The diagnostic performance of micro-RNA and metabolites in lung cancer: A meta-analysis.

BACKGROUND: The diagnosis of lung cancer is based on the microscopic exam of tissue or liquid. During the recent decade, many biomarkers have been pointed to have a potential diagnostic role. These biomarkers may be assessed in blood, pleural effusion or sputum and they could avoid biopsies or other risky procedures. The authors aimed to assess the diagnostic performances of biomarkers focusing on micro-RNA and metabolites. METHODS: This meta-analysis was conducted under the PRISMA guidelines during a nine-year-period (2013-2022). the Meta-Disc software 5.4 (free version) was used. Q test and I2 statistics were carried out to explore the heterogeneity among studies. Meta-regression was performed in case of significant heterogeneity. Publication bias was assessed using the funnel plot test and the Egger's test (free version JASP). RESULTS: According to our inclusion criteria, 165 studies from 79 articles were included. The pooled SEN, SPE and dOR accounted, respectively, for 0.76, 0.79 and 13.927. The AUC was estimated to 0.859 suggesting a good diagnostic accuracy. The heterogeneity in the pooled SEN and SPE was statistically significant. The meta-regression analysis focusing on the technique used, the sample, the number of biomarkers, the biomarker subtype, the tumor stage and the ethnicity revealed the biomarker number (p = 0.009) and the tumor stage (p = 0.0241) as potential sources of heterogeneity. CONCLUSION: Even if this meta-analysis highlighted the potential diagnostic utility of biomarkers, more prospective studies should be performed, especially to assess the biomarkers' diagnostic potential in early-stage lung cancers.

Designing a serious game about critical appraisal of medical literature for pregraduate students.

Critical appraisal of medical literature is a crucial step in the evidence-based-medicine practice, especially for pregraduate medical students who used to deal more with background questions than with patients' health problems. Using serious games seems to be attractive in order to link between a serious purpose, which is handling a health problem and gaming. The authors aimed to describe the process they adopted in order to develop, without a game developer, a serious game dedicated to third-year-medical students. All the steps of the process design were described. Besides, they performed a pilot study in order to assess the students' satisfaction using a think aloud process and a likert-scale questionnaire and aimed to evaluate the effectiveness of the process by comparing pre and post-tests scores.

Liquid Biopsy as Surrogate to Tissue in Lung Cancer for Molecular Profiling: A Meta-Analysis.

BACKGROUND: The accurate microscopic diagnosis of lung cancer has become insufficient due to the concept of personalized medicine. Tissue samples are used not only for microscopic diagnosis but also for the assessment of the different targets. Biopsies are performed in 80% of the patients and they are not sufficient for molecular diagnosis in 30% of the cases. Liquid biopsy (LB) has been reported as a possible surrogate to tissue samples and has been introduced in the management scheme of the patients since 2014. We aimed to highlight the diagnostic value of liquid biopsy in assessing the molecular profile of non small cell carcinomas in comparison with tissue biopsy. METHODS: We retracted eligible articles from PubMed, Embase and Cochrane databases. We calculated the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR). A summary receiver operating characteristic curve (SROC) and area under curve (AUC) were used to evaluate the overall diagnostic performance using the Meta-Disc software 5.1.32. The heterogeneity was assessed using I square statistics. A meta-regression was performed in case of heterogeneity. In case of absence of covariates, a sensitivity analysis was done in order to assess publications that induced a statistical bias. RESULTS: 39 eligible studies involving 4782 patients were included. The overall statistical studies showed heterogeneity in the SEN, SPE, PLR, NLR and DOR. No threshold effect was revealed. The meta-regression incorporating the ethnicity, the test, the technique used in tissue and plasma and the use of plasma or serum as covariates showed no impact of these factors. A sensitivity analysis allowed achieving the homogeneity in the SPE and DOR. The overall pooled SEN and SPE were 0.61 and 0.95 respectively. The PLR was 9.51, the NLR was 0.45 and DOR was 24.58. The SROC curve with AUC of 0,93 indicated that the liquid biopsy is capable of identifying wild type samples from mutated ones with a relatively high accuracy. CONCLUSION: This meta-analysis suggested that detection of molecular mutations by cfDNA is of adequate diagnostic accuracy in association to tissues. The high specificity and the moderate sensitivity highlight the value of LB as a screening test.

Prognostic value of Pheochromocytoma of the Adrenal Gland Scaled Score (Pass score) tests to separate benign from malignant neoplasms.

