Seasonality of the incidence of bronchiolitis in infants — Brazil, 2016-2022: An interrupted time-series analysis / Sazonalidade da incidência de bronquiolite em lactentes — Brasil, 2016-2022: Uma análise de série temporal interrompida

ABSTRACT Objective: To evaluate the seasonality of acute bronchiolitis in Brazil during the 2020-2022 season and compare it with the previous seasons. Methods: Data from the incidence of hospitalizations due to acute bronchiolitis in infants <1 year of age were obtained from the Department of Informatics of the Brazilian Public Health database for the period between 2016 and 2022. These data were also analyzed by macro-regions of Brazil (North, Northeast, Southeast, South, and Midwest). To describe seasonal and trend characteristics over time, we used the Seasonal Autoregressive Integrated Moving Averages Model. Results: Compared to the pre-COVID-19 period, the incidence of hospitalizations related to acute bronchiolitis decreased by 97% during non-pharmacological interventions (March 2020 - August 2021) but increased by 95% after non-pharmacological interventions relaxation (September 2021 - December 2022), resulting in a 16% overall increase. During the pre-COVID-19 period, hospitalizations for acute bronchiolitis followed a seasonal pattern, which was disrupted in 2020-2021 but recovered in 2022, with a peak occurring in May, approximately 4% higher than the pre-COVID-19 peak. Conclusions: This study underscores the significant influence of COVID-19 interventions on acute bronchiolitis hospitalizations in Brazil. The restoration of a seasonal pattern in 2022 highlights the interplay between public health measures and respiratory illness dynamics in young children.

RESUMO Objetivo: Avaliar a sazonalidade da bronquiolite aguda no Brasil durante a temporada 2020-2022 e compará-la com a das temporadas anteriores. Métodos: Os dados de incidência de internações por bronquiolite aguda em lactentes <1 ano de idade foram obtidos do Departamento de Informática da base de dados da Saúde Pública Brasileira para o período entre 2016 e 2022. Esses dados também foram analisados por macrorregiões do Brasil (Norte, Nordeste, Sudeste, Sul e Centro-Oeste). Para descrever características sazonais e de tendência ao longo do tempo, utilizamos o Modelo de Médias Móveis Integradas Autorregressivas Sazonais. Resultados: Em comparação com o período pré-COVID-19, a incidência de hospitalizações relacionadas com bronquiolite aguda diminuiu 97% durante as intervenções não farmacológicas (março de 2020 - agosto de 2021), mas aumentou 95% após a flexibilização das intervenções não farmacológicas (setembro de 2021 - dezembro de 2022), resultando no aumento geral de 16%. Durante o período pré-COVID-19, as hospitalizações por bronquiolite aguda seguiram um padrão sazonal, que foi interrompido em 2020-2021, mas recuperaram-se em 2022, com um pico ocorrido em maio, aproximadamente 4% superior ao pico pré-COVID-19. Conclusões: Este estudo ressalta a influência significativa das intervenções contra a COVID-19 nas hospitalizações por bronquiolite aguda no Brasil. A restauração de um padrão sazonal em 2022 sublinha a interação entre as medidas de saúde pública e a dinâmica das doenças respiratórias em crianças pequenas.

Efficacy and safety of Optilume® Paclitaxel-coated urethral dilatation balloon in real-life: Experience in a Spanish Multicenter Study.

