TESTICULAR METASTASIS AS FIRST CLINICAL EXPRESSION OF UNKNOWN ORIGIN MALIGNANT MELANOMA

Resumen

Compositional and structural analysis of engineered stones and inorganic particles in silicotic nodules of exposed workers

Background Engineered stone silicosis is an emerging disease in many countries worldwide produced by the inhalation of respirable dust of engineered stone. This silicosis has a high incidence among young workers, with a short latency period and greater aggressiveness than silicosis caused by natural materials. Although the silica content is very high and this is the key factor, it has been postulated that other constituents in engineered stones can influence the aggressiveness of the disease. Different samples of engineered stone countertops (fabricated by workers during the years prior to their diagnoses), as well as seven lung samples from exposed patients, were analyzed by multiple techniques. Results The different countertops were composed of SiO2 in percentages between 87.9 and 99.6%, with variable relationships of quartz and cristobalite depending on the sample. The most abundant metals were Al, Na, Fe, Ca and Ti. The most frequent volatile organic compounds were styrene, toluene and m-xylene, and among the polycyclic aromatic hydrocarbons, phenanthrene and naphthalene were detected in all samples. Patients were all males, between 26 and 46 years-old (average age: 36) at the moment of the diagnosis. They were exposed to the engineered stone an average time of 14 years. At diagnosis, only one patient had progressive massive fibrosis. After a follow-up period of 8 +/- 3 years, four patients presented progressive massive fibrosis. Samples obtained from lung biopsies most frequently showed well or ill-defined nodules, composed of histiocytic cells and fibroblasts without central hyalinization. All tissue samples showed high proportion of Si and Al at the center of the nodules, becoming sparser at the periphery. Al to Si content ratios turned out to be higher than 1 in two of the studied cases. Correlation between Si and Al was very high (r = 0.93). Conclusion Some of the volatile organic compounds, polycyclic aromatic hydrocarbons and metals detected in the studied countertop samples have been described as causative of lung inflammation and respiratory disease. Among inorganic constituents, aluminum has been a relevant component within the silicotic nodule, reaching atomic concentrations even higher than silicon in some cases. Such concentrations, both for silicon and aluminum showed a decreasing tendency from the center of the nodule towards its frontier

New European union regulations related to whole slide image scanners and image analysis software

Whole slide imaging (WSI) scanners and automatic image analysis algorithms, in order to be used for clinical applications, including primary diagnosis in pathology, are subject to specific regulatory frameworks in each country. Until May 25, 2018, in the European Union (EU), in vitro diagnostic (IVD) medical devices were regulated by directive 98/79/EC (in vitro diagnostic medical device directive [IVDD]). Main scanner vendors have obtained a Conformité Européenne mark of their products that in Europe were classified as General Class IVDD, so that conformity is only based on a self-declaration of the manufacturer. This contrasts with the initial classification of the US Food and Drug Administration (FDA) of WSI system as Class III medical devices, although the first digital pathology WSI system to be cleared by FDA was classified as Class II, with special controls. Other digital pathology solutions (automated cervical cytology slide reader) are considered of higher risk by US and European regulations. There is also some disparity in the classification of image analysis solutions between Europe and the United States. All IVD-MDs must be approved under the new European regulation (in vitro diagnostic medical device regulation) 2017/746 after May 26, 2024. This means the need of a performance evaluation, including a scientific validity report, an analytical performance report, and a clinical performance report. According to its clinical use (e.g., screening, diagnosis, or staging of cancer), a WSI slide scanner can be now classified as Class C device. A special regulation is applied to companion diagnostics. The new EU regulation 2017/746 contemplates the use of standard unique identifiers for medical devices and the creation of a European database on medical devices (Eudamed). Existing validation studies and clinical guidelines already available in the literature are a sound basis to avoid that this new regulation becomes a barrier for digital pathology development in Europe

Evolution over Time of Ventilatory Management and Outcome of Patients with Neurologic Disease∗

OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p < 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p < 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p < 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease