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1.
Int J Spine Surg ; 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39107093

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is a well-known complication after spine surgery. As many cases of cervical spine disease result in severe gait disturbance due to myelopathy, it may harbor a higher risk of VTE than other spinal disorders. However, few studies have focused primarily on cervical spine surgery to date. This investigation sought to determine the prevalence of VTE after cervical spine surgery and identify patient-based risk factors. METHODS: The medical data of 341 consecutive patients (240 men and 101 women; mean age, 68.1 years) who underwent cervical spine surgery were retrospectively examined. Logistic regression models were employed to examine the prevalence, characteristics, and risk factors of postoperative VTE. RESULTS: In this study, 2.6% of cervical spine surgery patients experienced postoperative VTE. In comparisons of VTE and non-VTE groups, significant differences were found for age (79.6 years vs 67.7 years, P < 0.01), 1-week postoperative D-dimer level (10.6 µg/mL vs 2.7 µg/mL, P < 0.01), and cardiovascular disease (44.4% vs 11.1%, P = 0.011). Multivariate analysis identified elevated postoperative D-dimer level and cardiovascular disease as significantly associated with postsurgical VTE with respective odds ratios of 1.54 and 9.52. CONCLUSION: Postoperative VTE in cervical spine surgery was seen in 2.6% of cases. Patients with elevated postoperative D-dimer level and cardiovascular disease may be at increased risk of VTE and may require additional observation. CLINICAL RELEVANCE: Spine surgeons should take into account that patients with elevated postoperative D-dimer levels and cardiovascular disease may be at increased risk for VTE.

2.
J Cereb Blood Flow Metab ; : 271678X241270416, 2024 Aug 11.
Article in English | MEDLINE | ID: mdl-39129183

ABSTRACT

To effectively treat cerebral arteriovenous malformations (AVMs), peri-nidal flow regulation and metabolic status must be understood. In this study, we used 15O-oxygen positron emission tomography (PET) post-processing analysis to investigate vascular radioactivity in the nidal region of AVMs. Single-dynamic PET imaging was performed on seven unruptured AVM patients during the sequential inhalation of 15O2 and C15O2. A previously validated dual-tracer basis function method (DBFM) was employed to calculate parametric images. The results of our study were as follows. First, in remote and contralateral AVM regions, DBFM and a previous approach of dual-tracer autoradiography (DARG) showed strong positive correlations in cerebral blood flow (CBF), cerebral oxygen metabolism rate (CMRO2), and oxygen extraction fraction. Second, peri-nidal CBF and CMRO2 correlation was lower, and overestimation occurred with DARG compared to with DBFM. Third, on comparing DBFM to quantitative 123I-iodoamphetamine single-photon emission computed tomography (SPECT), CBF correlated significantly. In contrast, the correlation between DARG and quantitative 123I-iodoamphetamine-SPECT was weaker in the peri-nidal regions. Fourth, analysis of tissue time-activity curves demonstrated good reproducibility using the novel formulation in the control, peri-nidus, and core nidal regions, indicating the adequacy of this approach. Overall, the DBFM approach holds promise for assessing haemodynamic alterations in patients with AVMs.

3.
Eur Spine J ; 2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39095492

ABSTRACT

PURPOSE: We defined sagittal S-line tilt (SSLT) as the tilt of the line connecting the upper instrumented vertebra and the lower instrumented vertebra. This study aimed to: (1) examine the correlation between SSLT and proximal junctional angle (PJA) change values, and (2) determine the cut-off value of SSLT with respect to proximal junctional kyphosis (PJK) occurrence. METHODS: Eighty-six consecutive patients (81 female and 5 male; mean age: 15.8 years) with Lenke 5C AIS who underwent posterior selective spinal fusion. Pearson's correlation coefficients were used to examine the relationship between preoperative SSLT and changes in PJA from preoperative to 2 years postoperative. The impact of SSLT on PJK at 2 years after surgery was assessed using a receiver operating characteristic (ROC) curve. RESULTS: We observed a moderate positive correlation between preoperative SSLT and change in PJA (R = 0.541, P < 0.001). We identified 18 patients (21%) with PJK at 2 years postoperative. Mean preoperative SSLT in the PJK group and the non-PJK group differed significantly at 23.3 ± 4.1° and 16.1 ± 5.0°, respectively (P < 0.001). The cut-off value of preoperative SSLT for PJK at 2 years postoperative was 18° in ROC curve analysis, with a sensitivity of 94%, specificity of 68%, and area under the ROC curve of 0.868. CONCLUSION: In selective lumbar fusion for AIS Lenke type 5C curves, preoperative SSLT was significantly correlated with PJA change from preoperative to 2 years postoperative. SSLT was a predictor of PJK occurrence, with a cut-off value of 18°.

