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1.
Am J Ophthalmol Case Rep ; 34: 102034, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38495594

RESUMO

Purpose: To report a case of a refractory foveal microaneurysm (MA) that was successfully treated by use of a new surgical procedure. Observations: This study involved a 79-year-old female with an active foveal MA associated with branch retinal vein occlusion in her left eye. Despite anti-vascular endothelial growth factor treatments, the MA remained active without closure, and best-corrected visual acuity (VA) gradually decreased from 20/20 to 20/200. After our new surgical procedure was explained in detail to the patient, written informed consent was obtained from the patient and the surgery was performed. Briefly, following pars plana vitrectomy, the internal limiting membrane in her left eye was peeled and the retina of the external wall of the MA was then gently incised. The exposed MA was then directly grabbed and pulled up onto the retina using 27-gauge microforceps, and photocoagulation was performed. At 3-months postoperative, closure of the MA and improvement in the retinal findings were observed, and best-corrected VA improved to 20/67. Conclusions and importance: We report a case of a refractory foveal MA that was successfully treated with a novel surgical technique that closed the MA, avoided thermal damage to the surrounding tissue, and resulted in improved postoperative VA.

2.
Surg Today ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38436719

RESUMO

PURPOSE: This study examined the impact of frailty and prefrailty on mid-term outcomes and rehabilitation courses after cardiac surgery. METHODS: A total of 261 patients (median age: 73 years; 30% female) who underwent elective cardiac surgery were enrolled in this study. The Japanese version of the Cardiovascular Health Study Frailty Index classified 86, 131, and 44 patients into frailty, prefrailty, and robust groups, respectively. We examined the recovery of walking ability, outcomes at discharge, mid-term all-cause mortality, and rehospitalization related to major adverse cardiovascular and cerebrovascular events (MACCE) across the three cohorts. RESULTS: The 3-year survival rates in the frailty, prefrailty, and robust groups were 87%, 97%, and 100%, respectively (p = 0.003). The free event rates of all-cause mortality and re-hospitalization related to MACCE were 59%, 79%, and 95%, respectively (p < 0.001), with a graded elevation in adjusted morbidity among patients in the prefrailty (hazard ratio [HR], 4.57; 95% confidence interval [CI], 1.08-19.4) and frailty (HR, 9.29; 95% CI 2.21-39.1) groups. Patients with frailty also experienced a delayed recovery of walking ability and a reduced number of patients with frailty were discharged home. CONCLUSION: Frailty and prefrailty adversely affect the mid-term prognosis and rehabilitation course after cardiac surgery.

3.
Respir Investig ; 62(3): 442-448, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38522360

RESUMO

BACKGROUND: Chronic cough is one of the most common symptoms of respiratory diseases and can adversely affect patients' quality of life and interfere with social activities, resulting in a significant social burden. A survey is required to elucidate the frequency and treatment effect of chronic cough. However, clinical studies that cover all of Japan have not yet been conducted. METHODS: Patients who presented with a cough that lasted longer than 8 weeks and visited the respiratory clinics or hospitals affiliated with the Japan Cough Society during the 2-year study period were registered. RESULTS: A total of 379 patients were enrolled, and those who did not meet the definition of chronic cough were excluded. A total of 334 patients were analyzed: 201 patients had a single cause, and 113 patients had two or more causes. The main causative diseases were cough variant asthma in 92 patients, sinobronchial syndrome (SBS) in 36 patients, atopic cough in 31 patients, and gastroesophageal reflux (GER)-associated cough in 10 patients. The time required to treat undiagnosed patients and those with SBS was significantly longer and the treatment success rate for GER-associated cough was considerably poor. CONCLUSIONS: We confirmed that the main causes of chronic cough were cough variant asthma, SBS, atopic cough, and their complications. We also showed that complicated GER-associated cough was more likely to become refractory. This is the first nationwide study in Japan of the causes and treatment effects of chronic cough.