INTRODUCTION: The Optilume® Paclitaxel-coated urethral dilatation balloon is an alternative to conventional endoscopic treatments that combines mechanical dilatation with local delivery of paclitaxel. OBJECTIVE: To describe the success rate and analyze the safety of the device in real clinical practice. To evaluate possible predictors of treatment failure. MATERIALS AND METHODS: Retrospective multicenter study in patients diagnosed with urethral stricture and treated with an Optilume® balloon in routine clinical practice. Data were collected from flowmetry, questionnaires (PROM and IPSS) and cystoscopy before surgery, and 3, 6 and 12 months after the procedure, according to standard practice. Surgical success was defined as the absence of subsequent urethral manipulation and a Qmax > 10 ml/s. RESULTS: 238 patients treated with Optilume® in 12 Spanish hospitals between May 2021 and April 2024 were included in the study. Of these, 156 who had a minimum follow-up of 3 months, were analyzed. Median stricture length: 1.5 cm (0.5 - 5.3), mainly in bulbar urethra (87.7%). Of the total, 12.8% of patients had a history of pelvic radiotherapy, and 81.4% had undergone prior urethral manipulation. Postoperative complications were reported in 14.2% of the total. The treatment success rate was 73.8%, with a median follow-up of 8 months (5-12). No predictors of stricture recurrence were identified. Recurrence rates were higher in strictures located in the posterior versus anterior urethra (42.9% vs. 24.6%, p = 0.126). No significant differences were observed between patients with and without prior urethral manipulation. CONCLUSION: Treatment with Optilume® has been shown to be safe and effective in short-term routine clinical practice.

Effects on growth, weight and body composition after CFTR modulators in children with cystic fibrosis.

BACKGROUND: Cystic Fibrosis (CF) is associated with compromised nutrition status, which is responsible for morbidity and mortality along with lung function decline. This study was designed to examine changes in anthropometric markers and body composition parameters by bioelectrical impedance analysis after CFTR modulator (CFTRm) treatment. METHODS: We compared anthropometric parameters and body composition before and after 6 and 12 months of CFTRm treatment. Results are stratified into subgroups according to the modulator used with dual therapy with lumacaftor + ivacaftor or tezacaftor + ivacaftor (LUMA/TEZ + IVA) or triple therapy with elexacaftor + tezacaftor + ivacaftor (ELE + TEZ + IVA). Body composition data are available in patients treated with ELE + TEZ + IVA. RESULTS: Two hundred and thirty-four children (55.1% male) were recruited. The median age was 13.6 years (inter-quartile range [IQR] 10.7-16.1). We can observe a statistically significant increase in the weight Z score and BMI Z score after CFTRm. In terms of changes in body composition, we observe a significant increase in fat mass (FM) expressed both in kilograms and as a percentage at 6 months (p < .05; Wilcoxon-test), with no such differences found at 12 months. We also observe a statistically significant increase in fat-free-mass (FFM), expressed in kilograms at 6 and 12 months (p < .05; Wilcoxon-test). CONCLUSION: Weight status improved and changes in body composition occurred in children after CFTRm therapy, including an increase of fat mass. Further studies are needed to confirm these changes in body composition and their impact on disease progression.

Laboratory and physiological aspects of substitute metazoan models for in vivo pharmacotoxicological analysis.

New methods are essential to characterize the performance of substitute procedures for detecting therapeutic action(s) of a chemical or key signal of toxicological events. Herein, it was discussed the applications and advantages of using arthropods, worms, and fishes in pharmacological and/or toxicology assessments. First of all, the illusion of similarity covers many differences between humans and mice, remarkably about liver injury and metabolism of xenobiotics. Using invertebrates, especially earthworms (Eisenia fetida), brine shrimps (Artemia salina, Daphnia magna), and insects (Drosophila melanogaster) and vertebrates as small fishes (Oryzias latipes, Pimephales promelas, Danio rerio) has countless advantages, including fewer ethical conflicts, short life cycle, high reproduction rate, simpler to handle, and less complex anatomy. They can be used to find contaminants in organic matters and water and are easier genetically engineered with orthologous-mutated genes to explore specific proteins involved in proliferative and hormonal disturbances, chemotherapy multidrug resistance, and carcinogenicity. As multicellular embryos, larvae, and mature organisms, they can be tested in bigger-sized replication platforms with 24-, 96-, or 384-multiwell plates as cheaper and faster ways to select hit compounds from drug-like libraries to predict acute, subacute or chronic toxicity, pharmacokinetics, and efficacy parameters of pharmaceutical, cosmetic, and personal care products. Meanwhile, sublethal exposures are designed to identify changes in reproduction, body weight, DNA damages, oxidation, and immune defense responses in earthworms and zebrafishes, and swimming behaviors in A. salina and D. rerio. Behavioral parameters also give specificities on sublethal effects that would not be detected in zebrafishes by OECD protocols.

