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1.
Langenbecks Arch Surg ; 408(1): 230, 2023 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-37301803

RESUMO

PURPOSE: Superficial surgical site infections (SSI) are a common complication after abdominal surgery. Additionally, multidrug-resistant organisms (MDRO) have shown an increasing spread in recent years with a growing importance for health care. As there is varying evidence on the importance of MDRO in different surgical fields and countries as causative agents of SSI, we report our findings of MDRO-caused SSI. METHODS: We assembled an institutional wound register spanning the years 2015-2018 including all patients with abdominal surgery and SSI only, including demographics, procedure-related data, microbiological data from screenings, and body fluid samples. The cohort was examined for the frequency of different MDRO in screenings, body fluids, and wound swabs and assessed for risk factors for MDRO-positive SSI. RESULTS: A total of 138 out of 494 patients in the register were positive for MDRO, and of those, 61 had an MDRO isolated from their wound, mainly multidrug-resistant Enterobacterales (58.1%) followed by vancomycin-resistant Enterococcus spp. (19.7%). As 73.2% of all MDRO-carrying patients had positive rectal swabs, rectal colonization could be identified as the main risk factor for an SSI caused by a MDRO with an odds ratio (OR) of 4.407 (95% CI 1.782-10.896, p = 0.001). Secondly, a postoperative ICU stay was also associated with an MDRO-positive SSI (OR 3.73; 95% CI 1.397-9.982; p = 0.009). CONCLUSION: The rectal colonization status with MDRO should be taken into account in abdominal surgery regarding SSI prevention strategies. Trial registration Retrospectively registered in the German register for clinical trials (DRKS) 19th December 2019, registration number DRKS00019058.


Assuntos
Infecção da Ferida Cirúrgica , Enterococos Resistentes à Vancomicina , Humanos , Infecção da Ferida Cirúrgica/epidemiologia , Farmacorresistência Bacteriana Múltipla , Reto/cirurgia , Fatores de Risco , Antibacterianos
2.
BMC Nephrol ; 23(1): 37, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-35042452

RESUMO

BACKGROUND: The aim of the study was to investigate the effect of recipient obesity on the short- and long-term outcomes of patients undergoing primary kidney transplantation (KT). PATIENTS AND METHODS: A total of 578 patients receiving primary KT in our department between 1993 and 2017 were included in the study. Patients were divided according to their body mass index (BMI) into normal weight (BMI 18.5-24.9 kg/m2; N = 304), overweight (BMI 25-29.9 kg/m2; N = 205) and obese (BMI ≥ 30 kg/m2; N = 69) groups. Their clinicopathological characteristics, outcomes, and survival rates were analyzed retrospectively. RESULTS: Obesity was associated with an increased rate of surgical complications such as wound infection (P < 0.001), fascial dehiscence (P = 0.023), and lymphoceles (P = 0.010). Furthermore, the hospital stay duration was significantly longer in the groups with obese patients compared to normal weight and overweight patients (normal weight: 22 days, overweight: 25 days, and obese: 33 days, respectively; P < 0.001). Multivariate analysis showed that recipient obesity (BMI ≥ 30) was an independent prognostic factor for delayed graft function (DGF) (OR 2.400; 95% CI, 1.365-4.219; P = 0.002) and postoperative surgical complications (OR 2.514; 95% CI, 1.230-5.136; P = 0.011). The mean death-censored graft survival was significantly lower in obese patients (normal weight: 16.3 ± 0.6 years, overweight: 16.3 ± 0.8 years, obese 10.8 ± 1.5 years, respectively; P = 0.001). However, when using the Cox proportional hazards model, the association between recipient obesity and death-censored renal graft failure disappeared, after adjustment for important covariates, whereas the principal independent predictors of graft loss were recipient diabetes mellitus and hypertension and kidneys from donors with expanded donor criteria. CONCLUSION: In conclusion, obesity increases the risk of DGF and post-operative surgical complications after primary KT. Appropriate risk-adapted information concerning this must be provided to such patients before KT. Furthermore, obesity-typical concomitant diseases seem to negatively influence graft survival and need to be considered after the transplantation of obese patients.