Assuntos
60522 , Refluxo Gastroesofágico , Humanos , 60521 , Japão/epidemiologia , Prevalência , Qualidade de Vida , Tosse/epidemiologia , Tosse/etiologia , Tosse/diagnóstico , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/epidemiologia , Doença Crônica
4.
Sci Rep ; 14(1): 6292, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491024

RESUMO

Recently, many phenotyping algorithms for high-throughput cohort identification have been developed. Prospective genome cohort studies are critical resources for precision medicine, but there are many hurdles in the precise cohort identification. Consequently, it is important to develop phenotyping algorithms for cohort data collection. Hypertensive disorders of pregnancy (HDP) is a leading cause of maternal morbidity and mortality. In this study, we developed, applied, and validated rule-based phenotyping algorithms of HDP. Two phenotyping algorithms, algorithms 1 and 2, were developed according to American and Japanese guidelines, and applied into 22,452 pregnant women in the Birth and Three-Generation Cohort Study of the Tohoku Medical Megabank project. To precise cohort identification, we analyzed both structured data (e.g., laboratory and physiological tests) and unstructured clinical notes. The identified subtypes of HDP were validated against reference standards. Algorithms 1 and 2 identified 7.93% and 8.08% of the subjects as having HDP, respectively, along with their HDP subtypes. Our algorithms were high performing with high positive predictive values (0.96 and 0.90 for algorithms 1 and 2, respectively). Overcoming the hurdle of precise cohort identification from large-scale cohort data collection, we achieved both developed and implemented phenotyping algorithms, and precisely identified HDP patients and their subtypes from large-scale cohort data collection.


Assuntos
Hipertensão Induzida pela Gravidez , Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Hipertensão Induzida pela Gravidez/diagnóstico , Gestantes , Estudos de Coortes , Estudos Prospectivos
6.
Chemistry ; : e202400883, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38556469

RESUMO

We report on the syntheses of NeuAc and NeuGc-containing glycosides via the use of double carbonyl-protected N-acetyl sialyl donors. The 7-O,9-O-carbonyl protection of an N-acyl-5-N,4-O-carbonyl-protected sialyl donor markedly increased the a-selectivity during glycosylation, particularly when glycosylating the C-8 hydroxyl group of sialic acids. The N-acyl carbamates were selectively opened with ethanethiol under basic conditions to provide N-acyl amines. It is noteworthy that N-glycolyl carbamate was more reactive to nucleophiles by comparison with the N-acetyl carbamate due to the electron-withdrawing oxygen in the N-acyl group and however, allowed selective opening of the carbamates without the loss of N-glycolyl groups. To demonstrate the utility of the approach, we began by synthesizing α(2,3) and α(2,6) sialyl galactosides. Glycosylation of the hydroxy groups of galactosides at the C-6 position with the NeuAc and NeuGc donors provided the corresponding sialyl galactoses in good yields with excellent a-selectivity. However, glycosylation of the 2,3-diol galactosyl acceptor selectively provided Siaα(2,2)Gal. Next, we prepared a series of α(2,8) disialosides composed of NeuAc and NeuGc. Glycosylation of NeuGc and NeuAc acceptors at the C-8 hydroxyl group with NeuGc and NeuAc sialyl donors provided the corresponding α(2,8) disialosides, and no significant differences were detected in the reactivities of these acceptors.

7.
Int J Urol ; 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38468553

RESUMO

OBJECTIVES: To evaluate the utility of magnetic resonance imaging (MRI) and MRI-ultrasound fusion targeted biopsy (TB) for predicting unexpected extracapsular extension (ECE) in clinically localized prostate cancer (CLPC). METHODS: This study enrolled 89 prostate cancer patients with one or more lesions showing a Prostate Imaging-Reporting and Data System (PI-RADS) score ≥3 but without morphological abnormality in the prostatic capsule on pre-biopsy MRI. All patients underwent TB and systematic biopsy followed by radical prostatectomy (RP). Each lesion was examined by 3-core TB, taking cores from each third of the lesion. The preoperative variables predictive of ECE were explored by referring to RP specimens in the lesion-based analysis. RESULTS: Overall, 186 lesions, including 81 (43.5%), 73 (39.2%), and 32 (17.2%) with PI-RADS 3, 4, and 5, respectively, were analyzed. One hundred and twenty-two lesions (65.6%) were diagnosed as cancer on TB, and ECE was identified in 33 (17.7%) on the RP specimens. The positive TB core number was ≤2 in 129 lesions (69.4%) and three in 57 lesions (30.6%). On the multivariate analysis, PI-RADS ≥4 (p = 0.049, odds ratio [OR] = 2.39) and three positive cores on TB (p = 0.005, OR = 3.07) were independent predictors of ECE. Lesions with PI-RADS ≥4 and a positive TB core number of 3 had a significantly higher rate of ECE than those with PI-RADS 3 and a positive TB core number ≤2 (37.5% vs. 7.8%, p < 0.001). CONCLUSIONS: Positive TB core number in combination with PI-RADS scores is helpful to predict unexpected ECE in CLPC.

