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BACKGROUND: Few reports have performed a prognostic analysis based on bioelectrical impedance analysis in patients with radical resection of pancreatic ductal adenocarcinoma (PDAC), and its usefulness in prognostic analysis remains unclear. This study aimed to evaluate body composition changes in patients undergoing radical resection for PDAC and analyze its impact on prognosis. METHODS: The medical records of radical resection for patients with PDAC were retrospectively reviewed, and the parameters of body composition, including body weight, skeletal muscle mass, body fat mass (BFM), and extracellular water-total body water ratio, from preoperatively to 12 months postoperatively, for each surgical procedure were measured based on direct segmental multifrequency bioelectrical impedance analysis with an InBody 770 (InBody Inc., Tokyo, Japan) device. The clinicopathological and prognostic factors were analyzed. RESULTS: Among 79 patients who underwent radical resection for PDAC, 36 (46%), 7 (8%), and 36 (46%) underwent pancreatoduodenectomy, total pancreatectomy, and distal pancreatectomy, respectively. The multivariate overall survival analysis demonstrated that BFM loss percentage at 1 month postoperatively â§14% (p = 0.021), lymph node metastasis (p = 0.014), and non-adjuvant chemotherapy (p < 0.001) were independent poor prognostic factors. Multivariate analysis revealed that preoperative BFM < 12 kg and preoperative albumin < 3.5 g/dL were independently associated with BFM loss percentage at 1 month postoperatively â§14% (p = 0.021 and p = 0.047, respectively). CONCLUSIONS: Loss of BFM in the early postoperative period may have a poor prognosis in radical resection of PDAC.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Estudos Retrospectivos , Impedância Elétrica , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/cirurgia , Prognóstico , Pancreatectomia/métodos , Tecido AdiposoRESUMO
Single nucleotide polymorphisms (SNPs) in FCGR3A can predict the susceptibility of liver transplant (LT) recipients to bloodstream infections (BSI) and clinical outcomes following living-donor LT (LDLT). Here, we retrospectively analyzed the relationship of adoptive immunotherapy with activated natural killer (NK) cells from perfusate effluents of liver allografts against BSI following LDLT. Higher BSI incidence and lower survival were observed in LT recipients with FcγRIIIa (158F/F or F/V) (n = 81) who did not receive adoptive immunotherapy (n = 55) than in those who did (n = 26) (BSI frequency, 36.4% vs. 11.5%; p = .033; log-rank p = .047). After matching patient background using propensity score, similar results were obtained (BSI ratio, 41.7% vs. 12.5%; p = .049; log-rank p = .039). The predominant BSI pathogens in patients who did and did not receive adoptive immunotherapy were gram-negative rods (n = 3, 100%) and gram-positive cocci (GPC) (n = 15, 65.2%), respectively. The proportion of NK cells administered to patients with BSI was significantly lower than that administered to patients without BSI (Number: 80.3 (29.9-239.2) × 106 cells vs. 37.1 (35.6-50.4) × 106 ; p = .033, percentage; 14.1 (13.3-17.8)% vs. 34.6 (16.5-47)%, p = .0078). Therefore, adoptive immunotherapy with NK cells was associated with the reduced post-transplant BSI related to GPCs due to FcγRIIIa SNP in LT recipients.
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Transplante de Fígado , Sepse , Predisposição Genética para Doença/etiologia , Humanos , Fatores Imunológicos , Imunoterapia Adotiva/efeitos adversos , Transplante de Fígado/efeitos adversos , Doadores Vivos , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Fatores de Risco , Sepse/etiologiaRESUMO
Human leukocyte antigen (HLA) molecular mismatch (MM) analysis improves the prediction of clinical outcomes in kidney transplantation compared with prediction via traditional antigen MM. However, it remains unclear whether the level of MM can be used for risk stratification among liver transplantation (LT) recipients. A retrospective observational study of 45 living donor LTs was performed to evaluate eplet MM as a risk factor for both T cell-mediated rejection (TCMR) in the first month and de novo donor-specific antibody (dnDSA) formation. A total of 9 (20%) patients displayed TCMR. HLA-A, HLA-B, HLA-C, and HLA-DRB1 eplet MM numbers were not associated with TCMR. By contrast, HLA-DQB1 eplet MM (DQB1-EpMM) number was significantly high in patients with TCMR. The predicted indirectly recognizable HLA epitopes (PIRCHE-II) score for the HLA-DQB1 locus (DQB1-PIRCHE-II) was also significantly higher in the TCMR group than in the no-TCMR group. There was a high probability for TCMR to occur with either a DQB1-EpMM ≥7 or a DQB1-PIRCHE-II ≥13. Pretransplant mixed lymphocyte response analyses indicated that there were no significant differences between the antidonor T cell proliferation activities of patients with low-number (<7) and high-number (≥7) DQB1-EpMMs. However, the proportion of CD25 expression on proliferating antidonor CD8+ T cells, used as a cytotoxic activity marker, was high in DQB1-EpMMs ≥7. Moreover, both DQB1-EpMMs ≥9 and DQB1-PIRCHE-II ≥3 were predictors of dnDSA formation. Thus, MM analysis may be applied toward tailored immunosuppression based on individual risks.
