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1.
Ann Vasc Dis ; 17(2): 142-149, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38919317

RESUMO

Objectives: The aim of this study was to evaluate the relationship between absolute lymphocyte count (ALC) and outcomes of infrainguinal bypass surgery for chronic limb-threatening ischemia (CLTI). Methods: From 2004 to 2020, 209 limbs of 189 patients who underwent infrainguinal bypass surgery for CLTI and whose ALCs were available were included. Patients with survival >2 years and limb salvage >2 years were considered discriminant groups, and an ALC cut-off value was calculated. The relationship between preoperative ALC and outcomes was evaluated. Results: Survivorship of the higher ALC group was significantly higher than that of the lower ALC group (cut-off value 1030/µL, p = 0.0009). The limb salvage rate of the higher ALC group was significantly higher than that of the lower ALC group (cut-off value 1260/µL, p = 0.0081). In the dialysis patient group (103 limbs), the limb salvage rate of the higher ALC group was significantly higher than that of the lower ALC group (cut-off value 1170/µL, p = 0.026). ALC was independently associated with limb loss in multivariate analysis. Conclusion: ALC is promising as a predictor of outcomes after bypass surgery in CLTI. In particular, ALC is expected to be useful for limb prognosis in hemodialysis patients.

2.
Front Pharmacol ; 15: 1358573, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601470

RESUMO

Accumulating evidence has demonstrated that both SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP1Ra) have protective effects in patients with diabetic kidney disease. Combination therapy with SGLT2i and GLP1Ra is commonly used in patients with type 2 diabetes (T2D). We previously reported that in combination therapy of SGLT2i and GLP1Ra, the effect on the renal composite outcome did not differ according to the preceding drug. However, it remains unclear how the initiation of combination therapy is associated with the renal function depending on the preceding drug. In this post hoc analysis, we analyzed a total of 643 T2D patients (GLP1Ra-preceding group, n = 331; SGLT2i-preceding group, n = 312) and investigated the differences in annual eGFR decline. Multiple imputation and propensity score matching were performed to compare the annual eGFR decline. The reduction in annual eGFR decline in the SGLT2i-preceding group (pre: -3.5 ± 9.4 mL/min/1.73 m2/year, post: -0.4 ± 6.3 mL/min/1.73 m2/year, p < 0.001), was significantly smaller after the initiation of GLP1Ra, whereas the GLP1Ra-preceding group tended to slow the eGFR decline but not to a statistically significant extent (pre: -2.0 ± 10.9 mL/min/1.73 m2/year, post: -1.8 ± 5.4 mL/min/1.73 m2/year, p = 0.83) after the initiation of SGLT2i. After the addition of GLP1Ra to SGLT2i-treated patients, slower annual eGFR decline was observed. Our data raise the possibility that the renal benefits-especially annual eGFR decline-of combination therapy with SGLT2i and GLP1Ra may be affected by the preceding drug.

3.
Angew Chem Int Ed Engl ; 63(10): e202317805, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38238265

RESUMO

Heterotrimeric G proteins are key mediators in the signaling of G protein-coupled receptors (GPCR) that are involved in a plethora of important physiological processes and thus major targets of pharmaceutical drugs. The cyclic depsipeptides YM-254890 and FR900359 are strong and selective inhibitors of the Gq subfamily of G proteins. FR900359 was first reported to be produced by unculturable plant symbiont, however, a culturable FR900359 producer was discovered recently by the standard strategy, screening of the producing strain from the environment. As another strategy, we introduce herein the different way to supply natural compounds of unculturable microorganism origin. We therefore embarked on constructing an artificial biosynthetic gene cluster (BGC) for FR900359 with YM-254890 BGC as a template using "in vitro module editing" technology, first developed for the modification of type-I PKS BGCs, to edit YM-254890 BGC. The resulting artificial BGCs coding FR900359 were heterologously expressed in the Pseudomonas putida KT2440 host strain.


