Effect of Pre-Transplant Recipient Underweight on the Postoperative Outcome and Graft Survival in Primary Kidney Transplantation.

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.

Rectal colonization is predictive for surgical site infections with multidrug-resistant bacteria in abdominal surgery.

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.

Microvascular invasion of hepatocellular carcinoma predicts microvascular invasion of its recurrence: potential implications for salvage liver transplantation?

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.

Prediction of the Postoperative Outcome in Liver Resection Using Perioperative Serum Lactate Levels.

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.

Intraoperative reperfusion assessment of human pancreas allografts using hyperspectral imaging (HSI).

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.

Recipient obesity as a risk factor in kidney transplantation.

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.

Surgical Revision Promotes Presence of Enterococcus spp. in Abdominal Superficial Surgical Site Infections.

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.

Influence of Multiple Donor Renal Arteries on the Outcome and Graft Survival in Deceased Donor Kidney Transplantation.

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.

The Value of Graft Implantation Sequence in Simultaneous Pancreas-Kidney Transplantation on the Outcome and Graft Survival.

BACKGROUND/OBJECTIVES: The sequence of graft implantation in simultaneous pancreas-kidney transplantation (SPKT) warrants additional study and more targeted focus, since little is known about the short- and long-term effects on the outcome and graft survival after transplantation. MATERIAL AND METHODS: 103 patients receiving SPKT in our department between 1999 and 2015 were included in the study. Patients were divided according to the sequence of graft implantation into pancreas-first (PF, n = 61) and kidney-first (KF, n = 42) groups. Clinicopathological characteristics, outcome and survival were reviewed retrospectively. RESULTS: Donor and recipient characteristics were similar. Rates of post-operative complications and graft dysfunction were significantly higher in the PF group compared with the KF group (episodes of acute rejection within the first year after SPKT: 11 (18%) versus 2 (4.8%); graft pancreatitis: 18 (18%) versus 2 (4.8%), p = 0.04; vascular thrombosis of the pancreas: 9 (14.8%) versus 1 (2.4%), p = 0.03; and delayed graft function of the kidney: 12 (19.6%) versus 2 (4.8%), p = 0.019). The three-month pancreas graft survival was significantly higher in the KF group (PF: 77% versus KF: 92.1%; p = 0.037). No significant difference was observed in pancreas graft survival five years after transplantation (PF: 71.6% versus KF: 84.8%; p = 0.104). Kidney graft survival was similar between the two groups. Multivariate analysis revealed order of graft implantation as an independent prognostic factor for graft survival three months after SPKT (HR 2.6, 1.3-17.1, p = 0.026) and five years (HR 3.7, 2.1-23.4, p = 0.040). CONCLUSION: Our data indicates that implantation of the pancreas prior to the kidney during SPKT has an influence especially on the early-post-operative outcome and survival rate of pancreas grafts.

Total Laparoscopic Resection of Hilar Cholangiocarcinoma Type 3b: Applying a Parachute Technique for Hepaticojejunostomy.

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.

Impact of pre-transplant dialysis modality on the outcome and health-related quality of life of patients after simultaneous pancreas-kidney transplantation.

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.

Sirtuin-1 expression and activity is diminished in aged liver grafts.

The cellular mechanisms underlying impaired function of aged liver grafts have not been fully elucidated, but mitochondrial dysfunction appears to be contributory. Sirtuin1 has been identified as a key mediator of mitochondrial recovery following ischemia-reperfusion injury. The purpose of this study was to determine whether differences exist in sirtuin-1 expression/activity in old vs. young liver grafts and to determine correlations with mitochondrial function, graft metabolic function, and graft injury. Old and young rat liver grafts (N = 7 per group) were exposed to 12 h of static cold storage (SCS), followed by a 2 h period of graft reperfusion ex vivo. Sirtuin1 expression and activity, mitochondrial function, graft metabolic function, and graft injury were compared. Sirtuin1 expression is upregulated in young, but not old, liver grafts in response to cold storage and reperfusion. This is associated with diminished tissue ATP, antioxidant defense, and graft metabolic function in old liver grafts. There was no evidence of increased inflammation or histologic injury in old grafts. Sirtuin1 expression is diminished in old liver grafts and correlates with mitochondrial and metabolic function. The sirtuin pathway may represent a target for intervention to enhance the function of aged liver grafts.

Donor Leukocyte Trafficking and Damage-associated Molecular Pattern Expression During Ex Vivo Lung Perfusion.

BACKGROUND: While ex vivo lung perfusion (EVLP) has become established in lung transplantation, the cellular processes occurring during this period are not yet fully understood. Prior studies demonstrated that donor leukocytes (DLs) migrate from the graft into the perfusate during EVLP, but the distribution of DLs in graft and perfusate compartments has not been characterized. Moreover, cell death of DLs has been implicated in mediating graft injury during EVLP, but the underlying mechanisms have not been elucidated. We hypothesized the following: (1) there is a nonspecific migration of DLs from the graft into perfusate and (2) cell death of DLs releases damage-associated molecular patterns (DAMPs) that contribute to the inflammatory milieu during EVLP. METHODS: EVLP was performed on rat lungs for 3 hours (N = 6). At the end of EVLP, flow cytometry was used to quantify the distribution of different DL cell types in both the graft and perfusate compartments. During EVLP, the perfusate was also sampled hourly to measure levels of DAMPs and downstream inflammatory cytokines generated during EVLP. RESULTS: At the conclusion of EVLP, there was a significantly higher proportion of T and B cells present in the perfusate compartment compared with the graft compartment. There was a time-dependent increase in extracellular DNA and tumor necrosis factor α in the perfusate during EVLP. CONCLUSIONS: T cells and B cells are enriched in the perfusate compartment during EVLP. Cell death of DLs contributes to an accumulation of DAMPs during EVLP.

