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1.
Cureus ; 16(8): e66081, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39224739

RESUMEN

The hip and lumbar spine are closely related and can create similar patterns of pain and dysfunction. Furthermore, diagnosing and treating hip and spine conditions can be challenging due to the overlap of symptoms. This report describes the successful treatment of a 54-year-old male with hip-spine syndrome following multiple surgeries for spondylolytic spondylolisthesis. The patient presented with low back pain (LBP) and bilateral hip pain, with radiological findings indicating spinal deformity and hip joint synovitis. Two years after two-stage corrective surgery, including pedicle subtraction osteotomy (PSO), the hip synovitis resolved and the symptoms improved. This case emphasizes the need to consider hip-spine syndrome as a possible complication of lumbosacral spine fusion surgery and demonstrates the efficacy of two-stage corrective surgery with pedicle subtraction osteotomy in treating this condition.

2.
J Clin Oncol ; : JCO2302626, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39088783

RESUMEN

PURPOSE: HERALD/EPOC1806 was conducted as a multicenter phase II trial assessing trastuzumab deruxtecan (T-DXd) therapy for patients with human epidermal growth factor receptor 2 (HER2)-amplified progressive stage solid tumors detected by cell-free DNA (cfDNA) testing. PATIENTS AND METHODS: Patients exhibited advanced solid tumors with HER2 amplification that was identified via next-generation sequencing of cfDNA testing, without the requirement for immunohistochemical HER2 testing. The studied group was administered T-DXd at 5.4 mg/kg once every 3 weeks until onset of disease progression or intolerable toxicity. RESULTS: Overall, 4,734 patients underwent cfDNA testing from December 2019 to January 2022, and 252 demonstrated HER2 amplification. Finally, the study included 62 patients with 16 cancer types with a median baseline plasma HER2 copy number (CN) of 8.55 (range, 2.4-73.9). Confirmed overall response rate (ORR) by investigator assessment was 56.5% (95% CI, 43.3 to 69.0), thus showing a value beyond the 5% threshold. Responses were evaluated for 13 cancer types, including KRAS-mutant colorectal (1/3), PIK3CA-mutant endometrial (5/6), and tissue HER2-negative gastric (1/2) cancers. Plasma HER2 CN above versus below the baseline median value did not differ for impact response; however, clearance of HER2 amplification in cfDNA on cycle 2 day 1 had higher response values compared with persistence. Median progression-free survival and response duration were 7.0 (95% CI, 4.9 to 9.7) and 8.8 (95% CI, 5.8 to 11.2) months, respectively, with the majority of complications being mild to moderate. Interstitial lung diseases were identified in 16 (26%) patients, including 14 patients with grade 1 disease, one patient with grade 2 disease, and one patient with grade 3 disease. CONCLUSION: T-DXd treatment demonstrated high ORR with durable response in patients with advanced HER2-amplified solid tumors determined with cfDNA testing.

4.
Int J Mol Sci ; 25(15)2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39125917

RESUMEN

Cell transplantation is being actively explored as a regenerative therapy for discogenic back pain. This study explored the regenerative potential of Tie2+ nucleus pulposus progenitor cells (NPPCs) from intervertebral disc (IVD) tissues derived from young (<25 years of age) and old (>60 years of age) patient donors. We employed an optimized culture method to maintain Tie2 expression in NP cells from both donor categories. Our study revealed similar Tie2 positivity rates regardless of donor types following cell culture. Nevertheless, clear differences were also found, such as the emergence of significantly higher (3.6-fold) GD2 positivity and reduced (2.7-fold) proliferation potential for older donors compared to young sources. Our results suggest that, despite obtaining a high fraction of Tie2+ NP cells, cells from older donors were already committed to a more mature phenotype. These disparities translated into functional differences, influencing colony formation, extracellular matrix production, and in vivo regenerative potential. This study underscores the importance of considering age-related factors in NPPC-based therapies for disc degeneration. Further investigation into the genetic and epigenetic alterations of Tie2+ NP cells from older donors is crucial for refining regenerative strategies. These findings shed light on Tie2+ NPPCs as a promising cell source for IVD regeneration while emphasizing the need for comprehensive understanding and scalability considerations in culture methods for broader clinical applicability.