Assuntos
Antineoplásicos , Depsipeptídeos , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Depsipeptídeos/química , Receptores Acoplados a Proteínas G/metabolismo
4.
Circ J ; 88(3): 319-328, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-37423757

RESUMO

BACKGROUND: The latest demographics, clinical and living conditions, and comorbidities of patients with thromboangiitis obliterans (TAO) in Japan are unknown.Methods and Results: We conducted a retrospective cross-sectional survey using the annual database of the Japanese Ministry of Health, Labour and Welfare medical support system for patients with TAO between April 2013 and March 2014. This study included 3,220 patients (87.6% male), with current age ≥60 years in 2,155 patients (66.9%), including 306 (9.5%) patients aged ≥80 years. Overall, 546 (17.0%) had undergone extremity amputation. The median interval from onset to amputation was 3 years. Compared with never smokers (n=400), 2,715 patients with a smoking history had a higher amputation rate (17.7% vs. 13.0%, P=0.02, odds ratio [OR]=1.437, 95% confidence interval [CI]=1.058-1.953). A lower proportion of workers and students was seen among patients after amputation than among amputation-free patients (37.9% vs. 53.0%, P<0.0001, OR=0.542, 95% CI=0.449-0.654). Comorbidities, including arteriosclerosis-related diseases, were found even in patients in their 20-30 s. CONCLUSIONS: This large survey confirmed that TAO is not a life-threatening but an extremity-threatening disease that threatens patients' professional lives. Smoking history worsens patients' condition and extremity prognosis. Long-term total health support is required, including care of extremities and arteriosclerosis-related diseases, social life support, and smoking cessation.


Assuntos
Arteriosclerose , Tromboangiite Obliterante , Humanos , Masculino , Feminino , Tromboangiite Obliterante/epidemiologia , Tromboangiite Obliterante/cirurgia , Japão/epidemiologia , Estudos Retrospectivos , Estudos Transversais , Demografia
5.
World J Surg ; 47(11): 2834-2845, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37540268

RESUMO

BACKGROUND: The prognostic benefit of preoperative chemotherapy leading to conversion surgery for unresectable colorectal liver metastases (CRLM) is well recognized, while that of neoadjuvant chemotherapy (NAC) compared with upfront surgery (UFS) for resectable CRLM is negligible. This study aims to assess the prognostic benefit and search for optimal indication of NAC for resectable advanced CRLM by establishing an objective definition of biologically borderline resectable (bBR) CRLM. METHODS: A bicentric retrospective analysis of patients with CRLM undergoing curative-intent initial liver resection between 2007 and 2021 was performed. An original classification matrix was established, which reassessed technical resectability using virtual hepatectomy and oncological favorability using Beppu's nomogram. Patients with technically resectable but biologically unfavorable CRLM were classified into the bBR group. The propensity score matching analysis using preoperatively available factors was performed to assess long-term outcomes of the bBR-UFS and bBR-NAC groups. RESULTS: Of 831 patients reviewed, 240 were categorized into the bBR group: bBR -UFS (n = 139) and bBR-NAC (n = 101). Ten (10%) in the bBR-NAC group (n = 101) experienced biological status change from unfavorable to favorable after NAC (Biological Conversion) and showed significantly longer overall survival (hazard ratio 5.63, 95% confidence interval 1.37-23.1; P = 0.016) than the bBR-UFS group. However, after propensity score matching, no significant difference between the UFS and NAC groups (n = 67 for each) was found in long-term outcomes. CONCLUSIONS: NAC for bBR-CRLM did not enhance the prognostic impact of the following liver resection, except for a limited number of optimal candidates experiencing the Biological Conversion.

