Health care accessibility and mobility in breast cancer: a Latin American perspective.

BACKGROUND: Latin America (LATAM) encompasses a vast region with diverse populations. Despite publicly funded health care systems providing universal coverage, significant socioeconomic and ethno-racial disparities persist in health care access across the region. Breast cancer (BC) incidence and mortality rates in Brazil are comparable to those in other LATAM countries, supporting the relevance of Brazilian data, with Brazil's health care policies and expenditures often serving as models for neighboring countries. We evaluated the impact of mobility on oncological outcomes in LATAM by analyzing studies of patients with BC reporting commuting routes or travel distances to receive treatment or diagnosis. METHODS: We searched MEDLINE (PubMed), Embase, Cochrane CENTRAL, LILACS, and Google Scholar databases. Studies eligible for inclusion were randomized controlled trials and observational studies of patients with BC published in English, Portuguese, or Spanish and conducted in LATAM. The primary outcome was the impact of mobility or travel distance on oncological outcomes. Secondary outcomes included factors related to mobility barriers and access to health services. For studies meeting eligibility, relevant data were extracted using standardized forms. Risk of bias was assessed using the Newcastle-Ottawa Scale. Quantitative and qualitative evidence synthesis focused on estimating travel distances based on available data. Heterogeneity across distance traveled or travel time was addressed by converting reported travel time to kilometers traveled and estimating distances for unspecified locations. RESULTS: Of 1142 records identified, 14 were included (12 from Brazil, 1 from Mexico, and 1 from Argentina). Meta-analysis revealed an average travel distance of 77.8 km (95% CI, 49.1-106.48) to access BC-related diagnostic or therapeutic resources. Nonetheless, this average fails to precisely encapsulate the distinct characteristics of each region, where notable variations persist in travel distance, ranging from 88 km in the South to 448 km in the North. CONCLUSION: The influence of mobility and travel distance on access to BC care is multifaceted and should consider the complex interplay of geographic barriers, sociodemographic factors, health system issues, and policy-related challenges. Further research is needed to comprehensively understand the variables impacting access to health services, particularly in LATAM countries, where the challenges women face during treatment remain understudied. TRIAL REGISTRATION: CRD42023446936.

Mitochondria dynamism: of shape, transport and cell migration.

Mitochondria are highly dynamic and functionally versatile organelles that continuously fragment and fuse in response to different physiological needs of the cell. The list of proteins that strictly regulate the morphology of these organelles is constantly growing, adding new players every day and new pieces to the comprehension and elucidation of this complex machinery. The structural complexity of mitochondria is only paralled by their functional versatility. Indeed, changes in mitochondria shape play critical roles in vertebrate development programmed cell death and in various processes of normal cell physiology, such as calcium signaling, reactive oxygen species production, and lifespan. Here, we present the latest findings on the regulation of mitochondrial dynamics and some of their physiological roles, focusing on cell migration. In cells where migration represents a crucial function in their physiology, such as T and tumoral metastatic cells, mitochondria need to be fragmented and recruited to specific subcellular regions to make movement possible. In depth analysis of this role of mitochondrial dynamics should help in identifying potential targeted therapy against cancer or in improving the immune system's efficiency.

Quality of life in children and adolescents with hemophilia A: A systematic review and meta-analysis.