4.
Spine Deform ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38995614

ABSTRACT

PURPOSE: Determine the effect of using the modified S-line vertebra (MSLV) as the upper instrumented vertebra (UIV) on postoperative trunk balance, L4 tilt, and clinical outcomes in selective thoracic fusion (STF) for adolescent idiopathic scoliosis (AIS) Lenke type 1C curve. METHODS: Twenty-eight consecutive patients (all female; mean age: 15.4±2.0 years) with AIS Lenke type 1C curve were retrospectively enrolled. Primary outcome measures were coronal balance (absolute distance between C7 and the center of the sacral vertical line), L4 tilt, and Scoliosis Research Society (SRS)-22r scores at 2 years postoperatively. The group with the MSLV at the UIV was designated as the MSLV group (18 patients), and the group with the MSLV proximal (12 patients) or distal (4 patients) to the UIV was defined as the non-MSLV group. RESULTS: We observed no significant differences between the groups regarding age, LIV and stable vertebra positioning, or preoperative X-ray parameters. Postoperative coronal balance was significantly better in the MSLV group (0.39±0.08 vs. 1.34±0.22 cm; P.

5.
Anticancer Res ; 44(8): 3663-3667, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39060067

ABSTRACT

BACKGROUND/AIM: Resection of brain metastases is a well-established treatment modality that can prolong the survival of patients for whom surgery is indicated. Whole-brain radiotherapy (WBRT) has been the standard postoperative therapy. In recent years, however, clinicians have increasingly avoided WBRT due to its associated adverse events. This study investigated the impact of postoperative WBRT and systemic chemotherapy as prognostic factors on the survival of patients who had undergone resection of brain metastases. PATIENTS AND METHODS: The study subjects were 172 patients who underwent surgical resection for brain metastases. Comparative analyses of survival after WBRT and systemic chemotherapy were performed. RESULTS: Postoperative WBRT had no survival-prolonging effect, whereas postoperative systemic chemotherapy prolonged survival. A comparison based on the number of systemic chemotherapy regimens administered prior to surgery showed that fewer regimens correlated with a better prognosis. CONCLUSION: The addition of WBRT after surgical resection of brain metastases is no longer a standard treatment strategy and systemic chemotherapy after surgery is a positive prognostic factor.


Subject(s)
Brain Neoplasms , Humans , Brain Neoplasms/secondary , Brain Neoplasms/therapy , Brain Neoplasms/surgery , Brain Neoplasms/mortality , Brain Neoplasms/radiotherapy , Male , Female , Middle Aged , Aged , Adult , Prognosis , Cranial Irradiation/methods , Combined Modality Therapy , Aged, 80 and over
6.
Heliyon ; 10(12): e33185, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-39021913

ABSTRACT

A wind turbine comprises multiple components constructed from diverse materials. This complexity introduces challenges in designing the blade structure. In this study, we developed a structural optimization framework for Vertical Axis Wind Turbines (VAWT). This framework integrates a parametric Finite Element Analysis (FEA) model, which simulates the structure's global behavior, with a Genetic Algorithm (GA) optimization technique that navigates the design domain to identify optimal parameters. The goal is to minimize the mass of VAWT structures while adhering to a suite of complex constraints. This framework quantifies the mass reduction impact attributable to material selection and structural designs. The optimization cases indicate that blades made from Carbon Fiber Reinforced Plastics (CFRP) materials are 47.1 % lighter than those made from Glass Fiber Reinforced Plastics (GFRP), while the structural parts are 44.8 % lighter. This work also provides further recommendations regarding the scale and design of the structures. With the materials and structural design established, future studies can expand to include more load cases and detailed designs of specific components.