6.
J Clin Med Res ; 15(6): 300-309, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37434770

RESUMO

Background: Pancreatic cancer is gastrointestinal cancer with a poor prognosis. Although surgical techniques and chemotherapy have improved treatment outcomes, the 5-year survival rate for pancreatic cancer is less than 10%. In addition, resection of pancreatic cancer is highly invasive and is associated with high rates of postoperative complications and hospital mortality. The Japanese Pancreatic Association states that preoperative body composition assessment may predict postoperative complications. However, although impaired physical function is also a risk factor, few studies have examined it in combination with body composition. We examined preoperative nutritional status and physical function as risk factors for postoperative complications in pancreatic cancer patients. Methods: Fifty-nine patients with pancreatic cancer who underwent surgical treatment and were discharged alive from January 1, 2018, to March 31, 2021, at the Japanese Red Cross Medical Center. This retrospective study was conducted using electronic medical records and a database of departments. Body composition and physical function were evaluated before and after surgery, and the risk factors between patients with and without complications were compared. Results: Fifty-nine patients were analyzed: 14 and 45 patients in the uncomplicated and complicated groups, respectively. The major complications were pancreatic fistulas (33%) and infections (22%). There were significant differences in: age, 74.0 (44 - 88) (P = 0.02); walking speed, 0.93 m/s (0.3 - 2.2) (P = 0.01); and fat mass, 16.50 kg (4.7 - 46.2) (P = 0.02), in the patients with complications. On Multivariable logistic regression analysis, age (odds ratio: 2.28; confidence interval (CI): 1.3400 - 569.00; P = 0.03), preoperative fat mass (odds ratio: 2.28; CI: 1.4900 - 168.00; P = 0.02), and walking speed (odds ratio: 0.119; CI: 0.0134 - 1.07; P = 0.05) were identified as risk factors. Walking speed (odds ratio: 0.119; CI: 0.0134 - 1.07; P = 0.05) was the risk factor that was extracted. Conclusions: Older age, more preoperative fat mass, and decreased walking speed were possible risk factors for postoperative complications.

7.
Injury ; 54(8): 110826, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37286444

RESUMO

BACKGROUND: Patients with heel pad degloving injury frequently develop ischemic necrosis of the area, necessitating soft-tissue reconstruction surgery. We have developed a technique for arterialization of the plantar venous system via vein graft (APV) as the primary revascularization treatment. The objective of this study was to clarify both the utility of APV for the preservation of degloved heel pads and the impact of this preservation on clinical outcomes. METHODS: Ten consecutive cases of degloving injury with devascularized heel pad were treated at a single trauma center from 2008 to 2018. Five cases underwent APV and five underwent conventional primary suture (PS) as the initial treatment. We evaluated the course according to the frequency of heel pad preservation, additional intervention after heel pad necrosis, post-operative complications, and outcomes using the Foot and Ankle Disability Index score (FADI) at the time of last follow-up. RESULTS: Among the five cases that underwent APV, the heel pad was preserved in three cases and flap surgery was required in two cases. All cases that underwent PS developed necrosis of the heel pad, requiring skin graft in one case and flap surgery in four. One skin graft case and one free flap case after PS developed plantar ulcers. The three cases with preserved heel pads exhibited higher FADI than the seven cases that developed necrosis. CONCLUSION: APV showed a relatively high frequency of heel pad preservation, which otherwise was uniformly lacking. Functional outcomes were improved in cases with preserved heel pad compared to those that developed necrosis and underwent additional tissue reconstruction.


Assuntos
Avulsões Cutâneas , Traumatismos do Pé , Retalhos de Tecido Biológico , Lesões dos Tecidos Moles , Humanos , Avulsões Cutâneas/cirurgia , Calcanhar/cirurgia , Calcanhar/irrigação sanguínea , Calcanhar/lesões , Transplante de Pele/métodos , Traumatismos do Pé/cirurgia , Lesões dos Tecidos Moles/cirurgia , Necrose/cirurgia
8.
Ann Vasc Surg ; 88: 174-181, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36058448

