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1.
Nat Immunol ; 17(12): 1447-1458, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27798619

RESUMO

Virus infection induces the development of T follicular helper (TFH) and T helper 1 (TH1) cells. Although TFH cells are important in anti-viral humoral immunity, the contribution of TH1 cells to a protective antibody response remains unknown. We found that IgG2 antibodies predominated in the response to vaccination with inactivated influenza A virus (IAV) and were responsible for protective immunity to lethal challenge with pathogenic H5N1 and pandemic H1N1 IAV strains, even in mice that lacked TFH cells and germinal centers. The cytokines interleukin-21 and interferon-γ, which are secreted from TH1 cells, were essential for the observed greater persistence and higher titers of IgG2 protective antibodies. Our results suggest that TH1 induction could be a promising strategy for producing effective neutralizing antibodies against emerging influenza viruses.


Assuntos
Centro Germinativo/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Virus da Influenza A Subtipo H5N1/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Infecções por Orthomyxoviridae/imunologia , Células Th1/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Células Cultivadas , Humanos , Imunoglobulina G/sangue , Interferon gama/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
2.
Nat Immunol ; 16(10): 1034-43, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26322480

RESUMO

Immunological memory is thought to be mediated exclusively by lymphocytes. However, enhanced innate immune responses caused by a previous infection increase protection against reinfection, which suggests the presence of innate immunological memory. Here we identified an important role for the stress-response transcription factor ATF7 in innate immunological memory. ATF7 suppressed a group of genes encoding factors involved in innate immunity in macrophages by recruiting the histone H3K9 dimethyltransferase G9a. Treatment with lipopolysaccharide, which mimics bacterial infection, induced phosphorylation of ATF7 via the kinase p38, which led to the release of ATF7 from chromatin and a decrease in repressive histone H3K9me2 marks. A partially disrupted chromatin structure and increased basal expression of target genes were maintained for long periods, which enhanced resistance to pathogens. ATF7 might therefore be important in controlling memory in cells of the innate immune system.


Assuntos
Fatores Ativadores da Transcrição/metabolismo , Epigênese Genética/imunologia , Memória Imunológica/genética , Memória Imunológica/imunologia , Macrófagos/imunologia , Fatores Ativadores da Transcrição/genética , Animais , Epigênese Genética/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Camundongos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
3.
Cancer Immunol Immunother ; 73(7): 126, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733406

RESUMO

BACKGROUND: Immuno-oncology (IO) drugs are essential for treating various cancer types; however, safety concerns persist in older patients. Although the incidence of immune-related adverse events (irAEs) is similar among age groups, higher rates of hospitalization or discontinuation of IO therapy have been reported in older patients. Limited research exists on IO drug safety and risk factors in older adults. Our investigation aimed to assess the incidence of irAEs and identify the potential risk factors associated with their development. METHODS: This retrospective analysis reviewed the clinical data extracted from the medical records of patients aged > 80 years who underwent IO treatment at our institution. Univariate and multivariate analyses were performed to assess the incidence of irAEs. RESULTS: Our study included 181 patients (median age: 82 years, range: 80-94), mostly men (73%), with a performance status of 0-1 in 87% of the cases; 64% received IO monotherapy. irAEs occurred in 35% of patients, contributing to IO therapy discontinuation in 19%. Our analysis highlighted increased body mass index, eosinophil counts, and albumin levels in patients with irAEs. Eosinophil count emerged as a significant risk factor for any grade irAEs, particularly Grade 3 or higher, with a cutoff of 118 (/µL). The group with eosinophil counts > 118 had a higher frequency of irAEs, and Grade 3 or higher events than the group with counts ≤ 118. CONCLUSION: IO therapy is a safe treatment option for patients > 80 years old. Furthermore, patients with elevated eosinophil counts at treatment initiation should be cautiously managed.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Estudos Retrospectivos , Masculino , Feminino , Idoso de 80 Anos ou mais , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Fatores de Risco , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Incidência
4.
Genes Cells ; 28(6): 411-421, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36871192

RESUMO

The CARMA1-Bcl10-MALT1 (CBM) signalosome is a crucial module of NF-κB activation in B cell receptor (BCR) signaling. Biophysical studies have shown that the E3 ubiquitin ligase TRAF6 cooperatively modifies the CBM signalosome; however, the specific details regarding how TRAF6 is involved in BCR signal-induced CBM formation remain unclear. In this study, we aimed to reveal the influences of TRAF6 on CBM formation and TAK1 and IKK activities using DT40 B cells which lack all the exons of TRAF6. In TRAF6-null cells we found: (i) attenuation of TAK1 activity and abolishment of IKK activity and (ii) sustained binding of CARMA1 to Bcl10. To account for the molecular mechanism causing these dynamics, we performed a mathematical model analysis. The mathematical model analysis showed that the regulation of IKK activation by TRAF6 can reproduce TAK1 and IKK activities in TRAF6 null cells, and that the TRAF6 related signal-dependent inhibitor suppresses CARMA1 binding to Bcl10 in wild-type cells. These results suggest that TRAF6 contributes to the positive regulation of IKK activation via TAK1, alongside the negative signal-dependent regulation of CARMA1 binding to Bcl10.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Fator 6 Associado a Receptor de TNF , Fator 6 Associado a Receptor de TNF/genética , Fator 6 Associado a Receptor de TNF/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Sinalização CARD/genética , Proteínas Adaptadoras de Sinalização CARD/metabolismo , NF-kappa B/metabolismo , Guanilato Ciclase/metabolismo
5.
J Vasc Surg ; 79(2): 316-322.e2, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37802402

