Correlation of Oxygenation and Radiographic Assessment of Lung Edema (RALE) Score to Lung Ultrasound Score (LUS) in Acute Respiratory Distress Syndrome (ARDS) Patients in the Intensive Care Unit.

BACKGROUND: Lung ultrasound score (LUS) as well as radiographic assessment of lung edema (RALE) score as calculated from chest radiography (CXR) have been applied to assess Acute Respiratory Distress Syndrome (ARDS) severity. CXRs, which are frequently performed in ARDS patients, pose a greater risk of radiation exposure to patients and health care staff. AIMS AND OBJECTIVES: The aim of the study was to evaluate if LUS had a better correlation to oxygenation (PaO2/FiO2) compared with the RALE score in ARDS patients. We also aimed to analyse if there was a correlation between RALE score and LUS. We wanted to determine the LUS and RALE score cut-off, which could predict a prolonged length of intensive care unit (ICU) stay (≥10 days) and survival. METHODS: Thirty-seven patients aged above 18 years with ARDS as per Berlin definition and admitted to the ICU were included in the study. It was a retrospective study done over a period of 11 months. On the day of admission to ICU, the global and basal LUS, global and basal RALE score, and PaO2 /FiO2 were recorded. Outcome and days of ICU stay were noted. RESULTS: Global LUS score and PaO2/FiO2 showed the best negative correlation (r = -0.491), which was significant (p = 0.002), followed by global RALE score and PaO2/FiO2 (r = -0.422, p = 0.009). Basal LUS and PaO2/FiO2 also had moderate negative correlation (r = -0.334, p = 0.043) followed by basal RALE score and PaO2/FiO2 (r = -0.34, p = 0.039). Global RALE score and global LUS did not show a significant correlation. Similarly, there was no significant correlation between basal RALE score and basal LUS. Global and basal LUS as well as global and basal RALE score were not beneficial in predicting either a prolonged length of ICU stay or survival as the area under curve was low. CONCLUSION: In ARDS patients, global LUS had the best correlation to oxygenation (PaO2/FiO2), followed by global RALE score. Basal LUS and basal RALE score also had moderate correlation to oxygenation. However, there was no significant correlation between global LUS and global RALE score as well as between basal LUS and basal RALE score. Global and basal LUS as well as global and basal RALE scores were not able to predict a prolonged ICU stay or survival in ARDS patients.

MicroRNAs in the Diagnosis of Malignancy of Supratentorial Brain Gliomas and Prognosis of Disease Progression.

INTRODUCTION: The study of brain tumors has shown that microRNAs can act as both oncogenes and tumor suppressors and, consequently, can be used as biomarkers for the diagnosis and prognosis of such tumors. Thus, big interest arises in the role of microRNA and its part in oncogenesis in the human brain to find key molecules that can act as tumor markers for diagnostic and prognostic purposes, as well as potential therapeutic agents. STUDY AIM: The sim of this study was to assess histological, molecular, and genetic metrics in patients with supratentorial gliomas, and indicate diagnostic and prognostic abilities of microRNA usage as biomarkers of the grade of malignancy of the tumor. MATERIALS AND METHODS: Clinical and genetic studies were performed in 107 operated patients with supratentorial gliomas of different malignancies. The expression levels of 10 microRNAs (-16, -21¸ -31, -124, - 125b, -181b, -191, -221, -223, and -451) were analyzed using real-time polymerase chain reaction (PCR). The results were analyzed statistically using Statistica 12.0 (Statistica, Hamburg, Germany) and GraphPad Prism 9 software (GraphPad Software Inc., Boston, Massachusetts, United States). RESULTS: Based on a comprehensive statistical analysis involving the database of the clinical results of treatment of all 107 patients (combined treatment methods, quality of life, and survival) and microRNA expression levels, specific profiles of microRNA expression typical of different histotypes of gliomas of different malignancy were identified, the prognostic significance of the studied microRNAs as potential predictors of survival in patients with brain gliomas was determined, and microRNAs with the highest prognostic value were identified among them.

Breathlessness Predicts Mortality in Adults: A Systematic Review and Meta-Analysis.