8.
Org Biomol Chem ; 22(13): 2544-2548, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38414338

RESUMO

The synthesis of D-glycero-D-manno-heptose-1ß,7-bisphosphate (HBP) from D-mannose is described. This synthetic approach is notable for the elongation of the seventh carbon, employing mannurono-2,6-lactone, the substrate-controlled establishment of the C-6 configuration, and the nucleophilic introduction of phosphate at the C-1 position through the utilization of 4,6-O-benzylidene-α-triflate.

9.
Cancer Sci ; 115(4): 1296-1305, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38402853

RESUMO

Tepotinib is a highly selective MET tyrosine kinase inhibitor (TKI) that has demonstrated robust and durable clinical activity in patients with MET exon 14 (METex14) skipping non-small-cell lung cancer (NSCLC). In the Phase II VISION study, patients received oral tepotinib 500 mg once daily. The primary endpoint was an objective response by an independent review committee (IRC) according to RECIST v1.1 criteria. The secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Here we report the analysis of the efficacy and safety of tepotinib in all Japanese patients with advanced METex14 skipping NSCLC from VISION (n = 38) with >18 months' follow-up. The median age of the Japanese patients was 73 years (range 63-88), 39.5% of patients were ≥75 years old, 68.4% were male, 55.3% had a history of smoking, 76.3% had adenocarcinoma, and 10.5% of patients had known brain metastases at baseline. Overall, the objective response rate (ORR) was 60.5% (95% confidence interval (CI): 43.4, 76.0) with a median DOR of 18.5 months (95% CI: 8.3, not estimable). ORR in treatment-naïve patients (n = 18) was 77.8% (95% CI: 52.4, 93.6), and in patients aged ≥75 years (n = 15), ORR was 73.3% (95% CI: 44.9, 92.2). The most common treatment-related adverse event (AE) with any grade was blood creatinine increase (65.8%), which resolved following tepotinib discontinuation. Other common treatment-related AEs were peripheral edema (60.5%), hypoalbuminemia (34.2%), diarrhea (28.9%), and nausea (15.8%). In summary, tepotinib demonstrated robust and durable clinical activity irrespective of age or therapy line, with a manageable safety profile in Japanese patients with METex14 skipping NSCLC enrolled in VISION.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Piperidinas , Piridazinas , Pirimidinas , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Japão , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Éxons/genética , Inibidores de Proteínas Quinases/efeitos adversos , Mutação
10.
Artigo em Inglês | MEDLINE | ID: mdl-38382879

RESUMO

BACKGROUND: The most common symptoms of pollen allergy are rhinitis and conjunctivitis. However, in real-world clinical practice, we sometimes encounter patients with pollen allergy suffering from severe extrarespiratory symptoms including skin, gastrointestinal, or flu-like symptoms in relation to exposure to sensitized pollen. OBJECTIVE: To elucidate the extrarespiratory symptoms in patients with pollen allergy. METHODS: We performed a non-drug-focused prospective study of patients with pollen allergy (n = 384). During the 1-year observational period, they were asked to complete a weekly electronic diary consisting of visual analog scale (VAS) scores to assess all symptoms experienced in various organs over the past week. An association between seasonal pollen levels and seasonal increase in VAS scores was evaluated using a mixed-effects model for repeated measures. A k-means cluster analysis was performed to identify a group of patients experiencing stronger extrarespiratory symptoms. RESULTS: In patients sensitized to grass or birch pollen, higher seasonal levels of these pollen grains were associated with higher VAS scores for headache, gastrointestinal symptoms, skin symptoms, and fatigue. A cluster analysis identified a group of severe pollen-allergic patients with higher extrarespiratory symptoms (n = 42). This group was characterized by a higher frequency of comorbid food allergy/atopic dermatitis, higher rate of IgE sensitization to pollens, and higher impaired activity and work productivity. CONCLUSIONS: This 1-year survey identified a small but nonnegligible group of patients with pollen-related extrarespiratory symptoms. More attention should be paid to this patient group considering their impaired activity and work productivity.

