Stereotactic body radiotherapy boost as an alternative to brachytherapy for cervical cancer: A scoping review.

PURPOSE: This scoping review aims to evaluate the evidence for stereotactic body radiotherapy (SBRT) boost as a potential alternative for brachytherapy (BCT) in treating cervical cancer. MATERIAL AND METHODS: A comprehensive literature search was conducted across multiple databases. Studies investigating SBRT boost in cervical cancer patients who were either contraindicated for or refused BCT were included. The review examined SBRT efficacy and safety. RESULTS: Sixteen studies were included, encompassing prospective (n = 4) and retrospective cohort studies (n = 8), as well as phase I and II trials (n = 4). The most common SBRT boost dose was 25 Gray(Gy)/5 fractions (ranging from 18 to 40 Gy/3-5 fractions). Local control rates at 1-year, 3-year, and 5-year ranged from 86 % to 100 %, 78-92 %, and 81-92 %, respectively. Overall survival (OS) rates at 1-year, 3-year, and 5-year rates ranged from 49 % to 95 %, 50-77 %, and 50-69 %, respectively. Two studies reported a pathological complete response rate of 93 % and 94 % three months after the SBRT boost. Most studies reported low rates of late grade 3 or higher genitourinary (0-14 %) and gastrointestinal (0-26 %) toxicities. The overall incidence of rectovaginal fistulas ranged from 0 % to 13 %. CONCLUSION: This scoping review suggests SBRT boost as a promising alternative to selected cervical cancer patients who cannot receive BCT. The results indicate a high local control with acceptable toxicity profiles. However, further research is needed to define optimal SBRT boost parameters, identify patient selection criteria, and address knowledge gaps regarding long-term outcomes and cost-effectiveness.

Influence of Body Composition Assessed by Computed Tomography on Mortality Risk in Young Women with Breast Cancer.

Background/Objectives: Increasing evidence indicates that body composition can significantly influence prognosis in women with breast cancer. However, alterations in body composition, particularly among young women (<40 years), remain largely unknown and underexplored. This study aimed to investigate the relationship of computed tomography (CT)-derived body composition with mortality rates among young women recently diagnosed with breast cancer, identifying the best-correlated cutoff value. Methods: This is a bi-set cohort study with retrospective data collection. Women newly diagnosed with ductal invasive breast cancer, aged 20 to 40 years, treated in reference oncology units were included. Body composition was assessed using CT scans at the third lumbar vertebra (L3) level, including muscle and adipose compartments. The outcome of interest was the incidence of overall mortality. A maximally selected log-rank Cox-derived analysis was employed to assess the cutoffs associated with mortality. Results: A total of 192 women were included before any form of treatment (median age of 35 years, IQ range: 31-37). Overall mortality occurred in 12% of the females. Stages III-IV were the most frequent (69.5%). Patients who died had a significantly lower muscle area index. CT-derived muscle area was inversely associated with mortality. Each 1 cm2/m2 decrease in skeletal muscle index increased the mortality hazard by 9%. Higher values of adiposity compartments were independently associated with higher mortality. Conclusions: Our study highlights the predictive significance of skeletal muscle area and adipose tissue in predicting survival among young women recently diagnosed with breast cancer.

Age-adjusted Charlson comorbidity index and its association with body composition and overall survival in patients with colorectal cancer.

OBJECTIVE: To examine the relationship between the age-adjusted Charlson comorbidity index (A-CCI) with body composition and overall survival in patients newly diagnosed with colorectal cancer (CRC). RESEARCH METHODS AND PROCEDURES: In this cohort study, patients (≥ 18 years old) with CRC were followed for 36 months. Computed tomography images of the third lumbar were analyzed to determine body composition, including skeletal muscle area (SMA), skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). Phenotypes based on comorbidity burden assessed by A-CCI and body composition parameters were established. RESULTS: A total of 436 participants were included, 50% male, with a mean age of 61 ± 13.2 years. Approximately half of the patients (50.4%) had no comorbidity, and the A-CCI median score was 4 (interquartile range: 3-6). A higher A-CCI score was a risk factor for 36-month mortality (HR = 3.59, 95% CI = 2.17-5.95). Low SMA and low SMD were associated with a higher A-CCI. All abnormal phenotypes (high A-CCI and low SMA; high A-CCI and low SMD; high A-CCI and high VAT) were independently associated with higher 36-month mortality hazard (adjusted HR 5.12, 95% CI 2.73-9.57; adjusted HR 4.58, 95% CI 2.37-8.85; and adjusted HR 2.36, 95% CI 1.07-5.22, respectively). CONCLUSION: The coexistence of comorbidity burden and abnormal body composition phenotypes, such as alterations in muscle or fat compartments, may pose an additional risk of mortality in patients newly diagnosed with CRC. Early assessment and management of these phenotypes could be crucial in optimizing outcomes in such patients.