RESUMO

OBJECTIVE: To examine limb salvage (LS) and wound healing in dialysis-dependent and -independent patients with chronic limb-threatening ischemia (CLTI) after infrainguinal bypass surgery or endovascular therapy (EVT). METHODS: We retrospectively analyzed the multi-center data of patients who underwent infrainguinal revascularization for CLTI with Wound, Ischemia, and foot Infection (WIfI) stage 2 to 4 between 2015 and 2020. The primary endpoint was LS. The secondary endpoint included wound healing, amputation-free survival (AFS), periprocedural complications, and 2-year survival. Comparison of these outcomes were made after propensity score matching. RESULTS: We analyzed 252 dialysis-dependent (318 limbs) and 305 dialysis-independent (354 limbs) patients. Propensity score matching extracted 202 pairs with no significant differences in characteristics. The LS rate in bypass surgery was better than that in EVT in dialysis-dependent patients (P < .001). There was no significant difference in the LS rates between bypass surgery and EVT in dialysis-independent patients (P = .168). The wound healing rate of bypass surgery was better than that of EVT both dialysis-dependent and -independent patients with CLTI. The AFS rate of bypass surgery was better than that of EVT in dialysis-dependent patients (P < .001). There was no significant difference in the AFS rates between bypass surgery and EVT in dialysis-independent patients (P = .099). There was no significant difference in the occurrence of Clavien-Dindo ≥ IV and V between bypass surgery and EVT in dialysis-dependent and -independent patients. Age ≥75 years, serum albumin levels <3.5 g/dL, and non-ambulatory status were risk factors for 2-year mortality in dialysis-dependent patients. The 2-year survival rates in dialysis-dependent patients with risk factors of 0, 1, 2, and 3 were 82.5%, 67.1%, 49.5%, and 10.2%, respectively (P < .001). CONCLUSIONS: For LS and wound healing, bypass surgery was preferred for revascularization in dialysis-dependent patients with WIfI stage 2 to 4. Although dialysis dependency was one of the risk factors for 2-year mortality, dialysis-dependent patients, who have 0 to 1 risk factors, may benefit from bypass surgery, as 2-year survival of >50% is expected.


Assuntos
Procedimentos Endovasculares , Doença Arterial Periférica , Humanos , Idoso , Isquemia Crônica Crítica de Membro , Estudos Retrospectivos , Procedimentos Endovasculares/efeitos adversos , Resultado do Tratamento , Diálise Renal/efeitos adversos , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/cirurgia , Salvamento de Membro/efeitos adversos , Fatores de Risco , Isquemia/diagnóstico por imagem , Isquemia/cirurgia
6.
J Vasc Surg ; 80(1): 204-212.e3, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38522583

RESUMO

OBJECTIVE: This study aimed to evaluate treatment outcomes after bypass surgery or endovascular therapy (EVT) in average- and high-risk patients with chronic limb-threatening ischemia (CLTI). METHODS: We retrospectively analyzed multicenter data of patients who underwent infra-inguinal revascularization for CLTI between 2015 and 2022. A high-risk patient was defined as one with estimated 30-day mortality rate ≥5% or 2-year survival rate ≤50%, as determined by the Surgical Reconstruction vs Peripheral Intervention in Patients With Critical Limb Ischemia (SPINACH) calculator. The amputation-free survival (AFS), limb salvage (LS), wound healing, and 30-day mortality were compared separately for the average- and high-risk patients between the bypass and EVT with propensity score matching. RESULTS: We analyzed 239 and 31 propensity score-matched pairs in the average- and high-risk patients with CLTI. In the average-risk patients, the 2-year AFS and LS rates were 78.1% and 94.4% in the bypass group and 63.0% and 87.7% in the EVT group (P < .001 and P = .007), respectively. The 1-year wound healing rates were 88.6% in the bypass group and 76.8% in the EVT group, respectively (P < .001). The 30-day mortality was 0.8% in the bypass surgery and 0.8% in the EVT group (P = .996). In the high-risk patients, there was no differences in the AFS, LS, and wound healing between the groups (P = .591, P = .148, and P = .074). The 30-day mortality was 3.2% in the bypass group and 3.2% in the EVT group (P = .991). CONCLUSIONS: Bypass surgery is superior to EVT with respect to the AFS, LS, and wound healing in the average-risk patients. EVT is a feasible first-line treatment strategy for high-risk patients with CLTI undergoing revascularization, based on the lack of significant differences in the 2-year AFS rate, between the bypass surgery and EVT cohorts.


