Bone aluminum accumulation in the current era / Acúmulo de alumínio no tecido ósseo na era atual

In the last few years, evidence from the Brazilian Registry of Bone Biopsy (REBRABO) has pointed out a high incidence of aluminum (Al) accumulation in the bones of patients with CKD under dialysis. This surprising finding does not appear to be merely a passive metal accumulation, as prospective data from REBRABO suggest that the presence of Al in bone may be independently associated with major adverse cardiovascular events. This information contrasts with the perception of epidemiologic control of this condition around the world. In this opinion paper, we discussed why the diagnosis of Al accumulation in bone is not reported in other parts of the world. We also discuss a range of possibilities to understand why bone Al accumulation still occurs, not as a classical syndrome with systemic signs of intoxication, as occurred it has in the past.

Nos últimos anos, evidências do Registro Brasileiro de Biópsia óssea (REBRABO) apontaram uma alta incidência de intoxicação por alumínio (Al) no tecido ósseo de pacientes com DRC em diálise. Essa surpreendente informação parece representar não apenas um acúmulo passivo deste metal, visto que dados prospectivos do REBRABO sugerem que a presença de Al no tecido ósseo pode estar independentemente relacionada a eventos cardiovasculares adversos maiores. Essas informações contrastam com a percepção mundial do controle epidemiológico dessa condição. Neste artigo de opinião, discutimos por que o diagnóstico de acúmulo ósseo de Al não é relatado em outras partes do mundo, e também discutimos uma gama de possibilidades para entender por que nós acreditamos que o acúmulo de Al no tecido ósseo ainda ocorre, não como se apresentava no passado, ou seja, como uma síndrome com sinais e sintomas sistêmicos de intoxicação.

Occupational risks associated with chronic kidney disease of non-traditional origin (CKDnt) in Brazil: it is time to dig deeper into a neglected problem / Riscos ocupacionais associados à doença renal crônica de origem não tradicional (DRCnt) no Brasil: é hora de nos aprofundarmos em um problema negligenciado

Abstract In the past decades, an epidemic of chronic kidney disease (CKD) has been associated with environmental and occupational factors (heat stress from high workloads in hot temperatures and exposure to chemicals, such as pesticides and metals), which has been termed CKD of non-traditional origin (CKDnt). This descriptive review aims to present recent evidence about heat stress, pesticides, and metals as possible causes of CKDnt and provide an overview of the related Brazilian regulation, enforcement, and health surveillance strategies. Brazilian workers are commonly exposed to extreme heat conditions and other CKDnt risk factors, including increasing exposure to pesticides and metals. Furthermore, there is a lack of adequate regulation (and enforcement), public policies, and strategies to protect the kidney health of workers, considering the main risk factors. CKDnt is likely to be a significant cause of CKD in Brazil, since CKD's etiology is unknown in many patients and several conditions for its development are present in the country. Further epidemiological studies may be conducted to explore causal associations and estimate the impact of heat, pesticides, and metals on CKDnt in Brazil. Moreover, public policies should prioritize reducing workers´ exposure and promoting their health and safety.

Resumo Nas últimas décadas, uma epidemia de doença renal crônica (DRC) tem sido associada a fatores ambientais e ocupacionais (estresse térmico decorrente de cargas de trabalho elevadas em altas temperaturas e exposição a produtos químicos, como agrotóxicos e metais), denominada DRC de origem não tradicional (DRCnt). Esta revisão descritiva tem como objetivo apresentar evidências recentes sobre estresse térmico, agrotóxicos e metais como possíveis causas de DRCnt e fornecer uma visão geral das estratégias brasileiras de regulamentação, fiscalização e vigilância sanitária relacionadas. Os trabalhadores brasileiros são comumente expostos a condições extremas de calor e outros fatores de risco de DRCnt, incluindo o aumento da exposição a agrotóxicos e metais. Além disso, há uma falta de regulamentação e fiscalização, políticas públicas e estratégias adequadas para proteger a saúde renal dos trabalhadores em relação aos principais fatores de risco. É provável que a DRCnt seja uma causa significativa de DRC no Brasil, uma vez que a etiologia da doença é desconhecida em muitos pacientes e diversas condições para seu desenvolvimento estão presentes no país. Estudos epidemiológicos devem ser realizados para explorar associações causais e estimar o impacto do calor, dos agrotóxicos e dos metais na DRCnt no Brasil. Além disso, as políticas públicas devem priorizar a redução da exposição dos trabalhadores e a promoção de sua saúde e segurança.

Estimated glomerular filtration rate in clinical practice: Consensus positioning of the Brazilian Society of Nephrology (SBN) and Brazilian Society of Clinical Pathology and Laboratory Medicine (SBPC/ML) / Estimativa da taxa de filtração glomerular na prática clínica: posicionamento consensual da Sociedade Brasileira de Nefrologia (SBN) e Sociedade Brasileira de Patologia Clínica e Medicina Laboratorial (SBPC/ML)

ABSTRACT Chronic kidney disease (CKD) represents one of today's main public health problems. Serum creatinine measurement and estimation of the glomerular filtration rate (GFR) are the main tools for evaluating renal function. There are several equations to estimate GFR, and CKD-EPI equation (Chronic Kidney Disease - Epidemiology) is the most recommended one. There are still some controversies regarding serum creatinine measurement and GFR estimation, since several factors can interfere in this process. An important recent change was the removal of the correction for race from the equations for estimating GFR, which overestimated kidney function, and consequently delayed the implementation of treatments such as dialysis and kidney transplantation. In this consensus document from the Brazilian Societies of Nephrology and Clinical Pathology and Laboratory Medicine, the main concepts related to the assessment of renal function are reviewed, as well as possible existing controversies and recommendations for estimating GFR in clinical practice.

