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1.
J Neurol Sci ; 466: 123235, 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39303349

ABSTRACT

BACKGROUND: Thrombectomy is a standard treatment for acute large vessel occlusion (LVO); however, its effectiveness in treating LVO related to intracranial atherosclerosis disease (ICAD) remains uncertain. This study aimed to compare thrombectomy outcomes in ICAD-related and embolic LVO, focusing on patients with similar symptom severities upon hospital admission. METHODS: This retrospective study was conducted at Jikei University Hospital and Jikei University Kashiwa Hospital between October 2017 and March 2023. Ischemic stroke patients with LVO who underwent thrombectomy were categorized into ICAD and embolism groups based on the occlusion mechanism. Groups were matched using National Institutes of Health Stroke Scale scores at the time of admission. A modified Rankin Scale score of 5 or 6 at 90 days after symptom onset was defined as a devastating outcome. The procedural outcomes and frequency of devastating outcomes were compared between the ICAD and embolism groups. RESULTS: The study included 33 matched pairs were included. The ICAD group showed lower rates of successful reperfusion (43 % vs. 82 %, p = 0.001), and longer procedural times (median 88 min vs. 50 min, p < 0.001) than the embolism group. The ICAD group had a significantly higher frequency of devastating outcomes than the non-ICAD group (39 % vs. 15 %, p = 0.027). Multivariate analysis identified ICAD as an independent factor associated with devastating outcomes (OR, 3.804; 95 % confidence interval (95 %CI), 1.148-12.603; p = 0.029). CONCLUSION: In thrombectomy therapy, reperfusion rates and outcomes are significantly worse in patients with ICAD-LVO than in patients with embolic LVO.

2.
Rinsho Shinkeigaku ; 2024 Sep 21.
Article in Japanese | MEDLINE | ID: mdl-39313367

ABSTRACT

A 28-year-old male presented with a sudden, transient visual impairment in the right eye. Brain MRI revealed no obvious ischemic lesions, and he was diagnosed with amaurosis fugax. Physical examination revealed characteristic features of Marfan syndrome, along with a family history of tall stature and valvular heart disease. Further investigation revealed: 1) an ascending aortic aneurysm, 2) a bicuspid aortic valve with fenestration and regurgitation, and 3) a mitral valve prolapse with regurgitation. Genetic testing identified a heterozygous variant c.6905G>A of FBN1, confirming the diagnosis of Marfan syndrome. Bentall operation and mitral valve replacement were performed, resulting in a favorable outcome. Pathological examination showed extensive myxomatous degeneration with thickening of the aortic and mitral valves, suggesting a potential source of embolism.

3.
J Atheroscler Thromb ; 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39231653

ABSTRACT

AIM: To determine whether the severity of cerebral small vessel disease (SVD) is associated with prehospital delay in acute ischemic stroke. METHODS: Consecutive patients with ischemic stroke were included in this study. We evaluated the SVD burden using the total SVD score. Patients were divided into 2 groups: onset-to-door time within 4.5 hours (early arrival group) and onset-to-door time over 4.5 hours (delayed arrival group). First, we assessed whether the total SVD score was related to prehospital delay using a logistic regression analysis. Second, we assessed which item of the score was independently associated with delays. Finally, we determined whether the item had a linear association with the delay. RESULTS: Of the 2,112 screened patients, 1,754 were enrolled in the study (1,253 males [71%]; median age, 69 years). There were 1,105 patients (63%) in the delayed arrival group. The total SVD score was independently associated with delay (OR 1.11, 95% CI 1.01-1.21, p=0.025). Among the 4 items of the score, only enlarged perivascular spaces (EPVS) in the basal ganglia was independently associated with delay (OR 1.37, 95% CI 1.05-1.80, p=0.022). A linear trend was observed between EPVS grade and delay with reference to EPVS grade 0-1 (EPVS grade 2: OR 1.22, 95% CI 0.92-1.62, p=0.170, EPVS grade 3: OR 1.69, 95% CI 1.20-2.38, p=0.002, EPVS grade 4: OR 2.17, 95% CI 1.37-3.44, p=0.001). CONCLUSIONS: Prehospital delay in acute ischemic stroke could be associated with the severity of SVD, particularly EPVS in the basal ganglia.