7.
J Cardiol ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38964710

ABSTRACT

In this study of 19,824 ST-elevated myocardial infarction (STEMI) patients from the J-PCI OUTCOME registry (January 1, 2017, to December 31, 2018), we investigated the association between door-to-balloon time (DTB) and 1-year post-discharge cardiovascular outcomes. Patients with DTB >90 min were older and had higher comorbidities. The incidence of 1-year major adverse cardiovascular events (MACE) showed an incremental increase: 3.7 %, 4.8 %, and 7.7 % for DTB ≤60, DTB 60-90, and DTB >90 groups, respectively. Adjusted hazard ratios (aHR) compared to the DTB 60-90 group were 0.83 (DTB ≤60, p = 0.03) and 1.25 (DTB >90, p = 0.005). Subgroup analysis revealed higher risk for MACE in DTB >90 group for patients aged <70, men, no history of coronary revascularization, and those with cardiac arrest or cardiogenic shock. Conversely, DTB ≤60 group without previous history had a lower MACE risk (aHR 0.80, p = 0.02). This study, the largest of its kind, demonstrates that a DTB below 90 min is associated with lower 1-year MACE risk, supporting current guidelines, and indicating additional benefits for specific patient subgroups, especially those experiencing their first acute coronary event. The findings suggest the importance of early intervention in primary prevention and emphasize the need for prompt detection of vulnerable plaque.

8.
Spine Surg Relat Res ; 8(3): 280-286, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38868795

ABSTRACT

Introduction: The Scoliosis Research Society-30 (SRS-30) is a questionnaire originally developed from the SRS-22r questionnaire and is used to evaluate adolescent idiopathic scoliosis (AIS). It comprised questions on five domains: function, pain, self-image, mental health, and satisfaction, with seven additional questions related to postoperative aspects. In addition to the original English version, translations in multiple languages have been effectively applied. Herein, we evaluated the internal consistency and external validity of the Japanese version of the SRS-30 for AIS patients. Methods: Among the 30 questions in SRS-30, the eight additional questions from SRS-22r were translated and back-translated to create a Japanese version of the SRS-30. This translated questionnaire was then used to survey patients with AIS who underwent corrective fusion surgery one year postoperatively. The internal consistency of the responses was evaluated using the Cronbach α coefficient. Additionally, the Spearman correlation analyses were conducted to assess the correlation between the scores obtained from the SRS-30 Japanese version and SRS-22r and the Oswestry Disability Index (ODI) for the overall scale and the five domains. Results: A total of 81 cases (eight males and 73 females; mean age at surgery 14.4 years) were enrolled. The mean preoperative Cobb angle was 51.0°. The Cronbach α coefficient for the overall SRS-30 was 0.861, indicating high internal consistency, while the coefficients for each domain were as follows: function/activity, 0.697; pain, 0.405; self-image/appearance, 0.776; mental health, 0.845; and satisfaction, 0.559. The SRS-30 total score significantly correlated with the SRS-22r total (r=0.945, P<0.001) and the ODI (r=-0.511, P<0.001). The SRS-30 domains highly correlated with the corresponding SRS-22r domains, with correlations ranging from r=0.826 to 0.901 (all P<0.001). Conclusions: The Japanese version of the SRS-30 demonstrated good internal and external validity. The SRS-30 can be used as an assessment tool for health-related quality of life in AIS patients.

10.
Article in English | MEDLINE | ID: mdl-38874259

ABSTRACT

Objective: To compare the effectiveness of "semiocclusive dressing (SOD)" treatment using plastic wrap or low-adherent absorbent wound dressings with that of occlusive dressing (OD) treatment for National Pressure Injury Advisory Panel stage III/IV pressure injuries in the inflammatory phase. Approach: This 12-week, open-label, randomized controlled trial was conducted at one hospital and three care facilities. Seventy-seven participants were enrolled; 40 comprised the SOD group and 37 comprised the OD group. The primary outcome was the surface area reduction. Secondary outcomes included the Bates-Jensen Wound Assessment Tool (BWAT) score reductions, incidence of adverse events, and material cost. This trial met the recommendations of the CONSORT 2010 statement. Results: The surface area reduction of the SOD group was greater than that of the OD group throughout the study period. The significant interaction was revealed between treatment and time course (p < 0.0001). The 95% confidence interval of the difference at 12 weeks was 3.4 to 21.9. The median BWAT score reduction of the SOD group at 12 weeks was 23, and that of the OD group was 18.5 (p = 0.0077). The incidence of adverse events was comparable between groups. The OD treatment cost was 3.0 times higher than the SOD treatment cost (p = 0.0012). Innovation: Because the SOD does not completely occlude the wound, excess exudate drains from the wound. Therefore, SOD can treat the wound with abundant exudate effectively and safely. Conclusion: SOD treatment is more effective and less expensive than OD treatment for stage III/IV pressure injuries. Clinical Trial Registration: UMIN Clinical Trials Registry [UMIN000023412]. Registered on July 31, 2016.