11.
J Vet Med Sci ; 86(3): 272-276, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38267039

RESUMO

Some reports have been published on clinical features in dogs with early recurrence of type I thoracolumbar intervertebral disk herniation (TL-IVDH), but there is little understanding of the changes involved. This retrospective study describes the clinical features, including radiographic image results at the time of recurrence, of dogs with type I TL-IVDH that had undergone hemilaminectomy but then suffered early recurrence. Our medical records were searched between June 2007 and December 2022. Nine dogs showed deterioration in neurological signs within 4 to 6 weeks after surgery. All nine were Miniature Dachshunds. Radiographic images at initial onset showed calcification at the affected intervertebral disk space in all 9 dogs. Disk herniations at the initial onset were located between T11-12 and L1-2. After the first surgery, neurological function improved in all dogs. Recurrence occurred at the same site as at initial onset in all dogs. No calcification was observed at the affected intervertebral disk space on images at the time of recurrence. The extruded disk materials were surgically removed, and neurological function improved after the second surgery. In conclusion, calcification at the affected disk space at the time of initial onset is indicative of residual nucleus materials not yet fully extruded, and is a risk factor for early recurrence of type I TL-IVDH.


Assuntos
Doenças do Cão , Deslocamento do Disco Intervertebral , Disco Intervertebral , Animais , Cães , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/veterinária , Estudos Retrospectivos , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/cirurgia , Doenças do Cão/etiologia , Laminectomia/efeitos adversos , Laminectomia/veterinária , Fatores de Risco , Disco Intervertebral/cirurgia
12.
Arthritis Rheumatol ; 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38268504

RESUMO

OBJECTIVE: We assess the clinical characteristics of patients with cryopyrin-associated periodic syndrome (CAPS) in Japan and evaluate the real-world efficacy and safety of interleukin-1 (IL-1) inhibitors, primarily canakinumab. METHODS: Clinical information was collected retrospectively, and serum concentrations of canakinumab and cytokines were analyzed. RESULTS: A total of 101 patients were included, with 86 and 15 carrying heterozygous germline and somatic mosaic mutations, respectively. We identified 39 mutation types, and the common CAPS-associated symptoms corresponded with those in previous reports. Six patients (5.9% of all patients) died, with four of the deaths caused by CAPS-associated symptoms. Notably, 73.7% of patients (100%, 79.6%, and 44.4% of familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and chronic infantile neurological cutaneous articular syndrome/neonatal onset multisystem inflammatory disease, respectively) achieved complete remission with canakinumab, and early therapeutic intervention was associated with better auditory outcomes. In some patients, canakinumab treatment stabilized the progression of epiphysial overgrowth and improved height gain, visual acuity, and renal function. However, 23.7% of patients did not achieve inflammatory remission with crucial deterioration of organ damage, with two dying while receiving high-dose canakinumab treatment. Serological analysis of canakinumab and cytokine concentrations revealed that the poor response was not related to canakinumab shortage. Four inflammatory nonremitters developed inflammatory bowel disease (IBD)-unclassified during canakinumab treatment. Dual biologic therapy with canakinumab and anti-tumor necrosis factor-α agents was effective for IBD- and CAPS-associated symptoms not resolved by canakinumab monotherapy. CONCLUSION: This study provides one of the largest epidemiologic data sets for CAPS. Although early initiation of anti-IL-1 treatment with canakinumab is beneficial for improving disease prognosis, some patients do not achieve remission despite a high serum concentration of canakinumab. Moreover, IBD may develop in CAPS after canakinumab treatment.

