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Background: Ankle fusion is considered a treatment of choice for end-stage ankle arthritis when a total ankle replacement procedure is not indicated. However, the potential risk of secondary arthritis in the adjacent joint after ankle fusion raises arguments on whether preserving the adjacent joint during an isolated tibiotalar (TT) fusion brings about any future benefits with regard to pain and gait discomfort. In this study, we intended to present midterm results following TT or tibiotalocalcaneal (TTC) fusion using an Ilizarov external fixator and to investigate whether spontaneous fusion occurred in the subtalar or midtarsal joint. Methods: This is a retrospective observational study. Medical records of patients who underwent TT or TTC fusion using an Ilizarov external fixator for substantial bone defects around the ankle joint between 1994 and 2018 were manually searched. Forty-one patients were included and the status of the joints adjacent to the fusion site was evaluated in radiographic examinations. Results: Of the 34 patients who underwent TT fusion, 30 patients (88.3%) had a spontaneous fusion in the adjacent joints. Specifically, 11 patients (29.4%) had subtalar joint fusion and 19 patients (55.9%) had both midtarsal joint and subtalar joint fusion. In TTC fusion, the midtarsal joint was spontaneously fused in all 7 patients. Conclusions: In this study, we observed spontaneous adjacent joint fusion following TT or TTC fusion using an Ilizarov external fixator for substantial bone defects around the ankle joint. Although a careful approach should be made since patients treated in this study may not represent typical candidates that need primary joint-sacrificing procedures, we believe that this study may draw attention from surgeons concerned about the fate of the adjacent joint status after TT or TTC fusion.
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Articulação do Tornozelo , Técnica de Ilizarov , Humanos , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Articulação do Tornozelo/cirurgia , Técnica de Ilizarov/instrumentação , Idoso , Artrodese/métodos , Artrodese/instrumentação , Fixadores Externos , Adulto , Articulação Talocalcânea/cirurgia , Calcâneo/cirurgiaRESUMO
Myeloid cell leukemia-1 (MCL-1), which belongs to the anti-apoptotic B cell lymphoma-2 family protein, is overexpressed in various cancers and is associated with cell immortality, malignant transformation, chemoresistance, and poor prognosis in humans. However, the significance of MCL-1 in canine mammary gland tumors (MGTs) remains unknown. This study aimed to examine MCL-1 expression in normal canine mammary glands and tumors and to assess its correlation with clinical and histologic variables. In total, 111 samples were examined, including 12 normal mammary gland tissues, 51 benign MGTs, and 48 malignant MGTs. Immunohistochemistry revealed that 53% of benign tumors and 75% of malignant tumors exhibited high MCL-1 expression, whereas only 8% of normal mammary glands exhibited high MCL-1 expression. High MCL-1 expression correlated with tumor malignancy (p < 0.001), large tumor size (> 3 cm) (p = 0.005), high Ki-67 expression (p = 0.046), and metastasis (p = 0.027). Survival curve analysis of dogs with malignant MGTs demonstrated a significant association between high MCL-1 expression and shorter median overall survival (p = 0.027) and progression-free survival (p = 0.014). Our study identified MCL-1 as a prognostic factor and potential therapeutic target in canine MGTs.