RESUMO A doença renal crônica (DRC) representa um dos principais problemas de saúde pública da atualidade. A dosagem da creatinina sérica e a estimativa da taxa de filtração glomerular (TFG) são as principais ferramentas para avaliação da função renal. Para a estimativa da TFG, existem diversas equações, sendo a mais recomendada a CKD-EPI (Chronic Kidney Disease - Epidemiology). Existem ainda algumas controvérsias com relação à dosagem da creatinina sérica e da estimativa da TFG, uma vez que vários fatores podem interferir nesse processo. Uma importante mudança recente foi a retirada da correção por raça das equações para estimativa da TFG, que superestimavam a função renal, e consequentemente retardavam a implementação de tratamentos como diálise e transplante renal. Neste documento de consenso da Sociedade Brasileira de Nefrologia e Sociedade Brasileira de Patologia Clínica e Medicina Laboratorial são revisados os principais conceitos relacionados à avaliação da função renal, possíveis controvérsias existentes e recomendações para a estimativa da TFG na prática clínica.

Analysis of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as inflammatory biomarkers in chronic kidney disease: impact of parathyroidectomy / Análise das relações neutrófilo/linfócito e plaqueta/linfócito como marcadores inflamatórios na doença renal crônica: impacto da paratireoidectomia

Abstract Introduction: Secondary hyperparathyroidism (SHPT) is one of the causes for inflammation in CKD. We assessed the impact of parathyroidectomy (PTX) on neutrophil-to-lymphocyte (N/L) and platelet-to-lymphocyte (P/L) ratios in SHPT patients. Methods: A total of 118 patients [hemodialysis (HD, n = 81), and transplant recipients (TX, n = 37)] undergoing PTX between 2015 and 2021 were analyzed. Results: There was a significant reduction in calcium and PTH levels in both groups, in addition to an increase in vitamin D. In the HD group, PTX did not alter N/L and P/L ratios. In the TX group, there was a reduction in N/L and P/L ratios followed by a significant increase in total lymphocyte count. Conclusion: N/L and P/L ratios are not reliable biomarkers of inflammation in SHPT patients undergoing PTX. Uremia, which induces a state of chronic inflammation in dialysis patients, and the use of immunosuppression in kidney transplant recipients are some of the confounding factors that prevent the use of this tool in clinical practice.

Resumo Introdução: O hiperparatireoidismo secundário (HPTS) é uma das causas de inflamação na DRC. Avaliamos o impacto da paratireoidectomia (PTX) nas relações neutrófilo/linfócito (N/L) e plaqueta/linfócito (P/L) em pacientes com HPTS. Métodos: Foram analisados 118 pacientes [hemodiálise (HD, n = 81) e transplantados (TX, n = 37)] submetidos à PTX entre 2015 e 2021. Resultados: Houve redução significativa de cálcio e PTH nos dois grupos, além de elevação de vitamina D. No grupo HD, a PTX não mudou as relações N/L e P/L. Já no grupo TX, houve redução nas relações N/L e P/L acompanhadas de elevação significativa do número de linfócitos totais. Conclusão: As relações N/L e P/L não são marcadores fidedignos de inflamação em pacientes com HPTS submetidos à PTX. A uremia, que induz um estado de inflamação crônica em pacientes dialíticos, e o uso de imunossupressão em pacientes transplantados renais são alguns dos fatores de confusão que impedem o uso dessa ferramenta na prática clínica.

Transitioning to peritoneal dialysis: it does not matter where you come from / Transição para diálise peritoneal: não importa de onde

Introduction: Patients with end-stage renal disease (ESRD) frequently change renal replacement (RRT) therapy modality due to medical or social reasons. We aimed to evaluate the outcomes of patients under peritoneal dialysis (PD) according to the preceding RRT modality. Methods: We conducted a retrospective observational single-center study in prevalent PD patients from January 1, 2010, to December 31, 2017, who were followed for 60 months or until they dropped out of PD. Patients were divided into three groups according to the preceding RRT: prior hemodialysis (HD), failed kidney transplant (KT), and PD-first. Results: Among 152 patients, 115 were PD-first, 22 transitioned from HD, and 15 from a failing KT. There was a tendency for ultrafiltration failure to occur more in patients transitioning from HD (27.3% vs. 9.6% vs. 6.7%, p = 0.07). Residual renal function was better preserved in the group with no prior RRT (p < 0.001). A tendency towards a higher annual rate of peritonitis was observed in the prior KT group (0.70 peritonitis/year per patient vs. 0.10 vs. 0.21, p = 0.065). Thirteen patients (8.6%) had a major cardiovascular event, 5 of those had been transferred from a failing KT (p = 0.004). There were no differences between PD-first, prior KT, and prior HD in terms of death and technique survival (p = 0.195 and p = 0.917, respectively) and PD efficacy was adequate in all groups. Conclusions: PD is a suitable option for ESRD patients regardless of the previous RRT and should be offered to patients according to their clinical and social status and preferences.