ESMO Recommendations on clinical reporting of genomic test results for solid cancers.

BACKGROUND: Genomic tumour profiling has a crucial role in the management of patients with solid cancers, as it helps selecting and prioritising therapeutic interventions based on prognostic and predictive biomarkers, as well as identifying markers of hereditary cancers. Harmonised approaches to interpret the results of genomic testing are needed to support physicians in their decision making, prevent inequalities in precision medicine and maximise patient benefit from available cancer management options. METHODS: The European Society for Medical Oncology (ESMO) Translational Research and Precision Medicine Working Group assembled a group of international experts to propose recommendations for preparing clinical genomic reports for solid cancers. These recommendations aim to foster best practices in integrating genomic testing within clinical settings. After review of available evidence, several rounds of surveys and focused discussions were conducted to reach consensus on the recommendation statements. Only consensus recommendations were reported. Recommendation statements were graded in two tiers based on their clinical importance: level A (required to maintain common standards in reporting) and level B (optional but necessary to achieve ideal practice). RESULTS: Genomics reports should present key information in a front page(s) followed by supplementary information in one or more appendices. Reports should be structured into sections: (i) patient and sample details; (ii) assay and data analysis characteristics; (iii) sample-specific assay performance and quality control; (iv) genomic alterations and their functional annotation; (v) clinical actionability assessment and matching to potential therapy indications; and (vi) summary of the main findings. Specific recommendations to prepare each of these sections are made. CONCLUSIONS: We present a set of recommendations aimed at structuring genomics reports to enhance physician comprehension of genomic profiling results for solid cancers. Communication between ordering physicians and professionals reporting genomic data is key to minimise uncertainties and to optimise the impact of genomic tests in patient care.

Benzbromarone as adjuvant therapy for cystic fibrosis lung disease: a pilot clinical trial.

OBJECTIVE: Cystic fibrosis (CF) affects multiple organs, the most severe consequences being observed in the lungs. Despite significant progress in developing CF transmembrane conductance regulator-specific treatments for CF lung disease, exploring alternative CF-targeted medications seems reasonable. We sought to evaluate the potential beneficial effects of oral benzbromarone as an adjuvant therapy in CF patients with reduced lung function. METHODS: This was a prospective open-label pilot study of oral benzbromarone (100 mg/day) administered once daily for 90 days. Patients were followed at a tertiary referral center in southern Brazil. Safety was assessed by the number of reported adverse events. Secondary objectives included percent predicted FEV1 (FEV1%) and pulmonary exacerbations. RESULTS: Ten patients were enrolled. Benzbromarone was found to be safe, with no serious drug-related adverse events. Eight patients completed the study; the median relative change in FEV1% tended to increase during the treatment, showing an 8% increase from baseline at the final visit. However, a nonparametric test showed that the change was not significant (p = 0.06). Of a total of ten patients, only one experienced at least one pulmonary exacerbation during the study. CONCLUSIONS: Oral benzbromarone appears to be safe, and improved FEV1% has been observed in patients with CF. Further assessment in larger trials is warranted to elucidate whether oral benzbromarone can be a potential adjuvant therapy for CF.

Recommendations for the use of next-generation sequencing (NGS) for patients with advanced cancer in 2024: a report from the ESMO Precision Medicine Working Group.

BACKGROUND: Advancements in the field of precision medicine have prompted the European Society for Medical Oncology (ESMO) Precision Medicine Working Group to update the recommendations for the use of tumour next-generation sequencing (NGS) for patients with advanced cancers in routine practice. METHODS: The group discussed the clinical impact of tumour NGS in guiding treatment decision using the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) considering cost-effectiveness and accessibility. RESULTS: As for 2020 recommendations, ESMO recommends running tumour NGS in advanced non-squamous non-small-cell lung cancer, prostate cancer, colorectal cancer, cholangiocarcinoma, and ovarian cancer. Moreover, it is recommended to carry out tumour NGS in clinical research centres and under specific circumstances discussed with patients. In this updated report, the consensus within the group has led to an expansion of the recommendations to encompass patients with advanced breast cancer and rare tumours such as gastrointestinal stromal tumours, sarcoma, thyroid cancer, and cancer of unknown primary. Finally, ESMO recommends carrying out tumour NGS to detect tumour-agnostic alterations in patients with metastatic cancers where access to matched therapies is available. CONCLUSION: Tumour NGS is increasingly expanding its scope and application within oncology with the aim of enhancing the efficacy of precision medicine for patients with cancer.