Assuntos
Amputação Cirúrgica , Isquemia Crônica Crítica de Membro , Procedimentos Endovasculares , Salvamento de Membro , Doença Arterial Periférica , Humanos , Estudos Retrospectivos , Masculino , Feminino , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Idoso , Fatores de Risco , Medição de Risco , Doença Arterial Periférica/cirurgia , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Doença Arterial Periférica/diagnóstico por imagem , Fatores de Tempo , Isquemia Crônica Crítica de Membro/cirurgia , Isquemia Crônica Crítica de Membro/mortalidade , Pessoa de Meia-Idade , Cicatrização , Enxerto Vascular/efeitos adversos , Enxerto Vascular/mortalidade , Enxerto Vascular/métodos , Idoso de 80 Anos ou mais , Resultado do Tratamento , Isquemia/cirurgia , Isquemia/mortalidade , Isquemia/fisiopatologia
7.
J Vasc Surg ; 80(3): 792-799.e1, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38649101

RESUMO

OBJECTIVE: This study aimed to compare the influence of inframalleolar (IM) P0/P1 on wound healing in bypass surgery vs endovascular therapy (EVT) in patients with chronic limb-threatening ischemia (CLTI). METHODS: We retrospectively analyzed the multicenter data of patients who underwent infra-inguinal revascularization for CLTI between 2015 and 2022. IM P represents target artery crossing into foot, with intact pedal arch (P0) and absent or severely diseased pedal arch (P1). The endpoints were wound healing, limb salvage (LS), and postoperative complications. RESULTS: We analyzed 66 and 189 propensity score-matched pairs in the IM P0 and IM P1 cohorts, respectively. In the IM P0 cohort, the 1-year wound healing rates were 94.5% and 85.7% in the bypass surgery and EVT groups, respectively (P = .092), whereas those in the IM P1 cohort were 86.2% and 66.2% in the bypass surgery and EVT groups, respectively (P < .001). In the IM P0 cohort, the 2-year LS rates were 96.7% and 94.1% in the bypass surgery and EVT groups, respectively (P = .625), and those in the IM P1 cohort were 91.8% and 81.5% in the bypass surgery and EVT groups, respectively (P = .004). No significant differences were observed between the bypass surgery and EVT in terms of postoperative complication rates in either the IM P0 or P1 cohorts. CONCLUSIONS: Bypass surgery facilitated better wound healing and LS than EVT in patients with IM P1. Conversely, no differences in wound healing or LS were observed between groups in patients with IM P0. Bypass surgery should be considered a better revascularization strategy than EVT in patients with tissue loss and IM P1 disease.


Assuntos
Isquemia Crônica Crítica de Membro , Procedimentos Endovasculares , Salvamento de Membro , Doença Arterial Periférica , Cicatrização , Humanos , Masculino , Feminino , Estudos Retrospectivos , Idoso , Procedimentos Endovasculares/efeitos adversos , Resultado do Tratamento , Pessoa de Meia-Idade , Doença Arterial Periférica/fisiopatologia , Doença Arterial Periférica/terapia , Doença Arterial Periférica/cirurgia , Doença Arterial Periférica/diagnóstico por imagem , Fatores de Tempo , Isquemia Crônica Crítica de Membro/cirurgia , Fatores de Risco , Idoso de 80 Anos ou mais , Complicações Pós-Operatórias/etiologia , Enxerto Vascular/efeitos adversos , Medição de Risco , Isquemia/fisiopatologia , Isquemia/cirurgia , Isquemia/terapia
8.
Artigo em Inglês | MEDLINE | ID: mdl-39362463

RESUMO

OBJECTIVE: The incidence and related factors of spontaneous occlusion of a patent inferior mesenteric artery (IMA) after endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) without pre-emptive embolisation remain unclear. This study aimed to elucidate the incidence, clinical implications and predictors of spontaneous IMA occlusion after EVAR. METHODS: This was a single centre, retrospective cohort study. Patients who underwent elective EVAR between 2007 and 2022 were categorised into three groups (group 1, spontaneous IMA occlusion; group 2, patent IMA with no type II endoleak (T2EL) from IMA; group 3, T2EL from IMA). Endpoints were the incidence of spontaneous IMA occlusion, sac enlargement, freedom from re-intervention, and overall survival after EVAR. RESULTS: Of 372 cases of elective EVAR for AAA, 230 who had patent IMA pre-operatively were analysed, after excluding 127 with pre-occluded IMA and 15 who underwent pre-emptive IMA embolisation. Spontaneous IMA occlusion occurred in 101 patients (43.9%). Sac enlargement rate was lower in group 1 than in groups 2 and 3. Freedom from re-intervention rate was higher in group 1 than in group 3 but did not differ between groups 1 and 2. Multivariate analysis revealed the absence of antiplatelet therapy, pre-operative higher haematocrit, absence of concomitant iliac artery aneurysm, posterior thrombus in the sac, and use of Endurant as predictors associated with spontaneous IMA occlusion. Spontaneous IMA occlusion was observed in 7.1% and 77.5% of patients with zero and four or five predictors, respectively. CONCLUSION: Spontaneous IMA occlusion occurred in nearly half of cases and was associated with positive clinical outcomes. In patients with a high prediction of spontaneous IMA occlusion, pre-emptive IMA embolisation may be omitted.

