miRNA patterns in male LUSC patients - the 3-way mirror: Tissue, plasma and exosomes.

Lung cancer remains one of the leading causes of cancer-related deaths worldwide. It is classified into two main histological groups: non-small cell lung cancer (NSCLC) and small cell lung cancer. Improving the outcome of cancer patients could be possible by enhancing the early diagnosis. In the current study, we evaluated the levels of three microRNAs - miR-21-5p, miR-155-5p, and miR-181a-5p in tumor (TT) vs adjacent normal tissue (NT), as well as their expression levels in plasma and extracellular vesicles (EVs) from plasma in lung squamous cell carcinoma (LUSC) male patients vs healthy individuals as means to identify a panel of miRNAs that could serve as novel biomarkers for the diagnosis of LUSC in male patients. Matched paired tissue samples from male LUSC (n=40) patients were used for miRNA expression analysis. MiR-21-5p and miR-155-5p in tumor tissue were overexpressed, while underexpression of miR-181a-5p was observed in LUSC TT vs NT. These results were further validated in the TCGA LUSC dataset, considering 279 male samples. These alterations of miR-21-5p, miR-181a-5p, and miR-155-5p in tumor tissue are also present in plasma and plasma extracellular vesicles in LUSC male patients. In addition, ROC curves were performed to assess the sensitivity and specificity of different combinations of these miRNAs, confirming a high diagnostic accuracy for LUSC of up to 88 % in male subjects. The expression levels in tissue samples and the abundance in plasma and plasma EVs of the three miRNAs combined - miR-21-5p, miR-155-5p and miR-181a-5p - could be considered for further studies on biomarkers for the early detection of LUSC in male subjects.

Opioids in Treatment of Refractory Dyspnea in Chronic Obstructive Pulmonary Disease: Yes, No or Maybe.

Chronic Obstructive Pulmonary Disease (COPD) is a complex condition with significant impact on prognosis, especially in advanced stages where symptom burden becomes critical. Breathlessness affects patients' quality of life, and despite various therapeutic strategies, the role of opioids in palliative care for COPD remains under investigation. The acceptance of a therapeutic trial of different types of opioids is increasing not only in end-of-life situations but also for stable COPD patients experiencing intolerable refractory breathlessness despite optimal conventional therapy. Recent clinical trials have raised questions about the overall clinical benefit of opioids in addressing breathlessness in COPD, prompting the need to clarify inconsistencies and identify specific subgroups that may benefit from opioid therapy. In the clinical setting, it is crucial to understand the attributes of patients who exhibit positive responses to opioids and what type of opioids could have a positive impact. This research paper aims to offer an update of the most recent evidence of opioid treatment in managing breathlessness among individuals with COPD with a head-to-head evaluation of the supporting and opposing proof in the medical literature.

PATTERNS OF FACIAL FRACTURES AND ASSOCIATED SOFT TISSUE INJURIES: A RETROSPECTIVE STUDY ON 1007 PATIENTS.

Background: Knowing the severity of a pathology in a population helps to both establish a rapid diagnosis and to prepare medical staff to provide adequate and complete treatment. The aim of this study was to determine the patterns of maxillofacial fractures and their associated soft tissue injuries in order to identify the specific types of maxillofacial fractures with the highest incidence of associated soft tissue injuries. Methods: A 10-year retrospective evaluation of maxillofacial trauma was performed on 1007 patients. All 1007 patients were clinically and paraclinically confirmed to have facial skeletal injuries. Results: The highest incidence of maxillofacial fractures was found in the mandible (62.16%), the mandibular angle being the most frequently involved (28.84%). Most of the fractures were complete (97.82%), displaced (87.98%) and closed (86.30%). Hematoma was the most common associated soft tissue injury (44.79%). In mandibular trauma, the incidence of hematoma and laceration was the highest in angle and simultaneous multiple fracture lines (p=0.002). In the midface, hematoma was more frequently associated with non-comminuted zygomatic bone fractures (p=0.003), while laceration was associated with multiple underlying fracture lines (p=0.002). Conclusions: Patients presenting with hematomas will most frequently have an underlying single closed fracture line, while patients with lacerations will most frequently present underlying multiple and displaced fractures.