Asunto(s)
Núcleo Pulposo , Receptor TIE-2 , Humanos , Núcleo Pulposo/metabolismo , Núcleo Pulposo/citología , Receptor TIE-2/metabolismo , Receptor TIE-2/genética , Adulto , Persona de Mediana Edad , Masculino , Femenino , Anciano , Factores de Edad , Adulto Joven , Proliferación Celular , Células Cultivadas , Regeneración , Células Madre/citología , Células Madre/metabolismo , Degeneración del Disco Intervertebral/terapia , Disco Intervertebral/metabolismo , Disco Intervertebral/citología , Diferenciación Celular , Adolescente , Trasplante de Células Madre/métodos , Animales
5.
J Dev Biol ; 12(3)2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-39051200

RESUMEN

The intervertebral disc (IVD) is the largest avascular organ of the human body and plays a fundamental role in providing the spine with its unique structural and biomechanical functions. The inner part of the IVD contains the nucleus pulposus (NP), a gel-like tissue characterized by a high content of type II collagen and proteoglycans, which is crucial for the disc's load-bearing and shock-absorbing properties. With aging and IVD degeneration (IDD), the NP gradually loses its physiological characteristics, leading to low back pain and additional sequelae. In contrast to surrounding spinal tissues, the NP presents a distinctive embryonic development since it directly derives from the notochord. This review aims to explore the embryology of the NP, emphasizing the pivotal roles of key transcription factors, which guide the differentiation and maintenance of the NP cellular components from the notochord and surrounding sclerotome. Through an understanding of NP development, we sought to investigate the implications of the critical developmental aspects in IVD-related pathologies, such as IDD and the rare malignant chordomas. Moreover, this review discusses the therapeutic strategies targeting these pathways, including the novel regenerative approaches leveraging insights from NP development and embryology to potentially guide future treatments.

7.
JOR Spine ; 7(2): e1348, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38919468

RESUMEN

Low back pain (LBP) and neck pain predominate as the primary causes of disability. Cell- and platelet-rich plasma (PRP) products are potential therapies with clinical trials and reviews promoting their efficacy. Nonetheless, they frequently disregard the clinical significance of reported improvements. In this systematic review, the effectuated improvements in pain, disability, quality of life (QoL), and radiographic images are comprehensively described and scored on their clinical significance. An electronic database literature search was conducted on July 2023 for in-human assessment of cell or PRP products to alleviate discogenic pain. Papers were screened on quantitative pain, disability, QoL, radiographic improvements, and safety outcomes. Risk of bias was assessed through MINORS and Cochrane Source of Bias tools. Reported outcomes were obtained, calculated, and assessed to meet minimal clinically important difference (MCID) standards. From 7623 screened papers, a total of 80 articles met the eligibility criteria, presenting 68 specific studies. These presented at least 1974 treated patients. Overall, cell/PRP injections could alleviate pain and disability, resulting in MCID for pain and disability in up to a 2-year follow-up, similar to those observed in patients undergoing spinal fusion. Included trials predominantly presented high levels of bias, involved heterogeneous study designs, and only a minimal number of randomized controlled trials. Nonetheless, a clear clinically significant impact was observed for cell- and PRP-treated cohorts with overall good safety profiles. These results highlight a strong therapeutic potential but also underline the need for future cost-effectiveness assessments to determine the benefits of cell/PRP treatments.