11.
Int J Cardiol ; 410: 132197, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38823533

ABSTRACT

BACKGROUND: The comparative efficacy and safety of adjusted- and standard-dose prasugrel in East Asian patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) remain unclear. This study aimed to comparatively assess the ischaemic and bleeding outcomes of adjusted-dose (maintenance dose: 3.75 mg) and standard-dose (maintenance dose: 10 mg) prasugrel in East Asian patients with AMI undergoing PCI. METHODS: From a combined dataset sourced from nationwide AMI registries in Japan and South Korea (n = 17,118), patients treated with either adjusted- or standard-dose prasugrel were identified. Patients who did not undergo emergent PCI, those on oral anticoagulants, and those meeting the criteria of contraindication of prasugrel in South Korea (age ≥ 75 years, body weight < 60 kg, or history of stroke) were excluded. Major adverse cardiovascular events (MACE) and Thrombolysis in Myocardial Infarction (TIMI) major bleeding events were compared between the adjusted-dose (n = 1160) and standard-dose (n = 1086) prasugrel groups. RESULTS: Within the propensity-matched cohort (n = 702 in each group), no significant difference was observed in the in-hospital MACE between the adjusted- and standard-dose prasugrel groups (1.85% vs. 2.71%, odds ratio [OR] 0.68, 95% confidence interval [CI] 0.33-1.38, p = 0.286). However, the incidence of in-hospital major bleeding was significantly lower in the adjusted-dose prasugrel group than in the standard-dose group (0.43% vs. 1.71%, OR 0.25, 95% CI 0.07-0.88, p = 0.031). The cumulative 12-month incidence of MACE was equivalent in both groups (4.70% vs. 4.70%, OR 1.00, 95% CI 0.61-1.64, p = 1.000). CONCLUSIONS: Among East Asian patients with AMI undergoing PCI, those administered adjusted-dose prasugrel exhibited a lower risk of in-hospital bleeding events than those administered standard-dose prasugrel, while maintaining a comparable 1-year incidence of MACE.


Subject(s)
Myocardial Infarction , Percutaneous Coronary Intervention , Prasugrel Hydrochloride , Aged , Female , Humans , Male , Middle Aged , Cohort Studies , Dose-Response Relationship, Drug , East Asian People , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Japan/epidemiology , Myocardial Infarction/epidemiology , Percutaneous Coronary Intervention/methods , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/adverse effects , Prasugrel Hydrochloride/administration & dosage , Prasugrel Hydrochloride/adverse effects , Registries , Republic of Korea/epidemiology , Treatment Outcome
12.
Eur Heart J Case Rep ; 8(5): ytae247, 2024 May.
Article in English | MEDLINE | ID: mdl-38807943

