Efficacy, safety of and adherence to adjustable compression wraps in the control phase of breast cancer-related lymphedema: A randomized controlled trial.

OBJECTIVE: To evaluate efficacy, safety, and adherence to using adjustable compression wraps (ACWs) for upper limb volume control in women with breast cancer-related lymphedema. DESIGN AND SETTING: Randomized controlled trial at a reference hospital for breast cancer treatment in Brazil. PARTICIPANTS: Women in control phase of the breast cancer-related lymphedema. INTERVENTIONS: Compared use of ACWs versus compressive mesh. MAIN MEASURES: Evaluated before treatment, at 30 days, and 6 months after initiating therapy. The primary outcome was the change in excess limb volume. Secondary outcomes included adherence, incidence of adverse events, functionality, quality of life, and hand grip. Statistical analysis involved calculating the effect size (ES) with a 95% confidence interval. RESULTS: Were included 71 women with mean excess limb volume of 321.79 mL (±194.98). In the 30-day analysis (Time 1), a reduction of 37.6 mL in volume was observed only in the ACW group (p = .041, ES 0.20), with improved functionality (p = .013, ES 0.22). In the six months analysis (Time 2), the compressive mesh group increased by 2.48% in volume (p = .023, ES 0.26) and demonstrated improvement functionality (p = .036, ES 0.27). Mild adverse events and satisfactory adherence were observed. However, in the intergroup comparison, no statistically significant difference was observed for any evaluated outcome-excess volume, incidence of adverse events, adherence, hand grip, quality of life, and functionality between the groups (p > .05) at both times. CONCLUSIONS: Both compression therapies achieved satisfactory adherence, were safe, effective and equivalent for controlling limb volume in breast cancer-related lymphedema.

Deciphering the needs of patients with hereditary breast and ovarian Cancer in the Process of Genetic Counseling to Inform the Development of a Mobile Support App: a qualitative study in Germany.

Patients with hereditary breast and ovarian cancer (HBOC) are not only concerned about their own health but also about that of their children, grandchildren, and other relatives. Therefore, they have specific needs for information and support. During genetic counseling guidance is provided to HBOC patients and other individuals who may be at risk for familial cancer. The purpose of the study was to identify the needs of HBOC patients during the genetic counseling process that could be addressed by digital solutions. Nine semi-structured qualitative interviews were conducted. Overall, the patients appreciated the personal contact with human geneticists as an especially positive factor in the genetic counseling process. However, patients noted the following needs (1) support in the time following genetic counseling, (2) support before genetic counseling by collecting own and familial medical information, (3) Need for contact options to support services, (4) Need for patient-friendly medical information, (5) Wish for administration-related components in a support app. The results will inform the development of a patient-centered mobile support app.

Genetic counselling legislation and practice in cancer in EU Member States.

BACKGROUND: Somatic and germline genetic alterations are significant drivers of cancer. Increasing integration of new technologies which profile these alterations requires timely, equitable and high-quality genetic counselling to facilitate accurate diagnoses and informed decision-making by patients and their families in preventive and clinical settings. This article aims to provide an overview of genetic counselling legislation and practice across European Union (EU) Member States to serve as a foundation for future European recommendations and action. METHODS: National legislative databases of all 27 Member States were searched using terms relevant to genetic counselling, translated as appropriate. Interviews with relevant experts from each Member State were conducted to validate legislative search results and provide detailed insights into genetic counselling practice in each country. RESULTS: Genetic counselling is included in national legislative documents of 22 of 27 Member States, with substantial variation in legal mechanisms and prescribed details (i.e. the 'who, what, when and where' of counselling). Practice is similarly varied. Workforce capacity (25 of 27 Member States) and genetic literacy (all Member States) were common reported barriers. Recognition and/or better integration of genetic counsellors and updated legislation and were most commonly noted as the 'most important change' which would improve practice. CONCLUSIONS: This review highlights substantial variability in genetic counselling across EU Member States, as well as common barriers notwithstanding this variation. Future recommendations and action should focus on addressing literacy and capacity challenges through legislative, regulatory and/or strategic approaches at EU, national, regional and/or local levels.

