Confirmatory validation analysis of the PROFFIT questionnaire to assess financial toxicity in cancer patients.

BACKGROUND: The Patient Reported Outcome for Fighting FInancial Toxicity (PROFFIT) questionnaire was developed to measure financial toxicity (FT) and identify its determinants. The aim of the present study was to confirm its validity in a prospective cohort of patients receiving anticancer treatment. PATIENTS AND METHODS: From March 2021 to July 2022, 221 patients were enrolled at 10 Italian centres. Selected items of the EORTC-QLQ-C30 questionnaire represented the anchors, specifically, question 28 (Q-28) on financial difficulties, and questions 29-30 measuring global health status/quality of life (HR-QOL). The study had 80% power to detect a 0.20 correlation coefficient (r) between anchors and PROFFIT-score (items 1-7, range 0-100, 100 indicating maximum FT) with bilateral alpha 0.05 and 80% power. Confirmatory factor analysis was conducted. FT determinants (items 8-16) were described. RESULTS: Median age of patients was 65 years, 116 (52.5%) were females, 96 (43.4%) had low education level. Confirmatory factor analysis confirmed goodness of fit of the PROFFIT-score. Significant partial correlation of PROFFIT-score was found with Q-28 (r = 0.51) and HR-QOL (r = -0.23). Mean (SD) PROFFIT-score at baseline was 36.5 (24.9); it was statistically significantly higher for patients living in South Italy, those with lower education level, those who were freelancer/unemployed at diagnosis and those who reported significant economic impact from the COVID-19 pandemic. Mean (SD) scores of determinants ranged from 17.6 (27.1) for item 14 (support from medical staff) to 49.0 (36.3) for item 10 (expenses for medicines or supplements). PROFFIT-score significantly increased with worsening response to determinants. CONCLUSIONS: External validation of PROFFIT-score in an independent sample of patients was successful. The instrument is now being used in clinical studies.

Cetuximab as third-line rechallenge plus either irinotecan or avelumab is an effective treatment in metastatic colorectal cancer patients with baseline plasma RAS/BRAF wild-type circulating tumor DNA: Individual patient data pooled analysis of CRICKET and CAVE trials.

The rechallenge strategy is based on the concept that a subset of patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) could still benefit of epidermal growth factor receptor (EGFR) inhibition, after progression to an anti-EGFR based-therapy. We performed a pooled analysis of two-phase II prospective trials to determine the role of rechallenge in third-line mCRC patients with RAS/BRAF WT baseline circulating tumor DNA (ctDNA). Individual data of 33 and 13 patients from CAVE and CRICKET trials that received as third-line therapy cetuximab rechallenge were collected. Overall survival (OS), Progression-free survival (PFS), Overall response rate (ORR), Stable disease (SD) >6 months were calculated. Adverse events were reported. For the whole 46 patient population, median PFS (mPFS) was 3.9 months (95% Confidence Interval, CI 3.0-4.9) with median OS (mOS) of 16.9 months (95% CI 11.7-22.1). For CRICKET patients, mPFS was 3.9 months (95% CI 1.7-6.2); mOS was 13.1 months (95% CI 7.3-18.9) with OS rates at 12, 18, and 24 months of 62%, 23%, and 0%, respectively. For CAVE patients, mPFS was 4.1 months (95% CI 3.0-5.2); mOS was 18.6 months (95% CI 11.7-25.4) with OS rates at 12, 18, 24 months of 61%, 52%, 21%, respectively. Skin rash was more frequently reported in CAVE trial (87.9% vs. 30.8%; p = 0.001), whereas a increased incidence of hematological toxicities was observed in CRICKET trial (53.8%% vs. 12.1%; p = 0.003). Third-line cetuximab rechallenge in combination with either irinotecan or avelumab in RAS/BRAF WT ctDNA mCRC patients represents a promising therapy.

Guideline Application in Real world: multi-Institutional Based survey of Adjuvant and first-Line pancreatic Ductal adenocarcinoma treatment in Italy. Primary analysis of the GARIBALDI survey.