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Transplante de Fígado , Formação de Anticorpos , Linfócitos T CD8-Positivos , Rejeição de Enxerto , Antígenos HLA , Teste de Histocompatibilidade , Humanos , Transplante de Fígado/efeitos adversos , Doadores Vivos , Estudos Retrospectivos , Doadores de TecidosRESUMO
Through multiple mechanisms, regulatory B cells (Breg) have been shown to play an important role in the development of allograft tolerance. However, a careful understanding of the role of antigen-specificity in Breg-mediated allograft tolerance has remained elusive. In experimental models of islet and cardiac transplantation, it has been established that Bregs can be induced in vivo by anti-CD45RB ± anti-TIM1antibody treatment, resulting in prolonged, Breg-dependent allograft tolerance. The importance of Breg antigen recognition has been suggested but not confirmed through adoptive transfer experiments, using tolerant WT C57BL/6 animals challenged with either BALB/c or C3H grafts. However, the importance of receptor-specificity has not been formally tested. Here, we utilize the novel ovalbumin-specific B cell receptor transnuclear (OBI) mice in multiple primary tolerance and adoptive transfer experiments to establish that Breg-dependent allograft tolerance relies on antigen recognition by B cells. Additionally, we identify that this Breg-dependent tolerance relies on the function of transforming growth factor-ß. Together, these experiments mark important progress toward understanding how best to improve Breg-mediated allograft tolerance.
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Linfócitos B Reguladores , Tolerância ao Transplante , Animais , Tolerância Imunológica , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Linfócitos T ReguladoresRESUMO
In transplantation, innate immunity plays a pivotal role in immunosurveillance and host defence against microbes and neoplastic cells. Liver-resident NK cells express TNF-related apoptosis-inducing ligand (TRAIL), which distinguishes them from conventional NK cells. In this study, we investigated the impact of mTOR inhibition on liver-resident NK cells in comparison with that on splenic NK cells in a mouse model. In mice that received everolimus (EVR) for 7 days (range: 0.0125-0.25 mg/kg/day), the proportion of splenic NK cells was unchanged, whereas the number of liver NK cells including TRAIL+ NK subpopulation increased for all doses of EVR. Consistently, liver-resident NK cells from the EVR-treated mice displayed enhanced cytotoxicity against TRAIL-sensitive neoplastic cells. EVR treatment inhibited the transition of the immature subset of liver NK cells to a mature state. The negative regulator of NK cells FoxO1 was activated as a consequence of impaired mTORC2-dependent AKT phosphorylation. Activated FoxO1 both reduced T-bet expression and induced TRAIL expression, thereby inhibiting NK cell maturation and promoting the antitumour activity of the immature subset of liver NK cells in response to EVR treatment. These findings indicate that EVR treatment enhances the antitumour activity of immature liver-resident NK cells through TRAIL upregulation.