8.
Sci Rep ; 14(1): 12846, 2024 06 04.
Artículo en Inglés | MEDLINE | ID: mdl-38834631

RESUMEN

Lumbar disc herniation (LDH) is often managed surgically. Enzymatic chemonucleolysis emerged as a non-surgical alternative. This systematic review and meta-analysis aims to assess the efficacy and safety of chemonucleolytic enzymes for LDH. The primary objective is to evaluate efficacy through "treatment success" (i.e., pain reduction) and severe adverse events (SAEs) rates. Additionally, differences in efficacy and safety trends among chemonucleolytic enzymes are explored. Following our PROSPERO registered protocol (CRD42023451546) and PRISMA guidelines, a systematic search of PubMed and Web of Science databases was conducted up to July 18, 2023. Inclusion criteria involved human LDH treatment with enzymatic chemonucleolysis reagents, assessing pain alleviation, imaging changes, and reporting on SAEs, with focus on allergic reactions. Quality assessment employed the Cochrane Source of Bias and MINORS tools. Meta-analysis utilized odds ratios (OR) with 95% confidence intervals (CI). Among 62 included studies (12,368 patients), chemonucleolysis demonstrated an 79% treatment success rate and significantly outperformed placebo controls (OR 3.35, 95% CI 2.41-4.65) and scored similar to surgical interventions (OR 0.65, 95% CI 0.20-2.10). SAEs occurred in 1.4% of cases, with slightly higher rates in chymopapain cohorts. No significant differences in "proceeding to surgery" rates were observed between chemonucleolysis and control cohorts. Limitations include dated and heterogeneous studies, emphasizing the need for higher-quality trials. Further optimization through careful patient selection and advances in therapy implementation may further enhance outcomes. The observed benefits call for wider clinical exploration and adoption. No funding was received for this review.


Asunto(s)
Desplazamiento del Disco Intervertebral , Humanos , Desplazamiento del Disco Intervertebral/terapia , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/patología , Resultado del Tratamiento , Quimiólisis del Disco Intervertebral/métodos
9.
Nat Med ; 30(7): 1933-1942, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38745009

RESUMEN

Trastuzumab deruxtecan (T-DXd) showed statistically significant clinical improvement in patients with human epidermal growth factor receptor 2-positive (HER2+) gastric cancer in the DESTINY-Gastric01 trial. Exploratory results from DESTINY-Gastric01 suggested a potential benefit in patients with HER2-low gastric cancer. Spatial and temporal heterogeneity in HER2 expression or gene alteration, an inherent characteristic of gastric cancer tumors, presents a challenge in identifying patients who may respond to T-DXd. Specific biomarkers related to therapeutic response have not been explored extensively. Exploratory analyses were conducted to assess baseline HER2-associated biomarkers in circulating tumor DNA and tissue samples, and to investigate mechanisms of resistance to T-DXd. Baseline HER2-associated biomarkers were correlated with objective response rate (ORR) in the primary cohort of patients with HER2+ gastric cancer. The primary cohort had 64% concordance between HER2 positivity and HER2 (ERBB2) plasma gene amplification. Other key driver gene amplifications, specifically MET, EGFR and FGFR2, in circulating tumor DNA were associated with numerically lower ORR. Among 12 patients with HER2 gain-of-function mutations, ORR was 58.3% (7 of 12). ORR was consistent regardless of timing of immunohistochemistry sample collection. Further investigations are required in larger studies.


Asunto(s)
Biomarcadores de Tumor , Camptotecina , Receptor ErbB-2 , Neoplasias Gástricas , Trastuzumab , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Trastuzumab/uso terapéutico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Femenino , Amplificación de Genes , Masculino , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/metabolismo , Inmunoconjugados/uso terapéutico , Inmunoconjugados/farmacología , Persona de Mediana Edad , ADN Tumoral Circulante/genética , ADN Tumoral Circulante/sangre , Anciano , Proteínas Proto-Oncogénicas c-met/genética , Proteínas Proto-Oncogénicas c-met/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo
10.
Int J Clin Oncol ; 29(9): 1237-1243, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38733489