BACKGROUND: Information about the adherence to scientific societies guidelines in the 'real-world' therapeutic management of oncological patients are lacking. This multicenter, prospective survey was aimed to improve the knowledge relative to 2017-2018 recommendations of the Italian Association of Medical Oncology (AIOM). PATIENTS AND METHODS: Treatment-naive adult patients with pancreatic adenocarcinoma were enrolled. Group A received adjuvant therapy, group B received primary chemotherapy, and group C had metastatic disease. The results on patients accrued until 31 October 2019 with a mature follow-up were presented. RESULTS: Since July 2017, 833 eligible patients of 923 (90%) were enrolled in 44 Italian centers. The median age was 69 years (range 36-89 years; 24% >75 years); 48% were female; 93% had Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1; group A: 16%, group B: 30%; group C: 54%; 72% Nord, 13% Center, 15% South. In group A, guidelines adherence was 68% [95% confidence interval (CI) 59% to 76%]; 53% of patients received gemcitabine and 15% gemcitabine + capecitabine; median CA19.9 was 29 (range 0-7300; not reported 15%); median survival was 36.4 months (95% CI 27.5-47.3 months). In group B, guidelines adherence was 96% (95% CI 92% to 98%); 55% of patients received nab-paclitaxel + gemcitabine, 27% FOLFIRINOX, 12% gemcitabine, and 3% clinical trial; median CA19.9 was 337 (range 0-20220; not reported 9%); median survival was 18.1 months (95% CI 15.6-19.9 months). In group C, guidelines adherence was 96% (95% CI 94% to 98%); 71% of patients received nab-paclitaxel + gemcitabine, 16% gemcitabine, 8% FOLFIRINOX, and 4% clinical trial; liver and lung metastases were reported in 76% and 23% of patients, respectively; median CA19.9 value was 760 (range 0-1374500; not reported 9%); median survival was 10.0 months (95% CI 9.1-11.1 months). CONCLUSIONS: The GARIBALDI survey shows a very high rate of adherence to guidelines and survival outcome in line with the literature. CA19.9 testing should be enhanced; nutritional and psychological counseling represent an unmet need. Enrollment to assess adherence to updated AIOM guidelines is ongoing.

Breast cancer patient-reported outcomes on level 1 and level 2 oncoplastic procedures using BREAST-Q®.

PURPOSE: In breast cancer management not only mortality and surgical morbidity measurements are important but also patient satisfaction indexes. The authors evaluated the satisfaction and health-related quality of life (HRQOL) using the breast-conserving therapy (BCT) and breast reduction (BR) modules of BREAST-Q®. METHODS: This is a cross-sectional study that analyzed breast cancer patients consecutively submitted to breast surgery between January 2011 and April 2018 using two modules of BREAST-Q®. 968 patients were contacted and 232 answers were gathered: 171 patients submitted to oncoplastic level 1 surgery answered the BCT module and 61 submitted to oncoplastic level 2 surgery answered the BR module. Clinical data were retrieved from patients' medical records. RESULTS: Among the 232 questionnaires received, the median scores for psychosocial well-being, sexual well-being and (postoperative) satisfaction with breasts for BCT and BR modules were, respectively, 77.0 and 73.5 (p = 0.17); 62.0 and 53.0 (p = 0.14); 72.0 and 66.0 (p = 0.66). The median of adverse effects of radiation in the BCT module was 87.0. The median satisfaction with outcome in the BR module was 86.0. Both groups of patients revealed high scores of satisfaction with care. For the BCT patients, satisfaction with breasts strongly correlated with sexual well-being and was moderately correlated with psychosocial and physical well-being. For the BR patients, the satisfaction with outcome strongly correlated with satisfaction with medical team and moderately correlated with the remaining scales. CONCLUSION: Both oncoplastic surgery levels yielded similar satisfaction outcomes when assessed using BCT and BR modules of BREAST-Q®.

Clinical efficacy of sequential treatments in KRASG12C-mutant metastatic colorectal cancer: findings from a real-life multicenter Italian study (CRC-KR GOIM).