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Citotoxicidade Imunológica , Everolimo , Células Matadoras Naturais/efeitos dos fármacos , Fígado/citologia , Neoplasias/imunologia , Ligante Indutor de Apoptose Relacionado a TNF , Animais , Everolimo/farmacologia , Proteína Forkhead Box O1 , Alvo Mecanístico do Complexo 2 de Rapamicina , Camundongos , Proteínas Proto-Oncogênicas c-akt , Baço/citologia , Proteínas com Domínio TRESUMO
BACKGROUND/AIMS: Liver transplantation (LT) is promising method of treatment for hepatocellular carcinoma (HCC) patients, but is limited by donor organ shortages and tumor progression during long wait periods. This study investigated the efficacy of salvage living donor LT (LDLT) after initial liver resection (LR) in HCC patients. METHODS: Sixty patients with HCC who underwent primary LDLT (n = 45) or salvage LDLT after initial LR (n = 15) were enrolled. Significant prognostic variables determined by univariate analysis were subjected to multivariate analysis using a Cox proportional hazard regression model. Cox proportional hazards models with inverse probability of treatment weighting (IPTW) based on propensity score were used to adjust for selection bias between groups. RESULTS: The salvage group had significantly higher Child-Pugh class A (p = 0.003), ≥3 pretransplant treatments (p = 0.007), and reoperation rates for postoperative bleeding (p = 0.032) than the primary LDLT group, whereas overall and recurrence-free survival rates were comparable. After IPTW matching, the salvage LDLT group had significantly more reoperations for postoperative bleeding (hazard ratio 7.948, p = 0.017). CONCLUSIONS: First-line LR followed by salvage LDLT allows survival equal to that of primary LDLT. Salvage LDLT following primary LR could be an effective therapy.
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Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/métodos , Doadores Vivos , Terapia de Salvação/métodos , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Reoperação , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Hepatopulmonary syndrome (HPS) is a severe complication in patients with chronic liver disease with poor prognosis. Liver transplantation (LT) is a promising treatment for HPS; however, very severe HPS, which is defined by an arterial oxygen pressure (PaO2 ) of less than 50 mmHg and a right-left intrapulmonary shunt rate of more than 20%, may be a contraindication to LT, including living donor LT (LDLT). Here, we report two cases of decompensated liver cirrhosis with very severe HPS which were resolved after adult-to-adult LDLT including ABO-incompatible LDLT. Both patients required oxygen supportive therapy in combination with specialized respiratory care postoperatively, followed by improvement of oxygenation and substantial decreases of intrapulmonary shunt rate. These findings suggest very severe HPS can be resolved by LDLT, including ABO-incompatible LDLT, and reduced graft volume did not impede the reversal of intrapulmonary shunting. Our current report may indicate that adult-to-adult LDLT, including ABO-incompatible LDLT, is becoming an effective therapeutic method and prompt a review of previous reports as well as our own files with particular regard to the indication of LDLT for decompensated liver cirrhosis with very severe HPS.
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INTRODUCTION: An isolated bile leakage is a relatively rare type of postoperative bile leakage. Most isolated bile leakages require invasive procedures such as surgical approaches. PRESENTATION OF CASES: The right hepatic duct was intraoperatively injured during right anterior sectionectomy. Bile leakage occurred postoperatively in the injured bile duct, although the injured bile duct was repaired with suturing and C-tube drainage was performed to decompress the bile duct during hepatectomy. Unfortunately, nonsurgical treatment was not possible. Therefore, bilio-enteric anastomosis between the right hepatic duct and jejunum was ultimately performed because of the small remnant liver volume and poor liver function. DISCUSSION: Bilio-enteric anastomosis can avoid sacrificing functioning liver parenchyma, but in cases of hepatocellular carcinoma recurrence, transarterial chemoembolization carries a high risk of liver abscess due to cholangitis in patients undergoing enteric revision. Liver resection or bilio-enteric anastomosis should be carefully selected based on clinical data, such as remnant liver volume, liver function, and primary liver disease. CONCLUSION: We report a case of isolated bile leakage after anterior sectionectomy for hepatocellular carcinoma that was managed with Roux-en-Y hepaticojejunostomy at the injured right hepatic duct.
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INTRODUCTION: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are two primary liver cancers. Synchronous occurrence of both types is rare. Here, we present a case of synchronous, double primary liver cancer in a patient who underwent successful surgical resection. PRESENTATION OF A CASE: A 77-year-old woman presented with two suspected liver tumors. Dynamic computed tomography (CT) and ethoxybenzyl-magnetic resonance imaging revealed two lesions, one in hepatic segments S8/4 and another in S5. Positron emission tomography (PET)/CT scans revealed an elevated maximum standardized uptake value (SUVmax) of 5.7 in the S8/4 tumor, and no elevation in the S5 tumor. The S8/4 tumor was diagnosed as either ICC or mixed-type liver cancer, while the S5 tumor was confirmed HCC. Surgical resection confirmed the diagnosis, while pathology identified the S8/4 tumor as ICC and the S5 tumor as HCC. Two months post-operation, the patient received adjuvant chemotherapy and completed eight courses with no recurrence one year later. DISCUSSION: Synchronous double-primary HCC and ICC is uncommon and exhibits diagnostic and therapeutic challenges. Notably, PET-CT scans can differentiate between the two cancers, with HCC typically showing similar uptake to the background liver tissue, whereas ICC is often found with higher accumulation. This highlights the potential utility of PET/CT in preoperative diagnoses and the potential benefit of postoperative adjuvant chemotherapy in patients with double primary HCC and ICC. CONCLUSION: We report a successful case of synchronous double primary liver cancer, emphasizing the potential role of PET/CT in preoperative differentiation, and the efficacy of postoperative adjuvant chemotherapy.
