Repeated kidney re-transplantation-the Eurotransplant experience: a retrospective multicenter outcome analysis.

In Eurotransplant kidney allocation system (ETKAS), candidates can be considered unlimitedly for repeated re-transplantation. Data on outcome and benefit are indeterminate. We performed a retrospective 15-year patient and graft outcome data analysis from 1464 recipients of a third or fourth or higher sequential deceased donor renal transplantation (DDRT) from 42 transplant centers. Repeated re-DDRT recipients were younger (mean 43.0 vs. 50.2 years) compared to first DDRT recipients. They received grafts with more favorable HLA matches (89.0% vs. 84.5%) but thereby no statistically significant improvement of patient and graft outcome was found as comparatively demonstrated in 1st DDRT. In the multivariate modeling accounting for confounding factors, mortality and graft loss after 3rd and ≥4th DDRT (P < 0.001 each) and death with functioning graft (DwFG) after 3rd DDRT (P = 0.001) were higher as compared to 1st DDRT. The incidence of primary nonfunction (PNF) was also significantly higher in re-DDRT (12.7%) than in 1st DDRT (7.1%; P < 0.001). Facing organ shortage, increasing waiting time, and considerable mortality on dialysis, we question the current policy of repeated re-DDRT. The data from this survey propose better HLA matching in first DDRT and second DDRT and careful selection of candidates, especially for ≥4th DDRT.

High-urgency kidney transplantation in the Eurotransplant Kidney Allocation System: success or waste of organs? The Eurotransplant 15-year all-centre survey.

BACKGROUND: In the Eurotransplant Kidney Allocation System (ETKAS), transplant candidates can be considered for high-urgency (HU) status in case of life-threatening inability to undergo renal replacement therapy. Data on the outcomes of HU transplantation are sparse and the benefit is controversial. METHODS: We systematically analysed data from 898 ET HU kidney transplant recipients from 61 transplant centres between 1996 and 2010 and investigated the 5-year patient and graft outcomes and differences between relevant subgroups. RESULTS: Kidney recipients with an HU status were younger (median 43 versus 55 years) and spent less time on the waiting list compared with non-HU recipients (34 versus 54 months). They received grafts with significantly more mismatches (mean 3.79 versus 2.42; P < 0.001) and the percentage of retransplantations was remarkably higher (37.5 versus 16.7%). Patient survival (P = 0.0053) and death with a functioning graft (DwFG; P < 0.0001) after HU transplantation were significantly worse than in non-HU recipients, whereas graft outcome was comparable (P = 0.094). Analysis according to the different HU indications revealed that recipients listed HU because of an imminent lack of access for dialysis had a significantly worse patient survival (P = 0.0053) and DwFG (P = 0.0462) compared with recipients with psychological problems and suicidality because of dialysis. In addition, retransplantation had a negative impact on patient and graft outcome. CONCLUSIONS: Facing organ shortages, increasing wait times and considerable mortality on dialysis, we question the current policy of HU allocation and propose more restrictive criteria with regard to individuals with vascular complications or repeated retransplantations in order to support patients on the non-HU waiting list with a much better long-term prognosis.

Liver transplantation followed by autologous stem cell transplantation for acute liver failure caused by AL amyloidosis. Case report and review of the literature.

 Hepatic involvement in AL amyloidosis may present as acute liver failure. Historically, liver transplantation in these cases has achieved poor outcomes due to progress of amyloidosis and non-hepatic organ damage. In the era of bortezomib treatment, the prognosis of AL amyloidosis has been markedly improved and may also result in better post-transplant outcomes. We present a case of isolated acute liver failure caused by AL amyloidosis, bridged to transplantation with bortezomib and treated with sequential orthotopic liver transplantation (OLT) and autologous stem cell transplantation. The patient is in stable remission 3 years after OLT.

Procalcitonin ratio and on-demand relaparotomy for septic peritonitis: validation of the focus index (FI).