BACKGROUND: The presence of KRASG12C mutation in metastatic colorectal cancer (mCRC) correlates with poor outcome. Although different selective inhibitors are under clinical development, the optimal treatment remains uncertain. Thus, we conducted a retrospective analysis in a large cohort of patients with KRASG12C mCRC treated in 12 Italian oncology units. PATIENTS AND METHODS: Patients with unresectable mCRC harboring KRASG12C mutation receiving a first-line chemotherapy doublet or triplet between 2011 and 2021 were included in the study. Evaluation of overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) analysis was carried out. RESULTS: A total of 256/6952 (3.7%) patients with mCRC displayed KRASG12C mutation; of these, 111 met the inclusion criteria. The ORR of first-line therapy was 38.7% (43/111). Median PFS (mPFS) was 9 months [95% confidence interval (CI) 7.5-10.5 months]. After progression, only 62% and 36% of the patients are fit to receive second or third lines of treatment, with limited clinical benefit. Median OS (mOS) was 21 months (95% CI 17.4-24.6 months). In patients receiving first-line triplet chemotherapy, ORR was 56.3% (9/16), mPFS was 13 months (95% CI 10.3-15.7 months) and mOS was 32 months (95% CI 7.7-56.3 months). For irinotecan-based doublets, ORR was 34.5 (10/29), mPFS was 9 months (95% CI 6.4-11.6 months) and mOS was 22 months (95% CI 16.0-28.0 months). With oxaliplatin-based doublets ORR was 36.4% (24/62), mPFS was 7 months (95% CI 4.6-9.4 months) and mOS was 18 months (95% CI, 13.6-22.4 months). CONCLUSION: Patients with KRASG12C-mutant mCRC had a disappointing response to standard treatments. Within the limitations of a retrospective study, these results suggest that first-line chemotherapy intensification with FOLFOXIRI is a valid option in fit patients.

Role of molecular genetics in the clinical management of cholangiocarcinoma.

The incidence of cholangiocarcinoma (CCA) has steadily increased during the past 20 years, and mortality is increasing. The majority of patients with CCA have advanced or metastatic disease at diagnosis, and treatment options for unresectable disease are limited, resulting in poor prognosis. However, recent identification of targetable genomic alterations has expanded treatment options for eligible patients. Given the importance of early and accurate diagnosis in optimizing patient outcomes, this review discusses best practices in CCA diagnosis, with a focus on categorizing molecular genetics and available targeted therapies. Imaging and staging of CCAs are discussed, as well as recommended biopsy collection techniques, and molecular and genomic profiling methodologies, which have become increasingly important as molecular biomarker data accumulate. Approved agents targeting actionable genomic alterations specifically in patients with CCA include ivosidenib for tumors harboring IDH1 mutations, and infigratinib and pemigatinib for those with FGFR2 fusions. Other agents currently under development in this indication have shown promising results, which are presented here.

Initial experience with targeted axillary dissection after neoadjuvant therapy in breast cancer patients.

BACKGROUND: Targeted axillary dissection (TAD) combines sentinel node biopsy (SNB) with the removal of the previously marked metastatic node. TAD is a promising concept for axillary restaging in node-positive breast cancer patients with pathological complete response (pCR) to neoadjuvant therapy (NAT). We aimed to evaluate TAD feasibility in this context. METHODS: A prospective observational study was conducted in biopsy-confirmed cN1 patients. The removal of the clipped node (CN) was guided by intraoperative ultrasound. SNB used indocyanine green and patent blue V dye. If the CN or sentinel lymph nodes (SLN) had any metastatic foci, or the TAD procedure was unsuccessful, the patient underwent axillary lymph node dissection (ALND). RESULTS: Thirty-seven patients were included. TAD and SNB identification rates were 97.3%. Every retrieved CN was also a SLN. At the individual level, SNB identification rate was 89.2% with indocyanine green and 85.5% with patent blue V dye. The CN identification rate was 81.1%, being higher when the CN was localized on the intraoperative ultrasound (84.4% vs 60.0%). Nodal pCR was achieved by 54.1% of our patients and was more frequent in HER2-positive and triple-negative tumors (p = 0.039). Nineteen patients were spared from ALND. CONCLUSION: TAD with intraoperative ultrasound-guided excision of the CN and SNB with indocyanine green and patent blue V dye is a feasible concept to identify patients without axillary residual disease after NAT, that can be spared from ALND, although the need for marking the biopsied node should be further investigated.