Assuntos
Transplante de Rim , Obesidade/complicações , Complicações Pós-Operatórias/etiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
3.
Ann Surg Oncol ; 28(4): 2030-2034, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33000370

RESUMO

BACKGROUND: Laparoscopic liver resection for perihilar cholangiocarcinoma (pCCA) is still in its infancy. The biliary-enteric reconstruction represents one of the most delicate parts of this minimally invasive procedure. METHODS: In this study, a 78-year old woman with perihilar cholangiocarcinoma (pCCA) type 3b underwent a hepaticojejunostomy performed by a parachute technique. RESULTS: The operation, performed totally by minimally invasive resections, was completed in 386 min, with a blood loss of less than 400 ml and no transfusion requirements. Two intraluminal stents were placed during the hepaticojenunostomy for splinting of the biliary-enteric anastomosis. The patient required prolonged antibiotic treatment for postoperative cholangitis and finally was discharged on postoperative day 15. The histopathologic grading displayed a G 2-3 adenocarcinoma, pT3 pN0, M0, L1, V1, pN1, UICC IIIc R0, and the patient was referred to adjuvant chemotherapy. CONCLUSION: Resections of pCCAs, performed totally by minimally invasive techniques, may be feasible and safe for a selected group of patients. With this approach, a running-suture hepaticojejunostomy using the parachute technique represents a worthwhile strategy for biliary-enteric reconstruction.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Laparoscopia , Idoso , Anastomose Cirúrgica , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiocarcinoma/cirurgia , Feminino , Hepatectomia , Humanos , Tumor de Klatskin/cirurgia , Fígado/cirurgia
4.
Health Qual Life Outcomes ; 18(1): 303, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32912255

RESUMO

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPKT) profoundly improves the health-related quality of life (HRQoL) of recipients. However, the influence of the pre-transplant dialysis modality on the success of the SPKT and post-transplant HRQoL remains unknown. METHODS: We analyzed the surgical outcome, long-term survival, as well as HRQoL of 83 SPKTs that were performed in our hospital between 2000 and 2016. Prior to transplant, 64 patients received hemodialysis (HD) and nineteen patients received peritoneal dialysis (PD). Physical and mental quality of life results from eight basic scales and the physical and mental component summaries (PCS and MCS) were measured using the Short Form 36 (SF-36) survey. RESULTS: Peri- and postoperative complications, as well as patient and graft survival were similar between the two groups. Both groups showed an improvement of HRQoL in all SF-36 domains after transplantation. Compared with patients who received HD before transplantation, PD patients showed significantly better results in four of the eight SF-36 domains: physical functioning (mean difference HD - PD: - 12.4 ± 4.9, P = < 0.01), bodily pain (- 14.2 ± 6.3, P < 0.01), general health (- 6.3 ± 2.8, P = 0.04), vitality (- 6.8 ± 2.6, P = 0.04), and PCS (- 5.2 ± 1.5, P < 0.01) after SPKT. In the overall study population, graft loss was associated with significant worsening of the HRQoL in all physical components (each P < 0.01). CONCLUSIONS: The results of this analysis show that pre-transplant dialysis modality has no influence on the outcome and survival rate after SPKT. Regarding HRQoL, patients receiving PD prior to SPKT seem to have a slight advantage compared with patients with HD before transplantation.


Assuntos
Transplante de Rim/mortalidade , Transplante de Pâncreas/mortalidade , Cuidados Pré-Operatórios/métodos , Qualidade de Vida , Adulto , Feminino , Sobrevivência de Enxerto , Humanos , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Transplante de Pâncreas/métodos , Diálise Peritoneal/estatística & dados numéricos , Inquéritos e Questionários
5.
Acta Chir Belg ; 120(4): 250-256, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30975040

RESUMO

Purpose: There is evidence from various surgical specialties that incisional negative pressure wound therapy (iNPWT) might reduce postoperative surgical site infections (SSIs). In visceral and general surgery, there is varying evidence of its efficacy in reducing surgical site infections.Methods: A prospectively registered patient cohort of 43 patients with abdominal wall and visceral surgery received treatment with iNPWT and was compared to a matched retrospective cohort to analyze its effects on SSI occurrence and respective risk factors. Groups were matched by procedure, sex, body mass index and age. We used two different systems of iNPWT: (i) PREVENATM or (ii) self-made epicutaneous iNPWT from common VAC material.Results: We could not find a total reduction in postoperative SSIs by application of iNPWT. But within the iNPWT cohort, patients with self-made iNPWT suffered more often from SSIs compared to the commercial iNPWT subgroup. No patient specific risk factors could be identified to advocate the use of iNPWT.Conclusion: Our data do not support the use of an incisional negative pressure wound therapy on closed wounds in midline laparotomy incisions. Although, differences exist between the commmercial and self-made systems.