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Background: Posthepatectomy liver failure (PHLF) is a serious complication associated with high mortality rates. Machine learning (ML) has rapidly developed and may outperform traditional models in predicting PHLF in patients who have undergone hepatectomy. This study aimed to predict PHLF using ML and compare its performance with that of traditional scoring systems. Methods: The clinicopathological data of 334 patients who underwent liver resection were retrospectively collected. The Pycaret library, a simple, open-source machine learning library, was used to compare multiple classification models for PHLF prediction. The predictive performance of 15 ML algorithms was compared using the mean area under the receiver operating characteristic curve (AUROC) and accuracy, and the best-fit model was selected among 15 ML algorithms. Next, the predictive performance of the selected ML-PHLF model was compared with that of routine scoring systems, the albumin-bilirubin score (ALBI) and the fibrosis-4 (FIB-4) index, using AUROC. Results: The best model was extreme gradient boosting (accuracy:93.1%; AUROC:0.863) among the 15 ML algorithms. As compared with ALBI and FIB-4, the ML PHLF model had higher AUROC for predicting PHLF. Conclusion: The novel ML model for predicting PHLF outperformed routine scoring systems.
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BACKGROUND: Tumors arising from catecholamine-producing chromophil cells in paraganglia are termed paragangliomas (PGLs), which biologically resemble pheochromocytomas (PCCs) that arise from the adrenal glands. Spontaneous rupture of a PGL is rare and can be fatal. Although elective surgery for ruptured PCCs after transcatheter arterial embolization (TAE) has been shown to provide good outcomes, the efficacy of TAE pretreatment for ruptured PGL remains unknown. CASE PRESENTATION: A 65-year-old female with hypertension and tachycardia was diagnosed with a 3-cm PGL located behind the inferior vena cava. The patient was scheduled to undergo an elective surgery with antihypertensive therapy. However, she presented with a chief complaint of abdominal pain and was diagnosed with intratumoral hemorrhage. Urgent TAE was performed that successfully achieved hemorrhage control. After TAE, serum levels of both epinephrine and norepinephrine were within the normal range. Abdominal computed tomography revealed resolving retroperitoneal hematoma. Elective open surgery was performed without significant intraoperative bleeding or fluctuations in blood pressure. CONCLUSION: We report a case of successful preoperative TAE for functional PGL to control intraoperative blood pressure fluctuations and bleeding. Preoperative TAE could be a useful procedure for the surgical preparation of functional PGL, including unruptured cases.
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Natural killer (NK) cells have immunosurveillance potential in hepatocellular carcinoma (HCC). We performed adaptive immunotherapy using donor-liver-derived natural killer (NK) cells after living-donor liver transplantation (LDLT) to prevent HCC recurrence. Dominant inhibitory signals tightly regulate NK cell activity via human leukocyte antigen (HLA)-specific inhibitory receptors, such as killer immunoglobulin-like receptors (KIRs). The functional recognition of HLA through KIR raises the NK cell capacity, which is a process termed "licensing." Here, we investigated the effect of polymorphic KIR-HLA genotypes on the efficacy of NK-cell-based immunotherapy after LDLT. Seventy-seven Japanese recipients with HCC who underwent LDLT and their corresponding donors between 1996 and 2016 were enrolled in this study. The median follow-up period was 8.3 years. The HCC recurrence risk was stratified using radiological and pathological assessments according to the Milan criteria. Of the 77 recipients, 38 received immunotherapy. Immunotherapy improves early post-transplantation survival and lowers the recurrence rate in the intermediate-risk recipients. We analyzed the genotypes of five inhibitory KIRs and HLA using sequence-specific polymorphism-based typing. The polymorphic KIR-HLA genotype revealed that genetically vulnerable liver transplant recipients with a poorly licensed NK genotype have an improved prognosis by immunotherapy with donor-liver-derived NK cells. Thus, the combination of recipient and donor KIR-HLA genotypes is worthy of attention for further investigation, especially considering the clinical application of NK-cell-based immunotherapy.