Bromelain as a natural anti-inflammatory drug: a systematic review.

Inflammation is a complex and necessary mechanism of an organ's response to biological, chemical and/or physical stimuli. In recent years, investigations on natural compounds with therapeutic actions for the treatment of different diseases have increased. Among these compounds, bromelain is highlighted, as a cysteine protease isolated from the Ananas comosus (pineapple) stem. This review aimed to evaluate the anti-inflammatory activity of bromelain, as well as its pathways on inflammatory mediators, through a systematic review with in vitro studies on different cell lines. The search was performed in PubMed, Science Direct, Scopus, Cochrane Library and Web of Science databases. Bromelain reduced IL-1ß, IL-6 and TNF-α secretion when immune cells were already stimulated in an overproduction condition by proinflammatory cytokines, generating a modulation in the inflammatory response through prostaglandins reduction and activation of a cascade reactions that trigger neutrophils and macrophages, in addition to accelerating the healing process.

Application of nanoformulations as a strategy to optimize chemotherapeutic treatment of glioblastoma: a systematic review.

The aim of this review was to explore the advances of nanoformulations as a strategy to optimize glioblastoma treatment, specifically focusing on targeting and controlling drug delivery systems to the tumor. This review followed the PRISMA recommendations. The studies were selected through a literature search conducted in the electronic databases PubMed Central, Science Direct, Scopus and Web of Science, in April 2023, using the equation descriptors: (nanocapsule OR nanoformulation) AND (glioblastoma). Forty-seven investigations included were published between 2011 and 2023 to assess the application of different nanoformulations to optimize delivery of chemotherapies including temozolomide, carmustine, vincristine or cisplatin previously employed in brain tumor therapy, as well as investigating another 10 drugs. Data demonstrated the possible application of different matrices employed as nanocarriers and utilization of functionalizing agents to improve internalization of chemotherapeutics. Functionalization was developed with the application of peptides, micronutrients/vitamins, antibodies and siRNAs. Finally, this review demonstrated the practical and clinical application of nanocarriers to deliver multiple drugs in glioblastoma models. These nanomodels might ideally be developed using functionalizing ligand agents that preferably act synergistically with the drug these agents carry. The findings showed promising results, making nanoformulations one of the best prospects for innovation and improvement of glioblastoma treatment.

Treatment patterns and outcomes in metastatic castration-resistant prostate cancer patients with and without somatic or germline alterations in homologous recombination repair genes.

BACKGROUND: Although germline BRCA mutations have been associated with adverse outcomes in prostate cancer (PC), understanding of the association between somatic/germline alterations in homologous recombination repair (HRR) genes and treatment outcomes in metastatic castration-resistant PC (mCRPC) is limited. The aim of this study was to investigate the prevalence and outcomes associated with somatic/germline HRR alterations, particularly BRCA1/2, in patients initiating first-line (1L) mCRPC treatment with androgen receptor signalling inhibitors (ARSi) or taxanes. PATIENTS AND METHODS: Data from 729 mCRPC patients were pooled for CAPTURE from four multicentre observational studies. Eligibility required 1L treatment with ARSi or taxanes, adequate tumour samples and biomarker panel results. Patients underwent paired normal and tumour DNA analyses by next-generation sequencing using a custom gene panel including ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2, RAD51B and RAD54L. Patients were divided into subgroups based on somatic/germline alteration(s): with BRCA1/2 mutations (BRCA); with HRR mutations except BRCA1/2 (HRR non-BRCA); and without HRR alterations (non-HRR). Patients without BRCA1/2 mutations were classified as non-BRCA. Radiographic progression-free survival (rPFS), progression-free survival 2 (PFS2) and overall survival (OS) were assessed. RESULTS: Of 729 patients, 96 (13.2%), 127 (17.4%) and 506 (69.4%) were in the BRCA, HRR non-BRCA and non-HRR subgroups, respectively. BRCA patients performed significantly worse for all outcomes than non-HRR or non-BRCA patients (P < 0.05), while PFS2 and OS were significantly shorter for BRCA than HRR non-BRCA patients (P < 0.05). HRR non-BRCA patients also had significantly worse rPFS, PFS2 and OS than non-HRR patients. Exploratory analyses suggested that for BRCA patients, there were no significant differences in outcomes associated with 1L treatment choice (ARSi or taxanes) or with the somatic/germline origin of the alterations. CONCLUSIONS: Worse outcomes were observed for mCRPC patients in the BRCA subgroup compared with non-BRCA subgroups, either HRR non-BRCA or non-HRR. Despite its heterogeneity, the HRR non-BRCA subgroup presented worse outcomes than the non-HRR subgroup. Screening early for HRR mutations, especially BRCA1/2, is crucial in improving mCRPC patient prognosis.