Factors delaying non-metastatic breast cancer adjuvant therapy and impact on prognosis in a cohort of Brazilian women.

OBJECTIVE: To identify factors associated with delays in beginning adjuvant therapy and prognosis impacts on non-metastatic breast cancer patients. METHODS: This assessment comprised a prospective cohort study concerning breast cancer patients treated at a public oncology centre. A time interval of ≥60 days between surgery and the beginning of the first adjuvant treatment was categorised as a delay. Factors associated with delays were evaluated through logistic regression analysis and the prognosis effects were assessed by a Cox regression analysis. RESULTS: The median time interval between surgery and the first adjuvant treatment for the 401 women included in this study was of 57.0 days (37.0-93.0). Independent factors associated with delays comprised not presenting an overexpression of the HER-2 protein, not having undergone neoadjuvant chemotherapy, and having undergone chemotherapy or other therapeutic modalities other than hormone therapy and chemotherapy as the first adjuvant treatment. Delays did not affect recurrence, distant metastasis, or death risks. Factors associated with recurrence and distant metastasis risks comprised a clinical staging ≥2B, having undergone neoadjuvant chemotherapy, presenting the luminal molecular subtype B and triple-negative tumours, and having children. Factors associated with death comprised triple-negative molecular tumours and neoadjuvant chemotherapy. CONCLUSION: Delays in beginning adjuvant treatment did not affect the prognosis of non-metastatic breast cancer patients. Clinical and treatment-related factors, on the other hand, were associated with delays, and recurrence, distant metastasis, and death risks.

Assessment of myosteatosis and functionality in pretreatment gynecological cancer patients.

PURPOSE: We aimed to investigate the relationship between pretreatment gynecologic cancer survival and the physical function of patients with myosteatosis. Understanding this relationship prior to treatment would help healthcare providers identify and refer patients with poor muscle quality to an exercise program prior to treatment. METHODS: We conducted a cross-sectional analysis of 73 GC patients. Physical function was quantified using handgrip strength and an adapted version of the Senior Fitness Test (aerobic endurance not included). The EORTC QLC-C30 was used to evaluate general health quality. Myosteatosis (values below the median muscle radiodensity), muscle mass, and adipose tissue variables were calculated from the computed tomography (CT) scan at the third lumbar vertebra using specific software. RESULTS: Seventy patients (50.9 ± 15.2) were included; 41.5% had stage III or IV disease, and 61.4% had cervical cancer. The myosteatosis group was 11.9 years older and showed reduced functioning compared to the normal-radiodensity group. Age and Timed Up and Go (TUG) test results were shown to be the most reliable predictors of muscle radiodensity in pretreatment gynecological patients according to multivariate regression analysis (R2 = 0.314). CONCLUSION: Gynecological healthcare professionals should be aware that prompt exercise programs might be especially beneficial for older patients with reduced TUG performance to preserve muscle function and quality.

Epidemiological profile of neuroendocrine tumors in adults in Brazil.

Objective: Neuroendocrine tumors (NETs) are a set of diseases that originate from neuroendocrine cells, which comprises a diffuse endocrine system present in various organs of the body. These tumors are more frequent in the gastrointestinal tract (70%) and the bronchopulmonary system (20%-30%). A NET incidence rate of 1-5 per 100,000 inhabitants has been estimated for several European countries and the USA employing 20 years of data. However, no comprehensive studies on this rare neoplasm are available in Brazil. In this context, the aim of this study was to characterize the epidemiological NET profile in the country. Materials and methods: This is a retrospective descriptive observational study based on data from Hospital Cancer Records available at the Brazilian National Cancer Institute and the São Paulo Oncocentro Foundation. Demographic, clinical and treatmentrelated variables were analyzed from selected cases employing descriptive statistics. Results and Conclusion: A total of 15,859 cases were identified, most occurring in males (53.4%) and in individuals under 65 years old (63.3%). Small cell carcinoma was the most frequent histological type (46.7%). Bronchopulmonary tumors were the most frequent NETs, followed by pancreatic tumors, with cases mostly concentrated in high complexity centers in the Brazilian Southeast and treated mainly with surgery and chemotherapy, with over half of the patients diagnosed in advanced stages of the disease.

