The impact of RAS mutation on the treatment strategy of colorectal cancer.

Kirsten rat sarcoma (KRAS) is the most frequently mutated oncogene in colorectal cancer, being present in 30% of patients with localized disease and in almost half of the patients that develop metastatic disease. While the development of chemotherapy doublets and targeted therapy have improved survival in recent years, KRAS mutation still has a controversial role regarding its prognostic and predictive value both in the adjuvant and in the metastatic setting. The impact of KRAS mutation on treatment strategy remains to be better defined. The development of new KRAS inhibitors promising new treatment options is on the horizon.

Barriers and Facilitators of Romanian HPV (Human Papillomavirus) Vaccination.

BACKGROUND: Many countries had initial success with HPV vaccination campaigns worldwide. The HPV vaccine coverage during the COVID-19 pandemic dropped consistently. The aim of our research is to assess the barriers and facilitators of the current Romanian HPV vaccination campaign. METHODS: An analytical cross-sectional observational survey was conducted in the Romanian general population; a self-administered questionnaire was used. RESULTS: 1122 responders were interviewed; 666 (59.36%) were parents, and 67 (5.97%) HPV vaccinated themselves. A multinominal logistic regression carried out in the parents' category showed that women with university studies and informed from medical sources have greater chances to HPV vaccinate. Reticence regarding vaccination comes from the high cost of the vaccine and a lack of information. Only 118 (10.51%) vaccinated against HPV. From the logistic regression analysis, gender (ORa 0.461 = 95% CI: (0.196; 1.083)), geographic area of residence (ORa = 0.517; 95% CI: (0.331; 0.807)), and the inclusion of the HPV vaccine in the National Vaccination Program (ORa = 2.4; 95% CI: (1.361; 4.235)) were the factors found most associated with HPV vaccination. CONCLUSIONS: In the general population, the inclusion of HPV vaccination in the National Vaccination Program would be the most important facilitator of HPV vaccination in Romania. In parents that did not vaccinate their children, one important barrier to HPV vaccination was the high cost of the HPV vaccine and the lack of proper information. The acceptability of HPV vaccination in Romania is low; therefore, public health educational programs are needed.

Correlation Between Pretreatment Neutrophil-to-Lymphocyte Ratio and Programmed Death-Ligand 1 Expression as Prognostic Markers in Non-Small Cell Lung Cancer.

Background The neutrophil-to-lymphocyte ratio (NLR) at baseline treatment is an important marker of systemic inflammation, which is correlated with survival benefits in lung, breast, ovarian, bladder, and colorectal cancer. Programmed death-ligand 1 (PD-L1) expression is a biomarker with discording results regarding survival benefits in lung cancer. In our research, we studied the relationship between these two markers in patients with lung cancer. Methods Patients with stage I, II, III, and IV lung cancer (n = 80) were included in this retrospective study. The NLR baseline was recorded before the initiation of treatment. The NLR cut-off value was 4. PD-L1 expression was determined by immunohistochemical staining. Univariate and multivariate survival analyses were conducted to test their prognostic value. Results NLR proved to be a significant prognostic factor for progression-free survival (PFS) (p=0.002, Log Rank) with a mean PFS of 27.7 months for low NLR patients and 12.8 months for high NLR patients. It was also significant for overall survival (OS) (p=0.007, Log Rank) with a mean OS of 52 months for low NLR patients and 41.6 months for high NLR patients. The prognostic impact of PD-L1 expression on PFS and OS was not statistically significant with a mean PFS of 23.1 months for PD-L1-negative patients and 15.8 months for PD-L1-positive patients (p=0.422, Log Rank). Mean OS was 49 months for PD-L1-negative patients while for PD-L1-positive patients, it was 43.3 months (p=0.550 Log Rank). Regarding the correlation between PD-L1 expression and NLR value, PFS mean survival times were 13.1 months for PD-L1(+)/NLR>4, 15.1 months for PD-L1(-)/NLR>4, 16.4 months for PD-L1(+)/NLR<4 and 27.8 months for PD-L1(-)/NLR<4. This correlation between PFS and the combined PD-L1 and NLR prognostic factor was statistically relevant (p=0.04). For OS, the PD-L1/NLR combined prognostic factor was not statistically relevant (p=0.055). A mean PFS time of 27.8 months was reported for PD-L1(-)/NLR<4 group patients while for the other groups, the mean PFS was 14.9 months (p=0.045). In univariate analysis, the elevated NLR was significantly associated with a decreased PFS time (HR=2.31, 95% CI =1.323- 4.051, p=0.03) as well as OS (HR=3.555, 95% CI=1.310- 9.652, p=0.013). In multivariate analysis, NLR remained statistically significant for PFS (HR=2.160, 95% CI=1.148- 4.062, p=0.013) and OS (HR=4.364, 95% CI=1.474- 12.921, p=0.008) after adjusting for the factors of age, gender, tumor stage, lymph node stage, clinical stage, histology, and PD-L1 expression. PD-L1 expression was not a valid prognostic factor for progression or death in either univariate or multivariate analysis. We also stratified the disease control rate (DCR) depending on PD-L1/NLR combined factor expression. In the PD-L1(-)/NLR<4 group, we had the highest number of partial responses (PRs) and only one complete response (CR) compared to the other groups (p=0.006). Conclusions As the number of patients is limited in the present analysis, it is hypothesized that these two markers can be useful in dividing patients into two prognostic groups: the good prognostic group reunites PD-L1(+)/NLR<4 and PD-L1(-)/NLR<4 and the poor prognostic group reunites PD-L1(+)/NLR>4 and PD-L1(-)/NLR>4.