ABSTRACT

Background: Hypereosinophilic syndrome (HES) is characterized by moderate to severe eosinophilia, exclusion of neoplastic or secondary origins of eosinophilia, and systemic involvement with end-organ damage. Coronary arteries can be affected to cause vasospastic angina (VSA); however, the association of the two diseases is not well recognized. Case summary: A 55-year-old woman who had a history of multiple allergic disease such as bronchial asthma and chronic sinusitis with nasal polyps was hospitalized due to attacks of chest pain at rest. During a spontaneous attack of chest pain, ECG revealed ST-segment elevation in the inferior leads and emergency coronary angiography showed focal spasms of the right and left anterior descending coronary arteries, both of which were relieved after intracoronary administration of nitroglycerine. She was diagnosed with VSA according to the Japanese Circulation Society guidelines. Despite conventional vasodilator therapies, her resting angina remained refractory. Laboratory findings were notable for moderate eosinophilia. A comprehensive evaluation to uncover the underlying cause of refractory VSA led to the diagnosis of HES, concomitant with eosinophilic pneumonia and eosinophilic chronic rhinosinusitis. Pericoronary inflammation by fat attenuation index (FAI) was increased in the proximal segment of the right coronary artery. Treatment was initiated with oral prednisolone at a starting dose of 30 mg/day. The response to treatment was rapid, with her symptoms disappearing and a regression of eosinophilia observed the following day. Discussion: Hypereosinophilic syndrome manifests with refractory VSA, and eosinophil-suppressing corticosteroid therapy proves effective in improving both conditions along with reduction of the pericoronary inflammation by FAI.

13.
Int J Spine Surg ; 2024 May 14.
Article in English | MEDLINE | ID: mdl-38744483

ABSTRACT

BACKGROUND: Atlantoaxial transarticular fixation, also called the Magerl technique, is said to be the most robust biomechanical method of fixation of the atlantoaxial vertebrae. However, the procedure carries a risk of spinal cord and vertebral artery injury during the insertion process, especially in patients with a high-riding vertebral artery. In this study, a computed tomography (CT)-based navigation system was used for preoperative planning and insertion. This investigation sought to determine the rate and direction of screw perforation as well as the incidence of screw loosening in computer-assisted atlantoaxial transarticular fixation. METHODS: Sixty patients (31 men and 29 women; mean ± SD age: 65.3 ± 19.6 years) who received atlantoaxial transarticular screw insertion with preoperative CT navigation were analyzed. We investigated screw position and loosening by CT at the final follow-up. RESULTS: Of the 108 screws inserted, the rate of Grade 2 or higher perforation was 4.6% (5/108). Nine of 81 (11.1%) screws inserted into the 44 patients who were followed for at least 6 months showed loosening. Logistic regression analysis revealed that unilateral insertion (odds ratio: 8.50, 95% confidence interval: 1.53-47.2, P = 0.014) was significantly associated with the incidence of screw loosening. CONCLUSIONS: The screw perforation rate of Grade 2 or higher in computer-assisted atlantoaxial transarticular screw fixation was 4.6%, with comparable frequencies of perforation direction. Unilateral insertion was a significant independent factor associated with screw loosening, which occurred in 11.1% of insertions. CLINICAL RELEVANCE: Spine surgeons should follow up with patients with caution because screws with unilateral insertion are prone to loosening.

14.
Naturwissenschaften ; 111(3): 31, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38780649

ABSTRACT

In social hymenopterans, monandry of the queen is an ancestral trait, and polyandry is a derived trait. Polyandry of the queen is the norm in a limited number of lineages, such as honeybees, leaf-cutting ants, Pogonomyrmex ants, and Vespula wasps, which presumably provide fitness advantages for the whole colony. The queen of the introduced bumblebee, Bombus terrestris, is polyandrous in Japan, whereas it is monandrous in native regions. We hypothesize that polyandry can evolve in a process that avoids the negative impacts of reproductive interference caused by interspecific mating and conducted genetic studies of the invasive species B. terrestris and two native subspecies, Bombus hypocrita sapporoensis and Bombus hypocrita hypocrita, in Japan. Our results revealed that although the native queens of B. hypocrita hypocrita allopatric with B. terrestris were strictly monandrous, the native queens of B. hypocrita sapporoensis sympatric with B. terrestris were polyandrous. These results suggested that the queens of native B. hypocrita sapporoensis do not experience negative impacts on interspecific mating from the invasive B. terrestris. We discuss the possibility that reproductive interference is a driving force in selection for multiple mating through an arms race between sympatric species.


