The expression of corticotropin-releasing hormone family peptides in premalignant and malignant vulvar lesions

Objectives To examine the relation of corticotropin-releasing hormone (CRH) family peptides with inflammatory processes and oncogenesis, emphasizing in vulvar inflammatory, premalignant and malignant lesions, as well as to investigate the possibility of lesion cells immunoescaping, utilizing FAS/FAS-L complex. Methods Immunohistochemical expression of CRH, urocortin (UCN), FasL and their receptors CRHR1, CRHR2 and Fas was studied in vulvar tissue sections obtained from patients with histologically confirmed diagnosis of lichen, vulvar intraepithelial neoplasia (VIN) and vulvar squamous cell carcinoma (VSCC). The patient cohort was selected from a tertiary teaching Hospital in Greece, between 2005 and 2015. For each of the disease categories, immunohistochemical staining was evaluated and the results were statistically compared. Results A progressive increase of the cytoplasmic immunohistochemical expression of CRH and UCN, from precancerous lesions to VSCC was observed. A similar increase was detected for Fas and FasL expression. Nuclear localization of UCN was demonstrated in both premalignant and VSCC lesions, with staining being significantly intensified in carcinomas, particularly in the less differentiated tumor areas or in the areas at invasive tumor front. Conclusions Stress response system and CRH family peptides seem to have a role in inflammation maintenance and progression of vulvar premalignant lesions to malignancy. It seems that stress peptides may locally modulate the stroma through Fas/FasL upregulation, possibly contributing to vulvar cancer development (AU)

The expression of corticotropin-releasing hormone family peptides in premalignant and malignant vulvar lesions.

OBJECTIVES: To examine the relation of corticotropin-releasing hormone (CRH) family peptides with inflammatory processes and oncogenesis, emphasizing in vulvar inflammatory, premalignant and malignant lesions, as well as to investigate the possibility of lesion cells immunoescaping, utilizing FAS/FAS-L complex. METHODS: Immunohistochemical expression of CRH, urocortin (UCN), FasL and their receptors CRHR1, CRHR2 and Fas was studied in vulvar tissue sections obtained from patients with histologically confirmed diagnosis of lichen, vulvar intraepithelial neoplasia (VIN) and vulvar squamous cell carcinoma (VSCC). The patient cohort was selected from a tertiary teaching Hospital in Greece, between 2005 and 2015. For each of the disease categories, immunohistochemical staining was evaluated and the results were statistically compared. RESULTS: A progressive increase of the cytoplasmic immunohistochemical expression of CRH and UCN, from precancerous lesions to VSCC was observed. A similar increase was detected for Fas and FasL expression. Nuclear localization of UCN was demonstrated in both premalignant and VSCC lesions, with staining being significantly intensified in carcinomas, particularly in the less differentiated tumor areas or in the areas at invasive tumor front. CONCLUSIONS: Stress response system and CRH family peptides seem to have a role in inflammation maintenance and progression of vulvar premalignant lesions to malignancy. It seems that stress peptides may locally modulate the stroma through Fas/FasL upregulation, possibly contributing to vulvar cancer development.

The expression and possible role of corticotropin-releasing hormone family peptides and their corresponding receptors in gynaecological malignancies and premalignant conditions: a systematic review.

The aim of this systematic review is to investigate the impact of corticotropin-releasing hormone (CRH) family peptides and their corresponding receptors on human physiology and disease onset, with a specific focus on gynaecological malignancies such as breast, endometrial, ovarian, vulvar, and cervical cancer. A comprehensive systematic review of 3 medical databases was conducted by 2 independent reviewers. We reviewed studies that explored the expression and role of CRH peptides in various aspects of cancer biology, in the context of breast, endometrial, ovarian, vulvar, and cervical cancer. Our findings reveal that CRH family peptides and their receptors, CRHR1 and CRHR2, are expressed in diverse gynaecological tissues, including cancer cells. Notably, we observed differential expression patterns among different gynaecological cancer types and stages, indicating potential associations with tumour aggressiveness and patient prognosis. Furthermore, CRH peptides were found to exert significant influences on critical cellular processes, such as cell proliferation, migration, invasion, and immune response, in gynaecological cancers. These findings highlight the multifaceted roles of CRH family peptides in gynaecological malignancies and emphasize the need for further research in this field. Therefore, understanding the mechanisms underlying the involvement of CRH family peptides in tumourigenesis may open new avenues for targeted therapeutic strategies in gynaecological malignancies.