Aspects Regarding the Influence of Obesity on the Molecular Characteristics of Breast Tumors.

The influence of excess adipose tissue on the evolution and prognosis of breast cancer has been evaluated in numerous papers over the years. The ways in which obesity can influence the development, progression, and prognosis of this neoplasia are complex and requires the design of new studies, both clinical and preclinical. The aim of this study is to highlight a possible correlation between obesity-specific tumor microenvironment markers (adipokine or leptin) and the different histological subtypes and aggressive characteristics of breast tumors. We prospectively monitored the prognostic values of 39 patients diagnosed with breast cancer who received oncologic-specific treatment or are in follow-up regarding some obesity markers. Our analysis included parameters such as age, body mass index, immunohistochemical characteristics, and plasma concentration of leptin. The methodology was designed to reveal a possible correlation between obesity (quantified by measuring body mass index and waist circumference), the plasma level of leptin, and breast tumor immunohistochemical characteristics. The patients diagnosed with aggressive tumors subtypes (HER2-positive and triple-negative) had a significantly higher body mass index than patients diagnosed with luminal type tumors (32 kg/sqm versus 27 kg/sqm), the difference being 5 kg/sqm. In patients with non-luminal type breast tumors (HER2-positive and triple-negative), serum concentration of leptin is 55 pg/ml compared to 48 pg/ml in luminal type, statistically significant, p=0.0168. Leptin plays an important role in the connection of specific microenvironment tumors to breast cancer. An increased serum concentration of this adipokine was found in patients with HER2-positive and triple-negative breast tumors compared with luminal-type breast tumors, which could open new directions in the research of breast cancer prognosis in obese patients.

Level of education, background and clinical stage as prognostic factors according to RMST function in patients with early and locally advanced breast cancer: a single institution experience from Romania.