PURPOSE: Secondary peritonitis remains challenging to manage and some recent evidence suggests that on-demand relaparotomy is more appropriate than planned relaparotomy. This study was designed to validate the predictive power of postoperative procalcitonin (PCT) changes in relation to elimination of the septic abdominal focus. METHODS: In this prospective trial, postoperative PCT serum levels were monitored in 234 surgical patients with secondary peritonitis. The PCT ratio on postoperative days (PODs) 1 and 2 (focus index; FI) was calculated and correlated with the success of the operation. RESULTS: A cutoff value of 1.1 was calculated for the FI. Values below 1.1 indicated insufficient elimination of the focus and values above 1.1 correlated with effective treatment. The optimal time for first PCT sampling was found to be 12-24 h after the index operation. After the respective data cleanup, successful elimination of the intraabdominal focus could be confirmed, with a sensitivity of 93 % and a specificity of 71 %. CONCLUSIONS: The FI is a single parameter-based reliable predictor of successful surgical eradication and strengthens the on-demand relaparotomy concept as the method of choice to treat secondary peritonitis.

Recurrence-free survival, but not surgical therapy per se, determines 583 patients' long-term satisfaction following primary pilonidal sinus surgery.

PURPOSE: With pilonidal sinus disease (PSD) incidence increasing and patients freely choosing their surgeon, patients' interest issues have been brought forward estimating patient satisfaction following pilonidal sinus surgery. The influence of wound healing time and long-term recurrence rate on patient satisfaction in primary PSD surgery has not been investigated yet. METHODS: Five hundred eighty-three patients (German military cohort) were interviewed, compiling wound healing time, aesthetic satisfaction, long-term recurrence-free survival and patient satisfaction having undergone primary open (PO) treatment, marsupialization (MARS) or primary midline closure (PMC) treatment. Recurrence rate was determined by Kaplan-Meier calculation following up to 20 years after primary PSD surgery. RESULTS: Patient satisfaction ranking from 1 to 10 (10 = max. satisfied) showed an average satisfaction of 8.2 (range 0-10; 95% confidence interval (CI) 7891-8250). In-hospital stay time was significantly longer in primary open (PO) and marsupialization (MARS) group as compared to primary midline closure (PMC; p < 0.0001, Kruskal-Wallis test). Satisfaction was comparable between treatment groups, and was neither linked to in-hospital stay time nor to longer outpatient wound care period or total treatment time. Recurrence-free survival, as seen in the PO and PMC treatment group, revealed a highly significant difference for all patients. Improvement in MARS patients with versus without recurrence was low, as satisfaction with primary treatment was lower as the other groups. CONCLUSIONS: Neither choice of surgical treatment nor treatment duration within hospital or after hospital influences patient satisfaction, as long as recurrence-free survival can be provided. Marsupialization was ranked lower in both groups (with or without recurrence), and should be abandoned, as patients are significantly less satisfied with either results, independent of recurrence.

Does Full Wound Rupture following Median Pilonidal Closure Alter Long-Term Recurrence Rate?

OBJECTIVE: The purpose of this study was to examine the recurrence rate of wound rupture in primary pilonidal sinus disease (PSD) after median closure. SUBJECTS AND METHODS: A total of 583 patients from the German military cohort were interviewed. We compared the choice of surgical therapy, wound dehiscence (if present) and long-term recurrence-free survival for patients with primary open treatment, marsupialization and primary median treatment (closed vs. secondary open, respectively). Actuarial recurrence rate was determined using the Kaplan-Meier calculation with a follow-up of up to 20 years after primary PSD surgery. RESULTS: Patients with excision followed by primary open wound treatment showed a significantly lower 5- than 10-year recurrence rate (8.3 vs. 11.2%) compared to the patients with primary midline closure (17.4 vs. 20.5%, p = 0.03). The 20-year recurrence rate was 28% in primary open wound treatment versus 44% in primary midline closure without wound rupture. In contrast to these findings, long-term recurrence rates following secondary open wound treatment (12.2% at 5 years vs. 17.1% at 10 years) tended to be higher (although not significantly, p = 0.57) compared to primary open treatment (8.3% at 5 years vs. 11.2% at 10 years). There was no statistical difference in long-term recurrence rates between secondary open and primary midline closure (p = 0.7). Hence, despite only a short wound closure time experienced before wound rupture, the patient does not fully benefit from an open wound treatment in terms of recurrence rate. CONCLUSION: The postoperative pilonidal sinus wound rupture of primary midline closures did not significantly increase the 5- and 10-year long-term recurrence rates compared to uneventfully healing primary midline closures.