Breathlessness is a commonly encountered symptom, and although its relationship with mortality is well established for many conditions, less clear is this relationship in healthy adults. This systematic review and meta-analysis examines whether breathlessness is associated with mortality in a general population. This is important in understanding the impact of this common symptom on a patient's prognosis. This review was registered with PROSPERO (CRD42023394104). Medline, EMBASE, CINAHL and EMCARE were searched for the terms 'breathlessness' and 'survival' or 'mortality' on January 24, 2023. Longitudinal studies of >1,000 healthy adults comparing mortality between breathless and non-breathless controls were eligible for inclusion. If an estimate of effect size was provided, studies were included in the meta-analysis. Eligible studies underwent critical appraisal, data extraction and risk of bias assessment. A pooled effect size was estimated for the relationship between the presence of breathlessness and mortality and levels of severity of breathlessness and mortality. Of 1,993 studies identified, 21 were eligible for inclusion in the systematic review and 19 for the meta-analysis. Studies were of good quality with a low risk of bias, and the majority controlled for important confounders. Most studies identified a significant relationship between the presence of breathlessness and increased mortality. A pooled effect size was estimated, with the presence of breathlessness increasing the risk of mortality by 43% (risk ratio (RR): 1.43, 95% confidence interval (CI): 1.28-1.61). As breathlessness severity increased from mild to severe, mortality increased by 30% (RR: 1.30, 95% CI: 1.21-1.38) and 103%, respectively (RR: 2.03, 95% CI: 1.75-2.35). The same trend was seen when breathlessness was measured using the modified Medical Research Council (mMRC) Dyspnoea Scale: mMRC grade 1 conferred a 26% increased mortality risk (RR: 1.26, 95% CI: 1.16-1.37) compared with 155% for grade 4 (RR: 2.55, 95% CI: 1.86-3.50). We conclude that mortality is associated with the presence of breathlessness and its severity. The mechanism underlying this is unclear and may reflect the ubiquity of breathlessness as a symptom of many diseases.

Brainstem Infiltration Predicts Survival in Patients With High-grade Gliomas Treated With Chemoradiotherapy.

BACKGROUND/AIM: High-grade gliomas have a poor prognosis despite standard treatment. The aim of the study was to identify new prognostic factors to select patients who need more intense treatment. PATIENTS AND METHODS: Forty-three consecutive patients underwent surgery plus chemoradiotherapy for pathologically diagnosed high-grade gliomas (grade III, IV). RESULTS: The median survival time was 989 days, and the 1-year survival rate was 87.6%. Among patients with grade IV disease, the median survival time, 1-year, and 2-year survival rate were 814 days, 82.6%, and 58.7%, respectively. In the univariate analysis, unmethylated MGMT promoter (p=0.0495), brainstem infiltration (p=0.0004), basal ganglia as the primary lesion site (p=0.0056), 3-dimensional conformal radiotherapy (p=0.0286), and <50 Gy (p=0.0049) were associated with a poor prognosis. In the multivariate analysis, only brainstem infiltration retained significance (HR for death, 0.21; 95% CI=0.06-0.70; p=0.011). CONCLUSION: Brainstem infiltration is a novel prognostic factor for poor prognosis in patients with high-grade gliomas.

Pretreatment C-reactive protein/albumin ratio is associated with poor survival in patients with stage IB-IIA cervical cancer.

Previous studies have shown that the C-reactive protein/albumin ratio (CAR) is a prognostic indicator in multiple types of carcinomas. This study is the first to evaluate the prognostic significance of CAR in stage IB-IIA cervical cancer patients treated with radical surgery, as well as that of several other inflammation-based factors, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI). A total of 235 patients were enrolled in this study. The optimal cut-off values of CAR and other inflammation-based factors were determined by receiver operating characteristic curves. The Kaplan-Meier method and Cox regression model analysis were performed to determine the independent predictors of progression-free survival (PFS) and overall survival (OS). At a cut-off value of 0.15, patients with a high CAR had significantly shorter PFS and OS than those with a lower CAR (P < 0.001). A higher CAR was significantly associated with elevated scores of NLR and PLR and a decreased PNI (P < 0.001). Univariate analyses showed that elevated CAR preoperatively was significantly associated with poor survival; a similar trend was also noted for the NLR, PLR, and PNI. Multivariate analyses demonstrated that only CAR was an independent indicator for PFS (hazard ratio [HR]: 5.164; 95% confidence interval [CI]: 2.495-10.687; P < 0.001) and OS (HR: 4.729; 95% CI: 2.263-9.882; P < 0.001). In conclusion, preoperative CAR is a novel and superior predictor of poor survival in patients with stage IB-IIA cervical cancer.