9.
Eur J Vasc Endovasc Surg ; 67(5): 777-783, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38141957

RESUMO

OBJECTIVE: This study aimed to evaluate three survival prediction models: the JAPAN Critical Limb Ischaemia Database (JCLIMB), Surgical Reconstruction Versus Peripheral Intervention in Patients With Critical Limb Ischaemia (SPINACH), and Vascular Quality Initiative (VQI) calculators. METHODS: Multicentre data of patients who underwent infrainguinal revascularisation for chronic limb threatening ischaemia between 2018 and 2021 were analysed retrospectively. The prediction models were validated using a calibration plot analysis with the intercept and slope. The discrimination was evaluated using area under the curve (AUC) analysis. The observed two year overall survival (OS) was evaluated by the Kaplan - Meier method. The two year OS predicted by each model at < 50%, 50 - 70%, and > 70% was defined as high, medium, and low risk, respectively. RESULTS: A total of 491 patients who underwent infra-inguinal revascularisation were analysed. The rates of surgical revascularisation, endovascular therapy, and hybrid therapy were 26.5%, 70.1%, and 5.5%, respectively. The average age was 75.6 years, and the percentages of patients with diabetes mellitus and dialysis dependent end stage renal disease were 66.6% and 44.6%, respectively. The tissue loss rate was 85.7%. The intercept and slope were -0.13 and 1.18 for the JCLIMB, 0.11 and 0.82 for the SPINACH, and -0.15 and 1.10 for the VQI. The AUC for the two year OS of JCLIMB, SPINACH, and VQI were 0.758, 0.756, and 0.740, respectively. The observed two year OS rates of low, medium, and high risk using the JCLIMB calculator were 80.1%, 61.1%, and 28.5%, respectively (p < .001), using the SPINACH calculator were 81.0%, 57.0%, and 38.1%, respectively (p < .001), and using the VQI calculator were 77.8%, 45.8%, and 49.6%, respectively (p < .001). CONCLUSION: The JCLIMB, SPINACH, and VQI survival calculation models were useful, although the OS predicted by the VQI model appeared to be lower than the observed OS.


Assuntos
Isquemia Crônica Crítica de Membro , Procedimentos Endovasculares , Humanos , Idoso , Masculino , Feminino , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Estudos Retrospectivos , Medição de Risco/métodos , Japão/epidemiologia , Idoso de 80 Anos ou mais , Isquemia Crônica Crítica de Membro/cirurgia , Isquemia Crônica Crítica de Membro/mortalidade , Fatores de Risco , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidade , Resultado do Tratamento , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/cirurgia , Doença Arterial Periférica/complicações , Pessoa de Meia-Idade , Salvamento de Membro , Fatores de Tempo , Valor Preditivo dos Testes , Bases de Dados Factuais
10.
Colorectal Dis ; 26(4): 760-765, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38321510

RESUMO

Carbon ion radiotherapy (CIRT) has received attention for the treatment of locally recurrent rectal cancer. When the surrounding primary organs are close to the irradiation site, a spacer is required to ensure safe irradiation. This work describes a novel technique using a bioabsorbable polyglycolic acid spacer placed laparoscopically and presents a technical report with five case studies. The short-term surgical outcomes were as follows: mean operating time 235 min with blood loss of 38 mL. CIRT was planned, and the patients underwent irradiation within 2 months of surgery. No pelvic infections occurred, and all procedures were performed safely. Herein, were present a technical report with reference to a video of the surgical procedure.


Assuntos
Implantes Absorvíveis , Laparoscopia , Recidiva Local de Neoplasia , Ácido Poliglicólico , Neoplasias Retais , Humanos , Neoplasias Retais/cirurgia , Neoplasias Retais/radioterapia , Laparoscopia/métodos , Recidiva Local de Neoplasia/cirurgia , Pessoa de Meia-Idade , Feminino , Masculino , Idoso , Resultado do Tratamento , Duração da Cirurgia
11.
Ann Vasc Surg ; 108: 171-178, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38950852