Cow's Milk in Human Nutrition and the Emergence of Plant-Based Milk Alternatives.

Cow's milk is considered a complete food, providing high-quality protein and essential micronutrients, including vitamins and minerals. For medical reasons or as a lifestyle choice, consumers are replacing cow's milk with plant-based milk alternatives (PBMA); some perceive them as healthier alternatives to cow's milk due to their low saturated fatty acid content and no cholesterol content. However, the nutritional composition of PBMA is quite variable between different types and even within, which makes a comparison with cow's milk a complex issue. Furthermore, the consumption of PBMA has been associated with the development of some diseases in infants and children. Meanwhile, the consumption of cow's milk in human health is a controversial issue since it has been associated with a favorable effect in some diseases (such as obesity, type 2 diabetes, and Alzheimer's) and a negative effect in others (such as prostate cancer risk and Parkinson's disease); while in some diseases, there is no consensus in the cow's milk consumption effect. The aim of this review is to make a nutritional comparison of cow's milk with PBMA and to clarify the potential health issues related to their consumption.

The molecular profiling of solid tumors by liquid biopsy: a position paper of the AIOM-SIAPEC-IAP-SIBioC-SIC-SIF Italian Scientific Societies.

The term liquid biopsy (LB) refers to the use of various biological fluids as a surrogate for neoplastic tissue to achieve information for diagnostic, prognostic and predictive purposes. In the current clinical practice, LB is used for the identification of driver mutations in circulating tumor DNA derived from both tumor tissue and circulating neoplastic cells. As suggested by a growing body of evidence, however, there are several clinical settings where biological samples other than tissue could be used in the routine practice to identify potentially predictive biomarkers of either response or resistance to targeted treatments. New applications are emerging as useful clinical tools, and other blood derivatives, such as circulating tumor cells, circulating tumor RNA, microRNAs, platelets, extracellular vesicles, as well as other biofluids such as urine and cerebrospinal fluid, may be adopted in the near future. Despite the evident advantages compared with tissue biopsy, LB still presents some limitations due to both biological and technological issues. In this context, the absence of harmonized procedures corresponds to an unmet clinical need, ultimately affecting the rapid implementation of LB in clinical practice. In this position paper, based on experts' opinions, the AIOM-SIAPEC-IAP-SIBIOC-SIF Italian Scientific Societies critically discuss the most relevant technical issues of LB, the current and emerging evidences, with the aim to optimizing the applications of LB in the clinical setting.

[Length of hospital stay and functional status in patients with delayed start of physical therapy]. / Estancia hospitalaria y funcionalidad en pacientes con retraso en el inicio de tratamiento de fisioterapia.

OBJECTIVE: To evaluate the association between hospital stay, functional status and physical therapy delay (PT delay) in patients admitted to a surgery unit of a high complexity hospital. MATERIALS AND METHODS: Observational, analytic and cross-sectional study. We included 279 patients (124 women). Days of PT delay (calculated as the difference between hospital admission and start of PT), days of bed rest, prolonged hospital stay (75th percentile of bed rest days), and functional status were registered to investigate the influence of PT delay on these variables. RESULTS: The number of days of PT delay was strongly associated with the number of bed rest days (r2 = 0.74, p < 0.05). Moreover, a PT delay of five days or more was associated with extended lengths of stay in our sample (p < 0.05). However, physical therapy had similar effects on functional status, even when there were PT delays (p > 0.05). CONCLUSIONS: PT delay is associated with extended length of stay in patients admitted to a surgery unit of a high complexity hospital. Future studies should investigate the associated factors that could explain the occurrence of PT delays in surgical patients.

