Comprehensive Analysis of CXCR4, JUNB, and PD-L1 Expression in Circulating Tumor Cells (CTCs) from Prostate Cancer Patients.

CXCR4, JUNB and PD-L1 are implicated in cancer progression and metastasis. The current study investigated these biomarkers in CTCs isolated from metastatic prostate cancer (mPCa) patients at the RNA and protein levels. CTCs were isolated from 48 mPCa patients using the Ficoll density gradient and ISET system (17 out of 48). The (CK/PD-L1/CD45) and (CK/CXCR4/JUNB) phenotypes were identified using two triple immunofluorescence stainings followed by VyCAP platform analysis. Molecular analysis was conducted with an EpCAM-dependent method for 25/48 patients. CK-8, CK-18, CK-19, JUNB, CXCR4, PD-L1, and B2M (reference gene) were analyzed with RT-qPCR. The (CK+/PD-L1+/CD45-) and the (CK+/CXCR4+/JUNB+) were the most frequent phenotypes (61.1% and 62.5%, respectively). Furthermore, the (CK+/CXCR4+/JUNB-) phenotype was correlated with poorer progression-free survival [(PFS), HR: 2.5, p = 0.049], while the (CK+/PD-L1+/CD45-) phenotype was linked to decreased overall survival [(OS), HR: 262.7, p = 0.007]. Molecular analysis revealed that 76.0% of the samples were positive for CK-8,18, and 19, while 28.0% were positive for JUNB, 44.0% for CXCR4, and 48.0% for PD-L1. Conclusively, CXCR4, JUNB, and PD-L1 were highly expressed in CTCs from mPCa patients. The CXCR4 protein expression was associated with poorer PFS, while PD-L1 was correlated with decreased OS, providing new biomarkers with potential clinical relevance.

Impact of SARS-CoV-2 Preventive Measures against Healthcare-Associated Infections from Antibiotic-Resistant ESKAPEE Pathogens: A Two-Center, Natural Quasi-Experimental Study in Greece.

The COVID-19 pandemic led to unprecedented stress on healthcare systems worldwide, forming settings of concern for increasing antimicrobial resistance. We investigated the impact of SARS-CoV-2 preventive measures against healthcare-associated infections (HAIs) from antibiotic-resistant bacteria in two tertiary-care hospitals. We compared infection rates between March 2019 and February 2020 (pre-intervention period) and March 2020 and February 2021 (COVID-19 intervention period) from drug-resistant ESKAPEE bacteria (methicillin-resistant Staphylococcus aureus; vancomycin-resistant Enterococci; carbapenem-resistant Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species and Escherichia coli). Over 24 months, 586 drug-resistant ESKAPEE HAIs occurred in 439 patients (0.3% of 179,629 inpatients) with a mean age of 63 years, with 43% being treated in intensive care units (ICUs), and having a 45% inpatient mortality rate. Interrupted time series analysis revealed increasing infection rates before the intervention that were sharply interrupted by abrupt drops for most pathogens and henceforth remained stable in the ICUs but progressively increased in ordinary wards. In the ICUs, the pooled infection rate was 44% lower over the intervention period compared to the pre-intervention period (incidence rate ratio (IRR) 0.56, 95%CI 0.41-0.75, p < 0.001). Pooled infection rates in the wards were slightly higher over the COVID-19 period (IRR 1.12, 95%CI 0.87-1.45, p = 0.368). The findings confirmed the ancillary beneficial impact of the enhanced bundle of transmission-based precautions adopted against SARS-CoV-2 in rapidly constraining antimicrobial-resistant HAIs in two Greek hospitals.

Vaccination coverage rates and attitudes towards mandatory vaccinations among healthcare personnel in tertiary-care hospitals in Greece.