Assuntos
Tratamento de Ferimentos com Pressão Negativa/métodos , Infecção da Ferida Cirúrgica/terapia , Cicatrização , Parede Abdominal , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Laparotomia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
6.
Ann Surg ; 270(2): 333-339, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-29958229

RESUMO

OBJECTIVE: To investigate trends in long-term graft and patient outcomes following liver transplantation using grafts from donors ≥60 years old. SUMMARY BACKGROUND DATA: The scarcity of donor livers has led to increased utilization of organs from donors ≥60 years old. However, few studies have examined how long-term transplant outcomes from older donors have evolved over time. METHODS: The OPTN/UNOS database was queried for all first-time isolated adult liver transplants. We identified 14,796 adult liver transplant using donors ≧60-year-old suitable for analysis from 1990 to 2014. Cohorts were then developed based on 5-year intervals of transplant date. Kaplan-Meier analysis was used to compare graft and patient survival for recipients from older donor across each 5-year era. RESULTS: Utilization of donor grafts ≥60 years old increased steadily for the first 15 years of the study, but has leveled off over the last 10 years. Comparison of the earliest and latest eras in the study was notable for an increase in median recipient age (51 vs. 59, P < 0.001) and reduction in median cold ischemic time (10 vs. 6 h, P = 0.001). Unadjusted 5-year graft and patient survival has improved significantly over time (P < 0.0001). More importantly, the discrepancy in survival between older and younger grafts has narrowed substantially over time (P < 0.0001). CONCLUSIONS: This study demonstrates significant improvement in transplant outcomes with donor grafts ≥60-years old and supports increased but judicious use of extended criteria donors liver grafts. Improved patient selection and reduction in cold ischemia time appear to be contributing factors.


Assuntos
Hepatopatias/cirurgia , Transplante de Fígado/métodos , Seleção de Pacientes , Sistema de Registros , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/métodos , Fatores Etários , Idoso , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Hepatopatias/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia
7.
Liver Transpl ; 25(4): 610-626, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30734488

RESUMO

Machine preservation (MP) has emerged as a promising technology in liver transplantation, but the cellular processes occurring during MP have not been characterized. Recent studies have noted the presence of inflammatory molecules generated during MP. We hypothesized that there is a metabolism-dependent accumulation of damage-associated molecular patterns (DAMPs) and inflammatory cytokines during MP and that these molecules provoke inflammation in the graft. To stratify groups by metabolic rate, MP was performed on rat livers from standard donors at 3 different temperatures: room temperature (RT), subnormothermic (30°C), and normothermic (37°C). Static cold storage at 4°C was included as a reference group. Following a 4-hour preservation period, graft reperfusion was performed ex vivo at 37°C (n = 6 for all groups). Levels of DAMPs and inflammatory cytokines were measured, and their biological activity was assessed by determining toll-like receptor (TLR) stimulation, inflammatory gene expression, and activation of cell death pathways. There was a time-dependent increase in levels of DAMPs during MP with high-mobility group box 1 and extracellular DNA levels increasing for all groups (P < 0.05, 30 versus 240 minutes). Tumor necrosis factor α levels in the perfusate also increased during MP for all groups (P < 0.05, 30 minutes versus 240 minutes). Levels of inflammatory molecules correlated with increased activation of TLRs (TLR3, P = 0.02, normothermic machine preservation [MP37] versus machine preservation at room temperature [MPRT]; TLR9, P = 0.02, MP37 versus MPRT). Priming of the NLRP3 inflammasome and activation of cell death pathways were reduced in grafts preserved by MP at room temperature. In conclusion, inflammatory molecules produced during MP have a biological impact on the graft. Therapies to attenuate DAMP-mediated inflammation during MP may further enhance this promising technology.


Assuntos
Alarminas/metabolismo , Transplante de Fígado , Preservação de Órgãos/efeitos adversos , Perfusão/efeitos adversos , Traumatismo por Reperfusão/imunologia , Alarminas/imunologia , Aloenxertos/irrigação sanguínea , Aloenxertos/imunologia , Aloenxertos/patologia , Animais , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Inflamassomos/imunologia , Inflamassomos/metabolismo , Fígado/irrigação sanguínea , Fígado/imunologia , Fígado/patologia , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Preservação de Órgãos/instrumentação , Preservação de Órgãos/métodos , Perfusão/instrumentação , Perfusão/métodos , Ratos , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Transdução de Sinais/imunologia , Temperatura , Receptores Toll-Like/imunologia , Receptores Toll-Like/metabolismo
8.
Exp Lung Res ; 45(7): 200-208, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31298956