Advances in Antitumor Effects Using Liposomal Citrinin in Induced Breast Cancer Model.

The study aimed to evaluate the antitumor and toxicogenetic effects of liposomal nanoformulations containing citrinin in animal breast carcinoma induced by 7,12-dimethylbenzanthracene (DMBA). Mus musculus virgin females were divided into six groups treated with (1) olive oil (10 mL/kg); (2) 7,12-DMBA (6 mg/kg); (3) citrinin, CIT (2 mg/kg), (4) cyclophosphamide, CPA (25 mg/kg), (5) liposomal citrinin, LP-CIT (2 µg/kg), and (6) LP-CIT (6 µg/kg). Metabolic, behavioral, hematological, biochemical, histopathological, and toxicogenetic tests were performed. DMBA and cyclophosphamide induced behavioral changes, not observed for free and liposomal citrinin. No hematological or biochemical changes were observed for LP-CIT. However, free citrinin reduced monocytes and caused hepatotoxicity. During treatment, significant differences were observed regarding the weight of the right and left breasts treated with DMBA compared to negative controls. Treatment with CPA, CIT, and LP-CIT reduced the weight of both breasts, with better results for liposomal citrinin. Furthermore, CPA, CIT, and LP-CIT presented genotoxic effects for tumor, blood, bone marrow, and liver cells, although less DNA damage was observed for LP-CIT compared to CIT and CPA. Healthy cell damage induced by LP-CIT was repaired during treatment, unlike CPA, which caused clastogenic effects. Thus, LP-CIT showed advantages for its use as a model of nanosystems for antitumor studies.

Exploring the basis of heterogeneity of cancer aggressiveness among the mutated POLE variants.

Germline pathogenic variants in the exonuclease domain of the replicative DNA polymerase Pol ε encoded by the POLE gene, predispose essentially to colorectal and endometrial tumors by inducing an ultramutator phenotype. It is still unclear whether all the POLE alterations influence similar strength tumorigenesis, immune microenvironment, and treatment response. In this review, we summarize the current understanding of the mechanisms and consequences of POLE mutations in human malignancies; we highlight the heterogeneity of mutation rate and cancer aggressiveness among POLE variants, propose some mechanistic basis underlining such heterogeneity, and discuss novel considerations for the choice and efficacy of therapies of POLE tumors.

Molecular genetic association of rs8099917 and rs1800795 polymorphisms in the progression of hepatitis Delta virus liver disease

Background: The relationship between viral infections and host factors holds high hopes for identifying the role of Interferon Lambda 3 (IFNL3) and Interleukin 6 (IL-6) polymorphisms in the development of Chronic Liver Disease (CLD) in patients infected with hepatitis Delta virus (HDV) in the Western Brazilian Amazon. Methods: Cross-sectional study conducted with a cohort of 40 chronic HDV patients, 27 with CLD and 13 without evident liver damage. Biological samples from the participants were analyzed using the polymerase chain reaction (PCR) technique, followed by sequencing by the automated Sanger method. Results: The rs8099917 T allele, from the IFNL3 gene, showed a higher frequency in both groups; however, it was not possible to establish an association with HDV infection [OR = 1.42 (0.42 - 4.75; p = 0.556 (95% CI). For IL-6, the rs1800795 G allele was superior to rs1800795 C. Analyzing both distributions in the studied groups, any association with HDV was absent (p > 0.05). Conclusion: The results suggest that the rs8099917 T/G (IFNL3) and rs1800795 G/C (IL-6) polymorphisms are not associated with the evolution of HDV in the studied population.