RESUMO

BACKGROUND: Chronic limb-threatening ischemia (CLTI) is frequently associated with crural artery occlusion. Complete revascularization beyond the diseased crural artery is preferable; however, complete revascularization is challenging in many cases for various reasons. On the other hand, partial reconstruction for inflow disease sometimes leads to complete relief of symptoms. It is not elucidated which patients may recover from CLTI with partial revascularization (PR). Therefore, we aimed to evaluate the factors affecting outcomes after PR. METHODS: We retrospectively reviewed the medical records of patients who underwent first-attempt PR, for CLTI, for limb salvage, in our institution, between April 2012 and December 2020. We divided these 103 cases into 2 groups: the salvage group (who achieved wound healing or relief from rest pain with PR; n = 81) and the nonsalvage group (who ended with major amputation or additional distal revascularization; n = 22). We evaluated the factors affecting the outcome of PR in terms of patient risk, limb severity (Society for Vascular Surgery Lower Extremity Threatened Limb Classification System; wound, ischemia, and foot infection [WIfI] classification), and anatomical pattern (Global Limb Anatomic Staging System; GLASS classification). RESULTS: Although patient risk between the 2 groups was not statistically significant, hypoalbuminemia (< 3.0 mg/dL) was more prevalent in the nonsalvage group without significance (P = 0.068). Regarding limb severity status, there was no significant difference in WIfI grades. Wound grade showed the strongest correlation (P = 0.11) and reduced wound grade suggested future wound healing. In terms of GLASS, infrapopliteal grade was statistically significant (P = 0.033). Upon a multivariate analysis, among infrapopliteal grade, hypoalbuminemia, and wound grade, infrapopliteal grade (P = 0.0096) and hypoalbuminemia (P = 0.2512) revealed significant differences. Wound grade also showed correlation (P = 0.085). CONCLUSIONS: The usefulness of the WIfI classification and GLASS classification to predict wound healing after PR for CLTI was validated.


Assuntos
Hipoalbuminemia , Doença Arterial Periférica , Humanos , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/cirurgia , Estudos Retrospectivos , Estimativa de Kaplan-Meier , Fatores de Risco , Resultado do Tratamento , Valor Preditivo dos Testes , Salvamento de Membro , Isquemia/diagnóstico por imagem , Isquemia/cirurgia , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Cicatrização , Dor/cirurgia
9.
J Clin Med ; 11(22)2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36431350

RESUMO

Thromboendarterectomy of the common femoral artery (CFA) for occlusive disease is a crucial procedure in vascular surgery. As an outcome reference for emerging endovascular procedures and new devices, we need more robust evidence of the outcome of this gold standard technique. The purpose of this study was to report 10-year results after femoral endarterectomy (FEA). A retrospective review of medical records at our institution identified eighty consecutive patients (91 limbs) who underwent FEA for CFA lesions. Indications for FEA included 50 limbs (55%) for intermittent claudication (IC) and 39 limbs (43%) with chronic limb-threatening ischemia (CLTI). Two limbs (2%) underwent FEA to prevent hemodynamic steal during extra-anatomical bypass. Adjunctive procedures included endovascular therapy in 32%. CFAs were closed with patch angioplasty in 44%. With a mean follow-up period of 39 months, the survival rates at 3 and 8 years were 85% and 77%, respectively. Limb salvage rates were 92% and 87%. Primary patencies were 98% and 84%. Freedom from target lesion revascularization was 95% at 3 years and 91% at 8 years. Our findings support the durability of FEA, with comparable long-term procedural results in CLTI patients as well as IC patients. Since the FEA is a gate maneuver for hybrid revascularization in CLTI patients, our findings support a strategy combining open and endovascular approaches. Femoral endarterectomy remains a durable solution for common femoral occlusive disease in IC and CLTI in the era of endovascular therapy.

10.
Transl Psychiatry ; 12(1): 404, 2022 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-36151082

RESUMO

Interleukin-18 (IL18) is an inflammatory cytokine that is related to psychiatric disorders such as depression and cognitive impairment. We previously found that IL18 deficiency may cause hippocampal impairment, resulting in depression-like behavioral changes. However, the potential role of IL18 in stressful conditions remains uncertain. In the present study, we examined the effect of IL18 on neural inflammation and stress tolerance during acute stress. Littermate Il18+/+ and Il18-/- mice were exposed to a single restraint stress for 6 h, and all assessments were performed 18 h after the mice were released from the restraint. In Il18-/- mice exposed to acute stress, the immobility times in both the forced swim test and tail suspension test were decreased, although no difference was observed in Il18+/+ mice. Il1ß, Il6, and Tnfα expression levels in the hippocampus of stressed Il18-/- mice were significantly higher than those in the other groups. Moreover, the numbers of astrocytes and microglia, including those in the active form, were also increased compared with those in other groups. Regarding the molecular mechanism, the HSF5 and TTR genes were specifically expressed in stressed Il18-/- mice. As a potential treatment, intracerebral administration of IL18 to Il18-/- mice resulted in partial recovery of changes in behavioral assessments. Our results revealed that IL18-deficient mice were more sensitive and had a longer response to acute stress than that in normal mice. In addition, neural inflammation and augmentation of glucocorticoid signals caused by stress were more intense and remained longer in Il18-/- mice, resulting in behavioral changes. In conclusion, IL18 might be an indispensable factor that modulates the stress response and maintains balance between neural inflammation and glucocorticoid signaling.