RESUMO

BACKGROUND: To examine the influence of liver function on patients with chronic limb-threatening ischemia (CLTI), we classified patients with CLTI after revascularization according to their modified albumin-bilirubin (ALBI) grades. METHODS: We retrospectively analyzed single-center data of patients who underwent revascularization for CLTI between 2015 and 2020. Patients were classified with ALBI grades 1, 2a, and 2b and 3 according to the ALBI score, which was calculated, based on serum albumin and total bilirubin levels. The endpoints were the 2-year amputation-free survival (AFS) and 1-year wound healing rates. RESULTS: We included 190 limbs in 148 patients, and 50, 54, and 86 cases were assigned as grade 1, 2a, and 2b and 3, respectively. The 2-year AFS rates for the grade 1, 2a, and 2b and 3 groups were 79 ± 6%, 66% ± 7%, and 45 ± 6%, respectively (P < 0.01). One-year cumulative wound healing rates for grade 1, 2a, and 2b and 3 groups were 68 ± 7%, 69% ± 6%, and 48% ± 5%, respectively (P = 0.01). Multivariate Cox proportional hazard analyses identified age (≥75 years), dependent ambulatory status, and modified ALBI grades 2b and 3 compared with grades 1 and 2a as significant independent predictors of AFS. The dependent ambulatory status and Wound, Ischemia, and foot Infection classification stage 4 were significant negative predictors of wound healing. CONCLUSIONS: Many patients with CLTI had high modified ALBI grades, and impaired liver function classified as modified ALBI grade 2b and 3 is a robust negative predictor of AFS.


Assuntos
Amputação Cirúrgica , Bilirrubina , Biomarcadores , Salvamento de Membro , Doença Arterial Periférica , Valor Preditivo dos Testes , Albumina Sérica Humana , Cicatrização , Humanos , Masculino , Feminino , Estudos Retrospectivos , Idoso , Bilirrubina/sangue , Albumina Sérica Humana/análise , Biomarcadores/sangue , Fatores de Tempo , Pessoa de Meia-Idade , Fatores de Risco , Idoso de 80 Anos ou mais , Medição de Risco , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Doença Arterial Periférica/cirurgia , Isquemia Crônica Crítica de Membro/cirurgia , Isquemia Crônica Crítica de Membro/sangue , Isquemia Crônica Crítica de Membro/diagnóstico , Isquemia Crônica Crítica de Membro/mortalidade , Resultado do Tratamento , Intervalo Livre de Progressão , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidade , Testes de Função Hepática , Isquemia/sangue , Isquemia/diagnóstico , Isquemia/cirurgia , Isquemia/fisiopatologia , Isquemia/mortalidade
12.
Ann Vasc Surg ; 106: 312-320, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38821471

RESUMO

BACKGROUND: This study aimed to analyze the clinical outcomes after revascularization for chronic limb-threatening ischemia (CLTI) in patients aged ≥ 80 years and < 80 years. METHODS: We retrospectively analyzed multicenter data of 789 patients who underwent infrainguinal revascularization for CLTI between 2015 and 2021. The end points were 2-year overall survival (OS), amputation-free survival (AFS), limb salvage (LS), and postoperative complications. RESULTS: A total of 90 patients aged ≥ 80 years and 200 patients aged < 80 years underwent bypass surgery (BSX), and 205 patients aged ≥ 80 years and 294 patients aged < 80 years underwent endovascular therapy (EVT). Before the propensity score matching, multivariate analyses showed that age ≥ 80 years, lower body mass index and serum albumin levels, nonambulatory status, and end-stage renal disease were independent risk factors for 2-year mortality in the BSX and EVT groups. After propensity score matching, the 2-year OS was better in the < 80 years cohort than in the ≥ 80 years cohort in both the BSX and EVT groups (P = 0.018 and P = 0.035, respectively). There was no difference in the 2-year LS rates between the < 80 years and the ≥ 80 years cohorts in both the BSX and EVT groups (P = 0.621 and P = 0.287, respectively). According to the number of risk factors, except for age ≥ 80 years, there was no difference in the 2-year AFS rates between the < 80 years and ≥ 80 years cohorts for the BSX and EVT groups with 0-1 risk factor (P = 0.957 and P = 0.655, respectively). However, the 2-year AFS rate was poor, especially in the ≥ 80 years cohort in the BSX with 2-4 risk factors (P = 0.015). The Clavien-Dindo ≥ IV complication rates tended to be higher in the ≥ 80 years cohort than in the < 80 years cohort only in the BSX with 2-4 risk factors (P = 0.056). CONCLUSIONS: Patients with CLTI aged ≥ 80 years had poorer OS than those aged < 80 years. However, there was no difference in LS between the ≥ 80 years and < 80 years cohorts in both the BSX and EVT groups. Although age ≥ 80 years was associated with poorer OS, patients with 0-1 risk factor may benefit from revascularization, including BSX, because no difference was observed in AFS or Clavien-Dindo ≥ IV complications.