4.
Front Neurol ; 15: 1424030, 2024.
Article in English | MEDLINE | ID: mdl-39258155

ABSTRACT

Background: Endovascular therapy (EVT) for distal medium vessel occlusions requires prioritizing effectiveness and safety. We developed a technique combining the deployment of only the distal basket segment of the EMBOTRAP III and an aspiration catheter (AC) for M2 occlusions, called the "ONE-SEG technique," and evaluated its clinical and technical impacts. Methods: This was a retrospective review of 30 consecutive patients with M2 segment middle cerebral artery occlusion treated using the ONE-SEG technique. This method involves deploying the EMBOTRAP III through a microcatheter in only one segment and guiding the AC to the M2 origin or distal M1. The rates of final-pass expanded thrombolysis in cerebral infarction (eTICI) scores of 2c/3 or 2b/2c/3, safety (symptomatic intracranial hemorrhage [sICH]), and clinical outcomes (modified Rankin Scale [mRS] score 0-2, 0-3 at 90 days, and mortality at 90 days) were evaluated. Results: Of the 30 cases, 36.7% were female, and the mean age was 75.6 ± 11.0 years. The ONE-SEG technique was used for 17 cases (56.7%, median NIHSS 10 [5-15.5]) with primary M2 occlusion and 13 cases (43.3%, median NIHSS 20 [14-22.5]) with secondary M2 occlusion after proximal thrombus removal. The successful final reperfusion rate (eTICI 2b/2c/3) was 90% overall (27/30 cases). One case (3.3%) developed sICH with secondary M2 occlusion. At 3 months, mRS scores 0-2 were seen in 64.7% of patients with primary M2 occlusion (11/17 cases) and in 23.1% (3/13 cases) with secondary M2 occlusion. Conclusion: EVT using the ONE-SEG technique appears to be safe and effective for M2 occlusion.

5.
J Neurol Sci ; 464: 123165, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39116487

ABSTRACT

INTRODUCTION: A major component of Lewy bodies is phosphorylated α-synuclein. This post-translational modification of α-synuclein, phosphorylation, may consume a great amount of serum phosphorus. We aimed to investigate serum phosphorus levels and their associations with clinical phenotype and the degeneration of cardiac sympathetic and nigrostriatal dopaminergic neurons in patients with Parkinson's disease (PD). MATERIALS AND METHODS: We examined serum phosphorus levels in 127 participants (drug-naïve PD, 97; age- and sex-matched controls, 30). Associations of serum phosphorus levels with clinical features, heart-to-mediastinum (H/M) ratio on cardiac 123I-metaiodobenzylguanidine scintigraphy and striatal specific binding ratio of 123I-2-carbomethoxy-3-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) were examined. RESULTS: Serum phosphorus levels were 3.4 ± 0.5 mg/dL in patients with PD and were not different from those in controls after controlling for age and sex (p = 0.850). Serum phosphorus levels were significantly lower in patients with PD and decreased H/M ratio than in those with PD and normal H/M ratio (3.3 ± 0.4 mg/dL vs. 3.6 ± 0.5 mg/dL, p = 0.003). Lower serum phosphorus levels were significantly associated with more severe degeneration of nigrostriatal dopaminergic neurons in patients with PD and decreased H/M ratio. However, this association was not observed in patients with PD and normal H/M ratio. CONCLUSIONS: Serum phosphorus levels and their association with nigrostriatal dopaminergic degeneration are different between patients with decreased H/M ratio and those with normal H/M ratio. Serum phosphorus levels may reflect the degree of nigrostriatal dopaminergic degeneration in patients with decreased H/M ratio, namely, Body-First PD.


Subject(s)
Corpus Striatum , Parkinson Disease , Phosphorus , Substantia Nigra , Humans , Male , Female , Parkinson Disease/blood , Parkinson Disease/diagnostic imaging , Phosphorus/blood , Aged , Middle Aged , Substantia Nigra/diagnostic imaging , Substantia Nigra/metabolism , Corpus Striatum/diagnostic imaging , Corpus Striatum/metabolism , Tropanes , Dopaminergic Neurons/metabolism , Dopaminergic Neurons/pathology
6.
Int J Clin Oncol ; 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39196470

ABSTRACT

BACKGROUND: FOLFOXIRI plus bevacizumab is a standard first-line chemotherapy for patients with metastatic colorectal cancer (mCRC). However, due to the severe toxicities, this regimen is not widely used. There is limited data on the real-world efficacy and safety. METHODS: We conducted a retrospective analysis of clinical data from mCRC patients who received FOLFOXIRI plus bevacizumab as first-line chemotherapy at 31 institutions. The initial dose was standardized according to the TRIBE regimen. Induction therapy was defined as a combination of oxaliplatin, irinotecan, and fluorouracil. RESULTS: Out of 104 patients who met the criteria, the median age was 58 years (range, 16-72). 81% of patients had an eastern cooperative oncology group performance status (PS) of 0. An initial dose reduction was observed in 63% of patients. The median number of preplanned induction therapy cycles was 12 (range, 4-12). The completion of scheduled induction therapy cycles was observed in 45% of patients, with treatment-related toxicities being the main reason for discontinuation (63%). The median progression-free survival and overall survival were 12.8 months (95% CI, 10.6-15.0) and 27.9 months (95% CI 21.6-34.2), respectively. The objective response rate and disease control rate were 63.7% and 98.9%, respectively. The R0 resection rate was 21.2%. The main grade 3 or higher toxicities were neutropenia (51%), febrile neutropenia (10%), and nausea/vomiting (5%). No treatment-related deaths were observed. CONCLUSION: In a real-world clinical setting, FOLFOXIRI plus bevacizumab demonstrated efficacy and safety comparable to previous clinical trials.