Introdução: Pacientes com doença renal em estágio terminal (DRET) frequentemente mudam de modalidade de terapia renal substitutiva (TRS) por razões médicas ou sociais. Nosso objetivo foi avaliar desfechos de pacientes em diálise peritoneal (DP) segundo a modalidade anterior de TRS. Métodos: Realizamos estudo retrospectivo observacional unicêntrico, em pacientes prevalentes em DP, de 1º de janeiro de 2010 a 31 de dezembro de 2017, acompanhados por 60 meses ou até saírem de DP. Pacientes foram divididos em três grupos de acordo com a TRS anterior: hemodiálise prévia (HD), transplante renal malsucedido (TR) e DP como primeira opção (PD-first). Resultados: Entre 152 pacientes, 115 eram PD-first, 22 transitaram da HD e 15 de TR malsucedido. Houve tendência à maior ocorrência de falência de ultrafiltração em pacientes em transição da HD (27,3% vs. 9,6% vs. 6,7%; p = 0,07). A função renal residual foi melhor preservada no grupo sem TRS prévia (p < 0,001). Observou-se tendência à maior taxa anual de peritonite no grupo TR prévio (0,70 peritonite/ano por paciente vs. 0,10 vs. 0,21; p = 0,065). Treze pacientes (8,6%) tiveram um evento cardiovascular maior, cinco dos quais haviam sido transferidos de um TR malsucedido (p = 0,004). Não houve diferenças entre PD-first, TR prévio e HD prévia em termos de óbito e sobrevida da técnica (p = 0,195 e p = 0,917, respectivamente) e a eficácia da DP foi adequada em todos os grupos. Conclusões: A DP é uma opção adequada para pacientes com DRET, independentemente da TRS anterior, e deve ser oferecida aos pacientes de acordo com seu status clínico e social e suas preferências.

Caracterización de la situación problémica en un estudio psicosocial con pacientes con enfermedad renal crónica

Introducción: La enfermedad renal crónica es un problema de salud a nivel mundial, su manifestación más grave, la insuficiencia renal crónica, incide en el contexto cubano y determina el crecimiento de pacientes en hemodiálisis. El objetivo del texto es valorar los principales resultados del diagnóstico y caracterización de la situación problémica en un estudio de carácter psicosocial con pacientes con Insuficiencia Renal Crónica en la sala de Hemodiálisis del municipio Florida, de la provincia de Camagüey. Método: Es una investigación-acción participativa de corte experimental, que se desarrolla entre enero 2023 y diciembre del 2024 la cual constituye salida del proyecto de investigación Sistema de acciones psicosociales para el perfeccionamiento de la atención integral a los pacientes con enfermedades no transmisibles. El universo está constituido por 56 pacientes y la muestra por 22, que reciben tratamiento depurador y conservador, 22 familiares y 12 profesionales del servicio. El instrumento de investigación por excelencia fue la encuesta a participantes. Resultados: La edad de los pacientes no es definitiva de un grupo etario; predominan los hombres; se constata un elevado por ciento de pacientes con poca tolerancia a la adherencia al tratamiento e insuficiente desarrollo de las habilidades psicosociales y declaran la necesidad de poseer conocimientos para lograr estados de salud que conlleven a la sobrevida. Discusión: No existe coincidencia con lo constatado en la determinación de los grupos etarios de prevalencia para la enfermedad, pero los especialistas insisten en que la enfermedad no es privativa de un período de vida específico; reconocen la importancia del conocimiento de los factores de riesgo por el paciente para la prevención, promoción y educación en salud y resaltan la necesidad de la comunicación y la empatía entre el personal de salud y el paciente, para lograr resultados y estados emocionales favorables ante la enfermedad y el tratamiento.

Introduction: Chronic kidney disease is a global health problem. Its most serious manifestation, chronic kidney failure, affects the Cuban context and determines the growth of patients on hemodialysis. The objective of the text is to evaluate the main results of the diagnosis and characterization of the problematic situation in a psychosocial study with patients with Chronic Renal Failure in the Hemodialysis room of the Florida municipality, of the county of Camagüey. Method: It is an experimental participatory action research, which takes place between January 2023 and December 2024, which constitutes the output of the research project System of psychosocial actions for the improvement of comprehensive care for patients with non-communicable diseases. The universe is made up of 56 patients and the sample is made up of 22, who receive purifying and conservative treatment, 22 family members and 12 service professionals. The research instrument par excellence was the participant survey. Results: The age of the patients is not definitive of an age group; men predominate; A high percentage of patients are found to have low tolerance for adherence to treatment and insufficient development of psychosocial skills and declare the need to possess knowledge to achieve health states that lead to survival. Discussion: There is no coincidence with what was found in the determination of the prevalence age groups for the disease, but specialists insist that the disease is not exclusive to a specific period of life; recognize the importance of the patient's knowledge of risk factors for prevention, promotion and health education and highlight the need for communication and empathy between health personnel and the patient, to achieve favorable results and emotional states in the face of the disease and treatment.