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Doenças do Cão , Neoplasias Mamárias Animais , Proteína de Sequência 1 de Leucemia de Células Mieloides , Animais , Cães , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Feminino , Neoplasias Mamárias Animais/metabolismo , Neoplasias Mamárias Animais/patologia , Prognóstico , Doenças do Cão/metabolismo , Doenças do Cão/patologia , Biomarcadores Tumorais/metabolismo , Imuno-Histoquímica , Glândulas Mamárias Animais/metabolismo , Glândulas Mamárias Animais/patologiaRESUMO
Suprascapular nerve entrapment (SNE) syndrome is a commonly overlooked cause of shoulder weakness and pain. It frequently causes weakness over the posterior and lateral and posterior aspects of the shoulder, as well as pain of infraspinatus muscles. Therefore, we considered that the infraspinatus muscle cross-sectional area (IMCSA) might be a new morphological parameter to analyze SNE syndrome. We assumed that the IMCSA is an important morphologic parameter in SNE syndrome diagnosis. We acquired infraspinatus muscle data from 10 patients with SNE syndrome and from 10 healthy subjects who had undergone magnetic resonance imaging of the shoulder and who revealed no evidence of SNE syndrome. We analyzed the infraspinatus muscle thickness (IMT) and IMCSA at the shoulder on the imaging of the shoulder using our image analysis program. The IMCSA was measured as the whole infraspinatus muscle cross-sectional area that was most atrophied in the sagittal S-MR images. The IMT was measured as the thickest level of infraspinatus muscle. The mean IMT was 29.17â ±â 2.81 mm in the healthy subjects and 25.22â ±â 3.19 mm in the SNE syndrome group. The mean IMCSA was 1321.95â ±â 175.91 mm2 in the healthy group and 1048.38â ±â 259.94 mm2 in the SNE syndrome group. SNE syndrome patients had significantly lower IMT (Pâ <â .001) and IMCSA (Pâ <â .001) than the healthy group. The ROC curve shows that the optimal cutoff point of the IMT was 26.74 mm, with 70.0% sensitivity, 70.0% specificity, and an AUC of 0.83 (95% CI, 0.65-1.00). The best cutoff value of the IMCSA was 1151.02 mm2, with 80.0% sensitivity, 80.0% specificity, and AUC of 0.87 (95% CI, 0.69-1.00). The IMT and IMCSA were both significantly associated with SNE syndrome. And the IMCSA was a highly sensitive diagnostic tool.
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Imageamento por Ressonância Magnética , Síndromes de Compressão Nervosa , Humanos , Masculino , Feminino , Imageamento por Ressonância Magnética/métodos , Síndromes de Compressão Nervosa/diagnóstico por imagem , Pessoa de Meia-Idade , Adulto , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/inervação , Músculo Esquelético/patologia , Ombro/diagnóstico por imagem , Ombro/inervação , Idoso , Estudos de Casos e ControlesRESUMO
Purpose: Severe lymphopenia (SLP) has emerged as a significant prognostic factor in glioblastoma. Intensity-modulated radiation therapy (IMRT)-based radiation therapy (RT) is suggested to minimize the risk of SLP. This study aimed to evaluate SLP incidence based on multi-institutional database in patients with GBM treated with IMRT and develop a predictive nomogram. Patients and methods: This retrospective study reviewed data from 348 patients treated with IMRT-based concurrent chemoradiation therapy (CCRT) at two major hospitals from 2016 to 2021. After multivariate regression analysis, a nomogram was developed and internally validated to predict SLP risk. Results: During treatment course, 21.0% of patients developed SLP and SLP was associated with poor overall survival outcomes in patients with GBM. A newly developed nomogram, incorporating gender, pre-CCRT absolute lymphocyte count, and brain mean dose, demonstrated fair predictive accuracy (AUC 0.723). Conclusions: This study provides the first nomogram for predicting SLP in patients with GBM treated with IMRT-based CCRT, with acceptable predictive accuracy. The findings underscore the need for dose optimization and radiation planning to minimize SLP risk. Further external validation is crucial for adopting this nomogram in clinical practice.
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PURPOSE: We aimed to investigate the safety and efficacy of HL301, a standardized combination product of 7 medicinal plants, in radiation pneumonitis in patients with unresectable non-small cell lung cancer undergoing curative concurrent chemoradiotherapy. METHODS AND MATERIALS: The target accrual was 87 and a total of 63 patients were enrolled due to poor accrual rate. We randomly assigned the 63 patients to receive a placebo (arm A), or 1200 mg HL301 (arm B), or 1800 mg HL301 (arm C). Patients received weekly paclitaxel and carboplatin concurrently with intensity-modulated radiation therapy at 60 to 66 Gy in conventional fractionation. Durvalumab was administered as a maintenance treatment according to standard clinical practice. HL301 was administered orally, daily for 12 weeks. The primary endpoint was incidence of grade ≥2 radiation pneumonitis at 24 weeks postchemoradiotherapy. RESULTS: The baseline characteristics of the patients were well balanced. The drug was tolerable with a compliance rate of 86.6%, 86.2%, and 88.8% in arms A, B, and C, respectively (P = .874). None of the patients experienced severe drug-related adverse events. No significant difference in the rate of adverse events were observed between the treatment arms. The incidence of grade ≥2 radiation pneumonitis at 24 weeks postchemoradiotherapy was 37.5% (95% CI, 18.5%-61.4%), 55.6% (95% CI, 33.7%-75.4%), and 52.4% (95% CI, 32.4%-71.7%) in arms A, B, and C, respectively (P = .535). CONCLUSIONS: This is the first exploratory clinical trial to test the safety and efficacy of HL301 in patients with non-small cell lung cancer. Safety and feasibility of HL301 were established but no signals of efficacy in reducing radiation pneumonitis was observed in this dose level.