RESUMO

Aim: The aim of this study was to investigate the short-term effect of levofloxacin on the microbiota of healthy lungs. Material and methods: Male F344 rats received either no levofloxacin (n = 9), intravenous levofloxacin (n = 12), oral levofloxacin (n = 12), or subcutaneous levofloxacin (n = 14). Rats received a clinically applicable dose (5.56 mg/kg) of levofloxacin via the assigned delivery route once daily for three days. On day four, lung tissue was collected and the lung microbiota composition was investigated using 16S ribosomal RNA gene sequencing. Results: Untreated lungs showed a microbiota dominated by bacteria of the genera Serratia. After treatment with levofloxacin, bacteria of the genus Pantoea dominated the lung microbiota. This was observed for all routes of antibiotic administration, with a significant difference compared to no-antibiotic control group (PERMANOVA: P < 0.001; homogeneity of dispersions: P = 0.656). Conclusion: Our study is the first to demonstrate the effects of levofloxacin therapy on lung microbiota in laboratory rats. Levofloxacin treatment by any route of administration leads to profound changes in the rat lung microbiota, resulting in the predominance of bacteria belonging to the genus Pantoea. Further studies regarding the role of long-term application of broad spectrum antibiotics on induction of lung, allergic and autoimmune diseases are indicated.


Assuntos
Antibacterianos/efeitos adversos , Levofloxacino/efeitos adversos , Pulmão/microbiologia , Microbiota/efeitos dos fármacos , Animais , Avaliação Pré-Clínica de Medicamentos , Pulmão/efeitos dos fármacos , Masculino , Ratos Endogâmicos F344
9.
BMC Nephrol ; 20(1): 453, 2019 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-31815616

RESUMO

BACKGROUND: The effects of Simultaneous Pancreas Kidney Transplantation (SPKT) on Peripheral Vascular Disease (PVD) warrants additional study and more target focus, since little is known about the mid- and long-term effects on the progression of PVD after transplantation. METHODS: 101 SPKT and 26 Kidney Transplantation Alone (KTA) recipients with insulin-dependent diabetes mellitus (IDDM) were retrospectively evaluated with regard to graft and metabolic outcome. Special subgroup analysis was directed towards the development and progression of peripheral vascular complications (PVC) (amputation, ischemic ulceration, lower extremity angioplasty/ bypass surgery) after transplantation. RESULTS: The 10-year patient survival was significantly higher in the SPKT group (SPKT: 82% versus KTA 40%; P < 0.001). KTA recipients had a higher prevalence of atherosclerotic risk factors, including coronary artery disease (P < 0.001), higher serum triglyceride levels (P = 0.049), higher systolic (P = 0.03) and diastolic (P = 0.02) blood pressure levels. The incidence of PVD before transplantation was comparable between both groups (P = 0.114). Risk factor adjusted multivariate analysis revealed that patients with SPKT had a significant lower amount (32%) of PVCs (32 PVCs in 21 out of 101 SPKT; P < 0.001) when compared to the KTA patients who developed a significant increase in PVCs to 69% of cases (18 PVCs in 11 out of 26 KTA; P < 0.001). In line mean values of HbA1c (P < 0.01) and serum triglycerides (P < 0.01) were significantly lower in patients with SPKT > 8 years after transplantation. CONCLUSION: SPKT favorably slows down development and progression of PVD by maintaining a superior metabolic vascular risk profile in patients with IDDM1.


Assuntos
Transplante de Rim/mortalidade , Transplante de Rim/tendências , Transplante de Pâncreas/mortalidade , Transplante de Pâncreas/tendências , Doenças Vasculares Periféricas/mortalidade , Doenças Vasculares Periféricas/cirurgia , Adolescente , Adulto , Idoso , Criança , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/mortalidade , Diabetes Mellitus/cirurgia , Feminino , Seguimentos , Sobrevivência de Enxerto/efeitos dos fármacos , Sobrevivência de Enxerto/fisiologia , Humanos , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doenças Vasculares Periféricas/tratamento farmacológico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento , Adulto Jovem
10.
Exp Lung Res ; 44(4-5): 201-210, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30465452

RESUMO

AIM OF THE STUDY: The pulmonary microbiota is important for both normal homeostasis and the progression of disease, and may be affected by aspiration of gastric fluid. The aim of this study was to investigate changes in the lung microbiota induced by aspiration of gastric fluid in a laboratory rat model. MATERIAL AND METHODS: Using the intratracheal application method, male rats received aspiration with 0.9% normal saline (n = 11); gastric fluid (n = 24) or sterilized (gamma-irradiated) gastric fluid (n = 12) once-weekly for four weeks. On the fifth week, the animals were sacrificed, and the microbiota of the lung was assessed by 16S ribosomal RNA gene sequencing. RESULTS: Lungs without aspiration and lungs after aspiration with normal saline had similar microbial compositions, dominated by bacteria of the genera Serratia, Ralstonia and Brucella. Evaluation of the microbiota following aspiration of gastric fluid revealed a much different profile that was dominated by bacteria from the genera Romboutsia and Turicibacter and largely independent of sterilization of the gastric fluid. CONCLUSION: In a laboratory rat model, aspiration with gastric fluid caused a substantial shift of the lung microbiota that could be characterized as a shift from Proteobacteria towards Firmicutes, possibly of enteric origin. Bacteria contained in the gastric fluid are not apparently responsible for this change.