7.
J Neurol Sci ; 462: 123069, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38824817

ABSTRACT

OBJECTIVE: Although high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has shown benefits in chronic stroke, its application in subacute ischemic stroke remains underexplored. This study aims to investigate the effects and safety of lesion-side HF-rTMS in subacute ischemic stroke. METHODS: Prospective lesion-side HF-rTMS was conducted on consecutive ischemic stroke patients within 3 days of onset from February 2019 to June 2022. Inclusion criteria required persistent paralysis (NIHSS score ≥ 1 for at least 7 days). Exclusion criteria comprised cortical infarction, disturbance of consciousness, and age over 80 years. A conventional rehabilitation group meeting the same criteria from June 2015 to January 2019 served as a comparison. We compared the two groups regarding clinical background and outcome. We also evaluated incidence of epilepsy and exacerbation of the NIHSS score in the rTMS group. RESULTS: Seventy-eight patients participated, with 50% in the HF-rTMS group. Median time from onset to HF-rTMS initiation was 9 (IQR 7-12) days. A favorable outcome (modified Rankin Scale score 0-2) at 3 months was more frequent in the rTMS group (80% vs. 44%, p = 0.002). HF-rTMS was independently associated with a favorable outcome at 3 months (OR = 5.60, 95% CI = 1.53-20.50, p = 0.009). No cases of epilepsy or exacerbation of NIHSS score were observed. CONCLUSIONS: HF-rTMS demonstrates potential effectiveness and safety in subacute ischemic stroke patients.


Subject(s)
Ischemic Stroke , Transcranial Magnetic Stimulation , Humans , Male , Female , Transcranial Magnetic Stimulation/methods , Transcranial Magnetic Stimulation/adverse effects , Aged , Ischemic Stroke/therapy , Middle Aged , Treatment Outcome , Prospective Studies , Stroke Rehabilitation/methods
8.
J Atheroscler Thromb ; 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38825505

ABSTRACT

AIMS: Bathing-related ischemic stroke (BIS) is sometimes fatal. However, its mechanisms and risk factors remain unclear. We aimed to identify the incidence of stroke subtypes in BIS, and clarify the impact of cerebral small vessel disease (CSVD) on BIS. METHODS: Consecutive patients with ischemic stroke between October 2012 and February 2022 were retrospectively screened. The inclusion criteria were: 1) onset-to-door time within 7 days; and 2) availability of the results of MRI evaluation of CSVD markers during hospitalization. BIS was defined as an ischemic stroke that occurred while or shortly after bathing. We investigated the incidence of the stroke subtype and the correlation between CSVD markers and BIS. RESULTS: 1,753 ischemic stroke patients (1,241 [71%] male, median age 69 years) were included. 57 patients (3%) were included in the BIS group. A higher frequency of large artery atherosclerosis (LAA) (prevalence ratio [PR] 2.069, 95% confidence interval [CI] 1.089 to 3.931, p=0.026) and lower frequency of cardio-embolism (CES) (PR 0.362, 95% CI 0.132 to 0.991, p=0.048) in BIS cases were identified. Moreover, lower periventricular hyperintensity (PVH) Fazekas grade (PR 0.671, 95% CI 0.472 to 0.956, p=0.027) and fewer cerebral microbleeds (CMBs) in deep brain region (PR 0.810, 95%CI 0.657 to 0.999, p=0.049) were associated with BIS cases. CONCLUSIONS: The BIS group was more likely to develop LAA and less likely to develop CES. Lower PVH grade and fewer CMBs in deep brain region were associated with the development of BIS.

9.
Intern Med ; 63(15): 2199-2201, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38749730

ABSTRACT

A 57-year-old man presented with subacute-onset paraparesis, bilateral dysesthesia in his lower extremities, and bladder/bowel disturbance six weeks after being infected with severe acute respiratory syndrome coronavirus 2 infection [coronavirus disease 2019 (COVID-19)]. A neurological examination suggested transverse myelitis at the level of the lower thoracic spinal cord. However, repeated spinal magnetic resonance imaging (MRI) showed no abnormalities in the spinal cord. Laboratory and cerebrospinal fluid (CSF) tests ruled out other etiologies of myelitis, eventually suggesting COVID-19-associated myelitis. Aggressive immunosuppressive therapy, started soon after hospitalization, dramatically improved his symptoms. Early aggressive immunosuppressive therapy should therefore be considered in cases of MRI/CSF-negative myelitis associated with COVID-19.