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In a recent stereotactic body radiation therapy animal model, radiation pneumonitis and radiation pulmonary fibrosis were observed at around 2 and 6 weeks, respectively. However, the molecular signature of this model remains unclear. This study aimed to examine the molecular characteristics at these two stages using RNA-seq analysis. Transcriptomic profiling revealed distinct transcriptional patterns for each stage. Inflammatory response and immune cell activation were involved in both stages. Cell cycle processes and response to type II interferons were observed during the inflammation stage. Extracellular matrix organization and immunoglobulin production were noted during the fibrosis stage. To investigate the impact of a 10 Gy difference on fibrosis progression, doses of 45, 55, and 65 Gy were tested. A dose of 65 Gy was selected and compared with 75 Gy. The 65 Gy dose induced inflammation and fibrosis as well as the 75 Gy dose, but with reduced lung damage, fewer inflammatory cells, and decreased collagen deposition, particularly during the inflammation stage. Transcriptomic analysis revealed significant overlap, but differences were observed and clarified in Gene Ontology and KEGG pathway analysis, potentially influenced by changes in interferon-gamma-mediated lipid metabolism. This suggests the suitability of 65 Gy for future preclinical basic and pharmaceutical research connected with radiation-induced lung injury.
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Lesão Pulmonar , Fibrose Pulmonar , Lesões por Radiação , Animais , Lesão Pulmonar/genética , Fibrose Pulmonar/genética , Inflamação , Interferon gama/genética , Pulmão , Doses de RadiaçãoRESUMO
The differentiation of naive CD8+ T cells into effector cells is important for establishing immunity. However, the effect of heterogeneous naive CD8+ T cell populations is not fully understood. Here, we demonstrate that steady-state naive CD8+ T cells are composed of functionally heterogeneous subpopulations that differ in their ability to differentiate into type 17 cytotoxic effector cells (Tc17) in a context of murine inflammatory disease models, such as inflammatory bowel disease and graft-versus-host disease. The differential ability of Tc17 differentiation is not related to T-cell receptor (TCR) diversity and antigen specificity but is inversely correlated with self-reactivity acquired during development. Mechanistically, this phenomenon is linked to differential levels of intrinsic TCR sensitivity and basal Suppressor of Mothers Against Decapentaplegic 3 (SMAD3) expression, generating a wide spectrum of Tc17 differentiation potential within naive CD8+ T cell populations. These findings suggest that developmental self-reactivity can determine the fate of naive CD8+ T cells to generate functionally distinct effector populations and achieve immense diversity and complexity in antigen-specific T-cell immune responses.
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Linfócitos T CD8-Positivos , Inflamação , Camundongos , Animais , Modelos Animais de Doenças , Diferenciação Celular , Inflamação/patologia , Receptores de Antígenos de Linfócitos T/metabolismoRESUMO
Addressing age-related immunological defects through therapeutic interventions is essential for healthy aging, as the immune system plays a crucial role in controlling infections, malignancies, and in supporting tissue homeostasis and repair. In our study, we show that stimulating toll-like receptor 5 (TLR5) via mucosal delivery of a flagellin-containing fusion protein effectively extends the lifespan and enhances the healthspan of mice of both sexes. This enhancement in healthspan is evidenced by diminished hair loss and ocular lens opacity, increased bone mineral density, improved stem cell activity, delayed thymic involution, heightened cognitive capacity, and the prevention of pulmonary lung fibrosis. Additionally, this fusion protein boosts intestinal mucosal integrity by augmenting the surface expression of TLR5 in a certain subset of dendritic cells and increasing interleukin-22 (IL-22) secretion. In this work, we present observations that underscore the benefits of TLR5-dependent stimulation in the mucosal compartment, suggesting a viable strategy for enhancing longevity and healthspan.