Subject(s)
Reproduction , Sexual Behavior, Animal , Animals , Japan , Bees/physiology , Sexual Behavior, Animal/physiology , Female , Reproduction/physiology , Male , Introduced Species
15.
Knee Surg Sports Traumatol Arthrosc ; 32(8): 2129-2140, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38813913

ABSTRACT

PURPOSE: To evaluate the relationship between pre- and postoperative joint line convergence angle (JLCA) changes and patient-reported outcome measures related to medial open-wedge high tibial osteotomy (MOWHTO). METHODS: Sixty-one patients (71 knees) who underwent MOWHTO were examined. Preoperative and 2-year postoperative radiographic parameters (hip-knee-ankle angle, weight-bearing line ratio, medial proximal tibial angle and JLCA) were measured, and knee injury and osteoarthritis outcome scores (KOOS) were assessed. Patients were divided into two groups: group D (decreased JLCA compared with preoperative status) included 44 knees with a ΔJLCA < 0° and group I (increased JLCA and no-change JLCA compared with preoperative status) included 27 knees with a ΔJLCA ≥ 0°. KOOS sub-scores and the proportion of patients whose improvement exceeded the minimum clinically important difference (MCID) were compared between both groups using Student's t tests, Mann-Whitney U tests and chi-square tests. Multiple regression analysis was performed to determine the factor that had an influential effect on the postoperative KOOS total. RESULTS: Significant differences in 2-year postoperative KOOS were observed between the two groups, including total, symptom, pain and activities of daily living scores. Group D had significantly more patients who achieved MCID for both KOOS symptoms and pain scores than group I did. Multivariate analysis indicated that JLCA change and body mass index were significantly associated with the postoperative KOOS total. CONCLUSION: Patients with decreased JLCA had better 2-year post-MOWHTO KOOS and better symptom and pain improvements. Therefore, strategies that reduce JLCA are crucial to improving clinical outcomes, and efforts should be made to improve JLCA in surgical techniques. LEVEL OF EVIDENCE: Level Ⅳ, Case series.


Subject(s)
Osteoarthritis, Knee , Osteotomy , Patient Reported Outcome Measures , Tibia , Humans , Osteotomy/methods , Female , Male , Tibia/surgery , Middle Aged , Osteoarthritis, Knee/surgery , Knee Joint/surgery , Knee Joint/diagnostic imaging , Adult , Retrospective Studies , Radiography , Treatment Outcome , Postoperative Period , Aged
16.
Biol Pharm Bull ; 47(5): 895-903, 2024.
Article in English | MEDLINE | ID: mdl-38692865

ABSTRACT

Epidermal growth factor (EGF)-EGF receptor (EGFR) signaling studies paved the way for a basic understanding of growth factor and oncogene signaling pathways and the development of tyrosine kinase inhibitors (TKIs). Due to resistance mutations and the activation of alternative pathways when cancer cells escape TKIs, highly diverse cell populations form in recurrent tumors through mechanisms that have not yet been fully elucidated. In this review, we summarize recent advances in EGFR basic research on signaling networks and intracellular trafficking that may clarify the novel mechanisms of inhibitor resistance, discuss recent clinical developments in EGFR-targeted cancer therapy, and offer novel strategies for cancer drug development.


Subject(s)
Antineoplastic Agents , ErbB Receptors , Neoplasms , Protein Kinase Inhibitors , Signal Transduction , Humans , ErbB Receptors/metabolism , ErbB Receptors/antagonists & inhibitors , Neoplasms/drug therapy , Neoplasms/metabolism , Signal Transduction/drug effects , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology , Animals , Drug Resistance, Neoplasm , Molecular Targeted Therapy/methods
17.
Cell Rep ; 43(4): 114104, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38602872

ABSTRACT

Clinical evidence has revealed that high-level activation of NRF2 caused by somatic mutations in NRF2 (NFE2L2) is frequently detected in esophageal squamous cell carcinoma (ESCC), whereas that caused by somatic mutations in KEAP1, a negative regulator of NRF2, is not. Here, we aspire to generate a mouse model of NRF2-activated ESCC using the cancer-derived NRF2L30F mutation and cancer driver mutant TRP53R172H. Concomitant expression of NRF2L30F and TRP53R172H results in formation of NRF2-activated ESCC-like lesions. In contrast, while squamous-cell-specific deletion of KEAP1 induces similar NRF2 hyperactivation, the loss of KEAP1 combined with expression of TRP53R172H does not elicit the formation of ESCC-like lesions. Instead, KEAP1-deleted cells disappear from the esophageal epithelium over time. These findings demonstrate that, while cellular NRF2 levels are similarly induced, NRF2 gain of function and KEAP1 loss of function elicits distinct fates of squamous cells. The NRF2L30F mutant mouse model developed here will be instrumental in elucidating the mechanistic basis leading to NRF2-activated ESCC.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Kelch-Like ECH-Associated Protein 1 , NF-E2-Related Factor 2 , NF-E2-Related Factor 2/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , Kelch-Like ECH-Associated Protein 1/genetics , Animals , Mice , Esophageal Squamous Cell Carcinoma/metabolism , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/pathology , Esophageal Neoplasms/genetics , Humans , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/genetics , Gain of Function Mutation , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/genetics , Loss of Function Mutation
18.
Eur Spine J ; 33(6): 2298-2303, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38573386