Benzbromarone as adjuvant therapy for cystic fibrosis lung disease: a pilot clinical trial

ABSTRACT Objective: Cystic fibrosis (CF) affects multiple organs, the most severe consequences being observed in the lungs. Despite significant progress in developing CF transmembrane conductance regulator-specific treatments for CF lung disease, exploring alternative CF-targeted medications seems reasonable. We sought to evaluate the potential beneficial effects of oral benzbromarone as an adjuvant therapy in CF patients with reduced lung function. Methods: This was a prospective open-label pilot study of oral benzbromarone (100 mg/day) administered once daily for 90 days. Patients were followed at a tertiary referral center in southern Brazil. Safety was assessed by the number of reported adverse events. Secondary objectives included percent predicted FEV1 (FEV1%) and pulmonary exacerbations. Results: Ten patients were enrolled. Benzbromarone was found to be safe, with no serious drug-related adverse events. Eight patients completed the study; the median relative change in FEV1% tended to increase during the treatment, showing an 8% increase from baseline at the final visit. However, a nonparametric test showed that the change was not significant (p = 0.06). Of a total of ten patients, only one experienced at least one pulmonary exacerbation during the study. Conclusions: Oral benzbromarone appears to be safe, and improved FEV1% has been observed in patients with CF. Further assessment in larger trials is warranted to elucidate whether oral benzbromarone can be a potential adjuvant therapy for CF.

Pacientes em pós-operatório imediato: recepção na unidade clínico-cirúrgica / Patients in the immediate postoperative period: admission to the clinical and surgical unit

Objetivo: Analisar a demanda de enfermagem nos cuidados de pacientes em pós-operatório imediato, desde sua recepção do centro cirúrgico até sua acomodação ao leito na unidade de internação. Métodos: Estudo prospectivo e analítico. A população foi constituída por pacientes adultos, egressos do centro cirúrgico. A amostra foi calculada considerando-se que o serviço realiza uma média de 118 cirurgias ao mês. Considerando que a amostra mínima seria de 91 pacientes com um intervalo de confiança de 95%, optou-se por trabalhar com amostra de 100 pacientes. Os dados foram coletados no momento em que os pacientes eram recebidos da SRPA. Resultados: Os grupos cirúrgicos Angiologia, Coloproctologia, Otorrinolaringologia e Urologia demandaram no máximo dois profissionais de enfermagem. Os grupos de Cirurgia de Cabeça e Pescoço, Cirurgia Plástica, Nefrologia e Ortopedia demandaram pelo menos dois profissionais. O grupo da Coloproctologia teve maior média de tempo de acomodação ao leito. Cerca de 15% dos pacientes demandaram oxigenoterapia, quase 50% receberam analgésicos e 34% estavam usando cateter vesical de demora. Conclusão: O tempo destinado à acomodação dos pacientes variou de 5 a 30 minutos, com média de 15,19 ± 4,7. Não há indícios de que mais ou menos profissionais atuando juntos alterem o tempo de acomodação do paciente. Descritores: Admissão do paciente; Transferência do paciente; Cuidados de enfermagem; Enfermagem perioperatória.

Objective: To analyze the nursing demand in the care of patients in the immediate postoperative period, from their admission to the surgical center to their accommodation in bed in the admission unit. Methods: Prospective and analytical study. The population consisted of adult patients, discharged from the surgical center. The sample was calculated considering that the service performs an average of 118 surgeries per month. Considering that the minimum sample would be 91 patients at a 95% confidence interval, we chose to work with a sample of 100 patients. Data were collected at the time patients were received from the PACU. Results: The Angiology, Coloproctology, Otorhinolaryngology and Urology surgical groups required a maximum of two nursing professionals. The Head and Neck Surgery, Plastic Surgery, Nephrology and Orthopedics groups required at least two professionals. The Coloproctology group had a higher average time of accommodation in bed. About 15% of the patients required oxygen therapy, almost 50% received analgesics and 34% were using an indwelling urinary catheter. Conclusion: The time allocated to the accommodation of patients ranged from 5 to 30 minutes, with an average of 15.19 ± 4.7. There are no indications that a greater or lesser number of professionals acting together alter the accommodation time of the patient. Descriptors: Patient admission; Patient transfer; Nursing care; Perioperative nursing.