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Poor post-vaccination production of antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a concern among solid organ transplant (SOT) recipients. Furthermore, the timing and kinetics of antibody titers after the second vaccine dose are unknown. We conducted a multicenter prospective observational study that included 614 SOT recipients: 460 kidney, 53 heart, 50 liver, 20 lung, and 31 simultaneous pancreas-kidney (SPK). The participants received two doses of the mRNA vaccine (Pfizer BNT162b2 or Moderna mRNA-1273), as indicated. Serum samples were collected before the first and second vaccinations and at 1, 3, and 6 months after the second vaccine dose, which were then assessed for SARS-CoV-2 antibodies. The overall seropositivity rate was 43% at 1 month after administration of the second vaccine dose; it gradually increased to 68% at 3 months after second dose administration and to 70% at 6 months. In addition, recipient of kidney, lung or SPK transplants had lower antibody titers at the 3- and 6-month time points than did the other recipients. SOT recipients acquired SARS-CoV-2 S-IgG antibodies slowly, and the peak titer differed significantly from that of the general population.
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PURPOSE: Surgical site infection (SSI) is a frequent complication of elective surgery for colorectal cancer. The classical clinical markers of infection-elevations in white blood cell count, C-reactive protein (CRP) level, and body temperature-do not precisely predict SSI after elective colorectal resection. The objective of this study was to evaluate the efficacy of procalcitonin (PCT) as a tool for diagnosis of SSI in elective surgery for colorectal cancer. METHODS: A total of 114 consecutive patients undergoing elective colorectal resection for cancer were evaluated. Routine blood samples, for determining PCT level, CRP plasma concentration, and white blood cell count, were obtained on postoperative days (POD) 1 and 3. Predictive values for each of the laboratory markers were examined. RESULTS: SSI was diagnosed in 18 (15.7 %) of 114 patients. Patients with SSI exhibited significantly higher PCT levels (on PODs 1 and 3) and CRP levels (on POD 3) than did patients without SSI. According to receiver operating characteristic analysis, PCT showed the highest area under the curve (AUC) for predicting SSI on both PODs 1 and 3 (AUC, 0.76 and 0.77, respectively). Multivariate logistic regression analysis showed that PCT (on PODs 1 and 3) was an independent predictor for SSI (odds ratio = 14.41 and 9.79, respectively). CONCLUSION: Serum PCT is more reliable laboratory marker for the early diagnosis of SSI after elective colorectal cancer surgery, compared with conventional inflammatory indicators. PCT could serve as an additional diagnostic tool for the early identification of SSI to improve clinical decision making.
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Proteína C-Reativa/análise , Calcitonina/sangue , Colectomia/efeitos adversos , Neoplasias Colorretais/cirurgia , Precursores de Proteínas/sangue , Infecção da Ferida Cirúrgica/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Calcitonina/análise , Peptídeo Relacionado com Gene de Calcitonina , Estudos de Coortes , Colectomia/métodos , Neoplasias Colorretais/patologia , Diagnóstico Precoce , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Febre/diagnóstico , Humanos , Mediadores da Inflamação/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Precursores de Proteínas/análise , Curva ROC , Medição de Risco , Infecção da Ferida Cirúrgica/diagnóstico , Resultado do TratamentoRESUMO
Chemotherapy for advanced colorectal cancer has developed remarkably in recent years. However, medical practitioners are occasionally unwilling to initiate a standard multi-agent chemotherapy regimen for patients whose general condition is poor. We report the case of a patient with aggressively growing liver metastases and impending organ failure and symptoms who was successfully treated with the induction of anti-epidermal growth factor receptor( EGFR) antibody single- agent therapy. With the selection of some biomarkers, induction with anti-EGFR antibody single-agent therapy might be a beneficial therapeutic option for the treatment of colorectal cancer in patients with imminent organ failure and severe symptoms caused by local tumor progression.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias do Colo Sigmoide/tratamento farmacológico , Cetuximab , Progressão da Doença , Humanos , Fígado/fisiopatologia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Neoplasias do Colo Sigmoide/patologiaRESUMO