Compressive taping to prevent postmastectomy seroma: patient adherence and satisfaction.

OBJECTIVE: Evaluate patient adherence and satisfaction concerning postmastectomy compressive taping. METHODS: This comprises a preintervention and postintervention study carried out with women ≥18 years old who underwent taping during the first 7 postoperative days at the Cancer Hospital III/National Cancer Institute. Good adherence was considered as taping maintenance for 7 days. Satisfaction levels were classified as satisfied and dissatisfied. RESULTS: A total of 124 women with a mean age of 56.54 (±11.24) were included in the study. Most lived without a partner (58.1%), had more than 8 years of study (59.7%), referred to themselves as white (68.5%) and considered their health status to be good or very good (69.4%). Regarding treatment adherence, 90.3% patients displayed adherence. Patients with no bullous lesions were more likely to adhere to taping (OR 7.00; 95% CI 1.98 to 24.74; p=0.003). Regarding satisfaction, 78.2% of the patients felt satisfied. The absence of local discomfort (OR 4.51; 95% CI 1.73 to 11.74; p=0.002) and non-existence of self-reported oedema (OR 5.81; 95% CI 1.81 to 18, 66; p=0.003) were associated with greater patient satisfaction. CONCLUSION: Patients exhibited good adherence and felt very satisfied with the use of postmastectomy compressive taping. TRIAL REGISTRATION NUMBER: NCT04471142.

An artificial intelligence-assisted clinical framework to facilitate diagnostics and translational discovery in hematologic neoplasia.

BACKGROUND: The increasing volume and intricacy of sequencing data, along with other clinical and diagnostic data, like drug responses and measurable residual disease, creates challenges for efficient clinical comprehension and interpretation. Using paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) as a use case, we present an artificial intelligence (AI)-assisted clinical framework clinALL that integrates genomic and clinical data into a user-friendly interface to support routine diagnostics and reveal translational insights for hematologic neoplasia. METHODS: We performed targeted RNA sequencing in 1365 cases with haematological neoplasms, primarily paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) from the AIEOP-BFM ALL study. We carried out fluorescence in situ hybridization (FISH), karyotyping and arrayCGH as part of the routine diagnostics. The analysis results of these assays as well as additional clinical information were integrated into an interactive web interface using Bokeh, where the main graph is based on Uniform Manifold Approximation and Projection (UMAP) analysis of the gene expression data. At the backend of the clinALL, we built both shallow machine learning models and a deep neural network using Scikit-learn and PyTorch respectively. FINDINGS: By applying clinALL, 78% of undetermined patients under the current diagnostic protocol were stratified, and ambiguous cases were investigated. Translational insights were discovered, including IKZF1plus status dependent subpopulations of BCR::ABL1 positive patients, and a subpopulation within ETV6::RUNX1 positive patients that has a high relapse frequency. Our best machine learning models, LDA and PASNET-like neural network models, achieve F1 scores above 97% in predicting patients' subgroups. INTERPRETATION: An AI-assisted clinical framework that integrates both genomic and clinical data can take full advantage of the available data, improve point-of-care decision-making and reveal clinically relevant insights promptly. Such a lightweight and easily transferable framework works for both whole transcriptome data as well as the cost-effective targeted RNA-seq, enabling efficient and equitable delivery of personalized medicine in small clinics in developing countries. FUNDING: German Ministry of Education and Research (BMBF), German Research Foundation (DFG) and Foundation for Polish Science.

The IL-7R antagonist lusvertikimab reduces leukemic burden in xenograft ALL via antibody-dependent cellular phagocytosis.