Background: Various instruments have been used to assess health-related quality of life (HRQoL) in children and adolescents with hemophilia A. Objective: We systematically reviewed the literature to summarize HRQoL measurement instruments and outcomes in this population. Methods: MEDLINE, Embase, Cochrane CENTRAL, and LILACS databases were searched. Studies published from 2010 to 2021, reporting HRQoL assessed by generic or hemophilia-specific instruments in individuals aged 0 to 18 years were included. Two independent reviewers performed screening, selection, and data abstraction. Data were meta-analyzed using the generic inverse variance method with the random-effects model for single-arm studies reporting instrument-specific mean total HRQoL scores. Prespecified subgroup meta-analyses were performed. Heterogeneity among studies was assessed using the I 2 statistic. Results: Six instruments were identified in 29 studies meeting the following inclusion criteria: 4 generic instruments (PedsQL [5 studies], EQ-5D-3L [3 studies], KIDSCREEN-52 [1 study], and KINDL [1 study]) and 2 hemophilia-specific instruments (Haemo-QoL [17 studies] and CHO-KLAT [3 studies]). The overall risk of bias was moderate to low. There was a substantial variability in the primary outcome (mean total HRQoL score) among studies using the same instrument (Haemo-QoL), with scores ranging from 24.10 to 89.58 on a scale from 0 to 100 (higher scores indicating higher HRQoL). Meta-regression with 14 studies using the Haemo-QoL questionnaire demonstrated that 79.34% (R 2 ) of the observed 94.67% total heterogeneity (I 2 ) was explained by the proportion of patients receiving effective prophylactic treatment. Conclusion: HRQoL assessment in young people with hemophilia A is heterogeneous and context specific. The proportion of patients on effective prophylactic treatment is positively correlated with HRQoL. The review protocol was registered prospectively with PROSPERO (CRD42021235453).

Accuracy of Physicians in Differentiating Type 1 and Type 2 Myocardial Infarction Based on Clinical Information.

BACKGROUND: Physicians commonly judge whether a myocardial infarction (MI) is type 1 (thrombotic) vs type 2 (supply/demand mismatch) based on clinical information. Little is known about the accuracy of physicians' clinical judgement in this regard. We aimed to determine the accuracy of physicians' judgement in the classification of type 1 vs type 2 MI in perioperative and nonoperative settings. METHODS: We performed an online survey using cases from the Optical Coherence Tomographic Imaging of Thrombus (OPTIMUS) Study, which investigated the prevalence of a culprit lesion thrombus based on intracoronary optical coherence tomography (OCT) in patients experiencing MI. Four MI cases, 2 perioperative and 2 nonoperative, were selected randomly, stratified by etiology. Physicians were provided with the patient's medical history, laboratory parameters, and electrocardiograms. Physicians did not have access to intracoronary OCT results. The primary outcome was the accuracy of physicians' judgement of MI etiology, measured as raw agreement between physicians and intracoronary OCT findings. Fleiss' kappa and Gwet's AC1 were calculated to correct for chance. RESULTS: The response rate was 57% (308 of 536). Respondents were 62% male; median age was 45 years (standard deviation ± 11); 45% had been in practice for > 15 years. Respondents' overall accuracy for MI etiology was 60% (95% confidence interval [CI] 57%-63%), including 63% (95% CI 60%-68%) for nonoperative cases, and 56% (95% CI 52%-60%) for perioperative cases. Overall chance-corrected agreement was poor (kappa = 0.05), consistent across specialties and clinical scenarios. CONCLUSIONS: Physician accuracy in determining MI etiology based on clinical information is poor. Physicians should consider results from other testing, such as invasive coronary angiography, when determining MI etiology.