RESECTION OF ANKLE TUMOR LESION AND RECONSTRUCTION WITH THE USE OF ALLOGRAFT.

Reconstruction of the distal third of the tibia due to resection of a malignant tumor has some hindering factors, such as a thin subcutaneous layer, neurovascular bundles that cross compartments, prolonged operative duration, specific orthopedic material, and a trained multidisciplinary team. Allografting with material from tissue banks is part of this orthopaedic arsenal. OBJECTIVE: To describe the protocol used at Instituto Nacional de Traumatologia e Ortopedia Jamil Haddad. METHODS: Series of six cases subjected to resection with oncologic margins, allograft reconstruction, and use of a retrograde ankle nail as limb-salvage surgery. Three of the six patients were women, the lesions were on average 9.3 cm long, and the average operative duration was 3.25 hours. RESULTS: The main short-term complication (≤ 30 days) was peroneal nerve palsy, while the main long-term complication (> 30 days) was surgical site infection (two cases). Consolidation of the two foci occurred in three patients, and two patients developed asymptomatic pseudoarthrosis of the proximal focus with consolidation of the distal focus. CONCLUSION: Despite the complications, the proposed surgery gives patients the chance to preserve their limb in the face of immediate radical surgery. Level of Evidence IV, Case Series.

A reconstrução do terço distal da tíbia devido à ressecção de tumor maligno apresenta alguns fatores que dificultam sua realização, como camada subcutânea delgada, feixes neurovasculares que transpassam os compartimentos, tempo cirúrgico prolongado, material ortopédico específico e equipe multidisciplinar treinada. O aloenxerto de banco de tecido faz parte deste arsenal ortopédico. Objetivo: Descrever o protocolo realizado no Instituto Nacional de Traumatologia e Ortopedia Jamil Haddad. Métodos: Série de seis casos submetidos à ressecção com margens oncológicas, reconstrução com aloenxerto e uso de haste retrógrada de tornozelo como cirurgia preservadora do membro. Três dos seis pacientes eram do sexo feminino, as lesões tinham em média 9,3 cm de comprimento e o tempo cirúrgico médio foi de 3,25 horas. Resultados: A principal complicação de curto prazo (≤ 30 dias) foi a paralisia do nervo fibular, enquanto a principal complicação de longo prazo (> 30 dias) foi a infecção do sítio cirúrgico (dois casos). A consolidação dos dois focos ocorreu em três pacientes, e dois pacientes evoluíram para pseudoartrose assintomática do foco proximal com consolidação do foco distal. Conclusão: Apesar das complicações, a cirurgia proposta permite ao paciente a chance de preservar seu membro diante de uma cirurgia radical imediata. Nível de Evidência IV, Série de Casos.

Prognostic Factors and Markers in Non-Small Cell Lung Cancer: Recent Progress and Future Challenges.

Lung cancer is a highly aggressive neoplasm and, despite the development of recent therapies, tumor progression and recurrence following the initial response remains unsolved. Several questions remain unanswered about non-small cell lung cancer (NSCLC): (1) Which patients will actually benefit from therapy? (2) What are the predictive factors of response to MAbs and TKIs? (3) What are the best combination strategies with conventional treatments or new antineoplastic drugs? To answer these questions, an integrative literature review was carried out, searching articles in PUBMED, NCBI-PMC, Google Academic, and others. Here, we will examine the molecular genetics of lung cancer, emphasizing NSCLC, and delineate the primary categories of inhibitors based on their molecular targets, alongside the main treatment alternatives depending on the type of acquired resistance. We highlighted new therapies based on epigenetic information and a single-cell approach as a potential source of new biomarkers. The current and future of NSCLC management hinges upon genotyping correct prognostic markers, as well as on the evolution of precision medicine, which guarantees a tailored drug combination with precise targeting.