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Longevidade , Receptor 5 Toll-Like , Animais , Camundongos , Flagelina/metabolismo , Mucosa Intestinal/metabolismo , Longevidade/genética , Pulmão/metabolismoRESUMO
Background: We aimed to comprehensively investigate the prognostic value of pretreatment laboratory parameters in elderly patients with glioblastoma treated with temozolomide (TMZ)-based chemoradiation. Methods: Patients agedâ ≥â 65 years from 4 institutions with newly diagnosed IDH-wild-type glioblastoma who received radiotherapy (RT) with concurrent TMZ between 2006 and 2021 were included. Patient factors (age, Karnofsky performance status (KPS), temporalis muscle thickness), molecular factors (MGMT promoter methylation, EGFR amplification, TERT promoter mutation, and TP53 mutation status), treatment factors (extent of resection, and RT dose), and pretreatment laboratory parameters (serum De Ritis ratio, glucose level, neutrophil-to-lymphocyte ratio, platelet count, and systemic immune-inflammation index) were included in the analysis. The primary endpoint was overall survival (OS). Results: In total, 490 patients were included in the analysis. The median follow-up period was 12.3 months (range, 1.6-149.9 months). Median OS was significantly prolonged in patients with De Ritis ratioâ <â 1.2 (18.2 vs 15.3 months, Pâ =â .022) and in patients with glucose levelâ <â 150 mg/dL (18.7 vs 16.5 months, Pâ =â .034) per univariate analysis. In multivariate analysis, KPSâ ≥â 70, MGMT promoter methylation, extent of resection greater than partial resection, De Ritis ratioâ <â 1.2, and glucose levelâ <â 150 mg/dL were significant prognostic factors for improved OS. Conclusions: Along with well-known prognostic factors, pre-RT serum biomarkers, including the De Ritis ratio and glucose level, also had prognostic value in elderly patients with glioblastoma treated with TMZ-based chemoradiation.
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Disability and pain associated with lumbar degenerative spondylolisthesis (LDS) result in a significant burden on both the healthcare costs and patients' quality of life. Currently, there exists controversy regarding employment of either nonsurgical management (NSM) or surgical management (SM) in a clinical setting. Spinal canal cross-sectional area (SCA) has been an important morphological parameter for the analysis of LDS. However, there is lack of research about the comparative value of NSM and SM according to SCA. Moreover, previous research have not yet evaluated the clinical most suitable cutoff values of SCA. The objective of this research was to evaluate the effective of NSM and SM for LDS using SCA as an objective morphological parameter. The axial T2 magnetic resonance imaging images were obtained from each patient. We collected SCA samples from 149 patients with LDS. 72 patients underwent SM and the rest did NSM. We measured SCA at the L4/5 LDS on magnetic resonance imaging using a picture archiving and communications system. We measured SCA at the intervertebral disk posterior border, turning down to reach the facet joint side on the opposite edge at the L4/5 level. The average SCA value was 114.34â ±â 48.11 mm2 in the NSM group and 69.88â ±â 27.87 mm2 in the SM group. Therefore, the SM group had considerably lower SCA (Pâ <â .001). In view of the effectiveness of SCA as a prediction factor of surgical option, Receiver Operating Characteristic curve analysis show the optimal cutoff value for SCA as 83.21 mm2, with 70.8% sensitivity, 71.4% specificity, and an area under the curve of 0.80 (95% CI, 0.73-0.87). The narrower the SCA, the higher the probability of SM. Thus, it is proposed that to evaluate surgical decision making, the pain physician should carefully inspect the SCA.
