Overview of the role of liquid biopsy in cancer management.

With the emergence of novel targeted therapeutic options in early-stage and advanced-stage malignancies, researchers have shifted their focus on developing personalized treatment plans through molecular profiling. Circulating tumor DNA (ctDNA) is a cell-free DNA (ctDNA) fragment, originating from tumor cells, and circulating in the bloodstream as well as biological fluids. Over the past decade, many techniques were developed for liquid biopsies through next-generation sequencing. This alternative non-invasive biopsy offers several advantages in various types of tumors over traditional tissue biopsy. The process of liquid biopsy is considered minimally invasive and therefore easily repeatable when needed, providing a more dynamic analysis of the tumor cells. Moreover, it has an advantage in patients with tumors that are not candidates for tissue sampling. Besides, it offers a deeper understanding of tumor burden as well as treatment response, thereby enhancing the detection of minimal residual disease and therapeutic guidance for personalized medicine. Despite its many advantages, ctDNA and liquid biopsy do have some limitations. This paper discusses the basis of ctDNA and the current data available on the subject, as well as its clinical utility. We also reflect on the limitations of using ctDNA in addition to its future perspectives in clinical oncology and precision medicine.

Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09-1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3-7.9; p=0.001) were independently associated with composite adverse fetal outcome. Conclusions Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.

Role of microRNAs in the predisposition to gastrointestinal malignancies.

MicroRNAs (miRNAs) are highly deregulated in cancer and play a role in the initiation of tumorigenesis. Recently, miRNAs have attracted attention in gastrointestinal (GI) cancers. Single nucleotide polymorphisms (SNPs) could affect the genes involved in each step of miRNA biosynthesis. Several meta-analyses of case-control studies have assessed the association between miRNA "pathway" gene-SNPs (including biosynthesis regulators and binding sites) and susceptibility to GI cancers. We present in this mini-review the current knowledge on the association between miRNAs "pathway" genes and GI cancer predisposition. The interaction between miRNA/regulators/binding site-SNPs and environmental as well as genomic factors is an interesting field that should be exploited in future studies.

Molecular characteristics of colorectal cancer in a Middle Eastern population in a single institution.

BACKGROUND: The few studies of the molecular biology of colorectal cancer (CRC) in Middle Eastern populations have included only small samples of patients. OBJECTIVE: Evaluate the frequency and prognostic effect of RAS, BRAF, PIK3CA, PTEN, and EGFR somatic mutations as well as mismatch repair (MMR) deficiency in Lebanese Middle Eastern patients. DESIGN: Retrospective single-center descriptive study. SETTING: Lebanese Middle Eastern patients in a tertiary medical cen.ter. METHODS: We included all patients diagnosed with CRC between January 2010 and December 2015, in whom RAS mutational status and the expression of MLH1 and MSH2 proteins were available. MAIN OUTCOME MEASURES: Genetic mutations detected by direct sequencing while MMR protein expression was evaluated by immunohistochemistry. SAMPLE SIZE: 645 patients. RESULTS: RAS, BRAF, EGFR, PI3KCA, and PTEN mutation rates were 38.5%,12.9%, 0%, 11.1% and 0% respectively. The MMR deficiency rate was 20.6%. No factor was associated with RAS mutation whereas MMR-deficient tumors were less likely to be metastatic at diagnosis. Among patients with wild-type RAS females fared better than males (median overall survival [OS]=1734 vs 1079 days respectively, P=.015) even after adjustment for confounding factors by Cox regression analy.sis. This finding was not reproduced in the RAS-mutated group. The median OS of patients with MMR-deficient tumors was not reached, while the median OS was 2475 days in patients who had maintained expression of both MLH1 and MSH2. CONCLUSION: The RAS mutation rate was similar to Western and East Asian countries, but not for the BRAF mutation and MMR deficiency. We also found a prognostic effect for sex in the RAS wild-type group, a finding worthy of further exploration. LIMITATIONS: Retrospective, single center and small sample size. Expression of MSH6 and PMS2 not analyzed. CONFLICT OF INTEREST: None.

Older melanoma patients aged 75 and above retain responsiveness to anti-PD1 therapy: results of a retrospective single-institution cohort study.