Background and aims: Our aim is to examine the relationship between the level of education, background, tumor size and lymph node status on the treatment outcome in a group of patients with early and locally advanced breast cancer (BC) by using the restricted mean survival time (RMST), which summarizes treatment effects in terms of event-free time over a fixed period of time. Methods: We evaluated the prognostic values in 143 patients treated for early BC at Elias University Emergency Hospital, Bucharest, Romania and followed up for a maximum of 36 months. The protocol was amended to include the levels of education (gymnasium, high school, or university), the background (urban or rural) and the clinical stage (primary tumor (T) and regional nodes (N)). The methodology consisted in using a Kaplan-Meier analysis and RMST for the entire sample and Cox regression, for the variables with statistical influence. The principal endpoints of the study were overall survival (OS) and progression free survival (PFS). Results: The level of education had impact both on RMST OS (35.30 vs. 26.70) and death HR (hazard ratio) in the group of patients with general school level, compared with those with graduated university. In this study, the urban or rural background did not impact the outcome, probably because in this study we included predominantly patients from urban areas (83%). Although clinical tumor size measurements did not impact the outcome, the clinical staged lymph node influenced both OS (p=0.0500) and PFS (p=0.0006) for the patients with palpable or imaging proof of lymph node involvement of station 2 or 3. Conclusions: RMST provides an intuitive and explicit way to express the effect of those risk factors on OS and PFS in a cohort of early breast cancer patients. Low level of education and high-grade clinical lymph node status negatively influences the outcome of this cohort of BC patients.

COVID-19 Parental Vaccine Hesitancy in Romania: Nationwide Cross-Sectional Study.

BACKGROUND: COVID-19 vaccination started in Romania in December 2020. Child vaccination started in 2021 with children aged 12-15 years in August. For children aged 5-11 years, vaccination started in January 2022. The aim of our study was to describe COVID-19 vaccination hesitancy in Romanian children and vaccine acceptability in the general population. As parental consent is required for child vaccination in Romania, these aspects have a significant association. METHODS: An analytical cross-sectional survey was conducted in October and November 2021 during the peak of the 4th COVID-19 wave. RESULTS: After validation, 1645 participants formed the main study group: median age 35 years, 72.83% women, and 35.44% from the medical domain. In total, 1311 (79.70%) participants were vaccinated against COVID-19 and 188 (11.42%) had vaccinated their 12-18-year-old children against COVID-19. Parents' level of education, geographic area of residence, and COVID-19 vaccination status were significantly associated with COVID-19 vaccination. The hesitancy factors of child vaccination included the novelty of COVID-19 vaccines (62, 47.32%), fear of adverse reactions (32, 24.42%), and anti-vaccinism in general (29, 22.13%). In the studied group, only 188 (11.42%) participants recommended vaccination of 5-11-year-old children. Vaccine acceptability was higher in the general population (1311, 79.70%) than in the medical domain (326 out of 583, 55.91%). General vaccine hesitancy was based mainly on beliefs regarding inefficiency (131, 39.22%) and fears about the side effects of the vaccine (76, 22.75%). CONCLUSIONS: Overall, the acceptability of COVD-19 vaccines in the Romanian population was influenced by the level of education, area of residence, and being a COVID-19-vaccinated parent. Public health intervention programs are essential.

Early COVID-19 Vaccination of Romanian Medical and Social Personnel.

BACKGROUND: In December 2020, the first doses of COVID-19 vaccines arrived in Romania and were made available to medical and social staff. Vaccine hesitancy appeared as a barrier to effectively ending the pandemic. The opinions of medical and social staff influence the opinion of the general population. This study assesess the attitudes, knowledge, and opinion of medical and social personnel toward COVID-19 vaccines and vaccination and the influencing factors. METHODS: 1025 persons participated in an online cross-sectional study from March until July 2021. RESULTS: Out of 1021 eligible responders, 719 (70.42%) had been vaccinated: 227 with one dose (22.23%) and 492 with two doses (48.18%). There were 302 responders who were not vaccinated at all. Out of them, 188 refused vaccinations. The participants showed a good understanding and knowledge of SARScoV-2 transmission and treatment. Geographic area, medical profession, and medical experience influenced COVID-19 vaccination (p < 0.001). There were no associations between willingness to vaccinate and vaccine/virus knowledge. Most of the responders who were vaccinated or wanted to be vaccinated indicated an mRNA vaccine as their first choice. The variables that were significantly associated with reporting COVID-19 vaccine acceptance after logistic regression were: living in an urban area (Ora = 1.58, 95% CI: 0.98-2.56), being female (Ora = 1.59; 95% CI:1.03-2.44), and being a medical doctor (Ora = 3.40; 95% CI: 1.84-6.26). CONCLUSIONS: These findings show that vaccine hesitancy persists in medical and social personnel in Romania, and, hence, it may be reflected in the hesitancy of the general population toward vaccination.