EBUS in optimizing non-small cell lung cancer diagnosis and treatment.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a commonly used minimally invasive method for the diagnosis and staging of lung cancer. In order to improve its diagnostic accuracy, rapid on-site cytologic evaluation (ROSE) is being utilized in some institutions. ROSE, performed by a cytopathologist in the examination room, allows the assessment of the adequacy of the collected samples, identifies malignant cells and sometimes establishes diagnosis on the spot, thus improving diagnostic sensitivity. As non-small cell lung carcinomas (NSCLC) require not only pathological subtyping, but also molecular characterization, obtaining the adequate amount of tissue is crucial. Only a limited number of studies have analyzed the suitability of EBUS-TBNA samples for assessment of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and programmed death-ligand 1 (PD-L1) status. AIM: We intended to examine the diagnostic yield of ROSE in NSCLC and the results and feasibility of molecular analysis performed on EBUS-TBNA small samples. METHODS: 100 patients with lung tumors and hilar and/or mediastinal lymphadenopathy on CT or PET/CT scans were retrospectively identified over a 3-year period, from a prospectively maintained EBUS-TBNA database. All examinations were accompanied by on-site cytological exam - ROSE, histopathological exam (HPE) and, in the case of NSCLC, molecular testing. After the sampling of the lymph nodes, specimens were Diff-Quik stained and a rapid preliminary diagnosis was established. Immunohistochemistry and mutational testing were performed using cell blocks. RESULTS: Adenocarcinoma was the most frequent diagnosis in both ROSE (34%) and histopathology (53%). Overall sensitivity and positive predictive value of ROSE in NSCLC, considering HPE the gold standard, were 92.18% and 93.65%, respectively, with a specificity and negative predictive value of 75% and 70.58%, respectively. All samples that were tested for EGFR mutation and ALK rearrangement were adequate for analysis. The adequacy ratio for PD-L1 was 91.66%; 37.5% of patients showed a high PD-L1 expression level, with a tumor proportion score TPS ≥50%. CONCLUSION: EBUS-TBNA is a valuable method for lung cancer diagnosis. ROSE proved to have a moderate prediction of the final diagnosis in NSCLC. Molecular analysis of EGFR, ALK and PD-L1 can be successfully accomplished on EBUS-TBNA small tissue samples.

An epidemiological analysis of maxillofacial fractures: a 10-year cross-sectional cohort retrospective study of 1007 patients.

BACKGROUND: Epidemiological data is providing vital indicators for organizing the financial resources related to a particular type of trauma, estimating expenses and training of dental practioners and ambulatory medical staff for collaboration with a certain pattern of patients. Knowing the etiology and epidemiology of a certain pathology is significant for approaching its means of prevention. METHODS: A 10-year retrospective statistical analysis of 1007 patients with maxillofacial fractures treated in a University Clinic of Oral and Maxillofacial Surgery in Romania was performed. The data were extracted from patients' medical records. Statistical analysis was performed. A value of p < 0.05 was considered statistically significant. RESULTS: The incidence of maxillofacial fractures was high among patients in the 20-29 age group (35.9%). Male patients (90.57%, M:F = 9.6:1), having a low level of education (46.60%) and living in urban areas (53.50%) were more affected. The main cause of maxillofacial fractures was interpersonal violence (59.37%), both in the mandibular and midface topographic regions (p = 0.001, p = 0.002). In urban areas, fractures caused by interpersonal violence and road traffic accidents were predominant, while in rural areas, most of the fractures were due to interpersonal violence, domestic accidents, work accidents and animal attacks (p = 0.001). CONCLUSIONS: Interpersonal violence is the main cause of maxillofacial fractures having epidemic proportions. Male patients aged 20-29 years with a low level of education represent the major risk category. Considering the wide area of interpersonal aggression, both the medical staff in the hospital and in the dental offices must be educated in order to collaborate with possible violent patients. Dentists must be prepared to work on a post-traumatic dento-periodontal field. Taking all measures to prevent inter-human aggression is imperative and will lead to a major decrease in maxillofacial fractures and an overall increase of oral health in a population.

Critical function of circular RNAs in lung cancer.

Lung cancer is one of the main causes of cancer-related death in the world, especially due to its frequency and ineffective therapeutically approaches in the late stages of the disease. Despite the recent advent of promising new targeted therapies, lung cancer diagnostic strategies still have difficulty in identifying the disease at an early stage. Therefore, the characterizations of more sensible and specific cancer biomarkers have become an important goal for clinicians. Circular RNAs (circRNAs), a type of RNA with covalently closed continuous loop structures that display high structural resistance and tissue specificity pointed toward a potential biomarker role. Current investigations have identified that circRNAs have a prominent function in the regulation of oncogenic pathways, by regulating gene expression both at transcriptional and post-transcriptional level. The aim of this review is to provide novel information regarding the implications of circRNAs in lung cancer, with an emphasis on the role in disease development and progression. Initially, we explored the potential utility of circRNAs as biomarkers, focusing on function, mechanisms, and correlation with disease progression in lung cancer. Further, we will describe the interaction between circRNAs and other non-coding species of RNA (particularly microRNA) and their biological significance in lung cancer. Describing the nature of these interactions and their therapeutic potential will provide additional insight regarding the altered molecular landscape of lung cancer and consolidate the potential clinical value of these circular transcripts. This article is categorized under: RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems RNA in Disease and Development > RNA in Disease RNA in Disease and Development > RNA in Development.