Assuntos
Amputação Cirúrgica , Isquemia Crônica Crítica de Membro , Procedimentos Endovasculares , Salvamento de Membro , Doença Arterial Periférica , Complicações Pós-Operatórias , Humanos , Estudos Retrospectivos , Masculino , Idoso de 80 Anos ou mais , Feminino , Fatores de Risco , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/cirurgia , Doença Arterial Periférica/terapia , Fatores de Tempo , Fatores Etários , Idoso , Medição de Risco , Isquemia Crônica Crítica de Membro/cirurgia , Isquemia Crônica Crítica de Membro/mortalidade , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Intervalo Livre de Progressão , Enxerto Vascular/efeitos adversos , Enxerto Vascular/mortalidade , Resultado do Tratamento , Isquemia/mortalidade , Isquemia/cirurgia , Isquemia/terapia , Isquemia/fisiopatologia
13.
Int J Clin Oncol ; 29(3): 266-275, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38227091

RESUMO

BACKGROUND: We previously showed that daily nutritional intervention with an oral elemental diet (ED) at 300 kcal/day for 6-8 weeks postoperatively decreased the percentage of body weight loss (%BWL), and that the effect was maintained for 1 year. This post hoc analysis aimed to determine whether this intervention decreased skeletal muscle mass loss 1-year post-gastrectomy. METHODS: Data from consecutive, untreated patients with histopathologically confirmed stage I-III gastric adenocarcinoma who planned to undergo total gastrectomy (TG) or distal gastrectomy (DG) and were enrolled in a previously published randomized trial were used. The primary endpoint was the percentage of skeletal muscle mass index (%SMI) loss from baseline at 1 year postoperatively, based on abdominal computed tomography images obtained preoperatively and at 1 year postoperatively. RESULTS: The overall median %SMI loss was lower in the ED versus control group, but the difference was not significant. The difference in %SMI loss in the ED and control groups was greater in patients with TG (10.1 vs. 13.0; P = 0.12) than in those with DG (5.5 vs. 6.8; P = 0.69). A correlation was observed between %BWL and %SMI loss in both groups (ED group, coefficient 0.591; control group, coefficient 0.644; P < 0.001 for both). Type of gastrectomy (coefficient 7.38; P = 0.001) and disease stage (coefficient - 6.43; P = 0.04) were independent predictors of postoperative skeletal muscle mass loss. CONCLUSION: ED administration for 6-8 weeks following gastrectomy had no inhibitory effect on skeletal muscle loss at 1 year postoperatively. CLINICAL TRIAL REGISTRATION: UMIN000023455.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Músculo Esquelético/patologia , Período Pós-Operatório , Adenocarcinoma/patologia , Gastrectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia
14.
Plant Cell ; 32(12): 3884-3901, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33093145

RESUMO

Posttranslational protein targeting requires chaperone assistance to direct insertion-competent proteins to integration pathways. Chloroplasts integrate nearly all thylakoid transmembrane proteins posttranslationally, but mechanisms in the stroma that assist their insertion remain largely undefined. Here, we investigated how the chloroplast chaperonin (Cpn60) facilitated the thylakoid integration of Plastidic type I signal peptidase 1 (Plsp1) using in vitro targeting assays. Cpn60 bound Plsp1 in the stroma. In isolated chloroplasts, the membrane integration of imported Plsp1 correlated with its dissociation from Cpn60. When the Plsp1 residues that interacted with Cpn60 were removed, Plsp1 did not integrate into the membrane. These results suggested Cpn60 was an intermediate in thylakoid targeting of Plsp1. In isolated thylakoids, the integration of Plsp1 decreased when Cpn60 was present in excess of cpSecA1, the stromal motor of the cpSec1 translocon that inserts unfolded Plsp1 into the thylakoid. An excess of cpSecA1 favored integration. Introducing Cpn60's obligate substrate RbcL displaced Cpn60-bound Plsp1; then, the released Plsp1 exhibited increased accessibility to cpSec1. These in vitro targeting experiments support a model in which Cpn60 captures and then releases insertion-competent Plsp1, whereas cpSecA1 recognizes free Plsp1 for integration. Thylakoid transmembrane proteins in the stroma can interact with Cpn60 to shield themselves from the aqueous environment.


Assuntos
Chaperoninas/metabolismo , Proteínas de Membrana/metabolismo , Chaperonas Moleculares/metabolismo , Pisum sativum/metabolismo , Serina Endopeptidases/metabolismo , Chaperoninas/genética , Cloroplastos/metabolismo , Proteínas de Membrana/genética , Chaperonas Moleculares/genética , Pisum sativum/genética , Estômatos de Plantas/genética , Estômatos de Plantas/metabolismo , Transporte Proteico , Serina Endopeptidases/genética , Proteínas das Membranas dos Tilacoides/genética , Proteínas das Membranas dos Tilacoides/metabolismo , Tilacoides/metabolismo
15.
Plant Cell ; 32(5): 1589-1609, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32169961