Thigh muscle by CT images as a predictor of mortality in patients with newly diagnosed colorectal cancer.

This study aimed to evaluate the prognostic value of thigh muscle assessed by CT images to predict overall mortality in patients with colorectal cancer (CRC). This was a multicenter cohort study including adults (≥ 18 years old) newly diagnosed with CRC, who performed a diagnostic computed tomography (CT) exam including thigh regions. CT images were analyzed to evaluate skeletal muscle (SM in cm2), skeletal muscle index (SMI in cm2/m2), and skeletal muscle density (SMD in HU). Muscle abnormalities (low SM, SMI, and SMD) were defined as the values below the median by sex. Kaplan-Meyer curves and hazard ratios (HRs) for low SM, SMI and SMD were evaluated for overall mortality, stratified by sex. A total of 257 patients were included in the final analysis. Patients' mean age was 62.6 ± 12.1 years, and 50.2% (n = 129) were females. In males, low thigh SMI was associated with shorter survival (log-rank P = .02). Furthermore, this low thigh SMI (cm2/m2) was independently associated with higher mortality rates (HR adjusted 2.08, 95% CI 1.03-4.18). Our additional findings demonstrated that low SMD was independently associated with overall mortality among early-stage patients (I-III) (HR adjusted 2.78, 95% CI 1.26-6.15).

Exploring the anti-inflammatory effects of postbiotic proteins from Lactobacillus delbrueckii CIDCA 133 on inflammatory bowel disease model.

Lactobacillus delbrueckii CIDCA 133 is a promising health-promoting bacterium shown to alleviate intestinal inflammation. However, the specific bacterial components responsible for these effects remain largely unknown. Here, we demonstrated that consuming extractable proteins from the CIDCA 133 strain effectively relieved acute ulcerative colitis in mice. This postbiotic protein fraction reduced the disease activity index and prevented colon shortening in mice. Furthermore, histological analysis revealed colitis prevention with reduced inflammatory cell infiltration into the colon mucosa. Postbiotic consumption also induced an immunomodulatory profile in colitic mice, as evidenced by both mRNA transcript levels (Tlr2, Nfkb1, Nlpr3, Tnf, and Il6) and cytokines concentration (IL1ß, TGFß, and IL10). Additionally, it enhanced the levels of secretory IgA, upregulated the transcript levels of tight junction proteins (Hp and F11r), and improved paracellular intestinal permeability. More interestingly, the consumption of postbiotic proteins modulated the gut microbiota (Bacteroides, Arkkemansia, Dorea, and Oscillospira). Pearson correlation analysis indicated that IL10 and IL1ß levels were positively associated with Bacteroides and Arkkemansia_Lactobacillus abundance. Our study reveals that CIDCA 133-derived proteins possess anti-inflammatory properties in colonic inflammation.

The detrimental role of galectin-3 and endoplasmic reticulum stress in the cardiac consequences of myocardial ischemia in the context of obesity.