Apendicitis aguda perforada con diagnóstico prequirúrgico y hernia inguinal bilateral en recién nacido de pretérmino / Acute perforated appendicitis with pre-surgical diagnosis and bilateral inguinal hernia in preterm infants

INTRODUCCIÓN: La apendicitis aguda neonatal es una patología de muy baja frecuencia, con escasos reportes en los últimos 30 años. La clínica e imágenes son inespecíficas, diagnosticándose la mayoría de las veces durante el procedimiento quirúrgico. OBJETIVO: Presentar un caso de apendicitis aguda perfora da en paciente prematura, con diagnóstico prequirúrgico y resolución laparoscópica, asociada a aparición posterior de hernia inguinal. CASO CLÍNICO: Recién nacido femenino de 34 semanas que a los 17 días de vida presentó fiebre, irritabilidad y aumento del residuo lácteo. Al examen físico destacaba distensión y sensibilidad del abdomen y tanto la radiografía como ecografía abdominales eran compatibles con apendicitis aguda perforada, por lo cual ingresó a pabellón para laparoscopía. Confirmado el diagnóstico, se realizó apendicectomía. Dos semanas después en consulta ambulatoria, se evidenció y confirmó con ecografía una hernia inguinal bilateral que se corrigió quirúrgicamente. CONCLUSIÓN: La apendicitis aguda debe considerarse dentro de los diagnósticos diferenciales en neonatos con clínica de abdomen agudo, principalmente en prematuros. En este caso, la ecografía permitió realizar el diagnóstico pre-operatorio. La posible asociación con hernia inguinal, debiera motivar a examinar siempre conductos inguinales durante la evaluación con imá genes y en el procedimiento quirúrgico.

INTRODUCTION: Acute neonatal appendicitis is a rare pathology, with few reports in the last 30 years. Since its clinical presentation and imaging studies are non-specific, most cases are diagnosed during a surgical pro cedure. OBJECTIVE: To describe a neonatal case of acute perforated appendicitis associated with later appearance of inguinal hernia, with pre-surgical diagnosis and treated through laparoscopy. CLINICAL CASE: A 17-day-old preterm female newborn presented with fever, irritability, and increased milk intolerance. Physical examination showed abdominal distention, tenderness and both, abdominal X- ray and ultrasound showed compatible images with acute perforated appendicitis. Once the diagnosis was confirmed, we performed an appendicectomy through laparoscopy. Two weeks later, during an outpatient visit, we observed a bilateral inguinal hernia which was confirmed by ultrasound, and then it was surgically corrected. CONCLUSION: Acute appendicitis should be considered within the differential diagnosis in neonates with acute abdominal symptoms, mainly in premature infants. In this case, ultrasound scan allowed us to make the pre-operative diagnosis. The possible association with inguinal hernias should motivate to examine inguinal ducts during imaging assessment and surgical procedure.

Evaluación de la infección por VIH en Chile: pronunciamiento del Comité VIH de la Academia Chilena de Medicina / Evaluation of HIV epidemic in Chile: a statement of the Chilean Academy of Medicine

The Chilean Academy of Medicine convened a commission to evaluate the status of HIV epidemic and the national response to it, regarding its achievements, gaps and challenges, aiming to recommend actions to optimize assessment quality and national response. This publication summarizes the agreed upon opinion of its members. The epidemic is overwhelmingly sexually transmitted, predominant in homo/bisexual men. Vertical transmission is very low. An increasing number of new diagnoses is occurring, with relative over representation of foreign people lately. There is a legal guarantee of confidentiality, nondiscrimination and treatment for those affected, both in the private and public sector. All public health services have active HIV care units. Modern antiviral drugs and monitoring tests are also available. Despite these clear achievements, insufficient, occasionally inadequate public policies and certain rigid regulations thwart optimal effectivity and efficiency of the programs, contributing to the slow and incomplete compliance with international commitments. Shortcomings worth highlighting are: suboptimal educational and preventive programs directed to youngsters, vulnerable and general population; persistent underdiagnosis of infected population; cumbersome requirements to request and inform diagnostic tests, thus discouraging testing; excessive centralization and long latency of diagnosis confirmation and monitoring tests; incomplete epidemiologic analysis and public reporting of findings; non flexibility and slow updating of therapeutic guidelines; insufficient adaptation of care and drug delivery modalities to patients' needs; excessive administrative requirements at care centers and restrictive legislation for outcome and interventional clinical research. Recommendations to deal with these issues were proposed.

Comprehensive germline mutation analysis and clinical profile in a large cohort of Brazilian xeroderma pigmentosum patients.