ABSTRACT: Acute lymphoblastic leukemia (ALL) arises from the uncontrolled proliferation of B-cell precursors (BCP-ALL) or T cells (T-ALL). Current treatment protocols obtain high cure rates in children but are based on toxic polychemotherapy. Novel therapies are urgently needed, especially in relapsed/refractory (R/R) disease, high-risk (HR) leukemias and T-ALL, in which immunotherapy approaches remain scarce. Although the interleukin-7 receptor (IL-7R) plays a pivotal role in ALL development, no IL-7R-targeting immunotherapy has yet reached clinical application in ALL. The IL-7Rα chain (CD127)-targeting IgG4 antibody lusvertikimab (LUSV; formerly OSE-127) is a full antagonist of the IL-7R pathway, showing a good safety profile in healthy volunteers. Here, we show that ∼85% of ALL cases express surface CD127. We demonstrate significant in vivo efficacy of LUSV immunotherapy in a heterogeneous cohort of BCP- and T-ALL patient-derived xenografts (PDX) in minimal residual disease (MRD) and overt leukemia models, including R/R and HR leukemias. Importantly, LUSV was particularly effective when combined with polychemotherapy in a phase 2-like PDX study with CD127high samples leading to MRD-negativity in >50% of mice treated with combination therapy. Mechanistically, LUSV targeted ALL cells via a dual mode of action comprising direct IL-7R antagonistic activity and induction of macrophage-mediated antibody-dependent cellular phagocytosis (ADCP). LUSV-mediated in vitro ADCP levels significantly correlated with CD127 expression levels and the reduction of leukemia burden upon treatment of PDX animals in vivo. Altogether, through its dual mode of action and good safety profile, LUSV may represent a novel immunotherapy option for any CD127+ ALL, particularly in combination with standard-of-care polychemotherapy.

The landscape of cytogenetic and molecular genetic methods in diagnostics for hematologic neoplasia.

Improvements made during the last decades in the management of patients with hematologic neoplasia have resulted in increase of overall survival. These advancements have become possible through progress in our understanding of genetic basis of different hematologic malignancies and their role in the current risk-adapted treatment protocols. In this review, we provide an overview of current cytogenetic and molecular genetic methods, commonly used in the genetic characterization of hematologic malignancies, describe the current developments in the cytogenetic and molecular diagnostics, and give an outlook into their future development. Furthermore, we give a brief overview of the most important public databases and guidelines for sequence variant interpretation.

BRCA1, BRCA2, and TP53 germline and somatic variants and clinicopathological characteristics of Brazilian patients with epithelial ovarian cancer.

BACKGROUND: Approximately 3/4 of ovarian cancers are diagnosed in advanced stages, with the high-grade epithelial ovarian carcinoma (EOC) accounting for 90% of the cases. EOC present high genomic instability and somatic loss-of-function variants in genes associated with homologous recombination mutational repair pathway (HR), such as BRCA1 and BRCA2, and in TP53. The identification of germline variants in HR genes in EOC is relevant for treatment of platinum resistant tumors and relapsed tumors with therapies based in synthetic lethality such as PARP inhibitors. Patients with somatic variants in HR genes may also benefit from these therapies. In this work was analyzed the frequency of somatic variants in BRCA1, BRCA2, and TP53 in an EOC cohort of Brazilian patients, estimating the proportion of variants in tumoral tissue and their association with progression-free survival and overall survival. METHODS: The study was conducted with paired blood/tumor samples from 56 patients. Germline and tumoral sequences of BRCA1, BRCA2, and TP53 were obtained by massive parallel sequencing. The HaplotypeCaller method was used for calling germline variants, and somatic variants were called with Mutect2. RESULTS: A total of 26 germline variants were found, and seven patients presented germline pathogenic or likely pathogenic variants in BRCA1 or BRCA2. The analysis of tumoral tissue identified 52 somatic variants in 41 patients, being 43 somatic variants affecting or likely affecting protein functionality. Survival analyses showed that tumor staging was associated with overall survival (OS), while the presence of somatic mutation in TP53 was not associated with OS or progression-free survival. CONCLUSION: Frequency of pathogenic or likely pathogenic germline variants in BRCA1 and BRCA2 (12.5%) was lower in comparison with other studies. TP53 was the most altered gene in tumors, with 62.5% presenting likely non-functional or non-functional somatic variants, while eight 14.2% presented likely non-functional or non-functional somatic variants in BRCA1 or BRCA2.