Impact of Smoking Cessation and Charlson Comorbidity Index on Influenza Vaccination Efficacy in COPD Patients.

Chronic obstructive pulmonary disease (COPD) patients are particularly susceptible to respiratory infections like influenza, which exacerbate symptoms and increase healthcare utilization. While smoking cessation and influenza vaccination are recommended preventive measures, their combined impact on healthcare resource utilization is underexplored. The Charlson Comorbidity Index (CCI) assesses comorbidity burden in COPD patients and may influence healthcare outcomes. We conducted a retrospective analysis of 357 COPD patients, evaluating smoking cessation success over one year and influenza vaccination receipt, stratifying patients by CCI scores. Healthcare utilization outcomes included emergency room visits, hospitalizations, and medical expenses. Results showed that 51.82% of patients quit smoking and 59.66% received influenza vaccination, with higher comorbidity prevalence in advanced COPD stages (p = 0.002). Both smoking cessation and influenza vaccination independently correlated with decreased emergency room visits, hospital admissions, days, and costs. Patients who both quit smoking and received influenza vaccination exhibited the lowest healthcare utilization rates. In conclusion, smoking cessation and influenza vaccination significantly reduce healthcare resource utilization in COPD patients, with the combination yielding synergistic benefits, particularly in those with lower CCI scores. Integrating these interventions and comorbidity management in COPD strategies is essential for optimizing patient outcomes and healthcare efficiency.

Enhanced Antitumor Activity by the Combination of Dasatinib and Selinexor in Chronic Myeloid Leukemia.

BACKGROUND: Chronic myeloid leukemia is a hematological malignancy characterized by the abnormal proliferation of leukemic cells. Despite significant progress with tyrosine kinase inhibitors, such as Dasatinib, resistance remains a challenge. The aim of the present study was to investigate the potential of Selinexor, an Exportin-1 inhibitor, to improve TKI effectiveness on CML. METHODS: Human CML cell lines (LAMA84 and K562) were treated with Selinexor, Dasatinib, or their combination. Apoptosis, mitochondrial membrane potential, and mitochondrial mass were assessed using flow cytometry. Real-time RT-PCR was used to evaluate the expression of genes related to mitochondrial function. Western blot and confocal microscopy examined PINK and heme oxygenase-1 (HO-1) protein levels. RESULTS: Selinexor induced apoptosis and mitochondrial depolarization in CML cell lines, reducing cell viability. The Dasatinib/Selinexor combination further enhanced cytotoxicity, modified mitochondrial fitness, and downregulated HO-1 nuclear translocation, which has been associated with drug resistance in different models. CONCLUSIONS: In conclusion, this study suggests that Dasatinib/Selinexor could be a promising therapeutic strategy for CML, providing new insights for new targeted therapies.

Survey of Potential Drug Interactions, Use of Non-Medical Health Products, and Immunization Status among Patients Receiving Targeted Therapies.

In recent years, several changes have occurred in the management of chronic immunological conditions with the emerging use of targeted therapies. This two-phase cross-sectional study was conducted through structured in-person interviews in 2018-2019 and 2022. Additional data sources included ambulatory medical records and the itemized reimbursement reporting interface of the National Health Insurance Fund. Drug interactions were analyzed using the UpToDate Lexicomp, Medscape drug interaction checker, and Drugs.com databases. The chi-square test was used, and odds ratios (ORs) were calculated. In total, 185 patients participated. In 53% of patients (n = 53), a serious drug-drug interaction (DDI) was identified (mean number: 1.07 ± 1.43, 0-7), whereas this value was 38% (n = 38) for potential drug-supplement interactions (mean number: 0.58 ± 0.85, 0-3) and 47% (n = 47) for potential targeted drug interactions (0.72 ± 0.97, 0-5) in 2018. In 2022, 78% of patients (n = 66) were identified as having a serious DDI (mean number: 2.27 ± 2.69, 0-19), 66% (n = 56) had a potential drug-supplement interaction (mean number: 2.33 ± 2.69, 0-13), and 79% (n = 67) had a potential targeted drug interactions (1.35 ± 1.04, 0-5). Older age (>60 years; OR: 2.062), female sex (OR: 3.387), and polypharmacy (OR: 5.276) were identified as the main risk factors. Screening methods and drug interaction databases do not keep pace with the emergence of new therapeutics.

Insights into Immune Exhaustion in Chronic Hepatitis B: A Review of Checkpoint Receptor Expression.