The association between cardiac fibrosis and galectin-3 was evaluated in patients with acute myocardial infarction (MI). The role of galectin-3 and its association with endoplasmic reticulum (ER) stress activation in the progression of cardiovascular fibrosis was also evaluated in obese-infarcted rats. The inhibitor of galectin-3 activity, modified citrus pectin (MCP; 100 mg/kg/day), and the inhibitor of the ER stress activation, 4-phenylbutyric acid (4-PBA; 500 mg/kg/day), were administered for 4 weeks after MI in obese rats. Overweight-obese patients who suffered a first MI showed higher circulating galectin-3 levels, higher extracellular volume, and LV infarcted size, as well as lower E/e'ratio and LVEF compared with normal-weight patients. A correlation was observed between galectin-3 levels and extracellular volume. Obese-infarcted animals presented cardiac hypertrophy and reduction in LVEF, and E/A ratio as compared with control animals. They also showed an increase in galectin-3 gene expression, as well as cardiac fibrosis and reduced autophagic flux. These alterations were associated with ER stress activation characterized by enhanced cardiac levels of binding immunoglobulin protein, which were correlated with those of galectin-3. Both MCP and 4-PBA not only reduced cardiac fibrosis, oxidative stress, galectin-3 levels, and ER stress activation, but also prevented cardiac functional alterations and ameliorated autophagic flux. These results show the relevant role of galectin-3 in the development of diffuse fibrosis associated with MI in the context of obesity in both the animal model and patients. Galectin-3 in tandem with ER stress activation could modulate different downstream mechanisms, including inflammation, oxidative stress, and autophagy.

Moral Distress of Nurses Working in Paediatric Healthcare Settings.

This scoping review aims to map the evidence on moral distress of nurses working in paediatric healthcare settings from homecare to hospital. It was conducted according to the Joanna Briggs Institute. International databases were searched according to the specific thesaurus and free search terms. Independent screening and analysis were conducted using Rayyan QCRI. This review considered a total of 54 studies, including quantitative and qualitative studies, systematic reviews, and grey literature; English and Portuguese languages were included. Moral distress is a phenomenon discussed in nursing literature and in the paediatric context but is considered absent from discussion in clinical practice. It is caused by disproportionate care associated with overtreatment. Nurses can present a variety of symptoms, characterising moral distress as a highly subjective experience. The paediatric contexts of practice should promote a healthy ethical climate and work towards a moral community built with peer support, education, communication, leadership, and management involvement. Moral distress is still a complex and challenging multidimensional concept, and the aim should be to promote a culture of prevention of the devastating consequences of moral distress and work towards moral resilience.

Reproductive Tract Microbiota of Mares.

The female reproductive tract microbiota is a complex community of microorganisms that might be crucial in maintaining a healthy reproductive environment. Imbalances in the bacterial community (dysbiosis) and the reduction of beneficial organisms and pathogen proliferation are associated with disease. Endometritis is a common cause of fertility problems in mares, and it is still challenging to diagnose and treat based on routine culture results of certain microorganisms. Although high-throughput sequencing studies provide helpful information regarding the composition of the reproductive tract microbiota in mares, there are still challenges in defining a "normal" microbiota. The primary objective of this literature review is to summarize the current knowledge regarding the microbiota present in the reproductive tract of mares, including the vagina, cervix, and uterus. The second objective is to describe the relevant factors that can impact the reproductive microbiota of mares, including the estrous cycle stage, the type of species (genera) investigated, season, and geographic location. The rationality of identifying the normal microbiota in the reproductive tract of a mare will likely aid in understanding the impact of the microbiota on the host's reproductive health and contribute to the treatment and prevention of equine sub and infertility issues.

Vaginal and Uterine Microbiota of Healthy Maiden Mares during Estrus.

This descriptive cross-sectional study compared the microbiota of the uterus, vagina, clitoral fossa (CF), and perineal skin in healthy maiden mares during estrus. Twelve synchronized, healthy maiden mares (3-4 years old) from one single recipient mare herd were included. Microbial communities were characterized by amplifying the V3-V4 region of the 16S rRNA gene using the Illumina MiSeq platform. The uterine and vaginal microbiota had significantly lower richness (Chao-1) than the skin (p < 0.05). The uterine and vagina bacterial composition was similar in presence and abundance and could be differentiated from that of the CF and perineal skin. The microbial composition (Jaccard and Bray-Curtis distances) significantly differed across body-site locations (p < 0.05), which explained approximately 14% and 19% of the variation in microbial composition for Jaccard and Bray-Curtis distances, respectively. Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes were the dominant taxa in the uterus and vagina, with higher proportions of Proteobacteria in the vaginal samples compared to the uterine samples. Streptococcaceae and Staphylococcaceae were present in high abundance in the uterine and vaginal samples, while Lactobacillaceae were not (<10%). We demonstrate that the uterine and vaginal microbiota of healthy maiden mares during estrus is similar but both distinct from that of the CF and perineal skin.