RESUMEN

After immune checkpoint inhibitor (ICI) comes into third-line treatment of advanced gastric cancer, the therapeutic strategy has been dramatically changed. Recent first-line regimen, which consists of ICI and chemotherapeutic agents, prolonged progression-free survival, and subsequent treatment options enabled continuous treatment beyond second-line therapy. Moreover, the advent of vascular endothelial growth factor (VEGF)-targeted agents including angiogenesis inhibitors and TKIs provides an opportunity of considering the interaction between ICI and anti-VEGF agents, and facilitating novel treatment proposal. Although clinical benefit of prolonged VEGF blockade after disease progression has not been confirmed in gastric cancer, combination therapy of cytotoxic agents and anti-VEGF agent, such as irinotecan plus ramucirumab demonstrated favorable objective response rate and progression-free survival in third- or later-line setting. In this review, we discuss recent progress and future directions of later-line treatments of HER2-negative advancer gastric cancer.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Receptor ErbB-2 , Terapia Recuperativa , Neoplasias Gástricas , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Humanos , Terapia Recuperativa/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Ramucirumab , Inhibidores de la Angiogénesis/uso terapéutico , Supervivencia sin Progresión , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/metabolismo
11.
World Neurosurg ; 188: e424-e433, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38802060

RESUMEN

OBJECTIVE: This retrospective study assesses the influence of osteoporosis on the short-term clinical outcomes of lateral lumbar interbody fusion (LLIF) surgery in patients with lumbar degenerative diseases (LDDs), focusing on complications, pain intensity, and quality of life (QOL) improvements. The primary aim of this study is to investigate the impact of osteoporosis on the short-term clinical outcomes following LLIF surgery in LDD patients, with a particular focus on the incidence of cage subsidence (CS) and overall patient well-being postoperatively. METHODS: A retrospective review was conducted on 73 patients who underwent LLIF for LDD. Patients were categorized into 2 groups based on osteoporosis status determined by dual-energy X-ray absorptiometry scans: those with osteoporosis (n = 20) and those without osteoporosis (n = 53). Data collection included demographics, surgical details, complications, magnetic resonance imaging analysis, pain intensity, and QOL (Japanese Orthopaedic Association Back Pain Evaluation Questionnaire). RESULTS: The groups had no significant differences regarding operative time, estimated blood loss, and hospital stay duration. However, the incidence of CS was 40% in patients with osteoporosis, compared to 17% in nonosteoporotic patients. Despite this, significant improvements in spinal canal dimensions were observed in both groups. Both groups experienced significant reductions in pain intensity, with notable improvements in functional outcomes assessed by the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, indicating the overall effectiveness of LLIF in enhancing patient well-being and functionality, irrespective of osteoporosis status. CONCLUSIONS: Osteoporosis increases the risk of CS in LLIF surgery for LDD patients but does not affect short-term pain relief and QOL improvements.


Asunto(s)
Vértebras Lumbares , Osteoporosis , Calidad de Vida , Fusión Vertebral , Humanos , Fusión Vertebral/métodos , Femenino , Estudios Retrospectivos , Masculino , Persona de Mediana Edad , Vértebras Lumbares/cirugía , Vértebras Lumbares/diagnóstico por imagen , Anciano , Osteoporosis/complicaciones , Osteoporosis/cirugía , Resultado del Tratamiento , Degeneración del Disco Intervertebral/cirugía , Degeneración del Disco Intervertebral/diagnóstico por imagen , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología
12.
World Neurosurg ; 186: e461-e469, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38580092