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Espondilolistese , Articulação Zigapofisária , Humanos , Espondilolistese/complicações , Espondilolistese/diagnóstico por imagem , Espondilolistese/cirurgia , Qualidade de Vida , Articulação Zigapofisária/patologia , Imageamento por Ressonância Magnética/métodos , Dor/patologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Vértebras Lombares/patologia , Canal MedularRESUMO
The purpose of this study was to determine the ratio of sagittal length to coronal length of the distal tibia for predicting the sagittal length of the distal tibia. A total of 202 ankles were measured based on CT imaging availability. We measured the coronal length (Width, W) parallel to the Chaput tubercle from CT scans. Sagittal length was divided into 3 points (Diameter D1, D2, D3) in the axial plane on the same level. The relationship between coronal length and each sagittal length was determined through correlation analysis. A prediction model was then developed using multiple regression. We also analyzed the quality of the prediction model and validated the prediction model with a validation cohort. Each sagittal length (D1, D2, D3) and coronal length had a significant positive correlation (p < .01). In the prediction model, sex, height, and W were significantly associated with D1, D2, and D3 (p < .05). Prediction models were made for each sagittal length (D1, D2, D3). Concordance correlation coefficient (CCC) values of prediction models for D1, D2, and D3 were 0.78, 0.72, and 0.72 for the derivation cohort and 0.69, 0.63, and 0.61 for the validation cohort, respectively. Accuracies of models as ± 2SD for D1, D2, and D3 were 93.9%, 94.9%, and 94.9%, respectively. This study predicted the sagittal length of the distal tibia for preoperative planning by measuring the coronal length of the distal tibia. Prediction of the sagittal length of the distal tibia can help foot and ankle surgeons fixate screws stably to prevent iatrogenic injury of posterior structures of the distal tibia.
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Tíbia , Tomografia Computadorizada por Raios X , Humanos , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Tornozelo , Articulação do TornozeloRESUMO
PURPOSE: Surgery, radiotherapy (RT), and chemotherapy have prolonged the survival of patients with anaplastic oligodendroglioma. However, whether RT induces long-term toxicity remains unknown. We analyzed the relationship between the RT dose to the fornix and symptomatic radiation necrosis (SRN). MATERIALS AND METHODS: A total of 67 patients treated between 2009 and 2019 were analyzed. SRN was defined according to the following three criteria: 1) radiographic findings, 2) symptoms attributable to the lesion, and 3) treatment resulting in symptom improvement. Various contours, including the fornix, were delineated. Univariate and multivariate analyses of the relationship between RT dose and SRN, as well as receiver operating characteristic curve analysis for cut-off values, were performed. RESULTS: The most common location was the frontal lobe (n=40, 60%). Gross total resection was performed in 38 patients (57%), and 42 patients (63%) received procarbazine, lomustine, and vincristine chemotherapy. With a median follow-up of 42 months, the median overall and progression-free survival was 74 months. Sixteen patients (24%) developed SRN. In multivariate analysis, age and maximum dose to the fornix were associated with the development of SRN. The cut-off values for the maximum dose to the fornix and age were 59 Gy (equivalent dose delivered in 2 Gy fractions) and 46 years, respectively. The rate of SRN was higher in patients whose maximum dose to the fornix was >59 Gy (13% vs. 43%, p=0.005). CONCLUSION: The maximum dose to the fornix was a significant factor for SRN development. While fornix sparing may help maintain neurocognitive function, additional studies are needed.
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Neoplasias Encefálicas , Oligodendroglioma , Humanos , Oligodendroglioma/tratamento farmacológico , Oligodendroglioma/radioterapia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Vincristina/efeitos adversos , Doses de Radiação , Necrose/induzido quimicamente , Necrose/tratamento farmacológicoRESUMO
Radiation-induced lung fibrosis (RILF) is a common complication of radiotherapy in lung cancer. However, to date no effective treatment has been developed for this condition. NXC736 is a novel small-molecule compound that inhibits NLRP3, but its effect on RILF is unknown. NLRP3 activation is an important trigger for the development of RILF. Thus, we aimed to evaluate the therapeutic effect of NXC736 on lung fibrosis inhibition using a RILF animal model and to elucidate its molecular signaling pathway. The left lungs of mice were irradiated with a single dose of 75 Gy. We observed that NXC736 treatment inhibited collagen deposition and inflammatory cell infiltration in irradiated mouse lung tissues. The damaged lung volume, evaluated by magnetic resonance imaging, was lower in NXC736-treated mice than in irradiated mice. NXC736-treated mice exhibited significant changes in lung function parameters. NXC736 inhibited inflammasome activation by interfering with the NLRP3-ASC-cleaved caspase-1 interaction, thereby reducing the expression of IL-1ß and blocking the fibrotic pathway. In addition, NXC736 treatment reduced the expression of epithelial-mesenchymal transition markers such as α-SMA, vimentin, and twist by blocking the Smad 2,3,4 signaling pathway. These data suggested that NXC736 is a potent therapeutic agent against RILF.
