructed wetland is able to further reduce the load of micropollutants, which could become a necessity, especially where the receiving water body is an effluent-dominant river and mitigation measures of the discharge impact are required to protect and safeguard the aquatic environment.

Hospital effluent: investigation of the concentrations and distribution of pharmaceuticals and environmental risk assessment.

A study was conducted in an area in north, Italy, on the effluent of two different sized hospitals and the influent and effluent of the receiving municipal treatment plant of one of the examined hospitals. The aim was to investigate 73 selected pharmaceuticals, belonging to twelve different classes, comparing their occurrence in the effluent directly exiting the hospital with that, mixed with the local urban effluent, at the point of its entry and exit from the treatment plant. Consistent differences were found in the concentrations of some antibiotics, analgesics and lipid regulators in the two wastewaters, confirming that hospital effluents should not be considered as possessing the same pollutant nature as urban wastewater. Furthermore, analysis of percentage contributions of the hospital to the treatment plant influent evidences that hospitals represent one of the main sources of pollutants, in particular antibiotics, receptor antagonists and lipid regulators. Hence, an environmental risk assessment, performed on the effluent from the hospital and the influent and effluent from the treatment plant, revealed a high risk for 9 pharmaceuticals in hospital effluent and for 4 of the 9 substances in the treatment plant influent and effluent, with antibiotics being the most critical compounds in terms of contribution and potential environmental risk for the hospital.

Expression of the Rai (Shc C) adaptor protein in the human enteric nervous system.

The adaptor protein Rai (ShcC/N-Shc) is almost exclusively present in the nervous system, although little is documented about its expression in the gut and the enteric nervous system (ENS). As Rai is a physiological substrate of Ret, an important factor for the development of ENS, we have evaluated the expression of Rai in the ENS in various segments of the human gastrointestinal tract. The expression of Rai was assessed by immunohistochemistry in disease-free human gut samples (oesophagus, stomach, small bowel and colon) obtained from subjects undergoing surgical procedures. Rai was not expressed in the epithelia or lymphoid tissue, whereas a moderate level of expression was observed in the endothelial cells of blood vessels and on the outer membrane of smooth muscle cells in both the muscularis mucosae and the muscularis propria. In the ENS, strong positivity was observed only in enteric glial cells, overlapping with GFAP and S100. In conclusion, Rai is expressed in the human gut, especially in the enteric glial cells. We conclude that Rai may provide an additional marker for this cell type.

COX-2, CDX2, and CDC2 immunohistochemical assessment for dysplasia-carcinoma progression in Barrett's esophagus.

BACKGROUND: Immunohistochemical changes associated with development of cancer in Barrett's esophagus offer potential areas of intervention to prevent and manage esophageal cancer. AIMS: To assess the role of cyclooxygenase 2, caudal-type homeobox transcription factor 2 and cell division cycle 2/cyclin-dependent kinase 1 in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence. PATIENTS AND METHODS: Specimens from 46 patients with Barrett's esophagus (39% without dysplasia, 33% with dysplasia and 28% with adenocarcinoma) were stained for cyclooxygenase 2, caudal-type homeobox transcription factor 2 and cell division cycle 2. RESULTS: Cyclooxygenase 2: No expression differences between groups were found, except for adenocarcinomas (p=0.04). Caudal-type homeobox transcription factor 2: Nuclear positivity decreased from Barrett's esophagus without dysplasia (71.6%), to Barrett's esophagus with low grade dysplasia (35.3%), to Barrett's esophagus with high grade dysplasia (17.14%); in adenocarcinoma these percentages were intermediate between high and low grade dysplasia (30.5%). Cell division cycle 2: Expression on deeper glandular structures was 40% in Barrett's esophagus without dysplasia, 55.47% in Barrett's esophagus with dysplasia, and 63.84% in adenocarcinoma, with no statistical differences between groups. Concerning cells of the superficial layer, Barrett's esophagus with low grade dysplasia expressed focal positivity (p=0.0001 vs. no dysplasia); Barrett's esophagus with high grade dysplasia displayed diffuse positivity (p=0.0001 vs. no dysplasia and low grade dysplasia). A diffuse positivity was found in Barrett's esophagus with adenocarcinoma (p=0.0001 vs. no dysplasia and low grade dysplasia). CONCLUSIONS: Further evaluation of cyclooxygenase 2, cell division cycle 2 and caudal-type homeobox transcription factor 2, in association with morphology, might help to improve the accuracy of diagnosis and be useful for the clinical-pathological assessment of patients with Barrett's esophagus.

[The activities of a pediatric emergency department. The emergency problems]. / L'attività di un pronto soccorso pediatrico. Problemi emergenti.

The authors reviewed records of admission at the Fist Ais-Emergency Service of "G. Gaslini" Children's Hospital, data referring both to in and outpatients. First of all we took into account epidemiological data analysing occurrence and types of diseases; at the same time a demographic study, which aimed to show a decrease in the child population in Genova, was performed. Secondly we compared these data with the real number of admitted patients: collected data showed that this service has been used excessively.

[Cerebral gigantism or Sotos' syndrome]. / Gigantismo cerebrale o sindrome di Sotos.

The paper describes a case of Sotos syndrome and reviews the world literature on the subject. Inheritance may be dominant autosomal as well as recessive, although the latter is quite rare. The pathophysiology is not well known but a common underlying basis between various syndromes (Sotos; Beckwith-Wiedemann; Klippel-Trenaunay) is hypothesised.

Fibrinogen Vicenza and Genova II: two new cases of congenital dysfibrinogenemia with isolated defect of fibrin monomer polymerization and inhibitory activity on normal coagulation.

Two new cases of congenital dysfibrinogenemia are presented in which defective fibrin monomer polymerization and inhibitory activity on normal coagulation were observed. They have been tentatively called fibrinogen Vicenza and Genova II. The first was discovered in a family with mild bleeding diathesis, the second in an asymptomatic family. In almost all reported cases of fibrinogens with defective fibrin monomer polymerization, additional functional or structural defects have been detected. In our cases, on the contrary, detailed investigations failed to show any other abnormality. Fibrinogen Genova II is apparently identical to fibrinogen Baltimore IV, whereas fibrinogen Vicenza is similar to fibrinogen Troyes and Genova I, but also exerts an evident inhibitory activity on normal coagulation and differs from fibrinogen Genova II and Baltimore IV showing a different kinetic pattern of fibrin monomer polymerization.

A case of congenital afibrinogenemia. Study of a new family.

A case of congenital afibrinogenemia is described. In the family studied, the defect is transmitted as an autosomal recessive trait. The possible heterogeneity of congenital afibrinogenemia is discussed.