RESUMEN

OBJECTIVE: This retrospective study aimed to determine the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ) cutoff scores for assessing patient satisfaction postlateral lumbar interbody fusion (LLIF) in degenerative lumbar spinal stenosis (DLSS) patients. METHODS: Analyzing 136 DLSS patients (83 males, 53 females), the study evaluated demographics, pain (Numeric Rating Scale), and JOABPEQ outcomes (low back pain, lumbar function, walking ability, social life, mental health). Patient satisfaction was surveyed, and based on their responses, patients were categorized into "Beneficial" and "Nonbeneficial" groups. Statistical analysis encompassed the Kolmogorov-Smirnov test, t-tests, Mann-Whitney U test, and Receiver Operating Characteristic (ROC) curve analysis for JOABPEQ cutoff determination. RESULTS: Postoperative improvements in JOABPEQ scores, especially in walking ability, social life function, and mental health, were significant. Pain intensity, assessed using the Numeric Rating Scale, also showed notable reductions. The Δ walking ability cutoff was set at 25.00, indicating substantial mobility improvement. This domain's area under the curve (AUC) was 0.815 (95% CI: 0.726-0.903), demonstrating high effectiveness in assessing patient satisfaction postsurgery. The study also found no significant differences in complication rates between groups for conditions like transient motor weakness, thigh pain/numbness, and revision surgery. CONCLUSIONS: This study underscores the value of patient-centered outcomes in evaluating LLIF surgery success for DLSS. The identified JOABPEQ cutoff values provide a quantitative tool for assessing patient satisfaction, emphasizing the necessity of comprehensive postoperative evaluations beyond traditional clinical metrics for improved patient care and life quality.


Asunto(s)
Vértebras Lumbares , Satisfacción del Paciente , Fusión Vertebral , Estenosis Espinal , Humanos , Masculino , Femenino , Estenosis Espinal/cirugía , Anciano , Vértebras Lumbares/cirugía , Persona de Mediana Edad , Estudios Retrospectivos , Encuestas y Cuestionarios , Dimensión del Dolor/métodos , Resultado del Tratamiento , Anciano de 80 o más Años , Degeneración del Disco Intervertebral/cirugía
13.
Future Oncol ; : 1-7, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38629456

RESUMEN

Due to the widespread use of cancer genetic testing in gastrointestinal cancer, the BRCA1/2 genetic mutation has been identified in biliary tract cancer as well as pancreatic cancer. Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor, and PARP inhibitors exert their cytotoxicity against cancer cells in the context of homologous recombination deficiency, such as BRCA mutations, via the mechanism of synthetic lethality. The aim of this phase II NIR-B trial is to evaluate the efficacy and safety of niraparib for patients with unresectable advanced or recurrent biliary tract cancer, pancreatic cancer or other gastrointestinal cancers with germline or somatic BRCA1/2 mutations revealed by genetic testing. The primary end point is an investigator-assessed objective response rate in each cohort.Clinical Trial Registration: jRCT2011200023 (ClinicalTrials.gov).


A clinical study to confirm the efficacy and safety of niraparib for people with advanced biliary tract, pancreatic and other abdominal cancers with the BRCA genetic mutation: the NIR-B trial.BRCA gene is involved in repairing DNA injury and plays an important role in cancer growth. Cells with a mutation in the BRCA gene cannot repair DNA using a method called homologous recombination repair. Niraparib is part of a class of drugs called 'PARP inhibitors' that inhibit enzymes called 'PARP' involved in repairing DNA injury, and has shown efficacy against cancers with BRCA gene mutations. BRCA gene mutations are infrequent but have been found in a variety of cancers. The NIR-B trial is a clinical trial to evaluate the efficacy and safety of niraparib for people with advanced biliary tract, pancreatic and other abdominal cancers with BRCA gene mutations.

14.
Global Spine J ; : 21925682241241518, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38511353

RESUMEN

STUDY DESIGN: A prospective study. OBJECTIVES: This study aims to explore the correlation between interleukin (IL)- 6 levels in intervertebral disc (IVD) tissue and clinical outcomes in patients undergoing lumbar surgery for lumbar degenerative disease (LDD). METHODS: This prospective study analyzed 32 patients (22 men and 10 women, average age 69.6 years) who underwent lateral lumbar interbody fusion (LLIF). IL-6 gene expression in IVD tissues collected during surgery was measured and correlated with pre- and postoperative clinical outcomes, including pain intensity assessed via Numeric Rating Scales (NRS) and quality of life (QOL) evaluated through the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ). RESULTS: IL-6 levels showed statistical correlations with postoperative intensity of low back pain (LBP) and several JOABPEQ domains. Patients with higher expression of IL-6 levels experienced more severe postoperative LBP and lower scores in lumbar function, walking ability, social life function, and mental health. The effectiveness rate of JOABPEQ scores was exceptionally high for low back pain (.548), walking ability (.677), and social functioning (.563), demonstrating the effectiveness of LLIF. The average operation time was 105.6 minutes, and the estimated blood loss was 85.6 mL. CONCLUSIONS: The study underscores IL-6 as a potential biomarker for predicting surgical outcomes in LDD. High IL-6 levels correlate with worse postoperative LBP and lower QOL scores. Integrating molecular markers like IL-6 with patient-reported outcomes could provide a more comprehensive approach to postoperative care in spinal disorders, aiming to improve the overall QOL for LDD patients undergoing LLIF surgery.