ABSTRACT

PURPOSE: Preoperative computed tomography (CT)-based navigation is used for cervical pedicle screw (CPS) insertion to mitigate the risk of spinal cord and vertebral artery injury. In vertebrae with osteosclerosis due to degeneration or other factors, however, probing may not proceed easily, with difficulty creating the CPS insertion hole. This study investigated the impact of osteosclerosis on the accuracy of CPS insertion. METHODS: A total of 138 patients with CPS inserted at the C3-C7 level using preoperative CT navigation were retrospectively analyzed. Pre- and postoperative CT was employed to investigate screw position and Hounsfield unit (HU) values at the lateral mass to evaluate the degree of osteosclerosis in the CPS insertion pathway. RESULTS: Among 561 CPS insertions, the Grade 3 perforation rate was 1.8%, and the Grade 2 or higher perforation rate was 8.0%. When comparing insertions with and without CPS perforation, HU values were significantly higher in the perforation group (578 ± 191 vs. 318 ± 191, p < 0.01). The frequency of CPS insertion into the mid-cervical spine was also significantly greater in the perforation group (68.9% vs. 62.5%, p < 0.01). Logistic regression analysis revealed that a high HU value at the lateral mass (odds ratio 1.09, 95% confidence interval: 1.07-1.11, p < 0.01) was a significant independent factor associated with CPS deviation. CONCLUSIONS: The screw perforation rate of Grade 2 or higher in CPS insertion using preoperative CT-based navigation was 8.0%. Since osteosclerosis was an independent factor related to CPS deviation, additional care may be required during insertion into affected vertebrae.


Subject(s)
Cervical Vertebrae , Osteosclerosis , Pedicle Screws , Tomography, X-Ray Computed , Humans , Male , Female , Cervical Vertebrae/surgery , Cervical Vertebrae/diagnostic imaging , Middle Aged , Aged , Retrospective Studies , Tomography, X-Ray Computed/methods , Adult , Osteosclerosis/diagnostic imaging , Osteosclerosis/surgery , Spinal Fusion/methods , Spinal Fusion/instrumentation , Spinal Fusion/adverse effects , Aged, 80 and over , Preoperative Care/methods
19.
ESC Heart Fail ; 11(4): 2223-2233, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38627993

ABSTRACT

AIMS: This study aimed to elucidate age-stratified clinical profiles and outcomes in patients with heart failure (HF) with preserved left ventricular ejection fraction (LVEF) (HFpEF). METHODS AND RESULTS: The Chronic Heart Failure Registry and Analysis in the Tohoku District-2 (CHART-2) Study included 2824 consecutive HFpEF patients with LVEF ≥ 50% (mean age 69.0 ± 12.3 years; 67.7% male) with a median follow-up of 9.8 years. We stratified them into five age groups: ≤54 (N = 349, 12.4%), 55-64 (N = 529, 18.7%), 65-74 (N = 891, 31.6%), 75-84 (N = 853, 30.2%), and ≥85 years (N = 202, 7.2%), and we categorized these age groups into younger (≤64 years) and older (≥65 years) groups. We compared the clinical profiles and outcomes of HFpEF patients across age groups. Younger HFpEF groups exhibited a male predominance, elevated body mass index (BMI), and poorly controlled diabetes (haemoglobin A1c > 7.0%). Older HFpEF groups were more likely to be female with multiple comorbidities, including coronary artery disease, hypertension, renal impairment, and atrial fibrillation. The positive association between elevated BMI and HFpEF was more pronounced with lower classes of age from ≥85 to ≤54 years, especially in males. With higher classes of age from ≤54 to ≥85 years, mortality rates increased, and HF death became proportionally more prevalent (Ptrend < 0.001), whereas sudden cardiac death (SCD) exhibited the opposite trend (Ptrend = 0.002). Poorly controlled diabetes emerged as the only predictor of SCD in the younger groups (adjusted hazard ratio 4.26; 95% confidence interval 1.45-12.5; P = 0.008). Multiple comorbidities were significantly associated with an increased risk of HF-related mortality in the older groups. CONCLUSIONS: Younger HFpEF patients (≤64 years) exhibit a male predominance, elevated BMI, and poorly controlled diabetes, highlighting the importance of glycaemic control in reducing SCD risk. Older HFpEF patients (≥65 years) are more likely to be female, with multiple comorbidities linked to an increased risk of HF-related mortality. These findings underscore the need for physicians to recognize age-related, distinct HFpEF phenotypes for personalized patient management.