The Gestational Effects of Maternal Bone Marker Molecules on Fetal Growth, Metabolism and Long-Term Metabolic Health: A Systematic Review.

Fetal exposure in adverse environmental factors during intrauterine life can lead to various biological adjustments, affecting not only in utero development of the conceptus, but also its later metabolic and endocrine wellbeing. During human gestation, maternal bone turnover increases, as reflected by molecules involved in bone metabolism, such as vitamin D, osteocalcin, sclerostin, sRANKL, and osteoprotegerin; however, recent studies support their emerging role in endocrine functions and glucose homeostasis regulation. Herein, we sought to systematically review current knowledge on the effects of aforementioned maternal bone biomarkers during pregnancy on fetal intrauterine growth and metabolism, neonatal anthropometric measures at birth, as well as on future endocrine and metabolic wellbeing of the offspring. A growing body of literature converges on the view that maternal bone turnover is likely implicated in fetal growth, and at least to some extent, in neonatal and childhood body composition and metabolic wellbeing. Maternal sclerostin and sRANKL are positively linked with fetal abdominal circumference and subcutaneous fat deposition, contributing to greater birthweights. Vitamin D deficiency correlates with lower birthweights, while research is still needed on intrauterine fetal metabolism, as well as on vitamin D dosing supplementation during pregnancy, to diminish the risks of low birthweight or SGA neonates in high-risk populations.

The Gestational Effects of Maternal Appetite Axis Molecules on Fetal Growth, Metabolism and Long-Term Metabolic Health: A Systematic Review.

Increased maternal food intake is considered a normal pregnancy adjustment. However, the overavailability of nutrients may lead to dysregulated fetal development and increased adiposity, with long-lasting effects on offspring in later life. Several gut-hormone molecules regulate maternal appetite, with both their orexigenic and anorectic effects being in a state of sensitive equilibrium. The aim of this manuscript is to systematically review literature on the effects of maternal gut-hormone molecules on fetal growth and metabolism, birth weight and the later metabolic health of offspring. Maternal serum ghrelin, leptin, IGF-1 and GLP-1 appear to influence fetal growth; however, a lack of consistent and strong correlations of maternal appetite axis hormones with birth weight and the concomitant correlation with fetal and birth waist circumference may suggest that these molecules primarily mediate fetal energy deposition mechanisms, preparing the fetus for survival after birth. Dysregulated intrauterine environments seem to have detrimental, sex-dependent effects on fetal energy stores, affecting not only fetal growth, fat mass deposition and birth weight, but also future metabolic and endocrine wellbeing of offspring.

A case report of psoriasis flare following immunotherapy: Report of an important entity and literature review.

Immune checkpoint inhibitors, such as anti-cytotoxic T-lymphocyte-associated antigen-4 and anti-programmed death-1, are a type of cancer immunotherapy approved for late-stage malignancy treatment. However, such therapies often induce immune-related adverse events. During anti-programmed death-1 blockade therapy, the most commonly reported adverse effects are skin toxicities, such as psoriasis-a chronic immune-mediated inflammatory disorder affecting the skin. We present the clinical characteristics of flared psoriasis in one patient under anti-programmed death-1 therapy who was diagnosed with T2N2M0/IIIB squamous lung carcinoma with a history of psoriasis for the past 5 years, exacerbated after the first cycle of nivolumab. After the third cycle, the extensive skin plaques necessitated treatment cessation. Following the discontinuation of anti-programmed death-1 treatment, skin lesions were treated locally. Possibly, anti-programmed death-1 immunotherapy can trigger immune-mediated diseases, such as psoriasis. Physicians should be alert to immune-related adverse events. Continuation or permanent cessation of treatment depends on the severity and reversibility of immune-related adverse events.

Combined EGFR/ALK Expression Analysis in Laryngeal Squamous Cell Carcinoma.