Background: Vaccination against severe acute respiratory syndrome coronavirus type 2 is highly effective in preventing infection and reducing the severity of coronavirus disease (COVID-19). However, acquired humoral immunity wanes within six months. Focusing on the different tempo of acquisition and attenuation of specific antibody titers in individuals, we investigated the impact of genetic polymorphisms on antibody production after COVID-19 vaccination. Methods: In total 236 healthcare workers from a Japanese municipal hospital, who received two doses of the vaccine were recruited. We employed a candidate gene approach to identify the target genetic polymorphisms affecting antibody production after vaccination. DNA samples from the study populations were genotyped for 33 polymorphisms in 15 distinct candidate genes encoding proteins involved in antigen-presenting cell activation, T cell activation, T-B interaction, and B cell survival. We measured total anti-SARS-Cov2 spike IgG antibody titers and analyzed the association with genetic polymorphisms at several time points after vaccination using an unbiased statistical method, and stepwise logistic regression following multivariate regression. Results: Significant associations were observed between seven SNPs in NLRP3, OAS1, IL12B, CTLA4, and IL4, and antibody titers at 3 weeks after the first vaccination as an initial response. Six SNPs in NLRP3, TNF, OAS1, IL12B, and CTLA4 were associated with high responders with serum antibody titer > 4000 BAU/ml as boosting effect at 3 weeks after the second vaccination. Analysis of long-term maintenance showed the significance of the three SNPs in IL12B, IL7R, and MIF for the maintenance of antibody titers and that in BAFF for attenuation of neutralizing antibodies. Finally, we proposed a predictive model composed of gene profiles to identify the individuals with rapid antibody attenuation by receiver operating characteristic (ROC) analysis (area under the curve (AUC)= 0.76, sensitivity = 82.5%, specificity=67.8%). Conclusions: The candidate gene approach successfully showed shifting responsible gene profiles and initial and boosting effect mainly related to the priming phase into antibody maintenance including B cell survival, which traces the phase of immune reactions. These gene profiles provide valuable information for further investigation of humoral immunity against COVID-19 and for building a strategy for personalized vaccine schedules.
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Formação de Anticorpos , COVID-19 , Humanos , Formação de Anticorpos/genética , Vacinas contra COVID-19 , Antígeno CTLA-4 , População do Leste Asiático , Proteína 3 que Contém Domínio de Pirina da Família NLR , COVID-19/genética , COVID-19/prevenção & controle , Vacinação , Anticorpos Neutralizantes , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Second warm ischemic injury during vascular anastomosis not only adversely affects immediate posttransplant function but also affects long-term patient and graft survival. We developed a pouch-type thermal barrier bag (TBB) composed of a transparent, biocompatible insulation material suitably designed for kidneys and conducted the first-in-human clinical trial. Methods: A living-donor nephrectomy was performed using a minimum skin incision procedure. After back table preparation, the kidney graft was placed inside the TBB and preserved during vascular anastomosis. The graft surface temperature was measured before and after vascular anastomosis using a noncontact infrared thermometer. After completion of the anastomosis, the TBB was removed from the transplanted kidney before graft reperfusion. Clinical data, including patient characteristics and perioperative variables, were collected. The primary endpoint was safety, which was assessed by evaluating adverse events. The secondary endpoints were the feasibility, tolerability, and efficacy of the TBB in kidney transplant recipients. Results: Ten living-donor kidney transplant recipients with a median age of 56 y (range, 39-69 y) were enrolled in this study. No serious adverse events related to the TBB were observed. The median second warm ischemic time was 31 (27-39) min, and the median graft surface temperature at the end of anastomosis was 16.1 °C (12.8-18.7 °C). Conclusions: TBB can maintain transplanted kidneys at a low temperature during vascular anastomosis, which contributes to the functional preservation of transplanted kidneys and stable transplant outcomes.