Clinical Correlation of Transcription Factor SOX3 in Cancer: Unveiling Its Role in Tumorigenesis.

Members of the SOX (SRY-related HMG box) family of transcription factors are crucial for embryonic development and cell fate determination. This review investigates the role of SOX3 in cancer, as aberrations in SOX3 expression have been implicated in several cancers, including osteosarcoma, breast, esophageal, endometrial, ovarian, gastric, hepatocellular carcinomas, glioblastoma, and leukemia. These dysregulations modulate key cancer outcomes such as apoptosis, epithelial-mesenchymal transition (EMT), invasion, migration, cell cycle, and proliferation, contributing to cancer development. SOX3 exhibits varied expression patterns correlated with clinicopathological parameters in diverse tumor types. This review aims to elucidate the nuanced role of SOX3 in tumorigenesis, correlating its expression with clinical and pathological characteristics in cancer patients and cellular modelsBy providing a comprehensive exploration of SOX3 involvement in cancer, this review underscores the multifaceted role of SOX3 across distinct tumor types. The complexity uncovered in SOX3 function emphasizes the need for further research to unravel its full potential in cancer therapeutics.

Examining variations in body composition among patients with colorectal cancer according to site and disease stage.

Patients with colorectal cancer (CRC) often exhibit changes in body composition (BC) which are associated with poorer clinical outcomes. Many studies group colon and rectal cancers together, irrespective of staging, potentially affecting assessment and treatment strategies. Our study aimed to compare BC in patients with CRC focusing on tumor location and metastasis presence. A total of 635 individuals were evaluated, with a mean age of 61.8 ± 12.4 years and 50.2% female. The majority had rectal cancer as the primary cancer site (51.0%), and 23.6% had metastatic disease. The first regression model showed tumor site and metastasis as independent factors influencing skeletal muscle (SM), skeletal muscle index (SMI), and visceral adipose tissue variability (all p values < 0.05). The second model, adjusted for BMI, indicated tumor site as the primary factor affecting SMI variations (adjusted R2 = 0.50 p < 0.001), with colon tumors inversely associated with SM (standardized ß - 2.15(- 3.3; - 0.9) p < 0.001). A third model, considering all the confounders from the directed acyclic graphs, was constructed and the found association remained independent. Our findings highlight significant BC variations in patients with CRC, influenced by tumor location and metastases presence, underscoring the need for location-specific assessment in CRC management.

Strength-to-muscle radiodensity: A potential new index for muscle quality.

BACKGROUND & AIMS: Although it is widely recognized that muscle quality significantly influences adverse outcomes in patients with cancer, the precise definition of muscle quality remains elusive. The muscle quality index (MQI), also known as muscle-specific strength, is a relatively recent functional concept of muscle quality. It is obtained through the ratio of muscle strength to muscle mass, but its predictive value in patients with cancer remains unknown. In this study, we explored the prognostic significance of MQI in patients with cancer. Furthermore, we introduce and assess the prognostic potential of a novel muscle quality metric: the strength-to-muscle-radiodensity index (SMRi). METHODS: A secondary analysis was conducted on a prospective cohort study. CT scans were opportunistically used to assess body composition parameters, including skeletal muscle mass (SM in cm2) and muscle radiodensity (SMD in HU) at the third lumbar vertebra (L3). Handgrip strength (HGS) was measured. MQICT was calculated using the ratio of HGS to SM (cm2). SMRi was calculated as the ratio of HGS to SMD (HU). For analysis purposes, low MQICT and SMRi were defined using two approaches: statistical cutoffs associated with survival, and median-based distribution data. RESULTS: A total of 250 patients were included (52.8% females, 52% adults, 20-90 years). Gastrointestinal tumors and stage III-IV were the most frequent diagnosis and stages. SMRi and MQICT were strongly positively correlated (ρ = 0.71 P < 0.001). Individual components of MQICT and SMRi were also positively correlated. Patients with both low MQICT and SMRi had shorter survival (log-rank P = 0.023 and P = 0.003, respectively). When applying median distribution cutoffs, SMRi emerged as the most accurate predictor of mortality (HR adjusted 3.18, 95% CI 1.50 to 6.75, C-index: 0.71), when compared to MQICT (HR adjusted 1.49, 95% CI 0.77 to 2.87, C-index: 0.68). CONCLUSION: This study introduces the concept and potential prognostic significance of the SMRi. The physiological and clinical implications of this new index warrant further investigation across a spectrum of diseases, including cancer.