Subject(s)
COVID-19 , Immunosuppressive Agents , Magnetic Resonance Imaging , Humans , Male , Middle Aged , COVID-19/complications , COVID-19/diagnostic imaging , Immunosuppressive Agents/therapeutic use , SARS-CoV-2 , Myelitis/diagnostic imaging , Myelitis/drug therapy , Myelitis/cerebrospinal fluid , Myelitis/etiology , Myelitis, Transverse/diagnostic imaging , Myelitis, Transverse/drug therapy , Myelitis, Transverse/etiology , Treatment Outcome , Spinal Cord/diagnostic imaging , Spinal Cord/pathology
10.
Clin Nutr ; 43(6): 1643-1651, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38772071

ABSTRACT

BACKGROUND & AIMS: Some ω3 polyunsaturated fatty acids (PUFAs) are said to demonstrate a dose-related risk of atrial fibrillation (AF), conversely, some ω6 PUFAs might have AF protective potential. However, few investigated the relation among ischemic strokes. Primarily, we aimed to examine a relation between ω3 and ω6 PUFAs and the presence of AF in ischemic strokes. Further, since, some PUFAs are said to affect the cardiac load, we secondarily aimed to investigate the association between ω3 and ω6 PUFAs and brain natriuretic peptide (BNP) and the occurrence of cerebral large vessel occlusion (LVO) in ischemic strokes with AF. METHODS: Consecutive patients with ischemic stroke admitted between 2012 and 2022 were retrospectively screened. Plasma levels of PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid, dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA), were assayed. Data were analyzed using a Poisson regression analysis with a robust variance estimator and a multiple linear regression analysis. RESULTS: We screened 2112 consecutive ischemic strokes, including 1574 (1119 [71%] males, median age 69 years). Lower DGLA (prevalence ratio (PR) 0.885, 95% CI 0.811-0.966, p = 0.006), lower AA (PR 0.797, 95% CI 0.649-0.978, p = 0.030), and higher EPA/AA ratio (PR 1.353, 95% CI 1.036-1.767, p = 0.026) were associated with AF. Checking the linearity between AF and PUFAs, negative linear trends were observed between DGLA quartiles (Q1: PR 1.901, Q2: PR 1.550, Q3: PR 1.423, Q4: 1.000, p < 0.001 for trend) and AA quartiles (Q1: PR 1.499, Q2: PR 1.204, Q3: PR 1.125, Q4: 1.000, p = 0.004 for trend), with positive linear trends between EPA/AA ratio quartiles (Q1: 1.000, Q2: PR 1.555, Q3: PR 1.612, Q4: PR 1.797, p = 0.001 for trend). Among patients with AF, a negative association between AA and BNP (unstandardized coefficient -1.316, 95% CI -2.290∼-0.342, p = 0.008) was observed, and lower AA was associated with LVO (PR 0.707, 95% CI 0.527-0.950, p = 0.021). CONCLUSION: Lower DGLA and AA and a higher EPA/AA ratio might be related to the development of AF in ischemic strokes. Further, AA might have a cardio-cerebrovascular protective role in ischemic strokes with AF.


Subject(s)
Atrial Fibrillation , Fatty Acids, Omega-3 , Fatty Acids, Omega-6 , Ischemic Stroke , Humans , Male , Female , Aged , Atrial Fibrillation/blood , Atrial Fibrillation/complications , Fatty Acids, Omega-3/blood , Ischemic Stroke/blood , Ischemic Stroke/epidemiology , Ischemic Stroke/etiology , Retrospective Studies , Fatty Acids, Omega-6/blood , Middle Aged , Aged, 80 and over , Natriuretic Peptide, Brain/blood , Brain Ischemia/blood , Brain Ischemia/epidemiology , Brain Ischemia/etiology , Risk Factors
11.
J Neurol ; 271(7): 4146-4157, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38581545

ABSTRACT

BACKGROUND: Accumulating evidence suggests that peripheral inflammation is associated with the pathogenesis of Parkinson's disease (PD). We examined peripheral immune profiles and their association with clinical characteristics in patients with DLB and compared these with values in patients with PD. METHODS: We analyzed peripheral blood from 93 participants (drug-naïve DLB, 31; drug-naïve PD, 31; controls, 31). Absolute leukocyte counts, absolute counts of leukocyte subpopulations, and peripheral blood inflammatory indices such as neutrophil-to-lymphocyte ratio were examined. Associations with clinical characteristics, cardiac sympathetic denervation, and striatal 123I-2-carbomethoxy-3-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) binding were also examined. RESULTS: Patients with DLB had lower absolute lymphocyte and basophil counts than did age-matched controls (both; p < 0.005). Higher basophil counts were marginally associated with higher global cognition (p = 0.054) and were significantly associated with milder motor severity (p = 0.020) and higher striatal 123I-FP-CIT binding (p = 0.038). By contrast, higher basophil counts were associated with more advanced PD characterized by decreased global cognition and severe cardiac sympathetic denervation. Although lower lymphocyte counts had relevance to more advanced PD, they had little relevance to clinical characteristics in patients with DLB. Higher peripheral blood inflammatory indices were associated with lower body mass index in both DLB and PD. CONCLUSIONS: As in patients with PD, the peripheral immune profile is altered in patients with DLB. Some peripheral immune cell counts and inflammatory indices reflect the degree of disease progression. These findings may deepen our knowledge on the role of peripheral inflammation in the pathogenesis of DLB.