Subject(s)
Heart Failure , Registries , Stroke Volume , Ventricular Function, Left , Humans , Male , Female , Stroke Volume/physiology , Heart Failure/physiopathology , Heart Failure/complications , Aged , Middle Aged , Aged, 80 and over , Age Factors , Ventricular Function, Left/physiology , Follow-Up Studies , Prognosis , Survival Rate/trends , Japan/epidemiology , Risk Factors , Retrospective Studies
20.
ESC Heart Fail ; 11(4): 2344-2353, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38685603

ABSTRACT

AIMS: The incidence and prognosis of symptomatic heart failure following acute myocardial infarction (AMI) in the primary percutaneous coronary intervention era have rarely been reported in the literature. This study aimed to (i) determine the incidence of heart failure admission among AMI survivors, (ii) compare 1 year outcomes between patients with heart failure admission and those without, and (iii) identify the independent risk factors associated with heart failure admission. METHODS AND RESULTS: The Japan Acute Myocardial Infarction Registry is a prospective multicentre registry from which data on consecutively enrolled patients with AMI from 50 institutions between 2015 and 2017 were obtained. Among the 3411 patients enrolled, 3226 who survived until discharge were included in this study. The primary endpoint was all-cause mortality. The secondary endpoints were major adverse cardiovascular events (defined as cardiovascular mortality, non-fatal myocardial infarction, or non-fatal cerebral infarction) and major bleeding events corresponding to Bleeding Academic Research Consortium Type 3 or 5. Clinical outcomes were compared between the patients who were and were not admitted for heart failure. Over a median follow-up of 12 months, 124 patients (3.8%) were admitted due to heart failure. Independent risk factors for heart failure admission included older age, female sex, Killip class ≥2 on admission, left ventricular ejection fraction <40%, estimated glomerular filtration rate ≤30 mL/min/1.73 m2, a history of malignancy, and non-use of angiotensin-converting enzyme inhibitors at discharge. The cumulative incidence of all-cause mortality was significantly higher in the heart failure admission group than in the no heart failure admission group (11.3% vs. 2.5%, P < 0.001). The rates of major adverse cardiovascular events (16.9% vs. 2.7%, P < 0.001) and major bleeding (6.5% vs. 1.6%, P < 0.001) were significantly higher in the heart failure admission group. Heart failure admission was associated with a higher risk of all-cause mortality, even after adjusting for potential confounders (adjusted hazard ratio: 2.41, 95% confidence interval: 1.33-4.39, P = 0.004). CONCLUSIONS: Utilizing real-world data of the contemporary percutaneous coronary intervention era from the Japan Acute Myocardial Infarction Registry database, this study demonstrates that the heart failure admission of AMI survivors was significantly associated with higher all-cause mortality rates.


Subject(s)
Heart Failure , Myocardial Infarction , Registries , Humans , Male , Heart Failure/complications , Heart Failure/epidemiology , Female , Aged , Myocardial Infarction/complications , Myocardial Infarction/epidemiology , Myocardial Infarction/mortality , Prognosis , Japan/epidemiology , Prospective Studies , Incidence , Follow-Up Studies , Risk Factors , Middle Aged , Survival Rate/trends , Hospitalization/statistics & numerical data , Cause of Death/trends , Percutaneous Coronary Intervention , Survivors/statistics & numerical data
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