Assuntos
Glucocorticoides , Interleucina-18 , Estresse Psicológico , Animais , Depressão/metabolismo , Glucocorticoides/metabolismo , Hipocampo/metabolismo , Inflamação/metabolismo , Interleucina-18/genética , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Estresse Psicológico/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
11.
Jpn J Clin Oncol ; 52(7): 716-724, 2022 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-35411926

RESUMO

BACKGROUND: This phase I/II study was conducted to evaluate the efficacy, safety and pharmacokinetics of streptozocin (STZ) in Japanese patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumors. METHODS: Twenty-two patients received up to 4 cycles of intravenous STZ at either 500 mg/m2 once daily for 5 consecutive days every 6 weeks (daily regimen) or at 1000-1500 mg/m2 once weekly for 6 weeks (weekly regimen). Tumor response was evaluated using the modified RECIST criteria ver. 1.1, and adverse events were assessed by grade according to the National Cancer Institute CTCAE (ver. 4.0). RESULTS: Fourteen (63.6%) patients completed the study protocol. No patients had complete response; partial response in 2 (9.1%), stable disease in 17 (77.3%), non-complete response/non-progressive disease in 2 (9.1%) and only 1 (4.5%) had non-evaluable disease. Excluding the latter, the response rate in the daily and weekly regimens was 6.7% (1/15) and 16.7% (1/6), respectively, with an overall response rate of 9.5% (2/21). However, the best overall response in each patient showed that the disease control rate was 100%.Adverse events occurred in all 22 patients, including 17 grade 3 adverse events in 11 patients; however, no grade 4 or 5 adverse events were reported. Prophylactic hydration and antiemetic treatment reduced the severity and incidence of nephrotoxicity, nausea and vomiting. Plasma STZ concentrations decreased rapidly after termination of infusion, with a half-life of 32-40 min. Neither repeated administration nor dose increases affected pharmacokinetic parameters. CONCLUSIONS: STZ may be a useful option for Japanese patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumors.


Assuntos
Tumores Neuroendócrinos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Neoplasias Intestinais , Japão , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas , Neoplasias Gástricas , Estreptozocina/efeitos adversos
12.
Mol Pharm ; 18(9): 3290-3301, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34365796

RESUMO

The antimicrobial protein CAP18 (approximate molecular weight: 18 000), which was first isolated from rabbit granulocytes, comprises a C-terminal fragment that has negatively charged lipopolysaccharide binding activity. In this study, we found that CAP18 (106-121)-derived (sC18)2 peptides have macropinocytosis-inducible biological functions. In addition, we found that these peptides are highly applicable for use as extracellular vesicle (exosomes, EV)-based intracellular delivery, which is expected to be a next-generation drug delivery carrier. Here, we demonstrate that dimerized (sC18)2 peptides can be easily introduced on EV membranes when modified with a hydrophobic moiety, and that they show high potential for enhanced cellular uptake of EVs. By glycosaminoglycan-dependent induction of macropinocytosis, cellular EV uptake in targeted cells was strongly increased by the peptide modification made to EVs, and intriguingly, our herein presented technique is efficiently applicable for the cytosolic delivery of the biologically cell-killing functional toxin protein, saporin, which was artificially encapsulated in the EVs by electroporation, suggesting a useful technique for EV-based intracellular delivery of biofunctional molecules.