INTRODUCTION: The utility of immunotherapy in elderly melanoma patients is debated. We aimed in this study to evaluate the efficacy and tolerability of immunotherapy among elderly patients. METHOD: This is a retrospective single-institution cohort study. Patients aged 75 years and above who had been treated with nivolumab, pembrolizumab or ipilimumab for advanced or metastatic melanoma, were included. Patients and disease characteristics were collected using electronic medical records. Objective response was determined according to the immune-related response criteria. Drug-related toxicities (DRT) were graded according to the CTCAE v4.03. RESULTS: 99 patients were included with a mean age of 80 years (SD = 4). One patient received nivolumab and ipilimumab combination, but died because of drug-related diverticulitis. Median PFS on pembrolizumab, nivolumab or ipilimumab were equal to 11.9 (95% CI 5.4-18.4), 1.4 (95% CI 0.01-2.8), and 2.8 months (95% CI 2.6-3), respectively, while objective response rates were equal to 51.6, 12.5, and 17.3%, respectively. Median OS was not reached in patients who received only pembrolizumab, 8.7 months in the ipilimumab only group, and 23 months in patients receiving several immune therapies sequentially. Pembrolizumab, nivolumab, and ipilimumab grade 3-4 DRT rates were equal to 24.2, 62.5, and 32.7% respectively, while discontinuation rates were equal to 43.5, 62.5, and 28.8%, respectively. CONCLUSIONS: Our study suggests that immunotherapy is effective and well tolerated in the elderly. The PFS on pembrolizumab was greater than expected, a finding that needs to be investigated further.

Attitudes vs. Purchase Behaviors as Experienced Dissonance: The Roles of Knowledge and Consumer Orientations in Organic Market.

This research focuses on the incongruity between positive attitudinal responses but a lack of purchase behavior in organic markets. According to cognitive dissonance theory, consumer orientations toward the benefits attributed to organic products (environmental protection, health, hedonic) relieve the dissonance that results from this attitude-behavior incongruity. Knowledge also functions as a transmitter, from positive attitudes to purchase behaviors, thereby reducing the incongruity. Using quota sampling in a survey study, this paper tests the hypotheses from linear regression models. The results show that orientations and knowledge improve the congruity between attitudes and purchase behaviors toward organic products. Moreover, interaction effects arise between the environmental protection orientation and knowledge and between the hedonic orientation and knowledge. Increasing knowledge mitigates the difference between attitudes and purchase behaviors, especially for consumers with environmental protection or hedonic orientations. These findings have several important implications for research and practice.

PULMONARY ARTERY ACCELERATED FLOW REVEALING HODGKIN'S LYMPHOMA.

We present a case in which transthoracic echocardiography was the first diagnostic tool to suspect mediastinal Hodgkin's lymphoma by revealing a change in the hemodynamic of left pulmonary artery flow, and it was used as a follow-up method for monitoring treatment efficacy by demonstrating a normalization of pulmonary artery hemodynamics.

Could contrast-enhanced CT detect STEMI prior to electrocardiogram?

We present here a case in which contrast-enhanced computed tomography (CT) was the first diagnostic tool to detect myocardial hypoperfusion in a patient with atypical symptoms and normal electrocardiogram (ECG) on admission. An ST-segment elevation was detected thereafter on a second ECG realized several minutes after CT with raised troponin levels. Percutaneous coronary intervention was performed after failure of thrombolysis and confirmed occlusion of the left anterior descending artery. Further studies are needed to evaluate the role of high-resolution contrast-enhanced CT with or without coronary angiography in the workup of suspected myocardial infarction in the setting of a normal ECG.

TGFBR1*6A polymorphism in sporadic and familial colorectal Carcinoma: a case-control study and systematic literature review.

BACKGROUND: The role of genetic factors in colorectal cancer pathogenesis is widely accepted. Polymorphisms are actually thought to play a role in the unexplained colorectal cancer (CRC) susceptibility. There is conflicting data regarding the role of the transforming growth factor beta receptor 1 polymorphism 6A (TGFBR1*6A) in the increased incidence of CRC. PURPOSE: Our aim is to test the association between this polymorphism and sporadic/familial CRC in the Lebanese population paying attention to lead time bias in the control group. This is a case-control study conducted in two Lebanese hospital centers. MATERIALS AND METHODS: Cases were diagnosed with CRC during the period of 1 year prior to the study. Controls were healthy subjects aged >50 years with a history of normal colonoscopy during the period of 5 years prior to the beginning of the study. A total of 96 cases (57 sporadic/39 familial) and 97 controls were genotyped. The odds ratios for 6A carrier status was statistically significant for sporadic CRC, odds ratio (OR) = 2.314 (95 % confidence interval (CI) 1.030-5.195) but not for familial CRC. RESULTS: No association was found between 6A carrier status and mean age at diagnosis of CRC. This is the first article in the literature to evaluate the association between 6A polymorphism and total, sporadic, and familial CRC in a single study with reduction of bias in the control group. Results are in conjunction with other studies and meta-analysis.