Assuntos
Pulmão/microbiologia , Microbiota , Aspiração Respiratória/microbiologia , Animais , Líquidos Corporais/microbiologia , Firmicutes/genética , Firmicutes/isolamento & purificação , Masculino , Proteobactérias/genética , Proteobactérias/isolamento & purificação , RNA Ribossômico 16S/análise , Ratos , Estômago/microbiologia
11.
Exp Lung Res ; 43(9-10): 434-438, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29252074

RESUMO

AIM OF THE STUDY: The aim of this study was to investigate a new method for visualization and quantification of intrapulmonary liquid distribution after oropharyngeal gastric fluid aspiration in mice. MATERIAL AND METHODS: Eleven mice received oropharyngeal aspiration with a gastric fluid, India ink, and saline solution. Digital imaging and pixel calculation were used to analyze intrapulmonary fluid distribution selectively. RESULTS: Digital pixel analysis and orophanryngeal aspiration are both safe techniques in mice and deliver reproducible/valid results. Analysis revealed an average aspirate distribution of 86.8% of the total lung area. The proportional amount of the left lung was significantly greater than that of the right lung (P = 0.023). The lobe with the lowest mean distribution was the right lower lobe (79.2% ± 4.4%). CONCLUSION: Digital pixel calculation is a reliable method for quantitative, macroscopic evaluation of fluid distribution in the lung. This method is a useful tool for training purposes and it can be used to ensure interinvestigator reproducibility.


Assuntos
Líquidos Corporais/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Paracentese/métodos , Animais , Suco Gástrico , Camundongos , Modelos Animais , Modelos Teóricos , Orofaringe
12.
BMC Surg ; 17(1): 55, 2017 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-28490321

RESUMO

BACKGROUND: Transabdominal Preperitoneal (TAPP) and Lichtenstein operation are established methods for inguinal hernia repair in clinical practice. Meta-analyses of randomized controlled studies, comparing those two methods for repair of primary inguinal hernia, are still missing. In this study, a systematic review and meta-analysis of published randomized controlled trials was performed to compare early and long term outcomes of the two methods. METHODS: A literature search was carried out to identify randomized controlled trials, which compared TAPP and Lichtenstein repair for primary inguinal hernia. Outcome measures included duration of operation, length of hospital stay, acute postoperative and chronic pain, time to return to work, hematoma, wound infection, neuralgia, numbness, scrotal swelling, seroma and hernia recurrence. A quantitative meta-analysis was performed, using Odds Ratios (OR) or Standardized Mean Difference (SMD), and Confidence Interval (CI). RESULTS: Eight controlled randomized studies were identified suitable for the analysis. The mean duration of the operation was shorter in Lichtenstein repair (SMD = 6.79 min, 95% CI, -0.68 - 14.25), without significant difference. Comparing both techniques, patients of the laparoscopic group showed postoperatively significantly less chronic inguinal pain (OR = 0.42; 95% CI, 0.23-0.78). Analyses of the remaining outcome measures did not show any significant differences between the two techniques. CONCLUSION: The results of this analysis indicate that complication rate and outcome of both procedures are comparable. TAPP operation demonstrated only one advantage over Lichtenstein operation with significantly less chronic inguinal pain postoperatively.


Assuntos
Hérnia Inguinal/cirurgia , Laparoscopia/métodos , Dor Pós-Operatória/epidemiologia , Dor Crônica/etiologia , Humanos , Tempo de Internação , Dor Pós-Operatória/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Resultado do Tratamento
13.
Eur J Immunol ; 44(5): 1285-98, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24470136