SNUPN deficiency causes a recessive muscular dystrophy due to RNA mis-splicing and ECM dysregulation.

SNURPORTIN-1, encoded by SNUPN, plays a central role in the nuclear import of spliceosomal small nuclear ribonucleoproteins. However, its physiological function remains unexplored. In this study, we investigate 18 children from 15 unrelated families who present with atypical muscular dystrophy and neurological defects. Nine hypomorphic SNUPN biallelic variants, predominantly clustered in the last coding exon, are ascertained to segregate with the disease. We demonstrate that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients' primary fibroblasts and CRISPR/Cas9-mediated mutant cell lines. Additionally, mutant nuclei exhibit defective spliceosomal maturation and breakdown of Cajal bodies. Transcriptome analyses reveal splicing and mRNA expression dysregulation, particularly in sarcolemmal components, causing disruption of cytoskeletal organization in mutant cells and patient muscle tissues. Our findings establish SNUPN deficiency as the genetic etiology of a previously unrecognized subtype of muscular dystrophy and provide robust evidence of the role of SPN1 for muscle homeostasis.

Efficacy of supervised exercise on sleep of women who survived breast cancer: a systematic review with meta-analysis.

PURPOSE: To analyze the efficacy of supervised exercise (SE) compared with control protocols on sleep parameters of women who survived breast cancer. METHODS: This systematic review with meta-analysis searched studies using the following electronic databases: PubMed, Scopus, Physiotherapy Evidence Database (PEDro), Cochrane Library, and EMBASE. The PEDro scale assessed the bias risk, and the study protocol was registered in the PROSPERO (no. CRD42023420894). RESULTS: Of 3,566 identified studies, 13 randomized clinical trials involving 847 women diagnosed with breast cancer were included. Interventions consisted of SE in an outpatient setting (62%) or combined protocols with supervised and home exercises. Most interventions (85%) used multicomponent protocols with aerobic and resistance exercises. Usual care and health education were the most reported controls. SE decreased the sleep disturbance score (- 31.61 [95% confidence interval = - 39.40 to - 23.83]) of the European Organisation for Research and Treatment of Cancer quality of life questionnaire and daytime dysfunction score (- 0.41 [95% confidence interval = - 0.73 to - 0.09]) of the Pittsburgh Sleep Quality Index (PSQI). Also, SE presented a tendency to improve the self-reported sleep quality score of the PSQI (p = 0.06). CONCLUSION: SE increased the subjective sleep quality and immobility time and decreased sleep disturbance and daytime dysfunction symptoms in women who survived breast cancer. Most SE protocols were multicomponent, with aerobic and resistance exercises ranging from moderate to high intensity. IMPLICATIONS FOR CANCER SURVIVORS: Supervised exercise may improve sleep quality and reduce symptoms of sleep disorders, contributing to survival outcomes.

Optical genome mapping identifies structural variants in potentially new cancer predisposition candidate genes in pediatric cancer patients.

Genetic predisposition is one of the major risk factors for pediatric cancer, with ~10% of children being carriers of a predisposing germline alteration. It is likely that this is the tip of the iceberg and many children are underdiagnosed, as most of the analysis focuses on single or short nucleotide variants, not considering the full spectrum of DNA alterations. Hence, we applied optical genome mapping (OGM) to our cohort of 34 pediatric cancer patients to perform an unbiased germline screening and analyze the frequency of structural variants (SVs) and their impact on cancer predisposition. All children were clinically highly suspicious for germline alterations (concomitant conditions or congenital anomalies, positive family cancer history, particular cancer type, synchronous or metachronous tumors), but whole exome sequencing (WES) had failed to detect pathogenic variants in cancer predisposing genes. OGM detected a median of 49 rare SVs (range 27-149) per patient. By analysis of 18 patient-parent trios, we identified three de novo SVs. Moreover, we discovered a likely pathogenic deletion of exon 3 in the known cancer predisposition gene BRCA2, and identified a duplication in RPA1, which might represent a new cancer predisposition gene. We conclude that optical genome mapping is a suitable tool for detecting potentially predisposing SVs in addition to WES in pediatric cancer patients.