CONTEXTE: Les médecins déterminent généralement s'ils sont en présence d'un infarctus du myocarde (IM) de type 1 (thrombotique) ou de type 2 (demande accrue ou apport réduit en oxygène) sur la base des renseignements cliniques. On en sait cependant très peu au sujet de la justesse du jugement clinique des médecins à cet égard. Nous avons donc cherché à déterminer si les médecins réussissent à distinguer correctement les IM de type 1 et de type 2 dans les contextes périopératoire et non opératoire. MÉTHODOLOGIE: Nous avons mené une enquête en ligne en utilisant les cas de l'étude OPTIMUS ( Op tical Coherence T omographic Im aging of Thromb us ), qui avait évalué la prévalence des lésions causant un thrombus au moyen de la tomographie par cohérence optique (TCO) endocoronaire chez les patients subissant un IM. Nous avons choisi au hasard quatre cas d'IM stratifiés en fonction de leur cause : deux cas en contexte périopératoire et deux cas en contexte non opératoire. Les médecins avaient accès aux antécédents médicaux, aux résultats des analyses de laboratoire et aux électrocardiogrammes des patients, mais pas aux résultats de la TCO endocoronaire. Le principal paramètre d'évaluation était la justesse du jugement du médecin concernant la cause de l'IM, mesurée en fonction de la concordance approximative entre le jugement du médecin et les observations à la TCO endocoronaire. Les coefficients de concordance kappa de Fleiss et AC1 de Gwet ont servi à corriger pour le hasard. RÉSULTATS: Le taux de réponse était de 57 % (308 sur 536). Des participants, 62 % étaient des hommes et 45 % exerçaient depuis plus de 15 ans; l'âge médian était de 45 ans (écart-type : ± 11). La justesse globale avec laquelle les répondants ont déterminé la cause des IM était de 60 % (intervalle de confiance [IC] à 95 % : 57-63 %) : 63 % (IC à 95 % : 60-68 %) dans le cas des IM en contexte non opératoire et 56 % (IC à 95 % : 52-60 %) dans le cas des IM en contexte périopératoire. La concordance globale corrigée pour le hasard était faible (kappa = 0,05) et demeurait constante, sans égard au domaine de spécialité ou au scénario clinique. CONCLUSIONS: La justesse du jugement des médecins évaluant la cause d'un IM en fonction des renseignements cliniques est faible. Les médecins devraient envisager de recourir à des tests additionnels, y compris la coronarographie invasive, avant de déterminer la cause d'un IM.

Comparative Study of the Osteointegration of Irradiated and Non-irradiated Bone Grafts Used in Patients with Revision Hip Arthroplasty.

Objective To evaluate and compare the osteointegration of irradiated and non-irradiated frozen bone grafts used in 21 patients undergoing revision hip arthroplasty procedures with the Exeter technique. Methods A retrospective study of 21 patients undergoing revision hip arthroplasty with the Exeter technique using bone tissues treated or not with gamma radiation between 2013 and 2014. The patients were divided into two groups according to the use of grafts treated or not with ionizing radiation (gamma rays); as such, these groups were classified as irradiated or non-irradiated. The osteointegration results determined by radiographic analysis of these grafts were compared in the postoperative period of 6 and 12 months. Results Comparing the graft osteointegration in all patients at 6 and 12 months postoperatively, we noticed a significant difference in the radiographic evaluations in this period ( p = 0.031). Out of the patients studied, 7 were from the irradiated group, and 14 belonged to the non-irradiated group. No statistically significant differences were observed ( p = 0.804) regarding osteointegration when we compared the irradiated and non-irradiated groups. Conclusion There was no significant difference in the use of irradiated or non-irradiated grafts in revision hip arthroplasty procedures with the Exeter technique.

Effects of ionizing radiation on proteins in lyophilized or frozen demineralized human bone.

OBJECTIVE: The aim was to study the effects of application of ionizing radiation (gamma and electrons) as sterilizing agents at doses of 15 kGy, 25 kGy and 50 kGy, on lyophilized or frozen demineralized bone tissue for use in transplants. METHODS: Five human femoral diaphyses from different donors of musculoskeletal tissue were demineralized and preserved as lyophilized or frozen at -80 °C. The samples were divided into two groups: non-irradiated (control) and irradiated by means of gamma rays or an electron beam. The bone proteins were extracted and used to determine the concentrations of total protein and BMP 2 and 7. RESULTS: Decreases in total protein and BMP 2 and 7 concentrations were observed. The decreases in total protein concentrations, in comparison with the respective control groups, were significant in the lyophilized and frozen samples that were irradiated at a dose of 50 kGy of gamma radiation and electron beam, with reductions of more than 30%. Significant decreases in the levels of BMP 2 and 7 were also observed at higher doses and especially through use of the electron beam. CONCLUSION: The reductions in the concentrations of total proteins and osteoinductive proteins (BMP 2 and 7) were related to the radiation dose, i.e. they increased with higher doses of ionizing radiation type and the type of bone preservation. The largest reductions in concentrations were observed in the bones irradiated by means of an electron beam and at a dose of 50 kGy. However, this type of radiation and this high dose are not usual practices for sterilization of bone tissue.