RESUMO

Protein folding is a complex cellular process often assisted by chaperones, but it can also be facilitated by interactions with lipids. Disulfide bond formation is a common mechanism to stabilize a protein. This can help maintain functionality amid changes in the biochemical milieu, including those relating to energy-transducing membranes. Plastidic Type I Signal Peptidase 1 (Plsp1) is an integral thylakoid membrane signal peptidase that requires an intramolecular disulfide bond for in vitro activity. We have investigated the interplay between disulfide bond formation, lipids, and pH in the folding and activity of Plsp1. By combining biochemical approaches with a genetic complementation assay using Arabidopsis thaliana plants, we provide evidence that interactions with lipids in the thylakoid membrane have reconstitutive chaperoning activity toward Plsp1. Further, the disulfide bridge appears to prevent an inhibitory conformational change resulting from proton motive force-mimicking pH conditions. Broader implications related to the folding of proteins in energy-transducing membranes are discussed.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Membranas Intracelulares/enzimologia , Chaperonas Moleculares/metabolismo , Força Próton-Motriz , Serina Endopeptidases/metabolismo , Tilacoides/enzimologia , Proteínas de Arabidopsis/química , Ritmo Circadiano/efeitos dos fármacos , Cisteína/metabolismo , Dissulfetos/metabolismo , Ditiotreitol/farmacologia , Estabilidade Enzimática , Escherichia coli/metabolismo , Genes Supressores , Bicamadas Lipídicas/metabolismo , Modelos Biológicos , Mutação/genética , Oxirredução , Conformação Proteica , Serina Endopeptidases/química
16.
Gastric Cancer ; 26(2): 307-316, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36695982

RESUMO

BACKGROUND: Surgical resection of oligo-metastasis in gastric cancer (GC) is weakly recommended for patients without other incurable factors in the Japanese GC Treatment Guidelines. While post-operative chemotherapy is the standard treatment in patients with stage II or III GC, its efficacy for resected stage IV GC is unclear. This study aimed to evaluate the efficacy of post-operative chemotherapy after curative resection of GC with oligo-metastasis. METHODS: We retrospectively reviewed the medical records of patients with GC who were diagnosed with synchronous oligo-metastasis at 20 institutions in Japan between 2007 and 2012. The selection criteria were: adenocarcinoma, stage IV with oligo-metastasis at liver or lymph node without other distant metastasis, curative resection including synchronous oligo-metastasis, and no prior treatment of GC before surgery. RESULTS: A total of 110 patients were collected. Of the 94 eligible patients, 84 underwent gastrectomy with surgical resection of oligo-metastasis (39 [41%] liver metastasis and 55, [59%] distant lymph node metastasis), followed by post-operative chemotherapy with S-1 (S1: n = 55), S1 plus cisplatin (CS: n = 22), or Others (n = 7). Moreover, 10 patients did not receive post-operative chemotherapy (Non-Cx). The median overall survival (OS) was 35.2 and 11.1 months in the post-operative chemotherapy and Non-Cx groups (hazard ratio, 3.56; 95% confidence interval, 1.74-7.30; p < 0.001), respectively. In multivariable analysis, Non-Cx and age over 70 years were identified as poor prognostic factors for OS (p < 0.05). CONCLUSIONS: Curative resection followed by post-operative chemotherapy in patients with GC with synchronous oligo-metastasis showed favorable survival.


Assuntos
Neoplasias Gástricas , Humanos , Idoso , Neoplasias Gástricas/patologia , Estudos Retrospectivos , Cisplatino , Linfonodos/patologia , Excisão de Linfonodo , Gastrectomia , Prognóstico , Estadiamento de Neoplasias
17.
Surg Endosc ; 37(4): 2958-2968, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36512122

RESUMO

BACKGROUND: Late complications following gastric cancer surgery, including postgastrectomy syndromes, are complex problems requiring a solution. Reported risk factors for developing late complications include surgery-related factors, such as the surgical approach and the extent of resection and reconstruction. However, this has not been assessed in a prospective study with a large sample size. Therefore, this study aimed to evaluate associations between surgery-related factors and the development of late complications. Data from the JCOG0912 trial were used. It compared laparoscopy-assisted distal gastrectomy (LADG) to open distal gastrectomy (ODG) in clinical stage I gastric cancer patients. METHODS: This study included 881/921 patients enrolled in the JCOG0912 trial. The incidence of late complications was compared between the ODG and the LADG arms. In addition, associations between surgery-related factors and the development of late complications were assessed by multivariable analyses using the proportional odds model to identify relevant risk factors. RESULTS: There was no difference in the type or number of patients with late complications between the LADG and the ODG arms. The multivariable analysis for each late complication revealed that the Billroth-I reconstruction (vs. R-en-Y or Billroth-II) had a lower risk of cholecystitis [odds ratio (OR) 0.187, 95% confidence interval (CI) 0.039-0.905, P = 0.037] or ileus (OR 0.116, 95%CI 0.033-0.406, P < 0.001), and pylorus-preserving gastrectomy (vs. R-en-Y or Billroth-II) had a higher risk of reflux esophagitis (OR 3.348, 95% CI 1.371-8.176, P = 0.008). The surgical approach was not a risk factor for any late complications. CONCLUSION: Differences in surgical approaches did not constitute a risk for developing late complications after gastrectomy. Billroth-I reconstruction reduced the risk of ileus and cholecystitis, but pylorus-preserving gastrectomy carried a risk for reflux esophagitis.