Treatment outcomes of childhood PICALM::MLLT10 acute leukaemias.

The prognostic impact of PICALM::MLLT10 status in childhood leukaemia is not well described. Ten International Berlin Frankfurt Münster-affiliated study groups and the Children's Oncology Group collaborated in this multicentre retrospective study. The presence of the PICALM::MLLT10 fusion gene was confirmed by fluorescence in situ hybridization and/or RNA sequencing at participating sites. Ninety-eight children met the study criteria. T-cell acute lymphoblastic leukaemia (T-ALL) and acute myeloid leukaemia (AML) predominated 55 (56%) and 39 (40%) patients, respectively. Most patients received a chemotherapy regimen per their disease phenotype: 58% received an ALL regimen, 40% an AML regimen and 1% a hybrid regimen. Outcomes for children with PICALM::MLLT10 ALL were reasonable: 5-year event-free survival (EFS) 67% and 5-year overall survival (OS) 76%, but children with PICALM::MLLT10 AML had poor outcomes: 5-year EFS 22% and 5-year OS 26%. Haematopoietic stem cell transplant (HSCT) did not result in a significant improvement in outcomes for PICALM::MLLT10 AML: 5-year EFS 20% for those who received HSCT versus 23% for those who did not (p = 0.6) and 5-year OS 37% versus 36% (p = 0.7). In summary, this study confirms that PICALM::MLLT10 AML is associated with a dismal prognosis and patients cannot be salvaged with HSCT; exploration of novel therapeutic options is warranted.

Spontaneous remission and loss of monosomy 7: a window of opportunity for young children with SAMD9L syndrome.

Monosomy 7 is the most common cytogenetic abnormality in pediatric myelodysplastic syndrome (MDS) and associated with a high risk of disease progression. However, in young children, spontaneous loss of monosomy 7 with concomitant hematologic recovery has been described, especially in the presence of germline mutations in SAMD9 and SAMD9L genes. Here, we report on our experience of close surveillance instead of upfront hematopoietic stem cell transplantation (HSCT) in seven patients diagnosed with SAMD9L syndrome and monosomy 7 at a median age of 0.6 years (range, 0.4-2.9). Within 14 months from diagnosis, three children experienced spontaneous hematological remission accompanied by a decrease in monosomy 7 clone size. Subclones with somatic SAMD9L mutations in cis were identified in five patients, three of whom attained hematological remission. Two patients acquired RUNX1 and EZH2 mutations during the observation period, of whom one progressed to myelodysplastic syndrome with excess of blasts (MDS-EB). Four patients underwent allogeneic HSCT at a median time of 26 months (range, 14-40) from diagnosis for MDSEB, necrotizing granulomatous lymphadenitis, persistent monosomy 7, and severe neutropenia. At last follow-up, six patients were alive, while one passed away due to transplant-related causes. These data confirm previous observations that monosomy 7 can be transient in young children with SAMD9L syndrome. However, they also indicate that delaying HSCT poses a substantial risk of severe infection and disease progression. Finally, surveillance of patients with SAMD9L syndrome and monosomy 7 is critical to define the evolving genetic landscape and to determine the appropriate timing of HSCT (clinicaltrials gov. Identifier: NCT00662090).

Further delineation of the rare GDACCF (global developmental delay, absent or hypoplastic corpus callosum, dysmorphic facies syndrome): genotype and phenotype of 22 patients with ZNF148 mutations.

