RESUMO
Background: Balloon kyphoplasty (BKP) is a method for the management of osteoporotic vertebral body fracture (OVF). However, improvement in back pain (BP) is poor in some patients, also previous reports have not elucidated the exact incidence and risk factors for residual BP after BKP. We clarified the characteristics of residual BP after BKP in patients with OVF. Hypothesis: In this study, we hypothesize that some risk factors may exist for residual BP 2 years after the treatment of OVF with BKP. Patients and Methods: A multicenter cohort study was performed where patients who received BKP within 2 months of OVF injury were followed-up for 2 years. BP at 6 months after surgery and final observation was evaluated by Visual Analog Scale (VAS) score. Patients with a score of 40 mm or more were allocated to the residual BP group, and comparisons between the residual back pain group and the improved group were made for bone density, kyphosis, mobility of the fractured vertebral body, total spinal column alignment, and fracture type (fracture of the posterior element, pedicle fracture, presence or absence of posterior wall damage, etc.). Also, Short Form 36 (SF-36) for physical component summary (PCS) and mental component summary (MCS) at the final follow-up was evaluated in each radiological finding. Results: Of 116 cases, 79 (68%) were followed-up for 2 years. Two years after the BKP, 26 patients (33%) experienced residual BP. Neither age nor sex differed between the groups. In addition, there was no difference in bone mineral density, BKP intervention period (period from onset to BKP), and osteoporosis drug use. However, the preoperative height ratio of the vertebral body was significantly worse in the residual BP group (39.8% vs. 52.1%; p = 0.007). Two years after the operation, the vertebral body wedge angle was significantly greater in the residual BP group (15.7° vs. 11.9°; p = 0.042). In the multiple logistic regression model with a preoperative vertebral body height ratio of 50% or less [calculated by receiver operating characteristic (ROC) curve], the adjusted odds ratio for residual BP was 6.58 (95% confidence interval 1.64-26.30; p = 0.007); similarly, patients with vertebral body height ratio less than 50% had a lower score of SF-36 PCS 24.6 vs. 32.2 p = 0.08. Conclusion: The incidence of residual BP 2 years after BKP was 33% in the current study. The risk factor for residual BP after BKP was a preoperative vertebral body height ratio of 50% or less, which should be attentively assessed for the selection of a proper treatment scheme and to provide adequate stabilization. Level of Evidence: III.
RESUMO
BACKGROUND: Companion diagnostic tests play a crucial role in guiding treatment decisions for patients with non-small cell lung cancer (NSCLC). The Oncomine Dx Target Test (ODxTT) Multi-CDx System has emerged as a prominent companion diagnostic method. However, its efficacy in detecting driver gene mutations, particularly rare mutations, warrants investigation. AIMS: This study aimed to assess the performance of the ODxTT in detecting driver gene mutations in NSCLC patients. Specifically, we aimed to evaluate its sensitivity in detecting epidermal growth factor receptor (EGFR) mutations, a key determinant of treatment selection in NSCLC. MATERIALS AND METHODS: We conducted a retrospective analysis of NSCLC patients who underwent testing with the ODxTT at Keio University Hospital between May 2020 and March 2022. Patient samples were subjected to both DNA and RNA tests. Driver gene mutation status was assessed, and instances of missed mutations were meticulously examined. RESULTS: Of the 90 patients, five had nucleic acid quality problems, while 85 underwent both DNA and RNA tests. Driver gene mutations were detected in 56/90 (62.2%) patients. Of the 34 patient specimens, driver mutations were not detected using the ODxTT; however, epidermal growth factor receptor (EGFR) mutations were detected using polymerase chain reaction-based testing in two patients, and a KRAS mutation was detected by careful examination of the sequence data obtained using the ODxTT in one patient. For the above three cases, carefully examining the gene sequence information obtained using the ODxTT could identify driver mutations that were not mentioned in the returned test results. Additionally, we confirmed comparable instances of overlook results for EGFR mutations in the dataset from South Korea, implying that this type of oversight could occur in other countries using the ODxTT. EGFR mutation was missed in ODxTT in Japan (6.3%, 2/32), South Korea (2.0%, 1/49), and overall (3.7%, 3/81). CONCLUSION: Even if sufficient tumor samples are obtained, rare EGFR mutations (which are excluded from the ODxTT's genetic mutation list) might not be detected using the current ODxTT system due to the program used for sequence analysis. However, such rare EGFR mutations can still be accurately detected on ODxTT's sequence data using next-generation sequencing.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Estudos Retrospectivos , Mutação , Receptores ErbB/genética , DNA/uso terapêutico , RNARESUMO