BACKGROUND/AIM: Epidermal growth factor receptor (EGFR) acts as an oncogene in malignancies. Our aim was to examine the role of combined EGFR/ anaplastic lymphoma kinase (ALK) expression as molecular markers in laryngeal squamous cell carcinoma (LSCC) patients. MATERIALS AND METHODS: Fifty (n=50) tissue sections derived from twenty-five (n=25) primary LSCCs were analyzed by immunohistochemistry (IHC). RESULTS: EGFR overexpression was observed in 17/25 (68%) cases. Concerning ALK, 23/25 (92%) demonstrated low expression. EGFR expression was associated with grade (p=0.049), whereas ALK expression was correlated with stage (p=0.048). ALK overexpression was detected at advanced-stage EGFR-positive cases. A biphasic EGFR protein expression pattern was observed in five (n=5) LSCC cases, whereas ALK expression was stable in all cases. CONCLUSION: EGFR overexpression is frequently observed in LSCC combined with low ALK expression. LSCC patients with EGFR/ALK protein overexpression should be eligible for targeted therapeutic strategies.

Pharmaceutical Pricing Policy in Greece: Toward a Different Path.

BACKGROUND: Affordable, accessible, and innovation-promoting pharmaceutical care is essential to the operation of a sustainable health system. External reference pricing (ERP), a common pharmaceutical policy in Europe, suffers today from indigenous weaknesses that may cause market distortions and barriers to care, burdening mostly the weak economies, and hence, raising ethical and political worrying. OBJECTIVES AND METHODS: A non-randomized experiment was conducted, in order to examine the influence of flexible and adaptable to health systems' affordability ERP structures. Outcomes were assessed by measuring deviations from Greek prices' level ex ante, as well as effects on pharmaceutical markets affiliated to the European ERP system. RESULTS AND CONCLUSION: Pharmaceutical pricing models that fit prices to income and affordability are better in all aspects, as they produce fairer results, while resulting in low external costs for the European ERP network as a whole. Small sets of reference countries are preferred to large baskets, as they produce similar results, while presenting better qualities by increasing the flexibility of the reimbursement system and the transparency of the market.

The prevalence and treatment patterns of diabetes in the Greek population based on real-world data from the nation-wide prescription database.

AIMS: Epidemiological data regarding diabetes in Greece are based on regional, small-scale studies. We aimed to identify all citizens with prescribed pharmacological treatment for diabetes, to further explore type 1 diabetes prevalence and describe pharmacological treatment patterns in type 2 diabetes. METHODS: The electronic prescription database of the National Organization for Health Care Services Provision was used to identify individuals who received at least two prescriptions with an ICD-10 code relevant to diabetes, dispensed between June 1st, 2014 and May 31st, 2015. Type-1 diabetes was defined in those receiving at least two fully-reimbursable insulin prescriptions with an ICD-10 code of E10 (insulin-dependent diabetes). RESULTS: The study population consisted of 10,222,779 individuals, accounting for 95% of the Greek population. Prevalence of medication-prescribed diabetes was 7.0% (720,764 individuals), ranging from 0.08% in children and adolescents, to 8.2% in adults, and 30.3% in those ⩾75years old. Prevalence of type 1 diabetes was 0.24%, with a clear male predominance and more than half of cases developing after 14years of age. Metformin was the most frequently prescribed medication (77.4%) in type-2 diabetes followed by DPP-4 inhibitors (44.8%) and sulphonylureas (34.5%), while insulin was used by 19.4% of patients. CONCLUSIONS: This nation-wide real-world data analysis on medication-prescribed diabetes demonstrates that the current prevalence in Greece is 7.0%, with wide age variation and high figures in older adults. Identification of pharmacological patterns among patients with type 2 diabetes is a valuable guide in policy-makers' efforts to balance a cost-effective, quality-acceptable disease management.

Estimating the Fiscal Effects of Public Pharmaceutical Expenditure Reduction in Greece.

The purpose of the present study is to estimate the impact of pharmaceutical spending reduction on public revenue, based on data from the national health accounts as well as on reports of Greece's organizations. The methodology of the analysis is structured in two basic parts. The first part presents the urgency for rapid cutbacks on public pharmaceutical costs due to the financial crisis and provides a conceptual framework for the contribution of the Greek pharmaceutical branch to the country's economy. In the second part, we perform a quantitative analysis for the estimation of multiplier effects of public pharmaceutical expenditure reduction on main revenue sources, such as taxes and social contributions. We also fit projection models with multipliers as regressands for the evaluation of the efficiency of the particular fiscal measure in the short run. According to the results, nearly half of the gains from the measure's application is offset by financially equivalent decreases in the government's revenue, i.e., losses in tax revenues and social security contributions alone, not considering any other direct or indirect costs. The findings of multipliers' high value and increasing short-term trend imply the measure's inefficiency henceforward and signal the risk of vicious circles that will provoke the economy's deprivation of useful resources.