BACKGROUND: Pathogenic variants in the zinc finger protein coding genes are rare causes of intellectual disability and congenital malformations. Mutations in the ZNF148 gene causing GDACCF syndrome (global developmental delay, absent or hypoplastic corpus callosum, dysmorphic facies; MIM #617260) have been reported in five individuals so far. METHODS: As a result of an international collaboration using GeneMatcher Phenome Central Repository and personal communications, here we describe the clinical and molecular genetic characteristics of 22 previously unreported individuals. RESULTS: The core clinical phenotype is characterised by developmental delay particularly in the domain of speech development, postnatal growth retardation, microcephaly and facial dysmorphism. Corpus callosum abnormalities appear less frequently than suggested by previous observations. The identified mutations concerned nonsense or frameshift variants that were mainly located in the last exon of the ZNF148 gene. Heterozygous deletion including the entire ZNF148 gene was found in only one case. Most mutations occurred de novo, but were inherited from an affected parent in two families. CONCLUSION: The GDACCF syndrome is clinically diverse, and a genotype-first approach, that is, exome sequencing is recommended for establishing a genetic diagnosis rather than a phenotype-first approach. However, the syndrome may be suspected based on some recurrent, recognisable features. Corpus callosum anomalies were not as constant as previously suggested, we therefore recommend to replace the term 'GDACCF syndrome' with 'ZNF148-related neurodevelopmental disorder'.

Multilamellated Basement Membranes in the Capillary Network of Alveolar Capillary Dysplasia.

A minimal diffusion barrier is key to the pulmonary gas exchange. In alveolar capillary dysplasia (ACD), a rare genetically driven disease of early infancy, this crucial fibrovascular interface is compromised while the underlying pathophysiology is insufficiently understood. Recent in-depth analyses of vascular alterations in adult lung disease encouraged researchers to extend these studies to ACD and compare the changes of the microvasculature. Lung tissue samples of children with ACD (n = 12), adults with non-specific interstitial pneumonia (n = 12), and controls (n = 20) were studied using transmission electron microscopy, single-gene sequencing, immunostaining, exome sequencing, and broad transcriptome profiling. In ACD, pulmonary capillary basement membranes were hypertrophied, thickened, and multilamellated. Transcriptome profiling revealed increased CDH5, COL4A1, COL15A1, PTK2B, and FN1 and decreased VIT expression, confirmed by immunohistochemistry. In contrast, non-specific interstitial pneumonia samples showed a regular basement membrane architecture with preserved VIT expression but also increased COL15A1+ vessels. This study provides insight into the ultrastructure and pathophysiology of ACD. The lack of normally developed lung capillaries appeared to cause a replacement by COL15A1+ vessels, a mechanism recently described in interstitial lung disease. The VIT loss and FN1 overexpression might contribute to the unique appearance of basement membranes in ACD. Future studies are needed to explore the therapeutic potential of down-regulating the expression of FN1 and balancing VIT deficiency.

Epidemiological profile of neuroendocrine tumors in adults in Brazil

ABSTRACT Objective: Neuroendocrine tumors (NETs) are a set of diseases that originate from neuroendocrine cells, which comprises a diffuse endocrine system present in various organs of the body. These tumors are more frequent in the gastrointestinal tract (70%) and the bronchopulmonary system (20%-30%). A NET incidence rate of 1-5 per 100,000 inhabitants has been estimated for several European countries and the USA employing 20 years of data. However, no comprehensive studies on this rare neoplasm are available in Brazil. In this context, the aim of this study was to characterize the epidemiological NET profile in the country. Material and methods: This is a retrospective descriptive observational study based on data from Hospital Cancer Records available at the Brazilian National Cancer Institute and the São Paulo Oncocentro Foundation. Demographic, clinical and treatment-related variables were analyzed from selected cases employing descriptive statistics. Results and Conclusion: A total of 15,859 cases were identified, most occurring in males (53.4%) and in individuals under 65 years old (63.3%). Small cell carcinoma was the most frequent histological type (46.7%). Bronchopulmonary tumors were the most frequent NETs, followed by pancreatic tumors, with cases mostly concentrated in high complexity centers in the Brazilian Southeast and treated mainly with surgery and chemotherapy, with over half of the patients diagnosed in advanced stages of the disease.