BACKGROUND: Differentiating malignant from benign pheochromocytoma has been challenging when based on histologic features. This is due to the definition of malignant pheochromocytoma which are defined by the presence of metastases. A PASS score was developed and according to many authors, a PASS score> =4 identified potentially malignant tumors. AIM: To assess the prognostic value of PASS score in differentiating benign pheochromocytomas from malignant ones. METHODS: The records of 11 patients with tumors diagnosed as "pheochromocytoma" were identified from 1970 to 2010 in the files of the pathology, intern medicine and biochemistry departments of the Charles Nicolle hospital and Pasteur Institute. Receiver operating characteristics (ROC) curve analysis was performed to evaluate the diagnostic performance of PASS. The logistic model was developed using the 11 predictive variables. Its performance was evaluated by calculating the area under the ROC curve and comparing it with that of the PASS. RESULTS: In benign tumors, The PASS score was <4 in 3 cases and >=4 in 6 cases. In malignant tumors, the PASS score was >=4 in both cases. According to the ROC curve analysis, a PASS equal or superior to 4 identifies malignant pheochromocytoma with a sensitivity of 50% and a specificity of 45%. CONCLUSION: I think that PASS score, despite its low sensitivity, may help to reserve the more aggressive treatment and narrow follow up for potentially malignant tumors. Widespread of this called score with complete clinical data will help to validate these findings and to add other prognostic factors of value that could be a part of this scaled score such as immunohistochemical findings.

Lack of association between renin-angiotensin system (RAS) polymorphisms and hypertension in Tunisian type 2 diabetics.

BACKGROUND: The genes encoding renin-angiotensin system (RAS) components are potent candidate genes in both hypertension and diabetes namely ACE encoding the angiotensin converting enzyme and AGT encoding angiotensinogen. It has been suggested that the insertion/deletion (I/D) polymorphism in intron 16 of ACE gene is associated with ACE levels, and M235T gene polymorphism is associated with plasma AGT levels. AIM: We examined in this report the association between ACE I/D and AGT M235T polymorphisms with hypertension status in Tunisian type 2 diabetic subjects. METHODS: Thirty nine hypertensive and 22 normotensive type 2 diabetic Tunisian patients were recruited for this study. The I/D polymorphism of ACE gene was analysed with nested PCR in order to avoid mistyping heterozygous individuals and the M235T polymorphism of AGT gene was analysed using PCR and allele specific restriction. RESULTS: The distribution of DD, ID and II genotypes did not significantly differ between type 2 diabetic patients with or without hypertension (DD: 49%; ID: 41%; II: 10% vs DD: 36%; ID: 55%; II: 9%, respectively) (chi2=1.06, p=0.58). There was also no significant statistical difference between these two groups for the M235T polymorphism (TT: 20%; MT: 54%; MM: 26% vs TT: 27%; MT: 41%; MM: 32%, respectively) (chi2=0.95, p=0.62). CONCLUSION: RAS polymorphisms do not seem to play a role in the development of hypertension in the studied Tunisian type 2 diabetic subjects.

Lack of association between the angiotensin-converting enzyme gene (I/D) polymorphism and diabetic nephropathy in Tunisian type 2 diabetic patients.

OBJECTIVE: The aim of the present study was to investigate whether the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism is associated with diabetic nephropathy and type 2 diabetes in the Tunisian population. DESIGN: A case-control study was conducted among 141 unrelated type 2 diabetic patients with (90 patients) or without nephropathy (51 patients) and 103 non-diabetic controls with normal fasting blood glucose. Genotyping was performed using a nested polymerase chain reaction amplification in order to identify correctly heterozygous individuals. RESULTS: The distribution of DD, ID and II genotypes did not significantly differ between type 2 diabetic patients with or without nephropathy (DD: 44%; ID: 46%; II: 10% vs. DD: 41%; ID: 47 %; II: 12%, respectively). There was also no significant statistical difference between the genotype distribution and allele frequencies of the (I/D) polymorphism in all type 2 diabetic subjects compared to non-diabetic controls with normal fasting blood glucose (DD: 43%; ID: 46%; II: 11% vs. DD: 37%; ID: 48%; II: 15%, respectively). CONCLUSIONS: In the present preliminary study, the (I/D) polymorphism within the ACE gene is likely not associated with diabetic nephropathy nor with type 2 diabetes in the Tunisian studied population.

Familial aggregation and excess maternal transmission of type 2 diabetes in Tunisia.

AIM: To evaluate the degree of familial aggregation of type 2 diabetes mellitus in Tunisia and to investigate transmission patterns of the disease and their relationships with patients' clinical profiles. METHODS: Family history of diabetes and clinical data were collected for 132 unrelated type 2 diabetic Tunisian patients. Diabetes status was recorded for first degree relatives (parents, siblings) and second degree relatives (aunts and uncles from both maternal and paternal sides). Information about family history of diabetes was gathered for a total of 1767 individuals. RESULTS: Familial aggregation of type 2 diabetes was prominent and more important among first degree relatives than among second degree relatives (p = 0.01). Among studied subjects, 70% reported at least one relative with diabetes and 34% had at least one parent with diabetes. Diabetes was more frequent among mothers than fathers of probands (p = 0.03). This maternal effect extends to second degree relatives as diabetes was more common among maternal than paternal aunts and uncles (p = 0.01). There is no significant difference in clinical and metabolic profiles between patients according to transmission patterns of the disease. CONCLUSION: These results suggest familial aggregation and excess maternal transmission of type 2 diabetes in the Tunisian studied population.