OBJECTIVES: Our aim was to estimate vaccination and susceptibility rates against vaccine-preventable diseases among healthcare personnel (HCP) in eight hospitals. METHODS: Cross-sectional survey. RESULTS: A total of 1284 HCP participated (physicians: 31.3%, nursing personnel: 36.6%, paramedical personnel: 11.1%, administrative personnel: 13.2%, supportive personnel: 7.3%). Vaccination rates were 32.9% against measles and mumps, 38.1% against rubella, 5.7% against varicella, 9.2% against hepatitis A, 65.8% against hepatitis B, 31.8% against tetanus-diphtheria, 7.1% against pertussis, 60.2% against influenza, and 80.1% against COVID-19. Susceptibility rates were as follows: 27.8% for measles, 39.6% for mumps, 33.4% for rubella, 22.2% for varicella, 86.3% for hepatitis A, 34.2% for hepatitis B, 68.2% for tetanus-diphtheria, and 92.9% for pertussis. Older HCP had higher susceptibility rates against mumps, rubella, varicella, hepatitis A, hepatitis B, tetanus-diphtheria, and pertussis (p-values <0.001 for all). Mandatory vaccinations were supported by 81.85% of HCP. CONCLUSIONS: Although most HCPs supported mandatory vaccinations, significant vaccination gaps, and susceptibility rates were recorded. The proportion of susceptible HCP to measles, mumps, rubella, and varicella has increased in the past decade, mostly because of reduction in acquired cases of natural illness. Vaccination programs for HCP should be developed. A national registry to follow HCP's vaccination rates is urgently needed.

Determinants of intention to get vaccinated against COVID-19 among healthcare personnel in hospitals in Greece.

BACKGROUND: To investigate intention rates to get vaccinated against COVID-19 among healthcare personnel (HCP) in Greece. METHODS: Cross-sectional survey. RESULTS: The response rate was 14.5%. Of 1521 HCP with a known profession, 607 (39.9%) were nursing personnel, 480 (31.6%) physicians, 171 (11.2%) paramedical personnel, 72 (4.7%) supportive personnel, and 191 (12.6%) administrative personnel. Overall, 803 of 1571 HCP (51.1%) stated their intention to get vaccinated while 768 (48.9%) stated their intention to decline vaccination. Most HCP (71.3%) who reported intent to get vaccinated noted contributing to the control of the pandemic and protecting their families and themselves as their reasons, while the most common reason for reporting intent to decline vaccination was inadequate information about the vaccines (74.9%), followed by concerns about vaccine safety (36.2%). Logistic regression analysis revealed that the probability of intending to get vaccinated increased with male gender, being a physician, history of complete vaccination against hepatitis B, history of vaccination against pandemic A (H1N1) in 2009-2010, belief that COVID-19 vaccination should be mandatory for HCP, and increased confidence in vaccines in general during the COVID-19 pandemic. The following factors were associated with a lower intention to get vaccinated: no vaccination against influenza the past season, no intention to get vaccinated against influenza in 2020-2021, and no intention to recommend COVID-19 vaccination to high-risk patients. CONCLUSION: There is an urgent need to built safety perception towards COVID-19 vaccines and raise vaccine uptake rates by HCP, and thus to protect the healthcare workforce and the healthcare services.

Acute aortic occlusion due to tumor embolism in a patient with lung malignancy.

OBJECTIVES: Acute lower limb ischemia caused by tumor embolization is rare, despite the fact that cancer is a common cause of hypercoagulability predisposing to venous thrombosis. Arterial embolization is mostly associated with intracardiac tumors while lung malignancies are the second most common cause of tumor embolism. METHODS: In this report, we present a male patient who developed acute bilateral lower limb ischemia in the immediate postoperative period after a thoracotomy for attempted left upper lobe resection for lung cancer. RESULTS: The patient was treated with a subclavian-bifemoral bypass, since an initial attempted embolectomy was unsuccessful. Histopathological characteristics of thrombus obtained during embolectomy were consistent with the histopathology of the primary tumor. CONCLUSION: Acute ischemia is an emergency that should be diagnosed and treated immediately. Interestingly, in this case, the presence of epidural anesthesia masked the initial symptoms and delayed diagnosis. Preoperative assessment with transesophageal echocardiography may reveal patients at high risk for tumor embolism.

Pneumorachis associated with persistent tachycardia after blunt thoracic trauma.

Pneumorachis, or intraspinal air, can be a rare result of blunt thoracic trauma. We report the case of a 40-year-old man with multiple injuries and pneumorachis associated with persistent tachycardia. As factors that increase heart rate were gradually ruled out, intraspinal air was considered the potential culprit. Computed tomography revealed intraspinal air at the thoracic level, which possibly promoted cardiac arrhythmogenesis. Air may transiently compress the preganglionic cardiac sympathetic nerves and increase sympathetic output to the heart.