RESUMO

Suppressory B-cell function controls immune responses and is mainly dependent on IL-10 secretion. Pharmacological manipulation of B-cell-specific IL-10 synthesis could, thus, be therapeutically useful in B-cell chronic lymphocytic leukemia, transplantation, autoimmunity and sepsis. TLR are thought to play a protagonistic role in the formation of IL-10-secreting B cells. The aim of the study was to identify the molecular events selectively driving IL-10 production in TLR9-stimulated human B cells. Our data highlight the selectivity of calcineurin inhibitors in blocking TLR9-induced B-cell-derived IL-10 transcription and secretion, while IL-6 transcription and release, B-cell proliferation, and differentiation remain unaffected. Nevertheless, TLR9-induced IL-10 production was found to be independent of calcineurin phosphatase activity and was even negatively regulated by NFAT. In contrast to TLR9-induced IL-6, IL-10 secretion was highly sensitive to targeting of spleen tyrosine kinase (syk) and Bruton's tyrosine kinase. Further analyses demonstrated increased phosphorylation of Ca(2+) /calmodulin kinase II (CaMKII) in TLR9-stimulated B cells and selective reduction of TLR9-induced secretion of IL-10 upon treatment with CaMKII inhibitors, with negligible impact on IL-6 levels. Altogether, our results identify calcineurin antagonists as selective inhibitors of IL-10 transcription and syk/Bruton´s tyrosine kinase-induced Ca(2+) /calmodulin- and CaMKII-dependent signaling as a pathway regulating the release of TLR9-induced B-cell-derived IL-10.


Assuntos
Subpopulações de Linfócitos B/imunologia , Sinalização do Cálcio/fisiologia , Interleucina-10/imunologia , Receptor Toll-Like 9/imunologia , Transcrição Gênica/fisiologia , Tirosina Quinase da Agamaglobulinemia , Subpopulações de Linfócitos B/citologia , Calcineurina/imunologia , Calcineurina/metabolismo , Inibidores de Calcineurina , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/antagonistas & inibidores , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/imunologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proliferação de Células , Inibidores Enzimáticos/farmacologia , Feminino , Regulação da Expressão Gênica/fisiologia , Humanos , Interleucina-10/metabolismo , Interleucina-6/biossíntese , Interleucina-6/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Fatores de Transcrição NFATC/imunologia , Fatores de Transcrição NFATC/metabolismo , Proteínas Tirosina Quinases/imunologia , Proteínas Tirosina Quinases/metabolismo , Quinase Syk
14.
Clin Transplant ; 28(1): 37-46, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24171713

RESUMO

This is the first matched pair analysis on the puzzling clinical problem of whether to perform liver transplantation (LT) or liver resection (LR) for Child's A hepatocellular carcinoma (HCC) patients. A total of 201 patients diagnosed with HCC and Child's A liver cirrhosis were treated with LT transarterial chemoembolization (TACE) or LR between 1998 and 2012. To achieve the most accurate study design, two groups of 57 patients were matched retrospectively according to their tumor characteristics detected by the initial computerized tomography (CT) scan. Sixteen of 57 LT candidates were not transplanted due to tumor progress during pre-treatment (TACE). Nevertheless, the retrospective analysis of the matched pairs according to the intention-to-treat principle resulted in a better five-yr overall survival (OS) rate of 54.3% for the group of LT candidates compared with 35.7% for those receiving LR (p = 0.19). In patients meeting the University of California, San Francisco (UCSF) criteria, five-yr OS reached 58.4% after LT and 45.1% after LR (p = 0.56). For Milan criteria (MC) patients, LT resulted in 57.9% and LR in 42% five-yr OS rate (p = 0.29). In conclusion, the finding of a better OS rate in LT was not statistically significant. There was also a selection bias in favor of LT, which may have influenced the OS. Therefore, particularly in regard to organ scarcity, LR remains a viable treatment option for respectable HCC in Child's A cirrhosis.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Análise de Intenção de Tratamento , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Feminino , Seguimentos , Humanos , Cirrose Hepática/mortalidade , Neoplasias Hepáticas/mortalidade , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida
15.
Transplant Proc ; 55(7): 1521-1529, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37385839

RESUMO

BACKGROUND: The objective of this study was to evaluate the influence of recipient underweight on the short- and long-term outcomes of patients undergoing primary kidney transplantation (KT). PATIENTS AND METHODS: Three hundred thirty-three patients receiving primary KT in our department between 1993 and 2017 were included in the study. Patients were divided according to their body mass index (BMI) into underweight (BMI <18.5 kg/m2; N = 29) and normal weight (BMI 18.5-24.9 kg/m2; N = 304) groups. Clinicopathological characteristics, postoperative outcomes, and graft and patient survival were analyzed retrospectively. RESULTS: The postoperative rate of surgical complications and renal function were comparable between the groups. One year and 3 years after KT, 70% and 92.9%, respectively, of the pre-transplant underweight patients reached a normal BMI (≥18.5 kg/m2). The mean death-censored graft survival was significantly lower in pre-transplant underweight patients than in pre-transplant normal-weight patients (11.5 ± 1.6 years vs 16.3 ± 0.6 years, respectively; P = .045). Especially KT recipients with a moderate or severe pre-transplant underweight (BMI <17 kg/m2; N = 8) showed an increased rate of graft loss (5- and 10-year graft survival: 21.4% each). No statistical difference could be observed between the 2 groups regarding causes of graft loss. In multivariate analysis, recipient underweight (P = .024) remained an independent prognostic factor for graft survival. CONCLUSION: Being underweight did not affect the early postoperative outcome after primary KT. However, underweight, and especially moderate and severe thinness, is associated with reduced long-term kidney graft survival, and therefore this group of patients should be monitored with special attention.