Buthionine sulfoximine and chemoresistance in cancer treatments: a systematic review with meta-analysis of preclinical studies.

Buthionine sulfoximine (BSO) is a synthetic amino acid that blocks the biosynthesis of reduced glutathione (GSH), an endogenous antioxidant cellular component present in tumor cells. GSH levels have been associated with tumor cell resistance to chemotherapeutic drugs and platinum compounds. Consequently, by depleting GSH, BSO enhances the cytotoxicity of chemotherapeutic agents in drug-resistant tumors. Therefore, the aim of this study was to conduct a systematic review with meta-analysis of preclinical studies utilizing BSO in cancer treatments. The systematic search was carried out using the following databases: PubMed, Web of Science, Scopus, and EMBASE up until March 20, 2023, in order to collect preclinical studies that evaluated BSO, alone or in association, as a strategy for antineoplastic therapy. One hundred nine investigations were found to assess the cytotoxic potential of BSO alone or in combination with other compounds. Twenty-one of these met the criteria for performing the meta-analysis. The evidence gathered indicated that BSO alone exhibits cytotoxic activity. However, this compound is generally used in combination with other antineoplastic strategies, mainly chemotherapy ones, to improve cytotoxicity to carcinogenic cells and treatment efficacy. Finally, this review provides important considerations regarding BSO use in cancer treatment conditions, which might optimize future studies as a potential adjuvant antineoplastic therapeutic tool.

Niraparib plus abiraterone acetate with prednisone in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: second interim analysis of the randomized phase III MAGNITUDE trial.

BACKGROUND: Patients with metastatic castration-resistant prostate cancer (mCRPC) and BRCA alterations have poor outcomes. MAGNITUDE found patients with homologous recombination repair gene alterations (HRR+), particularly BRCA1/2, benefit from first-line therapy with niraparib plus abiraterone acetate and prednisone (AAP). Here we report longer follow-up from the second prespecified interim analysis (IA2). PATIENTS AND METHODS: Patients with mCRPC were prospectively identified as HRR+ with/without BRCA1/2 alterations and randomized 1 : 1 to niraparib (200 mg orally) plus AAP (1000 mg/10 mg orally) or placebo plus AAP. At IA2, secondary endpoints [time to symptomatic progression, time to initiation of cytotoxic chemotherapy, overall survival (OS)] were assessed. RESULTS: Overall, 212 HRR+ patients received niraparib plus AAP (BRCA1/2 subgroup, n = 113). At IA2 with 24.8 months of median follow-up in the BRCA1/2 subgroup, niraparib plus AAP significantly prolonged radiographic progression-free survival {rPFS; blinded independent central review; median rPFS 19.5 versus 10.9 months; hazard ratio (HR) = 0.55 [95% confidence interval (CI) 0.39-0.78]; nominal P = 0.0007} consistent with the first prespecified interim analysis. rPFS was also prolonged in the total HRR+ population [HR = 0.76 (95% CI 0.60-0.97); nominal P = 0.0280; median follow-up 26.8 months]. Improvements in time to symptomatic progression and time to initiation of cytotoxic chemotherapy were observed with niraparib plus AAP. In the BRCA1/2 subgroup, the analysis of OS with niraparib plus AAP demonstrated an HR of 0.88 (95% CI 0.58-1.34; nominal P = 0.5505); the prespecified inverse probability censoring weighting analysis of OS, accounting for imbalances in subsequent use of poly adenosine diphosphate-ribose polymerase inhibitors and other life-prolonging therapies, demonstrated an HR of 0.54 (95% CI 0.33-0.90; nominal P = 0.0181). No new safety signals were observed. CONCLUSIONS: MAGNITUDE, enrolling the largest BRCA1/2 cohort in first-line mCRPC to date, demonstrated improved rPFS and other clinically relevant outcomes with niraparib plus AAP in patients with BRCA1/2-altered mCRPC, emphasizing the importance of identifying this molecular subset of patients.