Evaluation of the Hepa Wash® treatment in pigs with acute liver failure.

BACKGROUND: Mortality of patients with acute liver failure (ALF) is still unacceptably high. Available liver support systems are still of limited success at improving survival. A new type of albumin dialysis, the Hepa Wash® system, was newly introduced. We evaluated the new liver support system as well as the Molecular Adsorbent Recycling System (MARS) in an ischemic porcine model of ALF. METHODS: In the first study animals were randomly allocated to control (n=5) and Hepa Wash (n=6) groups. In a further pilot study, two animals were treated with the MARS-system. All animals received the same medical and surgical procedures. An intraparenchymal intracranial pressure was inserted. Hemodynamic monitoring and goal-directed fluid therapy using the PiCCO system was done. Animals underwent functional end-to-side portacaval shunt and ligation of hepatic arteries. Treatment with albumin dialysis was started after fall of cerebral perfusion pressure to 45 mmHg and continued for 8 h. RESULTS: All animals in the Hepa Wash group survived the 13-hour observation period, except for one that died after stopping treatment. Four of the control animals died within this period (p=0.03). Hepa Wash significantly reduced impairment of cerebral perfusion pressure (23±2 vs. 10±3 mmHg, p=0.006) and mean arterial pressure (37±1 vs. 24±2 mmHg, p=0.006) but had no effect on intracranial pressure (14±1 vs. 15±1 mmHg, p=0.72). Hepa Wash also enhanced cardiac index (4.94±0.32 vs. 3.36±0.25 l/min/m2, p=0.006) and renal function (urine production, 1850 ± 570 vs. 420 ± 180 ml, p=0.045) and eliminated water soluble (creatinine, 1.3±0.2 vs. 3.2±0.3 mg/dl, p=0.01; ammonia 562±124 vs. 1382±92 µg/dl, p=0.006) and protein-bound toxins (nitrate/nitrite 5.54±1.57 vs. 49.82±13.27 µmol/l, p=0.01). No adverse events that could be attributed to the Hepa Wash treatment were observed. CONCLUSIONS: Hepa Wash was a safe procedure and improved multiorgan system failure in pigs with ALF. The survival benefit could be the result of ameliorating different organ functions in association with the detoxification capacity of water soluble and protein-bound toxins.

The influence of lifestyle (smoking and body mass index) on wound healing and long-term recurrence rate in 534 primary pilonidal sinus patients.

PURPOSE: With pilonidal sinus disease (PSD) incidence increasing, lifestyle issues have been suspected to be responsible to worsen the results of PSD surgery at the same time. The influence of smoking and body mass index (BMI) on long-term recurrence rate in primary PSD surgery has not been investigated yet. METHODS: A total of 534 patients (German military cohort) were analyzed, comparing the wound healing rates of non-smoker with smoker, as well as recurrence rates in either groups. Simultaneously, the impact of BMI on wound healing and recurrence was studied. Recurrence rate was determined by Kaplan-Meier calculation following up to 20 years after primary PSD surgery. RESULTS: Using primary open surgery, smokers' and non-smokers' recurrence rates did not differ statistically (p = 0.83; log rank). Comparable rates occurred following the primary midline closure technique (p = 0.14; log rank). A BMI of 25 and higher was not associated with adverse wound healing neither in the primary midline closure (p = 0.14) nor in the primary open treatment group (p = 0.3); nevertheless, a trend may be seen that a BMI of 25 and above could assist a favorable wound healing rate. CONCLUSIONS: The lifestyle parameter smoking and body weight statistically do not complicate wound healing or long-term recurrence rates for the first 20 years following primary PSD surgery in this study. As the BMI of 25 and above may have a beneficial influence on wound healing in primary open and primary midline closure, this observation has to be investigated for the today's surgical procedures of elective first choice-asymmetrical and flap procedures.