Assuntos
Sobrevivência de Enxerto , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Magreza/complicações , Magreza/diagnóstico , Obesidade/complicações , Estudos Retrospectivos , Transplantados , Resultado do Tratamento , Índice de Massa Corporal , Fatores de Risco
16.
J Clin Med ; 12(6)2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36983103

RESUMO

BACKGROUND: The aim of our study was to analyze perioperative lactate levels and their predictive value for postoperative mortality and morbidity after liver resection. METHODS: The clinicopathological characteristics and outcomes of 152 patients who underwent liver resection for benign and malign diagnoses were analyzed retrospectively. Lactate concentrations at three different time points, (1) before liver resection (LAC-PRE), (2) after liver resection on day 0 (LAC-POST), and (3) on day one after the operation (LAC-POD1) were assessed regarding the prognostic value in predicting postoperative complications and mortality according to the Clavien-Dindo (CD) classification. RESULTS: The rates of postoperative complications (CD ≥ IIIb) and mortality rates were 19.7% (N = 30) and 4.6% (N = 7), respectively. The LAC-PRE levels showed no correlation with the postoperative outcome. The ROC curve analysis showed that LCT-POST and LCT-POD1 values were moderately strong in predicting postoperative morbidity (0.681 and 0.768, respectively) and had strong predictive accuracies regarding postoperative mortality (0.800 and 0.838, respectively). The multivariate analysis revealed LAC-POST as a significant predictor of postoperative complications (CD ≥ IIIb: OR 9.28; 95% CI: 2.88-29.9; p < 0.001) and mortality (OR 11.69; 95% CI: 1.76-77.7; p = 0.011). CONCLUSION: Early postoperative lactate levels are a useful and easily practicable predictor of postoperative morbidity and mortality in patients after liver resection.

17.
Hepatobiliary Surg Nutr ; 12(2): 183-191, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37124699

RESUMO

Background: Microvascular invasion (MVI) can only be assessed on a full surgical specimen. We aimed at evaluating, whether the histology of the primary tumor is predictive of MVI in a hepatocellular carcinoma (HCC) recurrence. Methods: Patients, who underwent liver resection or orthotopic liver transplantation (OLT) for recurrent HCC from January 2001 until June 2018 were eligible for this retrospective analysis. Resected specimens were evaluated for HCC subtype/morphology, vessels encapsulating tumor clusters (VETC)-pattern and MVI. Dichotomous parameters were analyzed using χ2-test and ϕ-values, with P values <0.05 being considered significant. Results: Of 230 HCC recurrences, 37 (16.1%) underwent repeated liver resection (n=22) or OLT (n=15). Of these, 67.6% initially exceeded the Milan criteria. MVI correlated Milan criteria (P=0.005), tumor size (P=0.015) and VETC-pattern (P=0.034) in the primary specimen. The recurrences shared many features of the primary HCC such as tumor grade (P=0.002), VETC-pattern (P=0.035), and MVI (P=0.046). In recurrences, however, only the concordance with the Milan criteria correlated with MVI (P=0.018). No patient without MVI in the primary HCC revealed MVI on early recurrence (<2 years) (P=0.035). Conclusions: HCC recurrences share many biological features of the primary tumor. Moreover, early recurrences of MVI-negative HCC never revealed MVI. This finding offers novel concepts, e.g., patient selection for salvage OLT.