Subject(s)
Lewy Body Disease , Humans , Male , Female , Aged , Lewy Body Disease/immunology , Lewy Body Disease/blood , Aged, 80 and over , Middle Aged , Basophils/immunology , Parkinson Disease/immunology , Parkinson Disease/blood , Leukocyte Count , Lymphocytes/immunology , Inflammation/immunology , Inflammation/blood , Tropanes
12.
BMC Infect Dis ; 24(1): 425, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649870

ABSTRACT

BACKGROUND: Necrotising fasciitis (NF) is a life-threatening soft-tissue infection that rapidly destroys the epidermis, subcutaneous tissue, and fascia. Despite their low virulence, Lactobacillus spp. can cause NF, and because of its rare incidence, there is limited information about its molecular and clinicopathological characteristics. We report a rare case of NF in a patient with type 2 diabetes mellitus diagnosed on admission and severe obesity due to infection with two types of Lactobacillus spp. that manifested in extensive necrosis. CASE PRESENTATION: A 48-year-old woman was referred to our hospital with a complaint of difficulty walking due to severe bilateral thigh pain. She presented with mild erythema, swelling, and severe skin pain extending from the pubic region to the groin. The patient was morbidly obese, had renal dysfunction, and had diabetes mellitus diagnosed on admission.; her LRINEC (Laboratory Risk Indicator for Necrotising Fasciitis) score was 9, indicating a high risk of NF. An exploratory surgical incision was made, and NF was diagnosed based on fascial necrosis. Emergent surgical debridement was performed, and cultures of the tissue culture and aspirated fluid/pus revealed two types of Lactobacillus spp.: Lactobacillus salivarius and L. iners. The patient was admitted to the intensive care unit (ICU), where antibiotics were administered and respiratory and circulatory management was performed. Diabetic ketoacidosis was detected, which was treated by controlling the blood glucose level stringently via intravenous insulin infusion. The patient underwent a second debridement on day 11 and a skin suture and skin grafting on day 36. The patient progressed well, was transferred from the ICU to the general ward on day 41, and was discharged unassisted on day 73. CONCLUSIONS: Lactobacillus spp. are rarely pathogenic to healthy individuals and can scarcely trigger NF. However, these bacteria can cause rare infections such as NF in immunocompromised individuals, such as those with diabetes and obesity, and an early diagnosis of NF is imperative; surgical intervention may be required for the prevention of extensive necrosis. The LRINEC score may be useful for the early diagnosis of NF, even for less pathogenic bacteria such as Lactobacillus.


Subject(s)
Fasciitis, Necrotizing , Lactobacillus , Humans , Fasciitis, Necrotizing/microbiology , Fasciitis, Necrotizing/pathology , Female , Middle Aged , Lactobacillus/isolation & purification , Diabetes Mellitus, Type 2/complications , Anti-Bacterial Agents/therapeutic use , Debridement , Necrosis/microbiology , Gram-Positive Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/diagnosis , Gram-Positive Bacterial Infections/drug therapy , Gram-Positive Bacterial Infections/pathology
13.
Head Neck ; 46(5): E57-E60, 2024 05.
Article in English | MEDLINE | ID: mdl-38375754

ABSTRACT

BACKGROUND: A case of retropharyngeal abscess complicated by both artery and nerve injury has rarely been reported. METHODS: A 36-year-old woman suddenly presented with right eye visual loss, dilated pupil, reduced direct light reflex, ptosis and ocular motility disorder on the side of inflammation progression, and was diagnosed with retropharyngeal abscess due to Fusobacterium necrophorum. The patient was treated only with antibiotics and, no further surgery was necessary but tracheotomy. Four months later, MRA showed right ICA occlusion and left ICA stenosis. MRI revealed continuous spread of inflammation due to the abscess from the retropharyngeal to the intracranial space. RESULTS: These severe complications would be attributed to an endothelial damage to the arterial wall and an ischemic neuropathy caused by inflammation and thrombogenesis due to Fusobacterium necrophorum. CONCLUSIONS: This case should provide a better understanding of the mechanism of vascular and cranial nerve injury due to retropharyngeal infections, and highlights the need for early antibiotic therapy and repeated vascular evaluation.