The importance of androgen receptors in breast cancer.

BACKGROUND AND AIM: Breast cancer (BC) is the most common malignancy among women worldwide, and one of the leading causes of cancer-related deaths in females. For the breast malignant tumors there are numerous targeted therapies, depending on the receptors expressed. Regulating the process of epithelial-mesenchyme transcription, the steroid nuclear receptors are important in invasion and progression of BC cells. Till now, it is known that androgen receptor (AR) is present in about 60-80% of BC cells but, unfortunately, there is no targeted therapy available yet. METHODS: We revised the recent literature that included the AR mechanism of action in patients diagnosed with breast cancer, the preclinical, retrospective and clinical studies and the aspects related to the prognosis of these patients, depending on the molecular subtype. RESULTS: A total of 12 articles were eligible for this review. AR positivity was assessed using immunohistochemistry. Herein, neither 1 nor 10% cut-points were robustly prognostic. AR was an independent prognostic marker of BC outcome, especially in triple negative BC group. CONCLUSION: AR is a potential targeted pathway which can improve the prognostic of AR positive patients with BC. Further preclinical and clinical studies are necessary to clarify the mechanism of action and to establish the drugs which can be used, either alone or in combination.

Human Papillomavirus Infection at the Time of Delivery.

Human papillomavirus (HPV) is one of the most encountered viral etiologies of genital infections that are transmitted through the sexual route in sexually active females. In the genital area, condylomata acuminate warts and the Buschke-Loewenstein tumor (giant condyloma acuminatum) are described. These lesions are associated with benign HPV6 and HPV 11 types. Condylomata acuminate may appear as exophytic growth similar to a cauliflower and is usually asymptomatic. The Buschke-Loewenstein tumor appears as ulcerated cauliflower-like lesions, often associated with fistulas and abscesses. They present exophytic and endophytic growth, local invasion, and high recurrence rates. This type of lesion may be associated with malignant HPV types. Here we present the case of a 34-year-old year pregnant woman who presented herself at the emergency room in labor with no previous medical evaluation during the pregnancy. The local examination revealed normal pubic hair, vulvar hyperpigmentation, and tonic and continent anal sphincter. At the vulvar level, a bulky cauliflower-like formation appeared. All routine investigations were normal. Immunological tests revealed the presence of antibodies anti-HPV immunoglobulin M (IgM) and immunoglobulin G (IgG). Treponema pallidum hemagglutination (TPHA) and HIV tests were negative. Samples collected from the genital lesions tested positive for both 6 and 11 DNA/HPV. The patient was diagnosed with condylomata acuminate and C-section was indicated as the methodology of birth so HPV infection of the newborn was avoided. We believe that HPV infection during pregnancy must be documented and treated when detected in order to avoid transmitting it to the newborn baby in a manner similar to TORCH testing. In pregnant women and women that want to conceive, in order to avoid transmission of infectious diseases from the mother to the newborn baby, TORCH testing is recommended. TORCH represents an acronym that includes: toxoplasmosis, other infectious diseases, rubella, cytomegalovirus infection, and herpes simplex infection.

Socio-demographic factors predicting HIV test seeking behaviour among MSM in 6 EU cities.

Background: HIV testing is generally accepted as being the lynchpin of a prevention strategy to tackle the HIV epidemic among MSM. However, few studies have analysed in detail the factors that influence HIV test seeking behaviour. Methods: The objective of this article is to analyse the relationship between HIV test seeking behaviour and individual, social and demographic factors in a sample of MSM recruited though a multi-centre bio-behavioural cross-sectional study. A multi-level analysis was conducted to identify factors associated with HIV test seeking behaviour. Results: A total of 2400 men were included in the sample. Age, self-reported sexual orientation, residence, household composition, educational status and perceived homonegativity all seem to impact on test seeking behaviour. Conclusions: The results suggest the need for more targeted testing promotion strategies among MSM that take structural and environmental factors into consideration, as part of a comprehensive public health strategy to address the HIV epidemic.