Molecular profiling of EGFR family in chronic obstructive pulmonary disease: correlation with airway obstruction.

BACKGROUND: Growth factors mediate various cellular responses to environmental stimuli. Specifically, exposure of lung epithelium to oxidative stress induced by cigarette smoke stimulates aberrant epidermal growth factor receptor (ERBB) family activation. This study's objective was to evaluate the expression of ERBB1-4 receptors in the lung tissue of smokers with or without chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: ERBBs expression was measured by microarray analysis in lung tissue samples from five patients with COPD and five non-COPD smokers, and by quantitative real-time PCR in additional 20 patients with COPD (GOLD stage II), 15 non-COPD smokers and 10 nonsmoker controls. RESULTS: Microarray data analysis revealed that ERBB receptors expression was elevated in patients with COPD compared to non-COPD smokers, ranging from 1·62- to 2·45-fold, (P < 0·01). Real-time qPCR verified that patients with COPD had higher ERBB1-3 expression levels compared with non-COPD smokers (PERBB1  < 0·001; PERBB2  = 0·003; PERBB3  = 0·003) and nonsmokers (PERBB1  = 0·019; PERBB2  = 0·005; PERBB3  = 0·011). On the other hand, ERBB4 mRNA levels gradually increased from nonsmokers (0·74 ± 0·19) to non-COPD smokers (1·11 ± 0·05) to patients with COPD (1·57 ± 0·28) and were correlated with the degree of airflow obstruction (PFEV1  < 0·001). DISCUSSION: These data suggest that ERBB1-3 overexpression is not related only to smoking exposure but probably to epithelial remodelling and mucociliary system distortion, characterizing COPD. Additionally, the inverse correlation of ERBB4 with FEV1 exhibits a possible link between ERBB4 and COPD severity.

The value of cryosurgery in treating a case of thoracic chondrosarcoma.

Chondrosarcomas of the spine are rare and difficult to treat. In this paper a case of thoracic chondrosarcoma is presented. Chondrosarcomas of the spine are generally smaller, more difficult to excise and are followed by higher local recurrence compared with chondrosarcomas of the peripheral skeleton. The tumor is radio- and chemoresistant, making the surgical treatment of utmost importance. The most important prognostic factor for local control is wide or marginal tumor resection. Our patient was treated in two stages, with total excision of the tumor, using cryosurgery. Liquid nitrogen was used to freeze the damaged tissue at a cellular level and made the excision more efficient.

Expression analysis of angiogenic growth factors and biological axis CXCL12/CXCR4 axis in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is associated with aberrant repair, persistence of collagen deposition, and the development of vascular remodeling. However, the role of angiogenesis in the pathogenesis of IPF is still undetermined. The aim of this study was to evaluate the combined mRNA expression of vascular endothelial growth factor A (VEGFA), fibroblast growth factor 2 (FGF2), insulin-like growth factor 1 (IGF1) epidermal growth factor (EGF), and its receptor (EGFR) in lung tissue obtained from IPF patients. We have also investigated the expression of chemokine CXCL12/stromal cell-derived factor-1 (SDF-1) and its receptor, CXCR4, to identify alterations that maybe implicated in the pathogenesis of IPF. The subjects studied consisted of two distinct groups: patients with IPF (n = 25) and subjects (control) undergoing thoracic surgery for reasons other than interstitial lung disease (n = 10). Expression analysis of the aforementioned growth factors and biological axis CXCL12/CXR4 analysis were performed using real-time RT-PCR. IGF-1, EGF, and FGF2 mRNA levels are significantly decreased in the patients compared to the controls (p = 0.028, p = 0.023 and p = 0.009, respectively). SDF1-TR1 and SDF1-TR2 transcript levels were significantly lower in patients compared to controls (p = 0.017 and p = 0.001). Significant coexpression of VEGF mRNA with IGF mRNA was observed in the group of the patients (p = 0.017). An additional coexpression of VEGF mRNA with SDF1-TR1 mRNA was demonstrated(p = 0.030). Our results show a downregulation in angiogenetic mechanisms in IPF. However, our results should be further verified by measuring other angiogenetic pathways in more samples.