BACKGROUND: Xeroderma pigmentosum (XP) patients present a high risk of developing skin cancer and other complications at an early age. This disease is characterized by mutations in the genes related to the DNA repair system. OBJECTIVES: To describe the clinical and molecular findings in a cohort of 32 Brazilian individuals who received a clinical diagnosis of XP. METHODS: Twenty-seven families were screened for germline variants in eight XP-related genes. RESULTS: All patients (N = 32) were diagnosed with bi-allelic germline pathogenic or potentially pathogenic variants, including nine variants previously undescribed. The c.2251-1G>C XPC pathogenic variant, reported as the founder mutation in Comorian and Pakistani patients, was observed in 15 cases in homozygous or compound heterozygous. Seven homozygous patients for POLH/XPV variants developed their symptoms by an average age of 7.7 years. ERCC2/XPD, DDB2/XPE and ERCC5/XPG variants were found in a few patients. Aside from melanoma and non-melanoma skin tumours, a set of patients developed skin sebaceous carcinoma, leiomyosarcoma, angiosarcoma, mucoepidermoid carcinoma, gastric adenocarcinoma and serous ovarian carcinoma. CONCLUSIONS: We reported a high frequency of XPC variants in 32 XP Brazilian patients. Nine new variants in XP-related genes, unexpected non-skin cancer lesions and an anticipation of the clinical manifestation in POLH/XPV cases were also described.

[Acute perforated appendicitis with pre-surgical diagnosis and bilateral inguinal hernia in preterm infants]. / Apendicitis aguda perforada con diagnóstico prequirúrgico y hernia inguinal bilateral en recién nacido de pretérmino.

INTRODUCTION: Acute neonatal appendicitis is a rare pathology, with few reports in the last 30 years. Since its clinical presentation and imaging studies are non-specific, most cases are diagnosed during a surgical pro cedure. OBJECTIVE: To describe a neonatal case of acute perforated appendicitis associated with later appearance of inguinal hernia, with pre-surgical diagnosis and treated through laparoscopy. CLINICAL CASE: A 17-day-old preterm female newborn presented with fever, irritability, and increased milk intolerance. Physical examination showed abdominal distention, tenderness and both, abdominal X- ray and ultrasound showed compatible images with acute perforated appendicitis. Once the diagnosis was confirmed, we performed an appendicectomy through laparoscopy. Two weeks later, during an outpatient visit, we observed a bilateral inguinal hernia which was confirmed by ultrasound, and then it was surgically corrected. CONCLUSION: Acute appendicitis should be considered within the differential diagnosis in neonates with acute abdominal symptoms, mainly in premature infants. In this case, ultrasound scan allowed us to make the pre-operative diagnosis. The possible association with inguinal hernias should motivate to examine inguinal ducts during imaging assessment and surgical procedure.

Polivictimización y su relación con las conductas autoagresivas y con la depresión en adolescentes / Polyvictimization and its relation with self-aggressive behaviors and with depression in adolescents

Resumen Introducción: La acumulación de experiencias de distinto tipo de maltrato o violencia durante la infancia ha sido nominada como polivictimización. Se ha documentado que la polivictimización genera consecuencias negativas en la salud mental de las personas. En Chile, no existe suficiente investigación respecto de este fenómeno, únicamente se conocen algunas cifras que muestran que es prevalente. El objetivo del estudio es evaluar la frecuencia con que adolescentes han sido sometidos a diferentes niveles de polivictimización y su relación con los niveles de sintomatología depresiva y con la frecuencia de conductas autolesivas. Método: El estudio, descriptivo correlacional, encuesta a 114 adolescentes de entre 17 y 18 años de edad. Resultados: Se aprecia que el 40,3% de la muestra habría sufrido al menos 2 tipos diferentes de victimización y que la polivictimización se asocia a la sintomatología depresiva y a la frecuencia de las autoagresiones. Conclusión: Se concluye que los profesionales de salud mental debieran evaluar la posibilidad de que la psicopatología de sus pacientes específicos pudiese estar relacionados con experiencias de victimización infantojuvenil que debieran ser consideradas en los tratamientos.