18.
Hepatobiliary Surg Nutr ; 11(1): 67-77, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35284501

RESUMO

Background: The most common causes of early graft loss in pancreas transplantation are insufficient blood supply and leakage of the intestinal anastomosis. Therefore, it is critical to monitor graft perfusion and oxygenation during the early post-transplant period. The goal of our pilot study was to evaluate the utility of hyperspectral imaging (HSI) in monitoring the microcirculation of the graft and adequate perfusion of the intestinal anastomosis during pancreatic allotransplantation. Methods: We imaged pancreatic grafts and intestinal anastomosis in real-time in three consecutive, simultaneous pancreas-kidney transplantations using the TIVITA® HSI system. Further, the intraoperative oxygen saturation (StO2), tissue perfusion (near-infrared perfusion index, NIR), organ hemoglobin index (OHI), and tissue water index (TWI) were measured 15 minutes after reperfusion by HSI. Results: All pancreas grafts showed a high and homogeneous StO2 (92.6%±10.45%). Intraoperative HSI analysis of the intestinal anastomosis displayed significant differences of StO2 (graft duodenum 67.46%±5.60% vs. recipient jejunum: 75.93%±4.71%, P<0.001) and TWI {graft duodenum: 0.63±0.09 [I (Index)] vs. recipient jejunum: 0.72±0.09 [I], P<0.001}. NIR and OHI did not display remarkable differences {NIR duodenum: 0.68±0.06 [I] vs. NIR jejunum: 0.69±0.04 [I], P=0.747; OHI duodenum: 0.70±0.12 [I] vs. OHI jejunum: 0.68±0.13 [I], P=0.449}. All 3 patients had an uneventful postoperative course with one displaying a Banff 1a rejection which was responsive to steroid treatment. Conclusions: Our study shows that contact-free HSI has potential utility as a novel tool for real-time monitoring of human pancreatic grafts after reperfusion, which could improve the outcome of pancreas transplantation. Further investigations are required to determine the predictive value of intraoperative HSI imaging.

19.
J Gastrointest Surg ; 26(2): 444-452, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34661870

RESUMO

BACKGROUND: Superficial surgical site infections (SSSIs) are a major reason for morbidity after abdominal surgery. Microbiologic isolates of SSSIs vary widely geographically. Therefore, knowledge about the specific bacterial profile is of paramount importance to prevent SSSI. METHODS: We performed a subgroup analysis of the microbiological isolates from patients with SSSI after abdominal surgery that were included in our institutional wound register. We aimed at identifying predominant strains as well as risk factors that would predispose for SSSI with certain bacteria. RESULTS: A total of 494 patients were eligible for analysis. Of those 313 had received wound swaps, with 268 patients yielding a bacterial isolate. Enterobacterales (31.7%) and Enterococcus spp. (29.5%) were found as main bacteria in SSSI, with 62.3% of the wounds being polymicrobial. As risk factors for changes in bacterial isolates, we identified operative revision (OR 3.032; 95%CI 1.734-5.303) in multivariate analysis. Enterococcus spp. showed a significant increase in patients after revision surgery (p<0.001). Antibiotic therapy was neither influential on bacterial changes nor on the presence of Enterococcus spp. in SSSI. CONCLUSION: Our study accentuates the high frequency of Enterococcus spp. in SSSI after abdominal surgery, while identifying surgical revision as major risk factor. The results urge vigilance in the treatment of patients with surgical revisions to include Enterococcus spp. in the prevention and treatment strategies.


Assuntos
Enterococcus , Infecção da Ferida Cirúrgica , Antibacterianos/uso terapêutico , Humanos , Reoperação/efeitos adversos , Fatores de Risco , Infecção da Ferida Cirúrgica/etiologia
20.
J Clin Med ; 10(19)2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34640413

RESUMO

AIM: Complex arterial reconstruction in kidney transplantation (KT) using kidneys from deceased donors (DD) warrants additional study since little is known about the effects on the mid- and long-term outcome and graft survival. METHODS: A total of 451 patients receiving deceased donor KT in our department between 1993 and 2017 were included in our study. Patients were divided into three groups according to the number of arteries and anastomosis: (A) 1 renal artery, 1 arterial anastomosis (N = 369); (B) >1 renal artery, 1 arterial anastomosis (N = 47); and (C) >1 renal artery, >1 arterial anastomosis (N = 35). Furthermore, the influence of localization of the arterial anastomosis (common iliac artery (CIA), versus non-CIA) was analyzed. Clinicopathological characteristics, outcome, and graft and patient survival of all groups were compared retrospectively. RESULTS: With growing vascular complexity, the time of warm ischemia increased significantly (groups A, B, and C: 40 ± 19 min, 45 ± 19 min, and 50 ± 17 min, respectively; p = 0.006). Furthermore, the duration of operation was prolonged, although this did not reach significance (groups A, B, and C: 175 ± 98 min, 180 ± 35 min, and 210 ± 43 min, respectively; p = 0.352). There were no significant differences regarding surgical complications, post-transplant kidney function (delayed graft function, initial non-function, episodes of acute rejection), or long-term graft survival. Regarding the localization of the arterial anastomosis, non-CIA was an independent prognostic factor for deep vein thrombosis in multivariate analysis (CIA versus non-CIA: OR 11.551; 95% CI, 1.218-109.554; p = 0.033). CONCLUSION: Multiple-donor renal arteries should not be considered a contraindication to deceased KT, as morbidity rates and long-term outcomes seem to be comparable with grafts with single arteries and less complex anastomoses.

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