Thoracic ultrasound use in hospitalized and ambulatory adult patients: a quantitative picture.

INTRODUCTION AND OBJECTIVES: Thoracic ultrasound (TUS) has been established as a powerful diagnostic and monitoring tool in the Intensive Care Unit (ICU). However, studies outside the critical care setting are scarce. The aim of this study was to investigate the value of TUS for hospitalized or ambulatory community patients. MATERIALS AND METHODS: This was a retrospective study conducted from 2016 to 2020 in the TUS clinic at Heraklion University Hospital. TUS examination was performed using a standard ultrasound machine (EUB HITACHI 8500), and a high-frequency microconvex probe (5-8 MHz). Patients had been referred by their primary physician to address a range of different questions. The various respiratory system entities were characterised according to internationally established criteria. RESULTS: 762 TUS studies were performed on 526 patients due to underlying malignancy (n = 376), unexplained symptoms/signs (n = 53), pregnancy related issues (n = 42), evaluation of abnormal findings in X-ray (n = 165), recent surgery/trauma (n = 23), recent onset respiratory failure (n = 12), acute respiratory infection (n = 66) and underlying non-malignant disease (n = 25). Pleural effusion was the commonest pathologic entity (n = 610), followed by consolidation (n = 269), diaphragmatic dysfunction/paradox (n = 174) and interstitial syndrome (n = 53). Discrepancies between chest X-ray and ultrasonographic findings were demonstrated in 96 cases. The TUS findings guided invasive therapeutic management in 448 cases and non-invasive management in 43 cases, while follow-up monitoring was decided in 271 cases. CONCLUSIONS: This study showed that TUS can identify the most common respiratory pathologic entities encountered in hospitalized and community ambulatory patients, and is especially useful in guiding the decision making process in a diverse group of patients.

Sleep quality in survivors of critical illness.

PURPOSE: There is limited data regarding the sleep quality in survivors of critical illness, while the time course of the sleep abnormalities observed after ICU discharge is not known. The aim of this study was to assess sleep quality and the time course of sleep abnormalities in survivors of critical illness. METHODS: Eligible survivors of critical illness without hypercapnia and hypoxemia were evaluated within 10 days (1st evaluation, n = 36) and at 6 months after hospital discharge (2nd evaluation, n = 29). At each visit, all patients underwent an overnight full polysomnography and completed health-related quality of life questionnaires (HRQL). Lung function and electro-diagnostic tests (ED) were performed in 24 and 11 patients, respectively. RESULTS: At 1st evaluation, sleep quality and HRQL were poor. Sleep was characterised by high percentages of N1, low of N3 and REM stages, and high apnea-hypopnea index (AHI, events/h). Twenty-two out of 36 patients (61%) exhibited AHI ≥ 15 (21 obstructive, 1 central). None of the patients' characteristics, including HRQL and lung function, predicted the occurrence of AHI ≥ 15. At 6 months, although sleep quality remained poor (high percentages of N1 and low of REM), sleep architecture had improved as indicated by the significant increase in N3 [4.2% (0-12.5) vs. 9.8% (3.0-20.4)] and decrease in AHI [21.5 (6.5-29.4) vs. 12.8 (4.7-20.4)]. HRQL improved slightly but significantly at 6 months. Neither the changes in HRQL nor in lung function tests were related to these of sleep architecture. Six out of eight patients with abnormal ED at 1st evaluation continued to exhibit abnormal results at 6 months. CONCLUSIONS: Survivors of critical illness exhibited a high prevalence of obstructive sleep-disordered breathing and poor sleep architecture at hospital discharge, which slightly improved 6 months later, indicating that reversible factors are partly responsible for these abnormalities.

SPOP regulates prostate epithelial cell proliferation and promotes ubiquitination and turnover of c-MYC oncoprotein.

The E3 ubiquitin ligase adaptor speckle-type POZ protein (SPOP) is frequently dysregulated in prostate adenocarcinoma (PC), via either somatic mutations or mRNA downregulation, suggesting an important tumour suppressor function. To examine its physiologic role in the prostate epithelium in vivo, we generated mice with prostate-specific biallelic ablation of Spop. These mice exhibited increased prostate mass, prostate epithelial cell proliferation, and expression of c-MYC protein compared to littermate controls, and eventually developed prostatic intraepithelial neoplasia (PIN). We found that SPOPWT can physically interact with c-MYC protein and, upon exogenous expression in vitro, can promote c-MYC ubiquitination and degradation. This effect was attenuated in PC cells by introducing PC-associated SPOP mutants or upon knockdown of SPOP via short-hairpin-RNA, suggesting that SPOP inactivation directly increases c-MYC protein levels. Gene Set Enrichment Analysis revealed enrichment of Myc-induced genes in transcriptomic signatures associated with SPOPMT. Likewise, we observed strong inverse correlation between c-MYC activity and SPOP mRNA levels in two independent PC patient cohorts. The core SPOPMT;MYCHigh transcriptomic response, defined by the overlap between the SPOPMT and c-MYC transcriptomic programmes, was also associated with inferior clinical outcome in human PCs. Finally, the organoid-forming capacity of Spop-null murine prostate cells was more sensitive to c-MYC inhibition than that of Spop-WT cells, suggesting that c-MYC upregulation functionally contributes to the proliferative phenotype of Spop knock-out prostates. Taken together, our data highlight SPOP as an important regulator of luminal epithelial cell proliferation and c-MYC expression in prostate physiology, identify c-MYC as a novel bona fide SPOP substrate, and help explain the frequent inactivation of SPOP in human PC. We propose SPOPMT-induced stabilization of c-MYC protein as a novel mechanism that can increase total c-MYC levels in PC cells, in addition to amplification of c-MYC locus.