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Fibrose Pulmonar , Lesões por Radiação , Camundongos , Animais , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pulmão/patologia , Fibrose , Inflamassomos/metabolismo , Lesões por Radiação/metabolismo , Transdução de Sinais , Síndrome da Fibrose por RadiaçãoRESUMO
This study evaluates the suitability of the plantaris tendon (PT) as a tendon graft donor for sports trauma reconstruction and proposes a predictive model for estimating PT length by using an individual's height and leg length. Anatomical dissection of 50 cadavers (32 males and 18 females) yielded precise measurements of PT length and width while also recording height and leg length. Among the lower limbs, 89% were suitable for at least one recommended graft suitability criterion. In addition, PT length exhibited robust positive correlations with height and leg length. Predictive equations were established for estimating the PT length based on leg length and height with consistency across sexes and sides: PT length = 0.605 + 0.396 × leg length (r = 0.721) and PT length = 1.480 + 0.193 × height (r = 0.626). This study underscores the grafting potential of the PT, providing a predictive tool that can aid surgeons in addressing tendon graft challenges within sports trauma scenarios.
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BACKGROUND AND PURPOSE: The ability of the effective dose to immune cells (EDIC) and the pre-radiotherapy (RT) absolute lymphocyte count (ALC) to predict lymphopenia during RT, treatment outcomes, and efficacy of consolidation immunotherapy in patients with locally advanced non-small cell lung cancer was investigated. METHODS AND MATERIALS: Among 517 patients treated with concurrent chemoradiotherapy, EDIC was calculated using the mean doses to the lungs, heart, and total body. The patients were grouped according to high and low EDIC and pre-RT ALC, and the correlations with radiation-induced lymphopenia and survival outcomes were determined. RESULTS: Altogether, 195 patients (37.7%) received consolidation immunotherapy. The cutoff values of EDIC and pre-RT ALC for predicting severe lymphopenia were 2.89 Gy and 2.03 × 109 cells/L, respectively. The high-risk group was defined as EDIC ≥ 2.89 Gy and pre-RT ALC < 2.03 × 109 cells/L, while the low-risk group as EDIC < 2.89 Gy and pre-RT ALC ≥ 2.03 × 109 cells/L, and the rest of the patients as the intermediate-risk group. The incidences of severe lymphopenia during RT in the high-, intermediate-, and low-risk groups were 90.1%, 77.1%, and 52.3%, respectively (P < 0.001). The risk groups could independently predict both progression-free (P < 0.001) and overall survival (P < 0.001). The high-risk group showed a higher incidence of locoregional and distant recurrence (P < 0.001). Consolidation immunotherapy showed significant survival benefit in the low- and intermediate-risk groups but not in the high-risk group. CONCLUSIONS: The combination of EDIC and pre-RT ALC predicted severe lymphopenia, recurrence, and survival. It may potentially serve as a biomarker for consolidation immunotherapy.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Linfopenia , Humanos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Linfopenia/etiologia , Resultado do Tratamento , Quimiorradioterapia/efeitos adversos , Imunoterapia/efeitos adversos , Estudos RetrospectivosRESUMO
BACKGROUND: The standard of care for glioblastoma multiforme (GBM) is maximal surgical resection followed by conventional fractionated concurrent chemoradiotherapy (CCRT) with a total dose of 60 Gy. However, there is currently no consensus on the optimal boost technique for CCRT in GBM. METHODS: We conducted a retrospective review of 398 patients treated with CCRT between 2016 and 2021, using data from two institutional databases. Patients were divided into two groups: those receiving sequential boost (SEB, N = 119) and those receiving simultaneous integrated boost (SIB, N = 279). The primary endpoint was overall survival (OS). To minimize differences between the SIB and SEB groups, we conducted propensity score matching (PSM) analysis. RESULTS: The median follow-up period was 18.6 months. Before PSM, SEB showed better OS compared to SIB (2-year, 55.6% vs. 44.5%, p = 0.014). However, after PSM, there was no significant difference between two groups (2-year, 55.6% vs. 51.5%, p = 0.300). The boost sequence was not associated with inferior OS before and after PSM (all p-values > 0.05). Additionally, the rates of symptomatic pseudo-progression were similar between the two groups (odds ratio: 1.75, p = 0.055). CONCLUSIONS: This study found no significant difference in OS between SEB and SIB for GBM patients treated with CCRT. Further research is needed to validate these findings and to determine the optimal boost techniques for this patient population.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/terapia , Glioblastoma/tratamento farmacológico , Quimiorradioterapia/métodos , Estudos Retrospectivos , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/tratamento farmacológicoRESUMO