13.
Clin Transplant ; 38(1): e15196, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37975424

RESUMO

INTRODUCTION: Calcineurin inhibitor (CNI)-induced nephrotoxicity (CNI-T) is a post-transplantation complication that leads to graft dysfunction. Older-donor kidney grafts may be susceptible to chronic CNI exposure because of long-term arteriolar damage. The primary aim of this study was to examine the CNI-T incidence and time-course changes in the graft function according to donor age. METHODS: We included 334 kidney transplant recipients. CNI-T was defined by Banff arteriolar hyaline thickening scores of ≥2 based on allograft protocol biopsy. Depending on donor age, participants were divided into the D > 70 (≥70 years), D60 (60-69 years), D50 (50-59 years), and D < 49: (≤49 years) groups. We investigated the extent to which CNI-T affected the transplanted kidney function. Patients who did not develop CNI-T during the study period were included in the non-CNI-T group; the remaining were grouped into the CNI-T group. RESULTS: The CNI-T incidence was higher in donors aged >50 years. Compared to D < 49, the CNI-T risk was 1.86 times higher in D50 and 2.9 times higher in D > 70. Furthermore, the CNI-T group exhibited a significantly lower graft function 10 years after transplantation. CONCLUSION: CNI-T incidence increases in donors aged ≥50 years and affects renal function after 10 years.


Assuntos
Nefropatias , Transplante de Rim , Humanos , Idoso , Imunossupressores/efeitos adversos , Inibidores de Calcineurina/efeitos adversos , Transplante de Rim/efeitos adversos , Rim , Fatores de Risco , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto
14.
Clin Lung Cancer ; 25(1): 85-90, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37981477

RESUMO

BACKGROUND: According to the results of the KEYNOTE-407 trial, pembrolizumab plus platinum-based chemotherapy is the standard of care for patients with previously untreated advanced squamous non-small-cell lung cancer (NSCLC). Ubenimex, a potent aminopeptidase inhibitor, is an oral drug with immunostimulatory and antitumor activities. We aim to assess the safety and efficacy of ubenimex in combination with pembrolizumab, nab-paclitaxel, and carboplatin in patients with previously untreated advanced squamous NSCLC. PATIENTS AND METHODS: This prospective, single-arm, multicenter, phase II clinical trial is conducted to confirm the tolerability and efficacy of the tested drugs. Patients with previously untreated advanced squamous NSCLC will receive a predetermined daily dose of ubenimex orally plus 4 cycles of pembrolizumab, nab-paclitaxel, and carboplatin, followed by continuous administration of ubenimex and pembrolizumab for a maximum of 2 years. To confirm tolerability, the daily dose of ubenimex will begin at level 1 (30 mg), which will be increased to levels 2 (60 mg) and 3 (120 mg) according to the escalation criteria, with a standard 3 + 3 design for achieving the target dose-limiting toxicity rate of 33%. The efficacy, safety, and tolerability of ubenimex at the determined dose level will be analyzed. The primary endpoint of the efficacy evaluation will be the objective response rate assessed by an independent review committee. CONCLUSIONS: This is the first study to evaluate the efficacy and safety of ubenimex combined with pembrolizumab, nab-paclitaxel, and carboplatin in patients with previously untreated advanced squamous NSCLC. The results will help devise future treatment strategies.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Leucina/análogos & derivados , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carboplatina , Neoplasias Pulmonares/patologia , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Paclitaxel , Albuminas , Carcinoma de Células Escamosas/tratamento farmacológico
15.
Pigment Cell Melanoma Res ; 37(2): 276-285, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37920136

RESUMO

Epidermal melanocytes are continuously exposed to sunlight-induced reactive oxygen species (ROS) and oxidative stress generated during the synthesis of melanin. Therefore, they have developed mechanisms that maintain normal redox homeostasis. Cytoglobin (CYGB), a ubiquitously expressed intracellular iron hexacoordinated globin, exhibits antioxidant activity and regulates the redox state of mammalian cells through its activities as peroxidase and nitric oxide (NO) dioxygenase. We postulated that CYGB functions in the melanogenic process as a regulator that maintains oxidative stress within a physiological level. This was examined by characterizing normal human melanocytes with the knockdown (KD) of CYGB using morphological and molecular biological criteria. CYGB-KD cells were larger, had more dendrites, and generated more melanin granules in the advanced stages of melanogenesis than control cells. The expression levels of major melanogenesis-associated genes and proteins were higher in CYGB-KD melanocytes than in wild type (WT) cells. As expected, CYGB-KD melanocytes generated more ROS and NO than WT cells. In conclusion, CYGB physiologically contributes to maintaining redox homeostasis in the melanogenic activity of normal melanocytes by controlling the intracellular levels of ROS and NO.