Assuntos
Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Penetradores de Células/química , Sistemas de Liberação de Medicamentos/métodos , Exossomos/química , Saporinas/administração & dosagem , Animais , Células CHO , Cricetulus , Composição de Medicamentos/métodos , Células HeLa , Humanos , Células MCF-7 , Catelicidinas
13.
Int J Surg Case Rep ; 83: 106012, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34090195

RESUMO

INTRODUCTION: Neurofibromatosis type 1 (NF-1) or von Recklinghausen's disease, an autosomal dominant genetic disorder, is characterized by a café au lait spot and cutaneous neurofibromas. It typically involves the skin, nerves, bones, muscles, and eyes, and occasionally involves vascular complications and can lead to life-threatening hemorrhage. CASE PRESENTATION: We present the case of a 77-year-old female with a posterior tibial artery rupture with NF-1. She presented with sudden right lower leg swelling, pain, paresthesia, and paralysis; computed tomography images revealed popliteal artery aneurysm with surrounding hematoma, expanding from the posterior aspect of the knee to the calf. Diagnosed with compartment syndrome, due to a ruptured right popliteal artery aneurysm, she underwent prosthetic replacement of the popliteal aneurysm. Intraoperatively, the fragility of the popliteal artery was noted, although no perforation site was recognized despite the aneurysm; active bleeding originated from the hematoma between the calf muscles. Intraoperative digital subtraction angiography revealed an extravasation at the branch of the posterior tibial artery that was managed by coil embolization of the posterior tibial artery. CLINICAL DISCUSSION: Although the frequency of NF-1 vasculopathy is unknown, vasculopathy is the second most common cause of mortality in patients with NF-1, after malignancy. The less invasive endovascular approach might be preferable for treating NF-1-related aneurysm. The NF-related vasculopathy lesion sites are diverse, and intraoperative angiography would help confirm the diagnosis. CONCLUSION: NF-1-related vasculopathy may be associated with vascular fragility, and the endovascular approach might be preferable. Endovascular-first approach could have helped in correct diagnosis in the present case.

14.
J Surg Oncol ; 123(8): 1742-1749, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33657243

RESUMO

BACKGROUND AND OBJECTIVES: Portal vein embolization (PVE) is a safe and effective procedure used to increase the safety of extensive hepatectomy for selected patients. However, it is unknown whether PVE is safe for patients with impaired liver functional reserve. METHODS: Patients who underwent PVE from April 2007 to September 2016 in our hospital were retrospectively assessed. According to indocyanine green retention rate at 15 min (ICG-R15), we divided patients into Group A (≤10%), Group B (10%-20%), and Group C (>20%). We described and compared the treatment course and the outcome among the three groups. RESULTS: A total of 106 patients were assessed and divided into groups A (n = 46), B (n = 49), and C (n = 11). The morbidity and mortality after PVE showed no significant differences among the three groups (A:B:C = 37%:53%:64%, p = .16; A:B:C = 0%:0%:0%, p = 1.00, respectively). The morbidity and mortality after successive hepatectomy also showed no significant differences among the three groups (A:B:C = 55%:71%:78%, p = .19; A:B:C = 0%:2%:0%, p = 1.00, respectively). CONCLUSION: A patient with impaired liver functional reserve (ICG-R15 > 20%) can be a candidate for PVE and successive hepatectomy, as safely as a patient with normal and slightly impaired liver functional reserve (ICG-R15 ≤ 20%).


Assuntos
Carcinoma/cirurgia , Embolização Terapêutica , Hepatectomia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Veia Porta , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/complicações , Carcinoma/patologia , Feminino , Humanos , Testes de Função Hepática , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
15.
FEBS Open Bio ; 11(3): 753-767, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33533170

RESUMO

Exosomes (extracellular vesicles/EVs) participate in cell-cell communication and contain bioactive molecules, such as microRNAs. However, the detailed characteristics of secreted EVs produced by cells grown under low pH conditions are still unknown. Here, we report that low pH in the cell culture medium significantly affected the secretion of EVs with increased protein content and zeta potential. The intracellular expression level and location of stably expressed GFP-fused CD63 (an EV tetraspanin) in HeLa cells were also significantly affected by environmental pH. In addition, increased cellular uptake of EVs was observed. Moreover, the uptake rate was influenced by the presence of serum in the cell culture medium. Our findings contribute to our understanding of the effect of environmental conditions on EV-based cell-cell communication.