Access to Care for Multiple Sclerosis in Times of Economic Crisis in Greece--the HOPE II Study.

BACKGROUND: While there is currently no cure for multiple sclerosis (MS), treatment with biologic disease-modifying drugs (bDMDs) can reduce the impact of the condition on the lives of patients. In Greece, the regulatory change in the distribution system of bDMDs, limited their administration through the designated pharmacies of the National Organization for Healthcare Services Provision (EOPYY) or the National Health System (ESY) hospitals, thus potentially impacting access to MS treatment. In this context, the aim of this paper was to assess the barriers to bDMDs, by recording MS patients' experiences. METHODS: A survey research was conducted between January and February 2014 in Athens and 5 other major Greek cities with the methods of personal and telephone interview. A structured questionnaire was used to elicit socio-economic and medical information, information related to obstacles in accessing bDMDs and medical treatment, from MS patients that visited EOPYY pharmacies during the study period. RESULTS: During the last year 69% of 179 participants reported that the distribution system of bDMDs has improved. Thirteen percent of participants encountered problems in accessing their medication, and 16.9% of participants in accessing their physician, with the obstacles being more pronounced for non-Athens residents. Frequent obstacles to bDMDs were the distance from EOPYY pharmacies and difficulties in obtaining a diagnosis from an EOPYY/ESY physician, while obstacles to medical care were delays in appointment booking and travel difficulties. CONCLUSION: Even though the major weaknesses of the distribution system of bDMDs have improved, further amelioration of the system could be achieved through the home delivery of medicines to patients living in remote areas, and through the development of a national MS registry.

Cardiac echo-lab productivity in times of economic austerity.

The present study attempts to offer insight into the volume, cost, and productivity of the operation of a cardiac echocardiographic laboratory (echo-lab) in a major public hospital of Greece and thus to contribute, on a practical level, to the widening of knowledge in the strategic field of secondary and tertiary healthcare management. The conducted research includes the basic step of the deployment of a primary data registry in the echo-lab and unfolds in three levels, i.e. the variability measurement of the quantity and cost of medical services provided to different patient populations, the assessment of operating costs and the development of productivity indexes. The results show that the mean costs of provision do change among distinct patient populations. The most important, from a financial standpoint, population cluster appears to be the one corresponding to outpatients. Productivity indices presented in this analysis constitute an essential piece of information which the public healthcare system is currently largely lacking, and which, combined with the pricing and the diagnosis-related group coding system of hospitals, can be used to improve efficiency in the management of secondary and tertiary care.

Barriers to accessing biologic treatment for rheumatoid arthritis in Greece: the unseen impact of the fiscal crisis--the Health Outcomes Patient Environment (HOPE) study.

The latest regulatory change in the distribution system of biologic disease-modifying, antirheumatic drugs limited their sale only through the designated pharmacies of the National Organization for Healthcare Services Provision (EOPYY) or the National Health System (NHS) hospitals, adding to the complexity of access to effective treatment for rheumatoid arthritis (RA) in Greece. The aim of this paper was to assess the barriers to access RA treatment, by recording patients', rheumatologists' and EOPYY pharmacists' experiences. One twenty-three patients, 12 rheumatologists and 27 pharmacists from Athens and other urban areas in Greece participated in the study. Three types of standardized questionnaires were used to elicit information from each group of respondents using the method of personal interview for patients and the method of postal survey for doctors and pharmacists. During the last year, 26% of patients encountered problems in accessing their rheumatologist and 49% of patients experienced difficulties in accessing their medication. Ninety-two percent of rheumatologists and 96% of pharmacists confirmed that patients experience difficulties in accessing RA medication. The most commonly reported reasons for reduced access to medical treatment were travel difficulties and long distance from doctor's clinic, as well as delays in booking an appointment. The most frequently reported barriers to access pharmaceutical treatment were difficulties in the prescription process, distance from EOPYY pharmacies and medicine shortages in NHS hospitals. The study showed that RA patients are facing increased barriers to access timely and effective treatment. Redesign of the current system of distribution ensuring the operation of additional points of sale is deemed necessary.