Subject(s)
Carotid Stenosis , Cranial Nerve Diseases , Retropharyngeal Abscess , Female , Humans , Adult , Retropharyngeal Abscess/diagnosis , Retropharyngeal Abscess/diagnostic imaging , Carotid Stenosis/complications , Carotid Stenosis/diagnostic imaging , Fusobacterium necrophorum , Cranial Nerve Diseases/etiology , Inflammation , Carotid Artery, Internal
14.
Nat Med ; 30(3): 730-739, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38347302

ABSTRACT

Certain genetic alterations and right-sided primary tumor location are associated with resistance to anti-epidermal growth factor (EGFR) treatment in metastatic colorectal cancer (mCRC). The phase 3 PARADIGM trial (n = 802) demonstrated longer overall survival with first-line anti-EGFR (panitumumab) versus antivascular endothelial growth factor (bevacizumab) plus modified FOLFOX6 in patients with RAS wild-type mCRC with left-sided primary tumors. This prespecified exploratory biomarker analysis of PARADIGM (n = 733) evaluated the association between circulating tumor DNA (ctDNA) gene alterations and efficacy outcomes, focusing on a broad panel of gene alterations associated with resistance to EGFR inhibition, including KRAS, NRAS, PTEN and extracellular domain EGFR mutations, HER2 and MET amplifications, and ALK, RET and NTRK1 fusions. Overall survival was prolonged with panitumumab plus modified FOLFOX6 versus bevacizumab plus modified FOLFOX6 in patients with ctDNA that lacked gene alterations in the panel (that is, negative hyperselected; median in the overall population: 40.7 versus 34.4 months; hazard ratio, 0.76; 95% confidence interval, 0.62-0.92) but was similar or inferior with panitumumab in patients with ctDNA that contained any gene alteration in the panel (19.2 versus 22.2 months; hazard ratio, 1.13; 95% confidence interval, 0.83-1.53), regardless of tumor sidedness. Negative hyperselection using ctDNA may guide optimal treatment selection in patients with mCRC. ClinicalTrials.gov registrations: NCT02394834 and NCT02394795 .


Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Rectal Neoplasms , Humans , Panitumumab/therapeutic use , Bevacizumab/therapeutic use , Antibodies, Monoclonal/therapeutic use , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Colonic Neoplasms/drug therapy , Rectal Neoplasms/drug therapy , Biomarkers , ErbB Receptors/genetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Proto-Oncogene Proteins p21(ras)
15.
Nutr Metab Cardiovasc Dis ; 34(5): 1157-1165, 2024 May.
Article in English | MEDLINE | ID: mdl-38331645

ABSTRACT

BACKGROUND AND AIMS: Small ischemic lesions (SILs) accompanying intracerebral hemorrhage (ICH) might be induced by small-vessel vulnerability and hypercoagulation. Some polyunsaturated fatty acids (PUFAs) have been associated with hypercoagulation in cardiovascular diseases. Our aim here is to determine how pre-existing small-vessel disease (SVD) and PUFAs may affect SILs. METHODS AND RESULTS: We screened consecutive ICH patients (October 2012-December 2021) meeting two inclusion criteria: (1) the patients were hospitalized for acute ICH and were undergoing magnetic resonance imaging and (2) the patients' PUFA measurements were available. After excluding patients with isolated intraventricular hemorrhage, we evaluated whether three SVD markers (white matter hyperintensities, old lacunes, cerebral microbleeds) and PUFAs might be associated with the development of SILs. We selected 319 participants from 377 screened consecutive ICH patients (median age = 64, males = 207 [65 %]). Of the 319 patients, 45 patients (14 %) developed SILs. In a multivariable logistic regression analysis, the factors associated with SILs were old lacunes (OR 3.255, 95 % CI 1.101-9.622, p = 0.033) and DHA/AA ratio (OR 0.180, 95 % CI 0.046-0.704, p = 0.013). Furthermore, in our multivariable analysis using DHA/AA ratio tertiles with and without SILs, we observed a linear trend between SILs and the Higher Tertile of the DHA/AA ratio (DHA/AA ratio Mid-Tertile: OR 1.330, 95%CI 0.557-3.177, p = 0.521, and DHA/AA ratio Lower Tertile: OR 2.632, 95%CI 1.124-6.162, p = 0.026). CONCLUSION: The presence of old lacunes and lower DHA/AA ratios might be associated with SILs accompanying ICH.


Subject(s)
Cerebral Small Vessel Diseases , Male , Humans , Middle Aged , Cerebral Hemorrhage/diagnostic imaging , Magnetic Resonance Imaging/methods , Fatty Acids, Unsaturated
16.
Int J Cardiol ; 399: 131769, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38211671