Introduction: The accumulation of experiences of abuse or violence during childhood has been nominated as a polyvictimization. It has been documented that the polyvictimización generates negative consequences in the mental health of the people. In Chile there is not enough research on this phenomenon, only there is known that it is prevalent. The objective of the study is to evaluate the frequency of polyvictimization in the adolescents and its relation with the levels of depressive symptomatology and with the frequency of self-injurious behaviors. Method: This is a descriptive correlational study. We survey 114 adolescents between 17 and 18 years of age. Results: It was observed that 40.3% of the sample had suffered at least 2 different types of victimization and that polyvictimization is associated with depressive symptoms and with the frequency of self-harm. Conclusion: It is concluded that mental health professionals should evaluate the possibility that the mental health problems of their specific patients may be related to experiences of child and adolescent victimization, which should be considered in the treatments.

Ineffectiveness of information and access to health services: vulnerability to human papillomavirus.

AIM: To examine situations of vulnerability to human papillomavirus in the social representations of young women. BACKGROUND: Human papillomavirus is one of the most frequent sexually transmitted infections among women and constitutes a serious health problem among youth. This problem is embedded in psychosocial issues that promote situations of vulnerability and affect attitudes and behaviour in relation to prevention. METHODS: Qualitative study based on the theory of social representations, conducted among 64 female students in a high school in the city of Rio de Janeiro, Brazil. The study used personal semi-structured interviews, with a lexical analysis by Alceste 2010 software. FINDINGS: The inefficacy of information on the human papillomavirus pointed out individual and social vulnerabilities, and showed relationships between the difficulty of access and the perception of low quality in public health services, which also promotes institutional vulnerability. DISCUSSION: The representation of vulnerability to human papillomavirus infection is associated, not only with individual behaviours related to sexuality and gender identity but also to social and institutional conditions involving insufficient information and low quality of and ineffective access to public health services. CONCLUSION: Situations of vulnerability of young women to human papillomavirus infection influence ways of thinking and acting, when they generate feelings and behaviours that put them at risk. The social representations provided knowledge about how the participants appropriated consensual and reified universes in relation to vulnerability, influencing care and awareness of prevention. IMPLICATION FOR NURSING AND HEALTH POLICY: Situations of vulnerability, whether individual, social or institutional, warrant the attention of nurses and should be prioritized as public health policy goals to reduce the number of cases of human papillomavirus infection among younger women.

Economic burden of HPV9-related diseases: a real-world cost analysis from Italy.

INTRODUCTION: The objectives of this study were to estimate the economic burden of HPV in Italy, accounting for total direct medical costs associated with nine major HPV-related diseases, and to provide a measure of the burden attributable to HPV 6, 11, 16, 18, 31, 33, 45, 52, 58 infections. METHODS: A cost-of-illness incidence-based model was developed to estimate the incidences and costs of invasive cervical cancer, cervical dysplasia, cancer of the vulva, vagina, anus, penis, oropharyngeal, anogenital warts, and recurrent respiratory papillomatosis (RRP) in the context of the Italian National Health System (NHS). We used data from hospital discharge records (HDRs) of an Italian region and conducted a systematic literature review to estimate the lifetime cost per case, the number of incident cases, the prevalence of HPV9 types. Costs of therapeutic options not included in the diagnosis-related group (DRG) tariffs were estimated through a scenario analysis. RESULTS: In 2018, the total annual direct costs were €542.7 million, with a range of €346.7-€782.0 million. These costs could increase considering innovative therapies for cancer treatment (range €16.2-€37.5 million). The fraction attributable to the HPV9 genotypes without innovative cancers treatment was €329.5 million, accounting for 61% of the total annual burden of HPV-related diseases in Italy. Of this amount, €135.9 million (41%) was related to men, accounting for 64% of the costs associated with non-cervical conditions. CONCLUSIONS: The infections by HPV9 strains and the economic burden of non-cervical HPV-related diseases in men were found to be the main drivers of direct costs.

Altered gene expression in embryos and endometrium collected on day 8 of induced aluteal cycles in mares.