Hepatitis B, caused by the hepatitis B virus (HBV), often progresses to chronic infection, leading to severe complications, such as cirrhosis, liver failure, and hepatocellular carcinoma. Chronic HBV infection is characterized by a complex interplay between the virus and the host immune system, resulting in immune cell exhaustion, a phenomenon commonly observed in chronic viral infections and cancer. This state of exhaustion involves elevated levels of inhibitory molecules, cells, and cell surface receptors, as opposed to stimulatory counterparts. This review aims to elucidate the expression patterns of various co-inhibitory and co-stimulatory receptors on immune cells isolated from chronic hepatitis B (CHB) patients. By analyzing existing data, the review conducts comparisons between CHB patients and healthy adults, explores the differences between HBV-specific and total T cells in CHB patients, and examines variations between intrahepatic and peripheral immune cells in CHB patients. Understanding the mechanisms underlying immune exhaustion in CHB is crucial for developing novel immunotherapeutic approaches. This detailed analysis sheds light on the immune exhaustion observed in CHB and lays the groundwork for future combined immunotherapy strategies aimed at leveraging checkpoint receptors to restore immune function and improve clinical outcomes.

Luteolin promotes neuronogenesis in hippocampus of chronic unpredictable mild stress rats and primary hippocampus of fetal rats.

OBJECTIVE: To investigate the effects of luteolin on chronic unpredictable mild stress (CUMS)-induced depressive rats and corticosterone (CORT)-induced depressive primary hippocampal neurons, and to elucidate the mechanism behind the action. METHODS: The antidepressant mechanism of luteolin was studied by using CUMS rat model and primary hippocampal neurons in fetal rats. In vivo, novelty suppressed feeding, open-field and sucrose preference tests as well as Morris water maze were evaluated. The content of brain derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT), norepinephrine (NE), and dopamine (DA) in serum were detected by enzyme-linked immunosorbent assay. The mechanisms of luteolin were explored based on neurotrophin and hippocampal neurogenesis, and proliferation. Survival of the septo-temporal axis in hippocampus was assayed using the 5-bromo-2-deoxyuridine (BrdU), the expression of BDNF, neurotrophin-3 (NT-3), and nerve growth factor (NGF) in hippocampus dentate gyrus region were measured by Western-blotting. In vitro, BDNF, NT-3, tropomyosin receptor kinase B (TrkB), and phosphorylated cyclic adenosine monophosphate responsive element binding protein (p-CREB) were detected through the high content analysis (HCA) to investigate neurotrophin and apoptosis. RESULTS: Induction of CUMS in rats induced depressive symptoms, while luteolin significantly enhanced sucrose consumption, decreased feeding latency, increased locomotor activity, escape latency, distance of target quadrant and regulated the content of depressive-like biomarkers. Histology analysis revealed that luteolin increased the abundance of new born neurons that had been labeled with BrdU, BrdU + neuronal nuclear antigen, and BrdU + doublecortin in septo-temporal axis of S2 (mid-septal) and T3 (mid-temporal). Moreover, expression of BDNF, NT-3, and NGF increased significantly in the septo-temporal axis of S2 and T3. HCA showed increased expression of BDNF, NT-3, TrkB and p-CREB in primary hippocampal neurons. CONCLUSION: The results provided direct evidence that luteolin has an antidepressant effect and could effectively promote the regeneration of the septotemporal axis nerve and hippocampal neuronutrition, which suggested that the antidepressant effect of luteolin may be related to hippocampal neurogenesis.

Uncovering the action mechanism of Shenqi Tiaoshen formula in the treatment of chronic obstructive pulmonary disease through network pharmacology, molecular docking, and experimental verification.

OBJECTIVE: To reveal the potential underlying mechanism of the Shenqi Tiaoshen formula (, SQTS) in the treatment of chronic obstructive pulmonary disease (COPD) by utilizing network pharmacology, molecular docking, and experimental verification. METHODS: Multiple open-source databases and research related to Traditional Chinese Medicine or compounds were employed to screen active ingredients and corresponding potential targets of the SQTS. The protein-protein interaction network screened hub genes, the relevant molecular mechanism and gene regulation were initially identified through the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis, and molecular docking was used to confirm further the interaction of the main components bound to the core targets. In vivo experiments on the COPD combined Qi-deficiency syndrome rat model were performed to verify the intervention effects and predicted potential molecular mechanisms of the SQTS. RESULTS: This study selected 156 active compounds and 326 candidate targets for treating COPD. Quercetin, Nobiletin, Kaempferol, Luteolin, Ginsenoside Rh2 and Formononetin were probably the main active compounds of SQTS in COPD treatment as they affected the most COPD-related targets, and interleukin-1 (IL-6), signal transducing activator of transcription 3 (STAT3), matrix metalloproteinase-9 (MMP9), vascular endothelial growth factor A (VEGFA), protein kinase B (AKT1), hypoxia-inducible factor-1α (HIF-1α), and forkhead box O3 (FoxO3) were identified as the hub genes associated with its therapeutic effect. KEGG analysis was mainly enriched in the signaling pathways closely related to inflammation, immunity and oxidative stress, such as HIF-1, tumor necrosis factor (TNF), phosphatidylinositol 3 kinase (PI3K)-AKT, FoxO, apoptosis, IL-17, and toll-like receptor. Molecular docking confirmed that the main active components shared a good affinity with the hub genes. In vivo experiments, the SQTS was found to improve the body weight, exhaustive swimming time, tail-hanging immobility time and struggle times, airway inflammation, lung functions, and inflammatory factors in the rat model of COPD. The up-regulation of p-PI3K, p-AKT, HIF-1α, FoxO3α, toll like receptor 4, VEGFA, Caspase 3, TNF-α, and IL-17 in COPD rats were down-regulated by SQTS, consistent with the network pharmacology results. CONCLUSIONS: This study provides evidence that the SQTS plays a critical role in anti-inflammation via suppressing immune inflammation and oxidative stress related pathways, indicating that the SQTS is a candidate herbal drug for further investigation in treating COPD.