Infección por el virus de la hepatitis C en un hospital de primer nivel de ámbito rural: estudio descriptivo en la década 1991-1999 / Hepatitis C virus infection in a first level rural hospital: descriptive study in the decade 1991-1999

Conocer las características epidemiológicas y clínicas y el pronóstico de los sujetos diagnosticados de infección por el virus de la hepatitis C (VHC) en un Hospital Comarcal de ámbito rural. MÉTODOS: De forma retrospectiva, se estudiaron 142 pacientes diagnosticados de infección por el VHC en el Hospital de Llerena-Zafra, entre agosto de 1991 y diciembre de 1999. Se recogieron datos epidemiológicos y clínicos, tras un seguimiento medio de 2,7 años, y se analizaron los factores pronósticos. RESULTADOS: La infección por el VHC predominó en varones (69 por ciento) y la edad media fue de 48,3 19,3 años. Mecanismos de transmisión: desconocidos (46,5 por ciento), adicción a drogas por vía parenteral (ADVP) (39,4 por ciento) y transfusión (14,1 por ciento).El 23,2 por ciento de los pacientes estaban coinfectados por el virus de la inmunodeficiencia humana (VIH) y el 5,6 por ciento por el de la hepatitis B (VHB). En 111 pacientes (78,2 por ciento) no existían síntomas en el momento del diagnóstico; 26 (18,3 por ciento) debutaron con complicaciones de la hipertensión portal y 5 (3,5 por ciento) con síntomas extrahepáticos. En el 32,4 por ciento de todos los sujetos se observaron datos ecográficos de hipertensión portal. Se detectó hepatocarcinoma en 17 sujetos (12,0 por ciento) y neoplasias extrahepáticas en 14 (9,9 por ciento).Fallecieron 28 personas (19,7 por ciento). Factores de riesgo independientes para mortalidad fueron: coinfección por el virus de la hepatitis B (VHB) (odds ratio [OR], 26,9; intervalo de confianza [IC] del 95 por ciento, 2,19-331,47), datos ecográficos de hipertensión portal (OR, 11,0; IC 95 por ciento, 3,38-32,61) y diagnóstico de hepatocarcinoma (OR, 182,7; IC 95 por ciento, 14,85-2248,21). CONCLUSIONES: En nuestro hospital, durante la década 1990-1999, la infección por el VHC se diagnosticó con frecuencia en fases muy avanzadas de su evolución y se asoció a una mortalidad elevada, sobre todo en presencia de datos de hipertensión portal en la ecografía abdominal o de coinfección por el VHB (AU)

[Hepatitis C virus infection in a first level rural hospital: descriptive study in the decade 1991-1999]. / Infección por el virus de la hepatitis C en un hospital de primer nivel de ámbito rural: estudio descriptivo en la década 1991-1999.

INTRODUCTION: To assess epidemiology, clinical manifestations and prognostic factors in subjects diagnosed with hepatitis C virus (HCV) infection in a first level rural hospital. METHODS: This retrospective study includes 142 patients diagnosed with HCV infection at the Hospital de Llerena, from August 1991 to December 1999. Epidemiological and clinical parameters were collected at a mean of 2.7 years after diagnosis and prognostic factors were analyzed. RESULTS: HCV infection predominated in males (69%) and the mean age of patients was 48.3 6 19.3 years. Mechanisms of transmission included unknown (46.5%), intravenous drug use (39.4%), and transfusions (14.1%). Human immunodeficiency virus coinfection was present in 23% of patients and hepatitis B virus (HBV) coinfection in 5.6%. At the time of diagnosis, 111 patients (78.2%) were asymptomatic; 26 (18.3%) presented with complications of portal hypertension and 5 (3.5%) with extrahepatic symptoms. Ultrasonographic signs of portal hypertension were observed in 32.4% of cases. Hepatocarcinoma was detected in 17 patients (12.0%) and extrahepatic neoplasms in 14 (9.9%). Twenty-eight patients died (19.7%). Independent risk factors for mortality included HBV coinfection (OR 26.9; 95% CI 2.19-331.47), ultrasonographic signs of portal hypertension (OR 11.0; 95% CI 3.38-32.61) and diagnosis of hepatocarcinoma (OR 182.7; 95% CI 14.85-2248.21). CONCLUSIONS: Between 1990 and 1999 in our hospital HCV infection was frequently diagnosed in advanced stages and was associated with high mortality, particularly when ultrasonographic signs of portal hypertension or HBV coinfection were present.