Expression status of folate receptor alpha is a predictor of survival in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) has one of the poorest prognosis among malignancies. Thus, the identification of markers useful in developing innovative diagnostic and therapeutic methods is an imperative need. Folate receptor alpha (FRα) has been associated with prognosis in several cancers and has served as a target of novel anti-tumor therapies. However, FRα expression in PDAC and its correlation with the clinical course of the disease has not been thoroughly investigated. In this study, we analyzed FRα expression in 140 PDAC specimens and 7 PDAC cell lines in order to define the significance of FRα expression in PDAC and its potential role as a target for immunotherapy. Immunohistochemical analysis demonstrated that FRα expression intensity was low, intermediate and high in 22(16%), 73(52%) and 45(32%) PDACs, respectively. The staining was located in both membrane and cytoplasm in most cases (123, 88%). Lower FRα expression was associated with cigarette smoking (p<0.001), alcohol consumption (p<0.001), and lymphovascular invasion (p=0.002). Additionally, lower FRα expression was associated with poor overall survival (5-year overall survival: low 13%, intermediate 31%, high 33%; p=0.006). FRα expression (HR=0.61; p=0.03) and Charlson Comorbidity Index (HR=1.16; p=0.01) emerged as independent predictors of survival. The analysis by flow cytometry of 7 PDAC cell lines (AsPC-1, Capan-2, MIA PaCa-2, PANC-1, PDAC2, PDAC3, and PDAC5) demonstrated the highest expression of FRα on the PDAC3 cell line (45%). Therefore, a higher FRα expression is predictive of a favorable prognosis in PDAC and FRα may represent a promising target for novel treatments, including immunotherapy.

Neutrophil to lymphocyte ratio in the pre-treatment phase of final-line chemotherapy predicts the outcome of patients with recurrent ovarian cancer.

Inflammation and tumor immunology are associated with prognosis in a variety of cancers. The aim of the present retrospective study was to identify associations between the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), cancer antigen 125 (CA125) concentrations, tumor response, performance status (PS) and survival of patients that developed recurrent ovarian cancer subsequent to receiving chemotherapy. The NLR and PLR measured prior to fourth-line chemotherapy were significantly increased compared with those measured prior to second-line chemotherapy (P=0.029 and 0.049, respectively). By using receiver operating characteristic curves, the cut-off values were determined for the NLR, PLR and CA125 levels that were measured during the pre-treatment phase, which predicted the outcomes. According to univariate analyses, pre-treatment NLR >3.91, PLR >299.0 and PS 2 were each significantly associated with poor outcomes (P=0.001, 0.005 and 0.021, respectively). According to multivariate analyses, only pre-treatment NLR was associated with poor outcome (P=0.035). The present findings indicate that pre-treatment NLR is an important predictor of prognosis in patients with ovarian cancer that experience recurrence following chemotherapy.

The detox strategy in smoking comprising nutraceutical formulas of non-hydrolyzed carnosine or carcinine used to protect human health.

The increased oxidative stress in patients with smoking-associated disease, such as chronic obstructive pulmonary disease, is the result of an increased burden of inhaled oxidants as well as increased amounts of reactive oxygen species generated by various inflammatory, immune and epithelial cells of the airways. Nicotine sustains tobacco addiction, a major cause of disability and premature death. In addition to the neurochemical effects of nicotine, behavioural factors also affect the severity of nicotine withdrawal symptoms. For some people, the feel, smell and sight of a cigarette and the ritual of obtaining, handling, lighting and smoking a cigarette are all associated with the pleasurable effects of smoking. For individuals who are motivated to quit smoking, a combination of pharmacotherapy and behavioural therapy has been shown to be most effective in controlling the symptoms of nicotine withdrawal. In the previous studies, we proposed the viability and versatility of the imidazole-containing dipeptide-based compounds in the nutritional compositions as the telomere protection targeted therapeutic system for smokers in combination with in vitro cellular culture techniques being an investigative tool to study telomere attrition in cells induced by cigarette smoke (CS) and smoke constituents. Our working therapeutic concept is that imidazole-containing dipeptide-based compounds (non-hydrolyzed carnosine and carcinine) can modulate the telomerase activity in the normal cells and can provide the redox regulation of the cellular function under the terms of environmental and oxidative stress and in this way protect the length and the structure of telomeres from attrition. The detoxifying system of non-hydrolyzed carnosine or carcinine can be applied in the therapeutic nutrition formulations or installed in the cigarette filter. Patented specific oral formulations of non-hydrolyzed carnosine and carcinine provide a powerful manipulation tool for targeted therapeutic inhibition of cumulative oxidative stress and inflammation and protection from telomere attrition associated with smoking. It is demonstrated in this work that both non-hydrolyzed carnosine and carcinine are characterized by greater bioavailability than pure l-carnosine subjected to enzymatic hydrolysis with carnosinase, and perform the detoxification of the α,ß-unsaturated carbonyl compounds present in tobacco smoke. We argue that while an array of factors has shaped the history of the 'safer' cigarette, it is the current understanding of the industry's past deceptions and continuing avoidance of the moral implications of the sale of products that cause the enormous suffering and death of millions that makes reconsideration of 'safer' cigarettes challenging. In contrast to this, the data presented in the article show that recommended oral forms of non-hydrolyzed carnosine and carcinine protect against CS-induced disease and inflammation, and synergistic agents with the actions of imidazole-containing dipeptide compounds in developed formulations may have therapeutic utility in inflammatory lung diseases where CS plays a role.