Altered surfactant protein-A expression in type II pneumocytes in COPD.

BACKGROUND: Pulmonary surfactant protein A (SP-A) is a lectin, with multiple functions that contribute to innate host defense and the regulation of the inflammatory process in the lung. In normal conditions, SP-A seems to protect against the effects of smoking. However, studies in smokers with or without COPD are limited. METHODS: Western blots on lung tissue specimens from 60 male subjects (32 patients with COPD, 18 smokers without COPD, and 10 control nonsmokers) for SP-A and the housekeeping protein actin were carried out. Additionally, the SP-A expression pattern was evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded lung tissue sections from the same subjects. RESULTS: Western blots revealed significantly higher SP-A levels in control nonsmokers (4.8 +/- 0.05) when compared with patients with COPD (0.6 +/- 0.7) and smokers without COPD (2.4 +/- 0.9), (P < .05). However, differences that were not statistically significant were observed in SP-A levels among the patients with COPD and the smokers without COPD (P = .12). The immunohistochemical examinations showed an increase in the overall number of type II pneumocytes per high-power field in patients with COPD, but a decreased ratio of SP-A positive type II pneumocytes to total type II pneumocytes, compared with smokers without COPD (P = .001). This ratio was also correlated with FEV(1) (percent predicted [% pred]), (r = 0.490, P = .001). The overall number of alveolar macrophages per high-power field was significantly higher in patients with COPD compared with smokers without COPD (P = .001). The ratio of SP-A positive alveolar macrophages was increased in patients with COPD when compared with smokers without COPD (P = .002), while this was correlated with airway obstruction (FEV(1), % pred) (r = 0.281, P = .04). CONCLUSIONS: Our results indicate that altered SP-A expression could be another link to COPD pathogenesis and highlights the need for further studies on surfactant markers in COPD.

Pneumocephalus and presumed meningitis following inconspicuous penetrating periocular trauma.

PURPOSE: To report a case of serious intracranial complications in an adolescent youth following a seemingly trivial periocular injury. METHODS: An adolescent youth was examined and discharged after a small penetrating injury to his left medial canthus. He later presented with blurred vision, nausea and mild pyrexia and underwent a computed tomography (CT) scan of the head and orbits as well as a lumbar puncture. RESULTS: The CT scan revealed a fracture in the cribriform plate of the ethmoid bone and the medial orbital wall, as well as pneumocephalus. The lumbar puncture revealed 3000 white cells/mm3 in the cerebrospinal fluid (CSF). After treatment with meningitic doses of intravenous antibiotics, a significant improvement was noted. CONCLUSIONS: A CT scan, instead of an ordinary head radiograph, may be considered as a first-choice mode of diagnosis in evaluating even inconspicuous penetrating periocular wounds. Early administration of meningitic doses of antibiotics may significantly improve prognosis.

Video-assisted thoracoscopic surgery for thoracic empyema: primarily, or after fibrinolytic therapy failure?

BACKGROUND: Traditional and modern treatments are proposed for thoracic empyema. The efficacy of video-assisted thocoscopic surgery (VATS) has been studied when the method is applied either as primary treatment for thoracic empyema or after the failure of fibrinolytic therapy. METHODS: Thirty-eight patients treated with VATS for thoracic empyema have been reviewed. Of those, 20 patients (group 1) with empyema thoracis were referred to VATS after failure of the fibrinolytic treatment. Another 18 patients (group 2) with primary empyema thoracis were treated thoracoscopically immediately when empyema was diagnosed. Both groups were staged 5, 6, or 7 according to Light's criteria. RESULTS: The group 2 patients showed a higher empyema resolving rate (95% versus 85%), shorter hospital stay (4.5 versus 7.5 days), and significantly shorter duration of the procedure (70 +/- 14 versus 62 +/- 10 minutes) in comparison with the patients of group 1. CONCLUSIONS: The VATS technique for thoracic empyema is a well-tolerated, minimally invasive technique, with excellent therapeutic results, mild postoperative complications, and reduced hospitalization. VATS should be considered as the treatment of choice for thoracic empyema, in the fibrinopurulent stage, as it is more effective when applied primarily than when applied after fibrinolytic therapy.