15.
Global Spine J ; 14(2_suppl): 6S-13S, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38421322

RESUMEN

STUDY DESIGN: Guideline. OBJECTIVES: To develop an international guideline (AOGO) about the use of osteobiologics in anterior cervical discectomy and fusion (ACDF) for treating degenerative spine conditions. METHODS: The guideline development process was guided by AO Spine Knowledge Forum Degenerative (KF Degen) and followed the Guideline International Network McMaster Guideline Development Checklist. The process involved 73 participants with expertise in degenerative spine diseases and surgery from 22 countries. Fifteen systematic reviews were conducted addressing respective key topics and evidence was collected. The methodologist compiled the evidence into GRADE Evidence-to-Decision frameworks. Guideline panel members judged the outcomes and other criteria and made the final recommendations through consensus. RESULTS: Five conditional recommendations were created. A conditional recommendation is about the use of allograft, autograft or a cage with an osteobiologic in primary ACDF surgery. Other conditional recommendations are about the use of osteobiologic for single- or multi-level ACDF, and for hybrid construct surgery. It is suggested that surgeons use other osteobiologics rather than human bone morphogenetic protein-2 (BMP-2) in common clinical situations. Surgeons are recommended to choose 1 graft over another or 1 osteobiologic over another primarily based on clinical situation, and the costs and availability of the materials. CONCLUSION: This AOGO guideline is the first to provide recommendations for the use of osteobiologics in ACDF. Despite the comprehensive searches for evidence, there were few studies completed with small sample sizes and primarily as case series with inherent risks of bias. Therefore, high-quality clinical evidence is demanded to improve the guideline.

16.
Anticancer Res ; 44(3): 1219-1226, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38423630

RESUMEN

BACKGROUND/AIM: Trifluridine/tipiracil (FTD/TPI) is used to treat metastatic colorectal cancer (mCRC). Since the standard regimen of FTD/TPI features a complex dosing schedule and frequently results in severe hematological toxicities, a simplified regimen has emerged, in which FTD/TPI is orally administered biweekly. However, the survival benefits and potential adverse events associated with the biweekly FTD/TPI regimen have not been fully evaluated in previous reports. Therefore, in this study, the differences in efficacy and safety between the standard and biweekly FTD/TPI regimens were retrospectively investigated in patients with mCRC. PATIENTS AND METHODS: Data from 90 patients who received FTD/TPI for mCRC were extracted from the electronic medical records at the Osaka University Hospital. According to the inclusion and exclusion criteria, 85 of the 90 patients were enrolled in the study. We compared patient characteristics, overall survival (OS), progression-free survival (PFS), and adverse events between the standard (n=56) and biweekly groups (n=29). RESULTS: The biweekly group exhibited prolonged OS and PFS compared to patients in the standard group. Multivariate analysis for OS and PFS demonstrated that the biweekly regimen was the only significant factor that affected OS, and not PFS (HR=0.561, p=0.049). Kaplan-Meier analysis indicated that neutropenia (grade ≥3) in the biweekly group was significantly prolonged compared to the standard group (p=0.012). However, there were no significant differences in adverse events between the two groups (p>0.999). CONCLUSION: The biweekly FTD/TPI regimen, compared to the standard regimen, should enhance both OS and PFS in patients with mCRC without escalating any adverse event.