Incisional negative pressure wound therapy does not reduce surgical site infections in abdominal midline incisions: a case control study.

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.

Effects of simultaneous pancreas-kidney transplantation and kidney transplantation alone on the outcome of peripheral vascular diseases.

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.

Hepatitis B Vaccination in Patients with Liver Cirrhosis Evaluated for Liver Transplantation - A Simple Intervention Ensures High Adherence.

BACKGROUND There is an unmet need to improve the HBV vaccination status in patients with chronic liver diseases. Primary care physicians and outpatient hepatologists often fail to vaccinate as recommended. Thus, new strategies to improve the HBV vaccination rate are required. MATERIAL AND METHODS This study was performed in a cohort of patients with chronic liver diseases evaluated for liver transplantation. Vaccination status was taken from the patients' vaccination cards. HBsAg-, anti-HBc-, and anti-HBs-negative individuals were vaccinated against HBV at hospital discharge, and subsequent outpatient completion of the standard vaccination protocol was recommended in detail in the discharge letter. At months 2 and 8, titer controls were performed, and completion of vaccination was evaluated. RESULTS We prospectively recruited 37 patients. At baseline, the vaccination rate against HBV was 24% (N=9/37), and 3/9 HBV vaccinated patients presented with an anti-HBs-titer >10 IU/L. Thus, N=34 were vaccinated with Engerix® or Twinrix®. We evaluated 26/34 patients at month 2 and 10/26 again at month 8. The second vaccine dose was obtained by 21/26 (80%) of the patients seen at month 2, and 9/10 (90%) seen at month 8 obtained the third vaccine dose by primary care physicians or ambulant hepatologists. Only 2 patients presented with an anti-HBs-titer >10 IU/L at month 8. CONCLUSIONS Initiation of HBV vaccination during hospitalization and detailed recommendations on subsequent vaccinations in the discharge letter improve previously inadequate vaccination rates in the outpatient setting. Similar measures should be implemented at earlier time points of chronic liver diseases to achieve higher immune response rates.

Damage- and pathogen-associated molecular patterns play differential roles in late mortality after critical illness.

Multiple organ failure (MOF) is the leading cause of late mortality and morbidity in patients who are admitted to intensive care units (ICUs). However, there is an epidemiologic discrepancy in the mechanism of underlying immunologic derangement dependent on etiology between sepsis and trauma patients in MOF. We hypothesized that damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs), while both involved in the development of MOF, contribute differently to the systemic innate immune derangement and coagulopathic changes. We found that DAMPs not only produce weaker innate immune activation than counterpart PAMPs, but also induce less TLR signal desensitization, contribute to less innate immune cell death, and propagate more robust systemic coagulopathic effects than PAMPs. This differential contribution to MOF provides further insight into the contributing factors to late mortality in critically ill trauma and sepsis patients. These findings will help to better prognosticate patients at risk of MOF and may provide future therapeutic molecular targets in this disease process.

The effect of levofloxacin on the lung microbiota of laboratory rats.

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.

Machine Perfusion of Liver Grafts With Implantable Oxygen Biosensors: Proof of Concept Study in a Rodent Model.

BACKGROUND: Normothermic machine perfusion (NMP) is emerging as a novel preservation strategy in liver transplantation, but the optimal methods for assessing liver grafts during this period have not been determined. The aim of this study was to investigate whether implantable oxygen biosensors can be used to monitor tissue oxygen tension in liver grafts undergoing NMP. METHODS: Implantable phosphorescence-based oxygen sensors were tested in 3 different experimental groups: (1) in vivo during laparotomy, (2) during NMP of liver grafts with an acellular perfusate (NMP-acellular), and (3) during NMP with perfusate containing red blood cells (NMP-RBC). During in vivo experiments, intrahepatic oxygen tension was measured before and after occlusion of the portal vein (PV). In NMP experiments, intrahepatic oxygen tension was measured as a function of different PV pressure settings (3 vs 5 vs 8 mm Hg) and inflow oxygen concentration (95% O2 vs 6% O2). RESULTS: In vivo, intrahepatic oxygen tension decreased significantly within 2 minutes of clamping the PV (P < 0.05). In NMP experiments, intrahepatic oxygen tension correlated directly with PV pressure when high inflow oxygen concentration (95%) was used. Intrahepatic oxygen tension was significantly higher in the NMP-RBC group compared with the NMP-acellular group for all conditions tested (P < 0.05). CONCLUSIONS: Implantable oxygen biosensors have potential utility as a tool for real-time monitoring of intrahepatic oxygen tension during NMP of liver grafts. Further investigation is required to determine how intrahepatic oxygen tension during NMP correlates with posttransplant graft function.