Altered expression of miR-181 affects cell fate and targets drug resistance-related mechanisms.

MicroRNAs (miRNAs) are non-coding transcripts which regulate genetic and epigenetic events by interfering with mRNA translation. miRNAs are involved in regulation of cell fate due to their ability of interfering with physiological or pathological processes. In this review paper, we evaluate the role of miR-181 family members as prognostic or diagnostic markers or therapeutic targets in malignant pathologies in connection with the main hallmarks of cancer that are modulated by the family. Also, we take over the dual role of this family in dependency with the tumour suppressor and oncogenic features presented in cell and cancer type specific manner. Restoration of the altered expression levels contributes to the activation of cell death pathways or to a reduction in the invasion and migration mechanism; moreover, the mechanism of drug resistance is also modulated by miR-181 sequences with important applications in therapeutic strategies for malignant cells sensitisation. Overall, the main miR-181 family regulatory mechanisms are presented in a cancer specific context, emphasizing the possible clinical application of this family in terms of novel diagnosis and therapy approaches.

The Function of Non-Coding RNAs in Lung Cancer Tumorigenesis.

Lung cancer is the most prevalent and deadliest cancer worldwide. A significant part of lung cancer studies is dedicated to the expression alterations of non-coding RNAs. The non-coding RNAs are transcripts that cannot be translated into proteins. While the study of microRNAs and siRNAs in lung cancer received a lot of attention over the last decade, highly efficient therapeutic option or the diagnostic methods based on non-coding RNAs are still lacking. Because of this, it is of utmost importance to direct future research on lung cancer towards analyzing other RNA types for which the currently available data indicates that are essential at modulating lung tumorigenesis. Through our review of studies on this subject, we identify the following non-coding RNAs as tumor suppressors: ts-46, ts-47, ts-101, ts-53, ts-3676, ts-4521 (tRNA fragments), SNORD116-26, HBII-420, SNORD15A, SNORA42 (snoRNAs), piRNA-like-163, piR-35127, the piR-46545 (piRNAs), CHIAP2, LOC100420907, RPL13AP17 (pseudogenes), and uc.454 (T-UCR). We also found non-coding RNAs with tumor-promoting function: tRF-Leu-CAG, tRNA-Leu, tRNA-Val (tRNA fragments), circ-RAD23B, circRNA 100146, circPVT1, circFGFR3, circ_0004015, circPUM1, circFLI1, circABCB10, circHIPK3 (circRNAs), SNORA42, SNORA3, SNORD46, SNORA21, SNORD28, SNORA47, SNORD66, SNORA68, SNORA78 (snoRNAs), piR-65, piR-34871, piR-52200, piR651 (piRNAs), hY4 5' fragments (YRNAs), FAM83A-AS1, WRAP53, NKX2-1-AS1 (NATs), DUXAP8, SFTA1P (pseudogene transcripts), uc.338, uc.339 (T-UCRs), and hTERC.

The pathogenic microbial flora and its antibiotic susceptibility pattern in odontogenic infections.

Suppurative head and neck infections of odontogenic origin are the most frequent type of head and neck infections. According to the literature, 7-10% of all antibiotics are currently prescribed for their treatment. Since penicillin was invented, the overall antibiotic sensitivity and resistance pattern of the isolated pathogenic microflora has continuously changed. The response of microorganisms to antibiotics and the development of resistance to their action is a purely evolutive process characterized by genetic mutations, acquisition of genetic material or alteration of gene expression and metabolic adaptations. All this makes challenging and difficult the correct choice of empirical antibiotic treatment for head and neck space infections even today. The aim of this paper was to evaluate the literature and to evidence the most frequent locations of odontogenic head and neck infections, the dominant pathogenic microbial flora, the genetic mutations and metabolic changes necessary for bacteria in order to aquire antibiotic resistance and as well its susceptibility and resistance to common antibiotics. We also aimed to highlight the possible changes in bacterial resistance to antibiotics over time, and to assess whether or not there is a need for fundamental changes in the empirical antibiotic treatment of these infections and show which these would be.