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Demencia Frontotemporal , Pirrolidinas , Neoplasias del Recto , Timina , Humanos , Uracilo/efectos adversos , Estudios Retrospectivos , Trifluridina/efectos adversos , Demencia Frontotemporal/inducido químicamente , Neoplasias Colorrectales/patología , Neoplasias del Colon/inducido químicamente , Combinación de Medicamentos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
17.
Redox Biol ; 71: 103091, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38412803

RESUMEN

Low back pain (LBP) is a pervasive global health concern, primarily associated with intervertebral disc (IVD) degeneration. Although oxidative stress has been shown to contribute to IVD degeneration, the underlying mechanisms remain undetermined. This study aimed to unravel the role of superoxide dismutase 2 (SOD2) in IVD pathogenesis and target oxidative stress to limit IVD degeneration. SOD2 demonstrated a dynamic regulation in surgically excised human IVD tissues, with initial upregulation in moderate degeneration and downregulation in severely degenerated IVDs. Through a comprehensive set of in vitro and in vivo experiments, we found a suggestive association between excessive mitochondrial superoxide, cellular senescence, and matrix degradation in human and mouse IVD cells. We confirmed that aging and mechanical stress, established triggers for IVD degeneration, escalated mitochondrial superoxide levels in mouse models. Critically, chondrocyte-specific Sod2 deficiency accelerated age-related and mechanical stress-induced disc degeneration in mice, and could be attenuated by ß-nicotinamide mononucleotide treatment. These revelations underscore the central role of SOD2 in IVD redox balance and unveil potential therapeutic avenues, making SOD2 and mitochondrial superoxide promising targets for effective LBP interventions.


Asunto(s)
Degeneración del Disco Intervertebral , Disco Intervertebral , Superóxido Dismutasa , Humanos , Ratones , Animales , Superóxidos/metabolismo , Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/metabolismo , Estrés Oxidativo , Oxidación-Reducción , Homeostasis
18.
Eur Spine J ; 33(5): 1713-1727, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38416190

RESUMEN

PURPOSE: To investigate the therapeutic potential of extracellular vesicles (EVs) derived from human nucleus pulposus cells (NPCs), with a specific emphasis on Tie2-enhanced NPCs, compared to EVs derived from human bone marrow-derived mesenchymal stromal cells (BM-MSCs) in a coccygeal intervertebral disc degeneration (IDD) rat model. METHODS: EVs were isolated from healthy human NPCs cultured under standard (NPCSTD-EVs) and Tie2-enhancing (NPCTie2+-EVs) conditions. EVs were characterized, and their potential was assessed in vitro on degenerative NPCs in terms of cell proliferation and senescence, with or without 10 ng/mL interleukin (IL)-1ß. Thereafter, 16 Sprague-Dawley rats underwent annular puncture of three contiguous coccygeal discs to develop IDD. Phosphate-buffered saline, NPCSTD-EVs, NPCTie2+-EVs, or BM-MSC-derived EVs were injected into injured discs, and animals were followed for 12 weeks until sacrifice. Behavioral tests, radiographic disc height index (DHI) measurements, evaluation of pain biomarkers, and histological analyses were performed to assess the outcomes of injected EVs. RESULTS: NPC-derived EVs exhibited the typical exosomal morphology and were efficiently internalized by degenerative NPCs, enhancing cell proliferation, and reducing senescence. In vivo, a single injection of NPC-derived EVs preserved DHI, attenuated degenerative changes, and notably reduced mechanical hypersensitivity. MSC-derived EVs showed marginal improvements over sham controls across all measured outcomes. CONCLUSION: Our results underscore the regenerative potential of young NPC-derived EVs, particularly NPCTie2+-EVs, surpassing MSC-derived counterparts. These findings raise questions about the validity of MSCs as both EV sources and cellular therapeutics against IDD. The study emphasizes the critical influence of cell type, source, and culture conditions in EV-based therapeutics.