Periodontal pathogen Aggregatibacter actinomycetemcomitans JP2 correlates with colonic leukocytes decrease and gut microbiome imbalance in mice.

AIM: Evidence suggests that translocation of oral pathogens through the oral-gut axis may induce intestinal dysbiosis. This study aimed to evaluate the impact of a highly leukotoxic Aggregatibacter actinomycetemcomitans (Aa) strain on the gut microbiota, intestinal mucosal integrity and immune system in healthy mice. METHODS: Eight-week-old male C57BL6 mice were divided into control (n = 16) and JP2 groups (n = 19), which received intragastric gavage with PBS and with a suspension of Aa JP2 (HK921), respectively, twice a week for 4 weeks. Colonic lamina propria, fecal material, serum, gingival tissues, and mandibles were obtained for analyses of leukocyte populations, inflammatory mediators, mucosal integrity, alveolar bone loss, and gut microbiota. Differences between groups for these parameters were examined by non-parametric tests. RESULTS: The gut microbial richness and the number of colonic macrophages, neutrophils, and monocytes were significantly lower in Aa JP2-infected mice than in controls (p < .05). In contrast, infected animals showed higher abundance of Clostridiaceae, Lactobacillus taiwanensis, Helicobacter rodentium, higher levels of IL-6 expression in colonic tissues, and higher splenic MPO activity than controls (p < .05). No differences in tight junction expression, serum endotoxin levels, and colonic inflammatory cytokines were observed between groups. Infected animals presented also slightly more alveolar bone loss and gingival IL-6 levels than controls (p < .05). CONCLUSION: Based on this model, intragastric administration of Aa JP2 is associated with changes in the gut ecosystem of healthy hosts, characterized by less live/recruited myeloid cells, enrichment of the gut microbiota with pathobionts and decrease in commensals. Negligible levels of colonic pro-inflammatory cytokines, and no signs of mucosal barrier disruption were related to these changes.

[Correction to the Article "Ophthalmology Census 2021: A Demographic Characterisation of Ophthalmologists in Portugal", Published on Acta Med Port (In Press), https://doi.org/10.20344/amp.20321]. / Errata ao Artigo "Estudo Demográfico da População de Oftalmologistas em Portugal: Censo de Oftalmologia 2021", Publicado em Acta Med Port (In Press), https://doi.org/10.20344/amp.20321.

On page 5, 3rd paragraph, line 7, where it reads, (in red): "(...) considering the international recommendation (1:10 000)8" It should read (in blue): "(...) considering the international recommendation (0.5:10 000)8" Still on page 5, 5th paragraph, line 8, where it reads, (in red): "(...) in the 40 - 50-year age group" It should read (in blue): "(...) below the 40 - 50-year age group" On page 8, key of Table 1, line 5, where it reads, (in red): "1: PORTATA 2021;" It should read (in blue): "1: PORDATA 2021;" Article published with errors: https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/20321.

Na página 5, 3º parágrafo, linha 7, onde se lê, (a vermelho): "(...) considering the international recommendation (1:10 000)8" Deverá ler-se (a azul): "(...) considering the international recommendation (0.5:10 000)8" Ainda na página 5, 5º parágrafo, linha 8, onde se lê, (a vermelho): "(...) in the 40 - 50-year age group" Deverá ler-se (a azul): "(...) below the 40 - 50-year age group" Na página 8, legenda da Tabela 1, linha 5, onde se lê, (a vermelho): "1: PORTATA 2021;" Deverá ler-se (a azul): "1: PORDATA 2021;" Artigo publicado com erros: https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/20321.

Stroke related sarcopenia in individuals with different physical activity levels: A cross-sectional study.