Assuntos
Esofagite Péptica , Íleus , Obstrução Intestinal , Laparoscopia , Neoplasias Gástricas , Humanos , Esofagite Péptica/etiologia , Gastrectomia/efeitos adversos , Íleus/etiologia , Obstrução Intestinal/cirurgia , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Prospectivos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/complicações , Resultado do Tratamento
18.
Surg Today ; 53(8): 882-889, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36792834

RESUMO

PURPOSE: This study investigated the associations of personality traits and preoperative lifestyle improvements with early weight loss after sleeve gastrectomy. METHODS: This was a single-center, retrospective study of 57 patients who underwent preoperative lifestyle intervention with a multidisciplinary team approach based on cognitive behavioral therapy before sleeve gastrectomy. All patients underwent preoperative psychological testing with the Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI) and the Tokyo University Egogram New Version II (TEG II). We investigated the associations of psychological testing results and lifestyle improvements with percent total weight loss (%TWL) one year after surgery. RESULTS: The median %TWL at 1 year was 38.2% for patients with an improved lifestyle and 26.9% for those without improvement (P = 0.0008). Although TEG II factors were not associated with %TWL at 1 year, higher NEO-FFI extraversion (E) scores were significantly associated with a better %TWL at 1 year. The median %TWL at 1 year was 35.2% for patients with higher E scores and 25.4% for those with lower E scores (P = 0.0247). Lifestyle improvement and the NEO-FFI E score significantly influenced %TWL at 1 year based on a logistic regression analysis. CONCLUSION: The NEO-FFI E score and preoperative lifestyle improvement may be predictors of early weight loss after sleeve gastrectomy.


Assuntos
Laparoscopia , Obesidade Mórbida , Humanos , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Estilo de Vida , Gastrectomia/métodos , Redução de Peso , Laparoscopia/métodos , Personalidade
19.
BMC Surg ; 23(1): 314, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37845691

RESUMO

PURPOSE: This study aimed to examine the incidence of incisional hernia (IH) in elective laparoscopic colorectal surgery (LC) using regulated computed tomography (CT) images at intervals every 6 months. METHODS: We retrospectively examined the diagnosis of IH in patients who underwent LC for colorectal cancer at Kansai Medical University Hospital from January 2014 to August 2018. The diagnosis of IH was defined as loss of continuity of the fascia in the axial CT images. RESULTS: 470 patients were included in the analysis. IH was diagnosed in 47 cases at 1 year after LC. The IH size was 7.8 cm2 [1.3-55.6]. In total, 38 patients with IH underwent CT examination 6 months after LC, and 37 were already diagnosed with IH. The IH size was 4.1 cm2 [0-58.9]. The IH size increased in 17 cases between 6 months and 1 year postoperatively, and in 1 case, a new IH occurred. 47%(18/38) of them continued to grow until 1 year after LC. A multivariate analysis was performed on the risk of IH occurrence. SSI was most significantly associated with IH occurrence (OR:5.28 [2.14-13.05], p = 0.0003). CONCLUSION: IH occurred in 10% and 7.9% at 1 year and 6 months after LC. By examining CT images taken for the postoperative surveillance of colorectal cancer, we were able to investigate the occurrence of IH in detail.


Assuntos
Neoplasias Colorretais , Hérnia Incisional , Laparoscopia , Humanos , Hérnia Incisional/epidemiologia , Hérnia Incisional/etiologia , Hérnia Incisional/cirurgia , Estudos Retrospectivos , Laparoscopia/efeitos adversos , Colectomia/efeitos adversos , Colectomia/métodos , Incidência , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/complicações , Fatores de Risco
20.
Kyobu Geka ; 76(2): 148-151, 2023 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-36731851

RESUMO

Osteopetrosis is a heterogeneous group of heritable conditions. It varies greatly in severity, and fracture treatment remains a matter of controversy due to altered responses to fixation and the risk of osteomyelitis. Therefore, sternotomy outcomes in this condition are unclear. We report the case of a patient with osteopetrosis and coronary artery disease (CAD). A 78-year-old man with osteopetrosis presented with frequent chest pain. Coronary angiography revealed two-vessel CAD. Percutaneous coronary intervention was contraindication because of coronary aneurysm in the left main trunk. Considering risks in median sternotomy, we performed minimally invasive cardiac surgery through left minithoracotomy for coronary artery bypass grafting( CABG). But we needed to break the left fourth rib to obtain sufficient surgical views. To the best of our knowledge, this is the first case report on CABG for a patient with osteopetrosis and endoscopic surgery without rib retractor is recommended.


Assuntos
Doença da Artéria Coronariana , Osteopetrose , Masculino , Humanos , Idoso , Osteopetrose/complicações , Osteopetrose/diagnóstico por imagem , Osteopetrose/cirurgia , Resultado do Tratamento , Doença da Artéria Coronariana/cirurgia , Ponte de Artéria Coronária , Angiografia Coronária , Procedimentos Cirúrgicos Minimamente Invasivos
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