Assuntos
Melaninas , Animais , Humanos , Citoglobina/genética , Citoglobina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Melaninas/metabolismo , Melanócitos/metabolismo , Oxirredução , Mamíferos/metabolismo
16.
Cancer Chemother Pharmacol ; 93(2): 137-149, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37921901

RESUMO

PURPOSE: Peripheral T-cell lymphoma (PTCL) is an aggressive disease with a poor prognosis. Brentuximab vedotin (BV), an anti-CD30 monoclonal antibody linked to a microtubule-disrupting agent, has been approved for the treatment of PTCL. We evaluated a new effective combination partner of BV using non-clinical approaches that could potentially identify agents capable of improving survival times for patients with PTCL. METHODS: A high-throughput screening test was used to select the most synergistic partner of BV from 14 candidate drugs that were under development or available in clinical practice for PTCL. HH cells, originating from an aggressive cutaneous T-cell lymphoma, were used as an experimental model of PTCL. Apoptotic effects of the synergistic partner of BV were further investigated in vitro and in vivo using HH-cell xenograft mice. RESULTS: Chidamide (tucidinostat), a novel histone deacetylase inhibitor, was found to have the greatest synergistic effect with BV on HH cells. The combined effects of chidamide and BV were demonstrated in a study of HH-cell xenograft mice; mean tumor size following combined treatment was 22% of that observed in the control group, compared with 71% and 58% following chidamide and BV monotherapy, respectively. Further investigations in vitro and in vivo revealed that the levels of an anti-apoptotic protein, Bcl-2, and a rate-limiting factor of DNA replication, CDC45, were reduced in HH cells treated with chidamide combined with BV compared with the control group. CONCLUSION: The use of chidamide in conjunction with BV may positively affect and enhance T-cellular apoptotic pathways without offsetting each other.


Assuntos
Aminopiridinas , Benzamidas , Linfoma de Células T Periférico , Linfoma de Células T , Neoplasias Cutâneas , Humanos , Animais , Camundongos , Brentuximab Vedotin/farmacologia , Brentuximab Vedotin/uso terapêutico , Linfoma de Células T Periférico/tratamento farmacológico , Linfoma de Células T/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Apoptose , Proliferação de Células
17.
ACS Appl Bio Mater ; 7(1): 246-255, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37967519

RESUMO

Antibacterial materials composed of biodegradable and biocompatible constituents that are produced via eco-friendly synthetic strategies will become an attractive alternative to antibiotics to combat antibiotic-resistant bacteria. In this study, we demonstrated the antibacterial properties of nanosheet-shaped crystalline assemblies of enzymatically synthesized aminated cellulose oligomers (namely, surface-aminated synthetic nanocelluloses) and their synergy with a metal-chelating antibacterial agent, ethylenediaminetetraacetic acid (EDTA). Growth curves and colony counting assays revealed that the surface-aminated cellulose assemblies had an antibacterial effect against Gram-negative Escherichia coli (E. coli). The cationic assemblies appeared to destabilize the cell wall of E. coli through electrostatic interactions with anionic lipopolysaccharide (LPS) molecules on the outer membrane. The antibacterial properties were significantly enhanced by the concurrent use of EDTA, which potentially removed metal ions from LPS molecules, resulting in synergistic bactericidal effects. No antibacterial activity of the surface-aminated cellulose assemblies was observed against Gram-positive Staphylococcus aureus even in the presence of EDTA, further supporting the contribution of electrostatic interactions between the cationic assemblies and anionic LPS to the activity against Gram-negative bacteria. Analysis using quartz crystal microbalance with dissipation monitoring revealed the attractive interaction of the surface-aminated cellulose assembly with LPS Ra monolayers artificially produced on the device substrate.