ABSTRACT

BACKGROUND AND OBJECTIVE: This study's objective is to investigate whether mild aortic arch plaque is associated with the development of atrial fibrillation (AF) in stroke patients with embolic stroke of undetermined source (ESUS) during the first year following the implantation of an insertable cardiac monitor (ICM). METHODS: The participants in this cross-sectional observational study were consecutive patients with ESUS, even after transesophageal echocardiography. We assessed the relationship between the thickness of the participants' aortic arch plaque and AF detected after ICM implantation. RESULTS: Of the 50 consecutive patients with ESUS enrolled in this study, 12 (24%) developed AF. We observed that thicker aortic arch plaque was associated with undetected AF (2.3 mm vs. 1.2 mm, p < 0.001). Aortic arch plaque thickness was independent associated with undetected AF (OR 54.00, 95% CI 2.706-1077.544, p = 0.009). When the cut-off value for aortic arch plaque thickness was 1.8 mm, the sensitivity and specificity were 71.1% and 91.7%, respectively (95% CI = 0.75-0.98, p < 0.001). Also, patients having both aortic arch plaque with a thickness < 1.8 mm and a CHADS2 score ≥ 4 were more likely to have detectable AF than no AF (88% vs. 12%, p < 0.001). CONCLUSION: A thinner aortic arch plaque was associated with the development of AF. Patients with mild aortic plaques below 4 mm but ≥1.8 mm in thickness and without other high-risk features are less likely to have paroxysmal AF on ICM, and these plaques may be a possible source of embolism for their strokes.


Subject(s)
Atrial Fibrillation , Embolic Stroke , Intracranial Embolism , Plaque, Atherosclerotic , Stroke , Humans , Atrial Fibrillation/diagnosis , Atrial Fibrillation/diagnostic imaging , Embolic Stroke/complications , Aorta, Thoracic/diagnostic imaging , Cross-Sectional Studies , Plaque, Atherosclerotic/diagnosis , Plaque, Atherosclerotic/diagnostic imaging , Stroke/diagnostic imaging , Stroke/epidemiology , Risk Factors , Intracranial Embolism/diagnostic imaging , Intracranial Embolism/etiology
17.
Clin Neurol Neurosurg ; 237: 108127, 2024 02.
Article in English | MEDLINE | ID: mdl-38290169

ABSTRACT

BACKGROUND AND PURPOSE: The total small vessel disease (SVD) score, calculated using magnetic resonance imaging (MRI), is used to assess the risk of cerebral infarction. Stroke patients with total SVD scores of three or higher are reported to have a significantly increased risk of recurrent stroke. Similar to the total SVD score, carotid ultrasonography findings have been reported to be indicators of atherosclerosis. Although the total SVD score effectively reflects SVD progression, its correlation with carotid ultrasonography findings remains unknown. We aimed to investigate whether there is a relationship between these two factors. METHODS: Patients with small-vessel occlusion within 24 h of onset were retrospectively selected. Atherosclerotic factors were evaluated using the left-right average Gosling pulsatility index (PI) in the internal carotid artery (ICA-PI) and cardio-ankle vascular index (CAVI). Differences in clinical backgrounds, including atherosclerotic factors, were evaluated by dividing patients into two groups: those with a total SVD score of two or less (low-score group) and those with scores of three or more (high-score group). RESULTS: A total of 122 patients were included in this study. ICA-PI was significantly higher in the high-score group than in the low-score group. A high score was independently correlated with ICA-PI after adjusting for age, CAVI, smoking, and history of secondary atherosclerosis. CONCLUSIONS: Increased ICA-PI was associated with a high total SVD score in acute small-vessel occlusion and may be an alternative method for predicting the total SVD score, enabling the administration of interventions to prevent stroke relapse without the need for MRI.


Subject(s)
Atherosclerosis , Cerebral Small Vessel Diseases , Stroke , Humans , Animals , Carotid Artery, Internal/diagnostic imaging , Carotid Artery, Internal/pathology , Retrospective Studies , Geese , Neoplasm Recurrence, Local , Stroke/etiology , Stroke/complications , Cerebral Small Vessel Diseases/complications , Atherosclerosis/complications
18.
Int J Clin Oncol ; 29(3): 276-285, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38286874

ABSTRACT

BACKGROUND: Previously, we reported SMR (skeletal muscle radiodensity) as a potential prognostic marker for colorectal cancer. However, there have been limited studies on the association between SMR and the continuation of adjuvant chemotherapy in colorectal cancer. METHODS: In this retrospective study, 143 colorectal cancer patients underwent curative surgery and adjuvant chemotherapy using the CAPOX regimen. Patients' SMRs were measured from preoperative CT images and divided into low (bottom quarter) and high (top three quarters) SMR groups. We compared chemotherapy cycles, capecitabine and oxaliplatin doses, and adverse effects in each group. RESULTS: The low SMR group had significantly fewer patients completing adjuvant chemotherapy compared to the high SMR group (44% vs. 68%, P < 0.01). Capecitabine and oxaliplatin doses were also lower in the low SMR group. Incidences of Grade 2 or Grade 3 adverse effects did not differ between groups, but treatment discontinuation due to adverse effects was significantly higher in the low SMR group. Logistic regression analysis revealed Stage III disease (odds ratio 18.09, 95% CI 1.41-231.55) and low SMR (odds ratio 3.26, 95% CI 1.11-9.56) as factors associated with unsuccessful treatment completion. Additionally, a higher proportion of low SMR patients received fewer than 2 cycles of chemotherapy (50% vs. 12%). CONCLUSION: The low SMR group showed higher treatment incompletion rates and received lower drug doses during adjuvant chemotherapy. Low SMR independently contributed to treatment non-completion in colorectal cancer patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Colorectal Neoplasms , Humans , Capecitabine/adverse effects , Oxaliplatin/adverse effects , Retrospective Studies , Risk Factors , Chemotherapy, Adjuvant/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Colorectal Neoplasms/pathology , Fluorouracil/adverse effects , Neoplasm Staging
19.
J Atheroscler Thromb ; 31(3): 306-315, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-37704430