BACKGROUND AND OBJECTIVE: Individuals after stroke are likely to deal with the possible development of sarcopenia and reduced physical activity levels. The purpose of this study was to compare sarcopenia of individuals with chronic stroke who were stratified according to their physical activity levels, and to evaluate the relationship between sarcopenia and physical activity levels. MATERIALS AND METHODS: This cross-sectional study was conducted with individuals after chronic stroke recruited from the general community. Individuals were submitted to sarcopenia screening (SARC-F questionnaire) and assessment of physical activity levels (Human Activity Profile questionnaire) to classify the individuals as impaired, moderately active, and active according to their Adjusted Activity Status (AAS). ANOVA was used to investigate the sarcopenia between groups and Pearson's coefficient to investigate the association among variables. RESULTS: Fifty-four individuals with a mean age of 56 ± 17.4 years were included. Twenty-one percent of the individuals were screened for sarcopenia. Inactive individuals had higher mean scores in the SARC-F (3.6 ± 2.1 points), whereas moderately active and active individuals presented lower mean scores in the same questionnaire, being 1.2 ± 1.1 points and 0.5 ± 0.7 points, respectively. A statistically significant inverse and high association was found between sarcopenia and physical activity levels (r = -0.716; p < 0.01). CONCLUSION: Sarcopenia was found to be higher in individuals after chronic stroke with lower physical activity levels considered inactive when compared to individuals with higher physical activity levels. Furthermore, there was an inverse relationship between sarcopenia and physical activity level in stroke survivors.

Methodology for the induction of myocardial infarction and cardiac function evaluation.

Cardiovascular disease (CVD) is the main cause of death worldwide, with myocardial infarction (MI) being the most prevalent pathology involved in CVD. MI is characterized by a deficiency in oxygen supply to the myocardium, thereby promoting ventricular remodeling of the ischemic and remote zone of the heart. Cardiac remodeling associated with MI could promote the development of heart failure and finally death. For these reasons, it is important to develop animal models that mimic human cardiac disease which could help to identify new mechanisms involved in the pathology and, consequently, develop new therapeutic strategies. We herein describe in detail a protocol for MI induction with low mortality rate (<15%) in rats by ligation of the left anterior descending artery. In addition, we also describe two imaging techniques which allow to evaluate cardiac structure and function-including deformation parameters in rats such as transthoracic echocardiography and cardiac magnetic resonance. This animal model could be useful for acute and chronic studies and for evaluating the potential usefulness of different treatments.

Metastatic cutaneous myxosarcoma in an adult horse.

A 25-year-old mixed-breed equine with separate nodular cutaneous lesions in the right thoracic limb (RTL) and right ventral abdominal region was admitted to a Veterinary Hospital in Belo Horizonte, Minas Gerais. Fine-needle aspiration cytology was performed on the RTL lesion and superficial cervical lymph node, and the results were suggestive of a malignant neoplasm known as myxosarcoma. Due to the unfavorable prognosis, the animal was euthanized. Based on the macroscopic and microscopic findings, the diagnosis of metastatic cutaneous myxosarcoma was confirmed. Although rare, this tumor should be considered as a differential diagnosis for cutaneous neoplasms in this species.

Ophthalmology Census 2021: A Demographic Characterisation of Ophthalmologists in Portugal.

INTRODUCTION: Human resources in ophthalmology have recently received particular attention, and it has been questioned whether there is a sufficient number of workers. The aim of this study was to analyze and characterize Portugal's ophthalmologist population. METHODS: In this descriptive, cross-sectional study, an online questionnaire was sent to all ophthalmologists registered with the Portuguese College of Ophthalmology in December 2021. Information on the following variables was collected and analyzed: demographic factors, professional qualifications, professional activity, weekly professional activity and medium-term plans. RESULTS: Among the 910 registered ophthalmologists, a response rate of 64.7% was achieved. There were 0.9 ophthalmologists for every 10 000 inhabitants, 0.45:10 000 working in the public sector (0.35:10 000 full-time equivalent). Among the respondents, 57.6% were over 50 years old (59.6% male), 97.3% were Portuguese, 46.7% completed their residency in the Lisbon region, 27.3% complemented their programme with additional training, 9.5% had a PhD and approximately 58% lived and worked in large urban centres. Regarding professional activity, 58.5% of the respondents worked in the public sector (4.2% exclusively), while 67.9% worked in different economic sectors. The median number of weekly working hours reported was 45 hours, with those in the public sector reporting 35 hours. Private/social sector work and public sector work accounted for 12 926 hours/week and 10 808 hours/week, respectively. It was found that 31.4% of the respondents provided emergency medical services and that 52.8% performed surgical procedures more than once a week. Looking ahead, 38.7% of the ophthalmologists intended to reduce their workload within the next five years due to family reasons, fatigue and demotivation. The projected rate of retirement or cessation of activity in the next five years was estimated to be 1.7%, while an average of 20 new ophthalmologists are expected to enter the profession annually, resulting in a generational balance of 0.8%. CONCLUSION: While the number of ophthalmologists in Portugal meets the international recommendations, there is a shortage in the public sector and most ophthalmologists work in large urban centres. The number of ophthalmologists in Portugal is expected to be stable for the next five years.