Aluteal cycles were induced in the mare to evaluate the effects of progesterone deprivation on the gene expression of embryos and endometrium collected eight days after ovulation. We hypothesized that the transcript expression would be altered during induced aluteal (AL) cycles (low progesterone <1 ng/mL) when compared with control cycles during diestrus (high progesterone; > 4 ng/mL) for 1) the embryonic expression of progesterone-mediated transcripts and those related to normal embryo growth and development and 2) the endometrial expression of progesterone-mediated transcripts and those related to prostaglandin synthesis and normal pregnancy establishment. Seven cyclic mares with a median age of 6.5 years (range 3-16) were utilized in a crossover design. Mares in estrus were artificially inseminated to a fertile stallion and randomly assigned to control or AL groups. Mares received either saline solution (control mares) or PGF2α (AL mares), twice daily on days 0, 1, and 2 and once daily on days 3 and 4. Serial blood samples were collected daily from day 0 (ovulation) until the day of embryo collection and endometrial biopsy on day 8. Mares were monitored until they returned to estrus, and artificially inseminated. Mares were switched to the opposite treatment group only after a successful embryo collection occurred during the previous cycle and only cycles that produced embryos were used for analyses. The study design resulted in paired samples from each mare for analyses. No significant rise in progesterone was observed in the AL group with mean concentrations of plasma progesterone remaining <1.0 ng/mL from ovulation until embryo collection on day 8. This is in sharp contrast to the control (luteal) cycle where a post-ovulatory rise in plasma progesterone was observed. Real-time RT-PCR was utilized to evaluate the expression of ESR1, PGR, CYP19A1, P19, SLC35A1, OCD, APOB, AQP3, NEU2 transcripts in the embryos and PTGS2, P19, ESR1, HK2, sPLA2, PGR, CTGF, IFNE, FGF9, SLC36A2 expression in the endometrium. Four transcripts showed increased expressed in embryos developed during AL cycles ESR1, P19, APOB and PGR (p < 0.05). Four transcripts showed increased expressed in endometrium developed during AL cycles sPLA2, PGR, ESR1, FGF9 (p < 0.05) and four transcripts showed decreased expression P19, CTGF, IFNE, HK2 (p < 0.05). Additionally, staining differences were present in endometrial staining for both ERα and PR receptor during AL cycles compared with control cycles. Embryos and endometrium developed in a progesterone-deprived environment during induced aluteal cycles demonstrated altered transcript expression. These results indicate that adequate progesterone levels may be a key mediator of the appropriate embryo-maternal environment during early preimplantation embryo development.

Immunohistochemical evaluation of Sonic Hedgehog signaling pathway proteins (Shh, Ptch1, Ptch2, Smo, Gli1, Gli2, and Gli3) in sporadic and syndromic odontogenic keratocysts.

AIMS: The aim of this study was to compare the clinical and demographic features of 62 patients presenting sporadic odontogenic keratocysts (OKCs) or OKCs associated with nevoid basal cell carcinoma syndrome (NBCCS). In conjunction with this, we also evaluated the immunohistochemical expression of Shh, Ptch1, Ptch2, Smo, Gli1, Gli2 and Gli3 proteins in 86 OKCs. By doing this, we add to the understanding of the biology of this type of lesion, providing tools that will help facilitate the early diagnosis of NBCCS in those patients where the first manifestation is that of OKCs. METHODS: This is a retrospective study; patients were classified into two groups: group 1 which consisted of those who were not affected by NBCCS (49 patients and 57 OKCs) and group 2 which consisted of those who were diagnosed with NBCCS (13 patients and 29 OKCs). The clinical and demographic features were studied and the immunohistochemical expression of Sonic Hedgehog proteins (Shh, Ptch1, Ptch2, Smo, Gli1, Gli2, and Gli3) was analyzed in all samples. RESULTS: There was an increase in the expression of three proteins in the syndromic OKC, when compared to that of sporadic cysts. Shh and Gli1 showed higher cytoplasmic expression, while Smo revealed stronger nuclear and cytoplasmic expressions. CONCLUSION AND CLINICAL RELEVANCE: Our findings suggest that the expression patterns of important Shh pathway proteins can represent valuable markers for early diagnosis of NBCCS-associated OKCs, as the major criterion for the diagnosis of NBCCS is currently based on the late appearance of basal cellular carcinomas. Thus, standardizing a new diagnostic tool for diagnosis of NBCCS could be of great importance in the identification of therapeutic targets. We therefore suggest, as based on our findings, that OKCs showing high expression of Shh, Smo, and Gli1 are potentially associated with NBCCS.