ABSTRACT

AIMS: Urinary immunoglobulin G (IgG) may be a stronger marker of atherosclerosis than microalbuminuria are because urinary IgG reflects proteinuria level and size-selectivity loss. Microalbuminuria-not urinary IgG-is associated with mild acute ischemic stroke (MAIS). METHODS: Using the Jikei University School of Medicine Stroke Registry, we selected and screened patients with symptomatic acute ischemic stroke (onset-to-door time ≤ 24 h). The exclusion criteria were (1) on-admission NIHSS scores >10, (2) a modified Rankin Scale (mRS) score ≥ 2 prior to stroke onset, (3) incomplete data (no urinalysis ≤ 3 days after admission or no mRS score at 90 days from stroke onset), and (4) an active malignancy. Patients at 90 days post-discharge were divided into those with favorable mRS scores of 0-1 and those with unfavorable mRS scores of 2-6. Clinical backgrounds were compared for (1) patients with positive and negative urinary IgG results, and (2) patients with favorable and unfavorable outcomes. RESULTS: Of our study's 210 patients (164=male, median age=68, median eGFR=53.2 ml/min/1.73 m2), 30 (14%) presented with positive urinary IgG, which was associated with cardiovascular risk factors. Higher BNP, higher D-dimer, lower eGFR, and higher CAVI were associated with higher positive urinary IgG. The favorable group, comprising 155 (74%) patients, had higher negative urinary IgG than the unfavorable group (89% vs 76%, P=0.026). No statistical difference emerged regarding microalbuminuria (29% vs 29%, P=1.000). CONCLUSION: In MAIS, urinary IgG was associated with both the presence of atherosclerosis and an unfavorable outcome at 90 days after stroke onset.


Subject(s)
Atherosclerosis , Brain Ischemia , Ischemic Stroke , Stroke , Humans , Male , Aged , Ischemic Stroke/complications , Immunoglobulin G , Aftercare , Patient Discharge , Stroke/etiology , Biomarkers , Atherosclerosis/diagnosis , Atherosclerosis/complications , Brain Ischemia/complications , Treatment Outcome
20.
J Neurol Sci ; 456: 122813, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38043333

ABSTRACT

BACKGROUND AND AIMS: Circadian variability of blood pressure (BP) and hypercoagulation in the morning have been proposed as underlying mechanisms of wake-up stroke (WUS). The aim was to determine the impact of cerebral microbleeds (CMBs), showing BP fluctuation and background hypercoagulability, on WUS. METHODS: Consecutive patients with acute ischemic stroke onset-to-door time within one week were screened. WUS was defined as an ischemic stroke that occurred during sleep at night. CMBs were categorized into three: "strictly Lobar", "strictly Deep (D) and/or Infratentorial (I)", and "Mixed". Moderate to severe CMBs were defined as having more than three in total. First, whether CMBs are associated with WUS was examined. Second, the same analysis was performed according to the stroke subtype classified as large-artery atherosclerosis (LAA), cardioembolism (CE), and small-vessel occlusion (SVO). RESULTS: A total of 1477 patients (1059 [72%] male, median age 69 years) were included, and WUS was observed in 363 (25%) patients. On Poisson regression analysis with a robust variance estimator in the total cohort, moderate to severe strictly D and/or I CMBs (PR 1.505, 95% CI 1.154-1.962, p = 0.003) were associated with WUS. From the perspective of stroke subtype, the same result was confirmed in LAA (PR 2.223, 95% CI 1.036-4.768, p = 0.040) and CE (PR 1.668, 95% CI 1.027-2.709, p = 0.039), not SVO. CONCLUSIONS: The presence of moderate to severe strictly D and/or I CMBs might be associated with the development of WUS. By stroke subtype, the same result was confirmed in LAA and CE.


Subject(s)
Atherosclerosis , Ischemic Stroke , Stroke , Humans , Male , Aged , Female , Cerebral Hemorrhage/complications , Cerebral Hemorrhage/diagnostic imaging , Stroke/complications , Stroke/diagnostic imaging , Atherosclerosis/complications , Atherosclerosis/diagnostic imaging , Magnetic Resonance Imaging , Arteries , Risk Factors
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