Real-world effectiveness of aromatase inhibitors and fulvestrant in HR+/HER2- advanced breast cancer: a snapshot of the last two years before conventional use of CDK 4/6 inhibitors in a Portuguese institution.

Background: Monotherapy with aromatase inhibitors and fulvestrant were the standard-of-care for hormone receptor-positive (HR+)/human epidermal growth factor receptor-type2 negative (HER2-) advanced breast cancer, before integration of cyclin-dependent kinase 4/6 inhibitors. Effectiveness data is essential for regulatory action, but little is known about real-world use of aromatase inhibitors and fulvestrant. Methods: A retrospective cohort study was conducted resorting to data from a cancer registry to identify adult women with HR+/HER- advanced breast cancer exposed to aromatase inhibitors or fulvestrant (31 May 2017-31 March 2019) at the main oncology hospital in Portugal. Cases were updated with follow-up until death or cut-off (31 March 2021) and pseudoanonymized data extracted. Primary outcome was overall survival (OS) and secondary time to treatment failure (TTF), estimated using survival analysis and compared with published trials. Results: 192 patients were distributed by subgroups according to the medicine. Letrozole: OS 30.8 (95% confidence interval (CI) 20.6-41.4); TTF 11.2 (95%CI 8.7-13.7). Exemestane: OS 22.1 (95%CI 9.7-34.6); TTF 6.0 (95%CI 4.1-7.8). Fulvestrant: OS 21.6 (95%CI 16.5-26.7); TTF 5.6 (95%CI 4.5-6.6). Conclusions: Estimated effectiveness (OS) of letrozole and fulvestrant was, respectively, 3.2-3.5 months lower than reported. The clinical meaning seems uncertain and may be explained a higher proportion of worse prognostic characteristics in patients treated in the real-world.

Assessment of bioactive peptides derived from laminin-111 as prospective breast cancer-targeting agents.

Breast cancer remains a pressing public health issue primarily affecting women. Recent research has spotlighted bioactive peptides derived from laminin-111, implicated in breast tumor development. Remarkably, the sequences IKVAV, YIGSR, and KAFDITYVRLKF from the α1, ß1, and γ1 chains, respectively, have garnered significant attention. This study aims to assess the potential of these radiolabeled peptides as targeting agents for breast cancer. The three peptides were synthesized using the Fmoc strategy, purified via reversed-phase high-performance liquid chromatography (RP-HPLC), and characterized through mass spectrometry. Iodine-131 (131I) radiolabeling was performed using the chloramine T method, exhibiting high radiochemical yield and stability for [131I]I-YIKVAV and [131I]I-YIGSR. Conversely, [131I]I-KAFDITYVRLKF demonstrated low radiochemical yield and stability and was excluded from the biological studies. The lipophilicity of the compounds ranged from - 2.12 to - 1.10. Serum protein binding assay for [131I]I-YIKVAV and [131I]I-YIGSR reached ≅ 48% and ≅ 25%, respectively. Affinity for breast cancer cells was evaluated using MDA-MB-231 and MCF-7 tumor cell lines, indicating the affinity of the radiopeptides with these tumor cells. Ex vivo biodistribution profiles of the radiopeptides were assessed in the MDA-MB-231 breast tumor animal model, revealing tumor tissue accumulation, supported by a high tumor-to-contralateral muscle ratio and autoradiography. These results signify the effective penetration of YIKVAV and YIGSR into tumor tissue. Therefore, the synthesized α1 and ß1 peptide fragments exhibit favorable characteristics as potential breast cancer-targeting agents, promising future exploration as radiopharmaceuticals for breast cancer.