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OBJECTIVES: Although the number of kidney transplants among elderly patients has been steadily increasing, no specific recommendations have been established for treatment of elderly patients. In general, elderly recipients are considered to be at lower risk of cell rejection and require less intense immunosuppression than younger recipients. However, a recent report from Japan reported that chronic T-cell-mediated rejection was more frequent in elderly living-donor kidney transplant recipients. In this study, we investigated the effects of aging on antidonor T-cell responses in living-donor kidney transplantrecipients. MATERIALS AND METHODS: We retrospectively evaluated 70 adultliving-donor kidney transplantrecipients with negative crossmatches and cyclosporine-based immunosuppressive regimens. To evaluate antidonor T-cell responses, serial mixed lymphocyte reaction assays were performed.We compared results in elderly (≥65 years) versus nonelderly recipients. RESULTS: Regarding donor characteristics, elderly recipients were more likely than nonelderly recipients to receive a transplant from their spouse. The number of mismatches at the HLA-DRB1 loci was significantly higher in the elderly group than in the nonelderly group. As a result, the proportion of patients with antidonor hyporesponsiveness in the elderly group did not increase over the postoperative course. CONCLUSIONS: Antidonor T-cell responses in elderly living-donor kidney transplant recipients were not attenuated over time. Thus, caution is required regarding the imprudent reduction of immunosuppressants in elderly living-donor kidney transplant recipients. A rigorously designed, large-scale, prospective study is required to validate these results.
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Transplante de Rim , Humanos , Idoso , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Estudos Retrospectivos , Linfócitos T , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Imunossupressores/efeitos adversos , Doadores Vivos , TransplantadosRESUMO
BACKGROUND: Risk prediction of de novo donor-specific antibody (dnDSA) formation is crucial for understanding the long-term prognostic impact of kidney transplantation (KT). Recently, follicular helper T (Tfh) cells, a subtype of CD4+ T cells, have been reported to play an important role in dnDSA formation after solid organ transplantation. Given the growing recognition of the importance of Tfh cells in generating a strong humoral immune response, we examined whether polymorphisms in Tfh cell-related molecules were associated with dnDSA formation after KT. METHODS: Eighty-three patients who underwent living-donor KT between January 2013 and February 2020 at Hiroshima University Hospital were included in the study. Six Tfh cell-related molecules (BCL6, CXCR5, CXCL13, ICOS, CD40L, and IL21) that are important for Tfh cell differentiation and maturation in secondary lymphoid tissues were investigated. CTLA4, which is important for Tfh-cell activation, was also investigated. Single nucleotide polymorphisms (SNPs) in the genes for these molecules were detected using Taq Man SNP genotyping and evaluated for their association with dnDSA formation after KT. RESULTS: Of the 83 KT recipients, 8 developed dnDSAs during the observation period. No statistically significant differences were observed in the baseline characteristics between patients with and without dnDSA formation, except for donor age. Among the 7 Tfh cell-related molecules, the incidence of dnDSA formation was associated with CXCR5 and CTLA4 SNPs. Furthermore, combining these 2 SNPs enabled more significant stratification of dnDSA formation. CONCLUSION: Our findings indicate that genetic polymorphisms in Tfh cell-related molecules are predisposing factors for dnDSA formation after KT.
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Transplante de Rim , Masculino , Humanos , Transplante de Rim/efeitos adversos , Células T Auxiliares Foliculares , Formação de Anticorpos , Antígeno CTLA-4 , Linfócitos T Auxiliares-Indutores , Anticorpos , Polimorfismo GenéticoRESUMO
BACKGROUND: Splenectomy is sometimes indicated for portal hypertension caused by cirrhosis, which is a risk for hepatic carcinogenesis. This study aimed to identify risk factors for hepatocellular carcinoma (HCC) development after splenectomy. METHODS: This retrospective study included 65 patients who underwent splenectomy for portal hypertension between 2009 and 2017. Cox regression analyses were performed to identify factors related to HCC development after splenectomy. The predictive index for HCC development was constructed from the results of multivariate analysis, and 3 risk-dependent groups were defined. Discrimination among the groups was estimated using Kaplan-Meier curves and the log-rank test. RESULTS: Post-splenectomy, 36.9% of patients developed HCC. In the univariate analysis, the etiology of cirrhosis (hepatitis C virus antibody, P = .005, and hepatitis B surface antigen, P = .008, referring to non-B and non-C patients, respectively), presence of HCC history (P < .001), and preoperative hemoglobin level (P = .007) were related to HCC development, and the presence of HCC history (P = .002) and preoperative hemoglobin level (P = .022) were independent risk factors. The predictive index classified three groups at risk; the hazards in each group were significantly different (low vs middle risk, P = .035, and middle vs high risk, P = .011). DISCUSSION: The etiology of cirrhosis, presence of HCC history, and hemoglobin level were associated with HCC development after splenectomy. The predictive model may aid in HCC surveillance after splenectomy for patients with portal hypertension.