Assuntos
Técnicas de Cultura de Células/métodos , Vesículas Extracelulares/metabolismo , Tetraspanina 30/genética , Transporte Biológico , Comunicação Celular , Meios de Cultura/química , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Proteínas Recombinantes de Fusão/metabolismo , Tetraspanina 30/metabolismo
16.
Chemphyschem ; 22(10): 915-923, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-33590933

RESUMO

Hyperpolarized [1-13 C]fumarate is a promising magnetic resonance imaging (MRI) biomarker for cellular necrosis, which plays an important role in various disease and cancerous pathological processes. To demonstrate the feasibility of MRI of [1-13 C]fumarate metabolism using parahydrogen-induced polarization (PHIP), a low-cost alternative to dissolution dynamic nuclear polarization (dDNP), a cost-effective and high-yield synthetic pathway of hydrogenation precursor [1-13 C]acetylenedicarboxylate (ADC) was developed. The trans-selectivity of the hydrogenation reaction of ADC using a ruthenium-based catalyst was elucidated employing density functional theory (DFT) simulations. A simple PHIP set-up was used to generate hyperpolarized [1-13 C]fumarate at sufficient 13 C polarization for ex vivo detection of hyperpolarized 13 C malate metabolized from fumarate in murine liver tissue homogenates, and in vivo 13 C MR spectroscopy and imaging in a murine model of acetaminophen-induced hepatitis.


Assuntos
Ácidos Graxos Insaturados/biossíntese , Fumaratos/metabolismo , Imageamento por Ressonância Magnética , Alcinos/química , Isótopos de Carbono , Teoria da Densidade Funcional , Ácidos Graxos Insaturados/química , Fumaratos/química , Hidrogenação
17.
J Vasc Surg ; 73(1): 285-290, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32473337

RESUMO

OBJECTIVE: The objective of this study was to evaluate the outcome of a short interposition using a small-diameter prosthetic graft as a flow-limiting procedure to manage symptomatic high-flow arteriovenous fistula (AVF). METHODS: A retrospective review of medical records on a case series was conducted. From June 2004 to April 2017, there were 25 patients with clinical symptoms of high output cardiac failure and progressive dilation of aneurysmal fistula vein due to high-flow AVF (≥1.5 L/min) who underwent short interposition with a 5-mm prosthetic graft at Saitama Medical Center. The primary outcome was the relief of clinical symptoms; other outcome measures included technical success, surgical complications, patency of vascular access, and postoperative changes in local and systemic hemodynamics as assessed by Doppler ultrasound. RESULTS: Twenty-five patients underwent short interposition for cardiac indications (n = 16) and aneurysmal dilation (n = 9). The technical success rate was 100%. The clinical symptoms were relieved in 24 patients (96.0%). Mean reduction in access blood flow was 52.4%. Cumulative primary unassisted patency rates (± standard error) at 1 year, 2 years, and 3 years were 76.2% ± 9.3%, 70.4% ± 10.3%, and 58.1% ± 11.6%, respectively. Secondary patency rates (± standard error) at 1 year, 2 years, and 3 years were 81.8% ± 8.2%, 71.5% ± 9.9%, and 71.5% ± 9.9%, respectively. Complications included access occlusion due to late thrombosis (n = 5 [21.7%]) and graft infection (n = 1 [4.3%]) in the median follow-up period of 3.9 years. CONCLUSIONS: Short interposition with a prosthetic graft is a simple, effective, and durable treatment option for end-stage renal disease patients with cardiac symptoms and progressive dilation of the fistula vein due to high-flow AVF, offering clinical symptom resolution while preserving the autologous behavior of the initial access.