Asunto(s)
Vesículas Extracelulares , Degeneración del Disco Intervertebral , Células Madre Mesenquimatosas , Núcleo Pulposo , Ratas Sprague-Dawley , Animales , Degeneración del Disco Intervertebral/terapia , Vesículas Extracelulares/trasplante , Vesículas Extracelulares/metabolismo , Células Madre Mesenquimatosas/fisiología , Núcleo Pulposo/metabolismo , Ratas , Humanos , Masculino , Células Cultivadas , Dolor
19.
World Neurosurg ; 183: e722-e729, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38199461

RESUMEN

OBJECTIVE: With an increasing prevalence of osteoporosis due to demographic shifts, accurate diagnostic methods are vital, particularly before spinal surgeries. This research investigated the correlation between bone mineral density T-scores of the lumbar spine and femoral neck, Hounsfield Unit (HU) values from computed tomography (CT), and vertebral bone quality (VBQ) scores from Magnetic Resonance Imaging (MRI) in patients with lumbar degenerative disease. METHODS: We analyzed data from 100 patients with lumbar degenerative disease who underwent CT, dual-energy X-ray absorptiometry (DXA), and MRI between 2019 and 2023. HU values were measured individually from L1 to L4, while T-scores were obtained from DXA scans of the lumbar spine and the femoral neck. The VBQ scores were derived from T1-weighted MRIs. RESULTS: A notable association between the lumbar and femoral neck T-scores and HU values was found. The VBQ score had a faint correlation with HU values and lacked any with the T-score. Notably, the HU values derived via the Youden index and regression closely matched. Lumbar spine HU values related to T-scores of 85.6 and 84.4 and femoral neck T-scores of 98.9 and 103.6, with a low T-score at 98.9 and 104.6. CONCLUSIONS: This study underscores a strong correlation between bone mineral density and HU values from CT scans in lumbar degenerative disease patients, suggesting the utility of HU measurements as an adjunct diagnostic tool for osteoporosis. However, the correlation with the VBQ score remains weak. Further multicenter studies are essential for more robust validation.


Asunto(s)
Densidad Ósea , Osteoporosis , Humanos , Estudios Retrospectivos , Osteoporosis/diagnóstico por imagen , Absorciometría de Fotón/métodos , Vértebras Lumbares/diagnóstico por imagen
20.
Bioengineering (Basel) ; 11(1)2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38247922

RESUMEN

BACKGROUND: Cartilage harvest and transplantation is a common surgery using costal, auricular, and septal cartilage for craniofacial reconstruction. However, absorption and warping of the cartilage grafts can occur due to inflammatory factors associated with wound healing. Transcription factor nuclear factor-κB (NF-κB) is activated by the various stimulation such as interleukin-1 (IL-1), and plays a central role in the transactivation of this inflammatory cytokine gene. Inhibition of NF-κB may have anti-inflammatory effects. The aim of this study was to explore the potential of an NF-κB decoy oligodeoxynucleotide (Decoy) as a chondroprotective agent. MATERIALS AND METHODS: Safe and efficacious concentrations of Decoy were assessed using rabbit nasal septal chondrocytes (rNSChs) and assays for cytotoxicity, proteoglycan (PG) synthesis, and PG turnover were carried out. The efficacious concentration of Decoy determined from the rNSChs was then applied to human nasal septal cartilage (hNSC) in vitro and analyzed for PG turnover, the levels of inflammatory markers, and catabolic enzymes in explant-conditioned culture medium. RESULTS: Over the range of Decoy conditions and concentrations, no inhibition of PG synthesis or cytotoxicity was observed. Decoy at 10 µM effectively inhibited PG degradation in the hNSC explant, prolonging PG half-life by 63% and decreasing matrix metalloprotease 3 (MMP-3) by 70.7% (p = 0.027). CONCLUSIONS: Decoy may be considered a novel chondroprotective therapeutic agent in cartilage transplantation due to its ability to inhibit cartilage degradation due to inflammation cytokines.

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