"Chronic bronchial foreign body managed by lobectomy and latissimus dorsi flap: case report".

INTRODUCTION AND IMPORTANCE: Foreign body aspiration is a common occurrence, with severe outcomes seen in all age groups. It can present like any chronic respiratory disease with a wide spectrum of misleading symptoms, resulting in misdiagnosis and delays in appropriate treatment. CASE PRESENTATION: Here we present a case of a 11 year boy diagnosed with occult foreign body aspiration, chronically impacted in the left secondary bronchus, presented with bronchiectasis and multiple failed attempts at bronchoscopic retrieval. CLINICAL DISCUSSION: Surgically managed by a left lower lobe lobectomy via a mini thoracotomy, reinforced with a pedicled latissimus dorsi flap. Upfront surgery will reduce the bronchoscopic morbidity incurred in repeated attempts needing pot-op ventilatory support due to edema and repeated general anaesthesia risks. CONCLUSION: A high degree of suspicion is a key to diagnosis. There should be a low threshold for surgical management in chronic impactions.

Preliminary investigation of endoscopic surgery for tympanic membrane perforation: Regenerative treatment compared with conventional surgery.

PURPOSE: To compare surgical outcomes of regenerative treatment (RT) including basic fibroblast growth factor (bFGF) (Group-R) with the conventional method (Group-C) for patients with tympanic membrane perforation (TMP), both of whom underwent transcanal endoscopic ear surgery. METHODS: The study population of Group-R included 61 ears of 59 patients treated with RT-TMP in which TMP edges were disrupted mechanically and a gelatin sponge immersed in bFGF was inserted into the TMP. Fibrin glue was then dripped over the sponge. Group-C consisted of 13 patients who underwent conventional surgery before adopting the RT-TMP. Patients' characteristics and outcomes including TMP closure rates, and change in hearing level were evaluated three or more weeks after the surgery. RESULTS: The baseline characteristics including size of TMP were not significantly different between the two groups. Although Group-R had significantly shorter operating time than Group-C, the complete TMP closure rates were 69 % (9/13) and 85 % (52/61), respectively. Air-conduction hearing thresholds showed significant improvements, and analysis of variance showed that Group-R achieved significant interactions other than at 8 kHz, implying better improvement in cases with TMP closure. The air-bone gaps also improved at all frequencies in both groups. Specifically, at 4 kHz, there was a trend showing better improvement in Group-R. CONCLUSION: RT-TMP had a high TMP closure rate and good hearing improvement, with no significant differences compared with those of conventional surgery. This new therapy is simple and safe, and requires less operating time, and it could help improve the quality of life of patients with TMP.

Multi-omics analysis identified IL-4-induced IL1RL1high eosinophils characterized by prominent cysteinyl leukotriene metabolism.

BACKGROUND: Clinical studies demonstrated that IL-4, a type 2 cytokine, plays an important role in the pathogenesis of chronic rhinosinusitis (CRS) and eosinophilic asthma (EA). However, the direct effect of IL-4 on eosinophils remains unclear. OBJECTIVE: We aim to elucidate the inflammatory effects of IL-4 on the functions of human eosinophils. METHODS: Multi-omics analysis comprising transcriptomics, proteomics, lipidomics, quantitative RT-PCR, and flow cytometry was performed using blood eosinophils from healthy subjects stimulated with IL-4, IL-5, or their combination. RESULTS: Transcriptomic and proteomic analyses revealed that both IL-4 and IL-5 upregulate the expression of gamma-gultamyl transferase 5 (GGT5), a fatty acid-metabolizing enzyme that converts leukotriene C4 (LTC4) into LTD4. In addition, IL-4 specifically upregulates the expression of IL1RL1, a receptor for IL-33 and transglutaminase 2 (TGM2). Additional transcriptomic analysis of cells stimulated with IL-13 revealed altered gene expression profiles, characterized by the upregulation of GGT5, TGM2, and IL1RL1. IL-13-induced changes were not totally different from IL-4-induced one. Lipidomic analysis revealed that IL-5 and IL-4 additively increased the extracellular release of LTD4. In vitro experiments revealed that STAT6 and IL-4 receptor α control the expression of these molecules in the presence of IL-4 and IL-13. Analysis of eosinophils derived from patients with allergic disorders indicated the involvement of IL-4 and IL-13 at the inflamed sites. CONCLUSIONS: IL-4 induces the pro-allergic phenotype of IL1RL1high eosinophils with prominent cysteinyl leukotriene metabolism via STAT6. These cellular changes represent potential therapeutic targets for CRS and EA.

Impact of Infrapopliteal Revascularisation Establishing In Line Flow to the Wound in Patients with Chronic Limb Threatening Ischaemia.