Assuntos
Derivação Arteriovenosa Cirúrgica/métodos , Prótese Vascular , Artéria Braquial/cirurgia , Veias Braquiocefálicas/cirurgia , Falência Renal Crônica/terapia , Fluxo Sanguíneo Regional/fisiologia , Grau de Desobstrução Vascular/fisiologia , Artéria Braquial/fisiopatologia , Veias Braquiocefálicas/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal/métodos , Estudos Retrospectivos
18.
Ann Vasc Dis ; 14(4): 334-340, 2021 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-35082938

RESUMO

Objective: We investigated the association between Controlling Nutritional Status (CONUT) scores and the outcomes of bypass surgery in patients with chronic limb-threatening ischemia (CLTI). Methods: We retrospectively calculated preoperative CONUT scores in 118 patients (127 limbs) with CLTI who underwent infrainguinal bypass surgery. Survival, graft patency, and limb salvage were compared between the high and low CONUT score groups based on the respective cutoff points. Results: The median and mean CONUT scores were 5 and 4.8, respectively. The postoperative survival rate was lower in the high CONUT score (3-12) group than in the low CONUT score (0-2) group (P=0.0043). The limb salvage rate after arterial reconstruction was also significantly lower in the high CONUT score (8-12) group than in the low CONUT score (0-7) group (P=0.0009). Conclusions: The CONUT score can predict infrainguinal bypass surgery outcomes in patients with CLTI. (This is a translation of J Jpn Coll Angiol 2020; 60: 35-41.).

19.
Surg Case Rep ; 6(1): 320, 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33315157

RESUMO

BACKGROUND: Tumor thrombus in the superior mesenteric vein secondary to colon cancer is rare. We report a case of tumor thrombus in the superior mesenteric vein and liver metastasis due to advanced colon cancer that was treated with chemotherapy and complete surgical resection. CASE PRESENTATION: A 72-year-old man after transverse colectomy with lymph node dissection for advanced colon cancer was diagnosed with tumor thrombus in the superior mesenteric vein and liver metastasis. He underwent adjuvant chemotherapy and had complete surgical tumor resection involving tumor thrombectomy and hepatectomy. There has been no recurrence at 36 months after surgery. CONCLUSION: Herein, we report a rare case of tumor thrombus in the superior mesenteric vein related to advanced colon cancer. The combination of chemotherapy and complete surgical tumor resection may provide long-term survival.

20.
Atherosclerosis ; 302: 1-7, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32361241

RESUMO

BACKGROUND AND AIMS: Endothelial glycocalyx covers the endothelium and maintains vascular integrity. However, its association with the severity and vulnerability of coronary artery disease (CAD) remains to be elucidated. METHODS: A total of 259 consecutive patients with stable CAD requiring percutaneous coronary intervention (PCI) were prospectively enrolled. Patients were classified into 2 groups according to the median value of serum syndecan-1, which is a core component of the endothelial glycocalyx (lower syndecan-1 group [syndecan-1 <99.0 ng/mL], n = 130; higher syndecan-1 group [syndecan-1 ≥99.0 ng/mL], n = 129). Severity of CAD and focal plaque vulnerability in culprit lesion were evaluated using angiography and optical coherence tomography. RESULTS: There was no significant difference in clinical characteristics between the lower syndecan-1 group and the higher syndecan-1 group other than the prevalence of family history of CAD (19 vs. 32%, p = 0.022), prior PCI history (45 vs. 60%, p = 0.015) and estimated glomerular filtration rate (57.8 ± 17.2 vs. 50.9 ± 25.6 ml/min/1.73 m2, p = 0.011). Although disease severity on angiogram was comparable between the 2 groups, the prevalence of lipid-rich plaque (40 vs. 19%, p = 0.004) and thin-cap fibroatheroma (20 vs. 6%, p = 0.006) was significantly higher in the lower syndecan-1 group than the higher syndecan-1 group. Lower syndecan-1 level was independently associated with higher prevalence of lipid-rich plaque (odds ratio 3.626, 95% confidence interval 1.535-8.566, p = 0.003). CONCLUSIONS: Lower syndecan-1 level was associated with higher prevalence of vulnerable plaque in patients with CAD. This finding suggests the association between impaired endothelial glycocalyx and the development of vulnerable plaque.


Assuntos
Doença da Artéria Coronariana , Endotélio Vascular/patologia , Glicocálix/patologia , Placa Aterosclerótica , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Humanos , Intervenção Coronária Percutânea , Tomografia de Coerência Óptica
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