OBJETIVO: Estudar os efeitos da aplicação das radiações ionizantes (gama e elétrons) como agentes esterilizantes, nas doses de 15 kGy, 25 kGy e 50 kGy, nos tecidos ósseos desmineralizados congelados e liofilizados para uso em transplantes. MÉTODOS: Cinco diáfises femorais humanas de doadores distintos de tecidos musculoesqueléticos foram desmineralizadas e preservadas como liofilizadas ou congeladas a −80 °C. As amostras foram divididas em grupos não irradiados (controle) e irradiados por raios gama ou feixe de elétrons. As proteínas ósseas foram extraídas e dosadas as concentrações de proteínas totais, BMP 2 e 7. RESULTADOS: Foi observada diminuição das concentrações de proteínas totais e BMP 2 e 7. A diminuição das concentrações de proteínas totais, quando comparada com o respectivo controle, foi significativa nos grupos de amostras liofilizadas e congeladas e irradiadas na dose de 50 kGy por radiação gama e feixe de elétrons com redução superiores a 30%. A diminuição significativa nas concentrações das BMP 2 e 7 também foi observada nas maiores doses e principalmente por feixe de elétrons. CONCLUSÃO: As reduções nas concentrações das proteínas totais e em proteínas osteoindutoras (BMP 2 e 7) foram relacionadas à dose de radiação, ou seja, aumentam com maiores doses, tipo de radiação ionizante e ao tipo de preservação dos ossos. As maiores reduções das concentrações foram observadas nos ossos irradiados por feixe de elétrons e na dose de 50 kGy. Porém esse tipo de radiação e essa alta dose não são práticas usuais para a esterilização dos tecidos ósseos.

Mitochondrial D310 D-Loop instability and histological subtypes in radiation-induced cutaneous basal cell carcinomas.

BACKGROUND: Basal cell carcinoma (BCC) is the most frequent skin cancer. An elevated prevalence of BCC has been associated with radiation, namely after the Tinea capitis epilation treatment, being these tumors described as more aggressive. Mitochondrial DNA (mtDNA) mutations have been reported in many human tumors, but their occurrence in BCC is poorly documented. OBJECTIVE: The purpose of this work was to evaluate BCC histological subtypes in individuals subjected to X-ray epilation for Tinea capitis treatment when compared to non-irradiated patients. Moreover we also wanted to evaluate mitochondrial D-Loop instability in both groups of BCCs in order to compare the frequency of D-Loop mutations in post-irradiation BCC versus sporadic BCC. METHODS: 228 histological specimens corresponding to BCCs from 75 irradiated patients and 60 non-irradiated patients were re-evaluated for histological subtype. Subsequently, we sequenced the D-Loop 310 repeat in blood, oral mucosa, tumor lesions and, whenever available, non-tumoral adjacent tissue from these patients. RESULTS: The infiltrative subtype of BCC, considered to be more aggressive, was significantly more frequent in irradiated patients. BCC D-Loop D310 mutation rate was significantly higher in irradiated BCCs than in the non-irradiated ones. Moreover, it was associated with a higher irradiation dose. The presence of mtDNA heteroplasmy in patients' blood was associated with a higher mutation rate in the BCCs suggesting that a more unstable genotype could predispose to mtDNA somatic mutation. CONCLUSIONS: Our results suggest that radiation-induced BCCs may be considered to be more aggressive tumors. Further studies are needed to clarify the role of mtDNA D-Loop mutations in tumors from irradiated patients.