UV-B radiation induces sunburn, and neutrophils are pivotal in this inflammation. In this study, we examined the potential involvement of neutrophil extracellular traps (NETs) in ultraviolet B (UVB)-induced skin inflammation, correlating the skin inflammation-mitigating effects of Hochu-ekki-to on UV-B irradiation and NETs. To elucidate NET distribution in the dorsal skin, male ICR mice, exposed to UVB irradiation, were immunohistologically analyzed to detect citrullinated histone H3 (citH3) and peptidylarginine deiminase 4 (PAD4). Reactive oxygen species (ROS) production in the bloodstream was analyzed. To establish the involvement of NET-released DNA in this inflammatory response, mice were UV-B irradiated following the intraperitoneal administration of DNase I. In vitro experiments were performed to scrutinize the impact of Hochu-ekki-to on A23187-induced NETs in neutrophil-like HL-60 cells. UV-B irradiation induced dorsal skin inflammation, coinciding with a significant increase in citH3 and PAD4 expression. Administration of DNase I attenuated UV-B-induced skin inflammation, whereas Hochu-ekki-to administration considerably suppressed the inflammation, correlating with diminished levels of citH3 and PAD4 in the dorsal skin. UV-B irradiation conspicuously augmented ROS and hydrogen peroxide (H2O2) production in the blood. Hochu-ekki-to significantly inhibited ROS and H2O2 generation. In vitro experiments demonstrated that Hochu-ekki-to notably inhibited A23187-induced NETs in differentiated neutrophil-like cells. Hence, NETs have been implicated in UV-B-induced skin inflammation, and their inhibition reduces cutaneous inflammation. Additionally, Hochu-ekki-to mitigated skin inflammation by impeding neutrophil infiltration and NETs in the dorsal skin of mice.
Assuntos
Desoxirribonuclease I , Medicamentos de Ervas Chinesas , Armadilhas Extracelulares , Raios Ultravioleta , Animais , Masculino , Camundongos , Calcimicina/farmacologia , Desoxirribonuclease I/farmacologia , Desoxirribonuclease I/metabolismo , Armadilhas Extracelulares/efeitos dos fármacos , Armadilhas Extracelulares/efeitos da radiação , Histonas/metabolismo , Peróxido de Hidrogênio/metabolismo , Inflamação/metabolismo , Camundongos Endogâmicos ICR , Neutrófilos/metabolismo , Desiminases de Arginina em Proteínas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Raios Ultravioleta/efeitos adversosRESUMO
Crohn's disease, a chronic and recurrent gastrointestinal disease, frequently causes intestinal fibrosis. Transient receptor potential melastatin 2 (TRPM2), a non-selective cation channel, is activated by reactive oxygen species. This study investigated the role of TRPM2 in acute colitis and chronic colitis-associated fibrosis progression. Acute colitis and chronic colitis-associated fibrosis were induced in TRPM2-deficient (TRPM2KO) and wild-type (WT) mice through single and repeated intrarectal injections of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Bone marrow-derived macrophages (BMDMs) from WT and TRPM2KO mice were stimulated using H2O2. In WT mice, a single TNBS injection induced acute colitis with upregulated inflammatory cytokines/chemokines and Th1/Th17-related cytokines, while repeated TNBS injections induced chronic colitis-associated fibrosis with upregulation of fibrogenic factors and Th2-related cytokines. Acute colitis and chronic colitis-associated fibrosis with cytokines/chemokine upregulation and fibrogenic factors were considerably suppressed in TRPM2KO mice. Treating BMDMs with H2O2 increased cytokine/chemokine expression and JNK, ERK, and p38 phosphorylation; however, these responses were significantly less in TRPM2KO than in WT mice. These findings suggest that TRPM2 contributes to acute colitis progression via Th1/Th17-mediated immune responses. Furthermore, TRPM2 may be directly involved in colitis-associated fibrosis induction, likely due to the regulation of Th2/TGF-ß1-mediated fibrogenesis in addition to a consequence of acute colitis progression.