Defining the molecular dynamics associated with T cell differentiation enhances our understanding of T cell biology and opens up new possibilities for clinical implications. In this study, we investigated the dynamics of CD5 expression in CD8+ T cell differentiation and explored its potential clinical uses. Using PBMCs from 29 healthy donors, we observed a stepwise decrease in CD5 expression as CD8+ T cells progressed through the differentiation stages. Interestingly, we found that CD5 expression was initially upregulated in response to T cell receptor stimulation, but diminished as the cells underwent proliferation, potentially explaining the differentiation-associated CD5 downregulation. Based on the proliferation-dependent downregulation of CD5, we hypothesized that relative CD5 expression could serve as a marker to distinguish the heterogeneous CD8+ T cell population based on their proliferation history. In support of this, we demonstrated that effector memory CD8+ T cells with higher CD5 expression exhibited phenotypic and functional characteristics resembling less differentiated cells compared to those with lower CD5 expression. Furthermore, in the retrospective analysis of PBMCs from 30 non-small cell lung cancer patients, we found that patients with higher CD5 expression in effector memory T cells displayed CD8+ T cells with a phenotype closer to the less differentiated cells, leading to favorable clinical outcomes in response to immune checkpoint inhibitor (ICI) therapy. These findings highlight the dynamics of CD5 expression as an indicator of CD8+ T cell differentiation status, and have implications for the development of predictive biomarker for ICI therapy.
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Diabetic foot ulcers (DFUs) are among the most serious complications of diabetes and are a source of reduced quality of life and financial burden for the people involved. For effective DFU management, an evidence-based treatment strategy that considers the patient's clinical context and wound condition is required. This treatment strategy should include conventional practices (surgical debridement, antibiotics, vascular assessment, offloading, and amputation) coordinated by interdisciplinary DFU experts. In addition, several adjuvant therapies can be considered for nonhealing wounds. In this narrative review, we aim to highlight the current trends in DFU management and review the up-to-date guidelines.
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Chondromalacia patella (CMP) is abnormal softening of the cartilage of the underside the patella. It is a cause of anterior knee pain. Previous study has demonstrated that the patellar cartilage hypertrophy is correlated with early signs of CMP (Grade 1 or 2). However, no studies have investigated the clinical cutoff value of patella cartilage hypertrophy. Thus, we devised the patellar cartilage cross-sectional area (PCCSA) as a new predictive parameter for diagnosing the CMP. The purpose of this research was to compare MR measured PCCSA between CMP patients and gender matched healthy controls. The PCCSA samples were collected from 50 patients with CMP, and from 50 healthy controls who underwent knee MRI with no evidence of CMP. The T2-weighted turbo spin echo transverse MRI images were acquired. We measured the PCCSA on MRI using a PACS system. The PCCSA was measured on the axial angled sections through the whole images by drawing outlines. The average PCCSA was 104.28â ±â 23.28 mm2 in the healthy controls and 134.09â ±â 26.55 mm2 in the CMP group. CMP patients had significantly higher PCCSA (Pâ <â .001). Regarding the validity of PCCSA as predictors of CMP, Receiver Operating Characteristic curve analysis showed that the best cutoff point for the PCCSA was 116.24 mm2, with 72.0% sensitivity, 72.0% specificity, and the area under curve (AUC) of 0.79 (0.71-0.88). The PCCSA is a sensitive measurement parameter to predict low grade CMP. Thus, to evaluate CMP patients, the treating physician carefully inspect the PCCSA.