Assuntos
Escherichia coli , Lipopolissacarídeos , Ácido Edético/farmacologia , Lipopolissacarídeos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Quelantes/farmacologia , Metais , Cátions , Celulose/farmacologia
19.
Hepatol Res ; 54(2): 201-212, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37796562

RESUMO

AIM: Metabolic dysfunction is a risk factor for esophageal squamous cell carcinoma (ESCC). We investigated the impact of the recently proposed metabolic dysfunction-associated fatty liver disease (MAFLD) and its subtypes on ESCC recurrence after endoscopic treatment. METHODS: This multicenter observational cohort study enrolled consecutive patients newly diagnosed with ESCC after endoscopic treatment. Patients were classified into MAFLD or non-MAFLD groups. The MAFLD group was further classified into non-obese and obese MAFLD groups with a body mass index cutoff value of 25 kg/m2 . The impact of MAFLD on the recurrence of ESCC was evaluated using a decision tree algorithm and random forest analysis. RESULTS: A total of 147 patients (average age 69 years; male : female, 127:20; observational period, 2.4 years) were enrolled. The 1-, 3-, and 5-year recurrence rates were 2.0%, 21.1%, and 33.7%, respectively. Independent risk factors for the recurrence of ESCC were MAFLD (HR 2.2812; 95% confidence interval 1.0497-4.9571; p = 0.0373), drinking status, and smoking status. Metabolic dysfunction-associated fatty liver disease was identified as the second most important classifier for recurrence, followed by drinking status. The cumulative incidence of ESCC recurrence was higher in the MAFLD group than in the non-MAFLD group. In a subanalysis, the cumulative incidence of recurrence was significantly higher in the non-obese than in the obese MAFLD group among abstainers/non-drinkers. Directed acyclic graphs revealed that MAFLD directly contributes to ESCC recurrence. CONCLUSIONS: MAFLD was independently and directly associated with ESCC recurrence after endoscopic treatment; a high recurrence rate was observed in patients with non-obese MAFLD. Metabolic dysfunction-associated fatty liver disease may identify patients at high risk for ESCC recurrence.

20.
Ann Vasc Surg ; 99: 209-216, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37805171

RESUMO

BACKGROUND: Entry closure with thoracic endovascular aortic repair (TEVAR) for Stanford type B aortic dissection (TBAD) results in aortic remodeling recently. This study aimed to evaluate the relationship between aortic diameter or timing of surgical intervention from onset and remodeling after TEVAR for uncomplicated nonacute TBAD. METHODS: Between April 2014 and December 2021, 83 consecutive patients underwent TEVAR for TBAD at our center. Forty patients with subacute and chronic uncomplicated TBADs with a patent false lumen, who could be followed up for at least 6 months, were included in this study. Indications for TEVAR included aortic diameter enlargement and preemptive treatment to prevent future aneurysmal changes in patients at risk of aortic diameter enlargement. Aortic remodeling was accessed, and data between the remodeling and nonremodeling groups were compared. RESULTS: The technical success rate was 97.5%, with a type Ia endoleak remaining in 1 patient. No operative or in-hospital mortality occurred. Paraparesis occurred in only 1 patient (2.5%). Follow-up was completed at a median of 53.5 months. Late death occurred in 3 cases, but there were no aortic-related deaths. Late aortic remodeling was achieved in 22 patients (55%). The preoperative maximum aortic diameter (PMAD) in the thoracic aortic region was 51.5 mm in the nonremodeling group, significantly larger than 42.5 mm in the remodeling group (P < 0.0001). The cutoff value of the PMAD for predicting aortic remodeling was 45 mm (area under the curve, 0.917; P = 0.028). The remodeling group had an earlier time from onset to intervention than the nonremodeling group, with a cutoff value of 6.3 months (area under the curve, 0.743; P = 0.021). CONCLUSIONS: TEVAR for nonacute uncomplicated TBAD resulted in a late aortic remodeling rate of 55%. This study suggested that a PMAD of >45 mm or a period >6.3 months between dissection onset and surgery hinders aortic remodeling after TEVAR.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Correção Endovascular de Aneurisma , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/efeitos adversos , Resultado do Tratamento , Fatores de Tempo , Estudos Retrospectivos , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Fatores de Risco
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