OBJECTIVE: This study aimed to determine the impact of infrapopliteal (IP) revascularisation establishing in line flow to the wound (IFW) on wound healing in chronic limb threatening ischaemia (CLTI), using a core laboratory assessment for wounds and in line flow. METHODS: The Wound-directed Angiosome RevasculaRIzation apprOach to patients with cRitical limb iSchaemia (WARRIORS) multicentre observational study enrolled patients with CLTI with tissue loss undergoing IP revascularisation in Japan, with scheduled two year follow up. The primary outcome measure was complete wound healing, defined as achievement of complete epithelialisation of all wounds without major amputation. IP revascularisation establishing IFW was defined as revascularisation after which a tibiopedal artery that actually fed an injured pedal unit was patent. The incidence of wound healing was compared between the IFW and non-IFW groups using inverse probability of treatment weighting based on the propensity score. RESULTS: A total of 440 patients with CLTI (median age, 75 years; male, 64.1%; diabetes mellitus, 72.0%; dialysis, 57.7%) with tissue loss (Wound, Ischemia, and foot Infection stage 4, 66.4%) who underwent IP revascularisation (endovascular procedure, n = 304; bypass grafting, n = 136) between October 2017 and June 2020 were registered. During a median follow up of 23.6 months, 51.1% achieved wound healing. Successful IP revascularisation with IFW was achieved in 68.2%. After analysis, the IFW group had a higher incidence of wound healing than the non-IFW group (34.5 vs. 16.1 per 100 person years; p = .030). The association of IFW with wound healing was not statistically different between patients undergoing bypass grafting and those undergoing an endovascular procedure (p for interaction = .38). There was no statistically significant interaction effect between IFW and direct revascularisation for wound healing (p for interaction = .51). CONCLUSION: IP revascularisation establishing IFW was statistically significantly associated with a higher wound healing rate in patients with CLTI.

Polysaccharides, the Active Component of Dendrobium officinale Flower, Ameliorates Chronic Pharyngitis in Rats via TLR4/NF-κB Pathway Regulation.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic pharyngitis persistently afflicts a large population and accounts for approximately one-third of otolaryngology patients. Currently, the treatment of CP remains controversial because of the poor outcomes. Dendrobium officinale is a well-used "Yin-nourishing" traditional Chinese medicinal and edible herb used for thousands of years in China. The flowers of D. officinale are often used in folk of China to make tea for voice protect on and throat clearing. AIM OF THE STUDY: This study was to evaluate beneficial effects of polysaccharides from D. officinale flower (DOFP) on CP and its potential mechanisms. METHODS: Chemical characterization of DOFP, including polysaccharide content and monosaccharide composition, structural characterization using Fourier transform infrared spectroscopy were performed. A CP model was established in rats by administering a mixture of Chinese Baijiu and chili pepper liquid, combined with low-concentration ammonia spraying. The general states, amount of oral secretion, and apparent state of the pharynx of CP rats were observed during the period of DOFP administration. Furthermore, hemorheological parameters were measured using an automatic hematology analyzer. The levels of tumor necrosis factor-α (TNF-α), interleukin 1ß (1L-1ß), lipopolysaccharide (LPS), and D-lactate (D-LA) in the serum were measured by enzyme-linked immunosorbent assay. Morphological changes in the pharynx and colon were observed by hematoxylin-eosin staining. The expression of nuclear factor-κB p65 (NF-κB p65), p-NF-κB p65, cyclooxygenase-2 (COX-2), interleukin 1ß（IL-1ß）and mucin 5AC (MUC5AC) in pharynx,Claudin-1, Occludin, and interleukin 6 (IL-6) in colon was detected by immunohistochemistry and Western Blot. The mRNA expression of TLR4, COX-2, and IL-1ß in the pharynx were determined using reverse transcription quantitative real-time PCR. RESULTS: In this study, DOFP with a total polysaccharide content of 71.44% and a composition of D-mannose, galacturonic acid, glucose, galactose, and arabinose in a molar ratio of 3.95:2.19:1.00:0.74:1.30, was isolated from the flowers of D. officinale. DOFP improved the general state and exhibited significant effects on reducing oral secretion, alleviating pharyngeal injury, suppressing inflammatory cell infiltration in the pharynx, decreasing the serum levels of TNF-α and IL-1ß, and reducing the number of white blood cells and lymphocytes in the model rats. Moreover, the expressions of TLR4, p-NF-κB p65, COX-2, IL-1ß and MUC5AC in the pharynx of model rats were obviously inhibited. In addition, the levels of LPS, D-LA in the serum and the protein expression of IL-6 in the colon were downregulated when the protein expression of Occludin and Claudin-1 in the colon were upregulated. CONCLUSIONS: DOFP exerts significant ameliorating effects on CP and it likely acts by inhibiting LPS/TLR4-associated inflammatory mediator activation and reducing excessive secretion of MUC5AC by repairing the intestinal barrier in CP rats.

Using Vascular Deserts as a Guide for Limb Preservation Outreach Programs Successfully Targets Underserved Populations.

OBJECTIVES: Vascular deserts, regions without vascular providers, previously described targets for limb salvage efforts. The CHAMPIONS programs targeted regions for outreach and evaluated the population using desert maps. METHODS: At two events targeting underserved regions between 2022-2023, providers screened and educated participants on peripheral arterial and cardiovascular disease. Demographics and cardiovascular risk factors were collected. Using ArcGIS, vascular surgeons, and VQI participating facilities were mapped with a 30-mile buffer. Participants were mapped with census data, and the Healthy Places Index (HPI) was overlayed for population and social determinants of health data analysis in Medical Service Study Areas (MSSA), a geographical analysis unit. (Figure 1) Results were compared to prior statewide deserts. RESULTS: Outreach program participants' mean age was 56 (range 6-88); 39% were male, and the majority were Hispanic (86%). 27% had no primary care provider. 30% had diabetes, 10% undiagnosed before the event, 38% had hypertension, 40% undiagnosed prior to the event, and 21% described intermittent claudication. 81% made <$30,000 annually, and 28% reported no health insurance. Similarities were observed when comparing program participant demographics to the population-level data from the targeted regions. Patients were more frequently Hispanic than other desert regions (68% vs. 36%, p<.001). Compared to other vascular desert regions, the target population was more disadvantaged in all HPI domains, including economic (18 vs. 38%, p<.001), education (21 vs. 39%, p<.001), and transportation (30 vs. 40%, p<.001). Worse education, financial, and transportation resources correspond to decreased care access due to poor literacy and travel burdens. CONCLUSIONS: CHAMPIONS programs successfully targeted populations needing care based on vascular care desert maps, demonstrating that at-risk populations can be successfully identified and screened for cardiovascular disease.

Timely integration of specialist palliative home care (SPHC) for patients with congestive heart failure, chronic obstructive pulmonary disease and dementia: qualitative evaluation of the experiences of SPHC physicians in the KOPAL trial.

OBJECTIVE: Chronic non-malignant diseases (CNMDs) are under-represented in specialist palliative home care (SPHC). The timely integration of SPHC for patients suffering from these diseases can reduce hospitalisation and alleviate symptom burdens. An intervention of an SPHC nurse-patient consultation followed by an interprofessional telephone case conference with the general practitioner (GP) was tested in the KOPAL trial ('Concept for strengthening interprofessional collaboration for patients with palliative care needs'). As part of the trial, the aim of this study was to gain in-depth insights into SPHC physicians' perspective on care with and without the KOPAL intervention for patients with congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD) and dementia (D). DESIGN: Qualitative evaluation of the KOPAL intervention from the perspective of SPHC physicians as part of the KOPAL trial. Thematic-focused narrative interviews analysed with grounded theory. SETTING: We conducted the KOPAL study and its qualitative evaluation in Lower Saxony and the greater Hamburg area, Germany. PARTICIPANTS: 11 physicians from 14 SPHC teams who participated in the trial were interviewed. RESULTS: A grounded theory of the necessity of collaboration between GPs and SPHC teams for patients with CHF, COPD and dementia was developed. From the perspective of SPHC physicians, patients with CNMD are generally difficult to manage in GP care. The timing of SPHC initiation is patient-specific, underscoring the need for collaboration between SPHC physicians and GPs. However, the primary mandate for healthcare should remain with GPs. SPHC physicians actively seek collaboration with GPs (eg, through the KOPAL intervention), viewing themselves as advisors for GPs and aspiring to collaborate as equal partners. CONCLUSION: Effective communication and the negotiation of future interprofessional collaboration are essential for SPHC teams. TRIAL REGISTRATION NUMBER: DRKS00017795.

Avoidance and Endurance Responses to Pain Before and with Advanced Chronification: Preliminary Results from a Questionnaire Survey in Adult Patients with Non-Cancer Pain Conditions.

Purpose: The Avoidance-Endurance Model postulates fear-avoidance responses and endurance responses as important psychological mechanisms in the development and maintenance of chronic pain. The present study aims to investigate potential differences in avoidance and endurance responses to pain before and with advanced chronification. Patients and Methods: Two samples of adults with non-cancer pain at two different stages of chronicity were compared: One with pain and risk factors for chronicity (n=26, part of the PAIN2020 project) and one with chronic pain (n=33 from a pain day care clinic). The German Pain Questionnaire, the Graded Chronic Pain Scale (GCPS) and medical reports were used to measure duration and severity of pain. Responses to pain were assessed with the Avoidance-Endurance Questionnaire (AEQ) and psychological strain with the Depression, Anxiety and Stress Scales (DASS). Results: Both groups were primarily affected by musculoskeletal pain. Although not yet chronified, the risk group reported comparable GCPS levels of pain intensity and disability. Depression and stress ratings were also similar, except for anxiety, which was significantly elevated in the chronic pain sample (p<.001). The AEQ scales did not differ between groups, neither on any of the fear-avoidance- nor endurance-related dimensions. A post-hoc regression analysis revealed a significant prediction of fear-avoidance by pain-related disability (p<.001). The regression model for endurance responses was not significant. Conclusion: Patients with risk factors of chronification experience substantial pain-related burden. Responses to pain in the realm of the Avoidance-Endurance model do not appear to vary as a function of chronification. While fear-avoidance and pain-related disability correlate positively, endurance could not be associated to any of our variables.