Incision and drainage preceding definite surgery achieves lower 20-year long-term recurrence rate in 583 primary pilonidal sinus surgery patients.

BACKGROUND: It has long been suspected that acute infection leads to less satisfactory results in soft tissue surgery. Its influence on long-term recurrence rate in primary pilonidal sinus surgery has not been investigated yet. PATIENTS AND METHODS: 583 patients (military cohort) were analyzed, comparing an incision and drainage (I&D) group preceding surgery (n = 286 pts) with a spontaneous abscess and empyema rupture group (n = 297 pts). Long-term recurrence rate up to 25 years following surgery was determined. RESULTS: The I&D group achieved a 20 year recurrence rate of 24 %, whereas the non-I&D-group had 35 % recurrences (p = 0.0034). Analyzing the subgroup with primary open wound treatment (n = 349 pts), the I&D group did significantly better after 20 years (16 % actuarial recurrence rate versus 34 %; p = 0.009; log-rank-test). CONCLUSIONS: Early I&D treatment preceding definite surgery for some weeks seem to give significant superior results compared to primary surgery without I&D. The combination of early I&D and asymmetric excision and out of the midline closure is expected to give even further improved results compared to this cohort. The optimum interval between I&D and definite surgery has still to be determined.

High RIPK3 expression is associated with a higher risk of early kidney transplant failure.

Renal ischemia-reperfusion injury (IRI) is associated with reduced allograft survival, and each additional hour of cold ischemia time increases the risk of graft failure and mortality following renal transplantation. Receptor-interacting protein kinase 3 (RIPK3) is a key effector of necroptosis, a regulated form of cell death. Here, we evaluate the first-in-human RIPK3 expression dataset following IRI in kidney transplantation. The primary analysis included 374 baseline biopsy samples obtained from renal allografts 10 minutes after onset of reperfusion. RIPK3 was primarily detected in proximal tubular cells and distal tubular cells, both of which are affected by IRI. Time-to-event analysis revealed that high RIPK3 expression is associated with a significantly higher risk of one-year transplant failure and prognostic for one-year (death-censored) transplant failure independent of donor and recipient associated risk factors in multivariable analyses. The RIPK3 score also correlated with deceased donation, cold ischemia time and the extent of tubular injury.

Heparin-induced thrombocytopenia (HIT II) in liver transplant recipients: a retrospective multivariate analysis of prognostic factors.

We investigated the prevalence of HIT II in liver transplant recipients and analysed associated factors. In recipients with clinically suspected HIT II in the 4Ts pretest clinical scoring system HIPA-assay was performed. Next, 37 clinical variables were analysed retrospectively for their association with HIT II. Factors significantly correlated to our findings in univariate analysis were included in a multivariate model and binary logistic regression analysis. Among 46 recipients 21 patients were suspicious in the 4Ts pretest and 14 of them (30.4%) were diagnosed HIT-antibody positive. Patient's age (P = 0.001), postoperative dialysis (P = 0.028), and postoperative hospital stay (P = 0.035) were significantly associated with development of HIT-antibodies in univariate analysis. Postoperative dialysis and postoperative hospital stay turned out as epiphenomena of patient's age, the only independent predictor (P = 0.021). Using multiple χ(2) -testing, a cut-off could be calculated, assigning patients younger than 59 years to a low risk group and patients of 59 years and older to a high risk group. High incidence of peri-operative HIT II seroconversion in liver transplant recipients is not associated with factors known to induce thrombocyte activation, like blood products or cell-saver. Only patients' age was identified as independent predictor.

[Trends in incidence and long-term recurrence rate of pilonidal sinus disease and analysis of associated influencing factors].

OBJECTIVES: To investigate the trends in incidence and long-term recurrence rate of pilonidal sinus disease (PSD) within the German Armed Forces, and analyse the influence of variable factors, such as different surgical methods, body constitution and smoking amount, to incidence and long-term recurrence rate of PSD. METHODS: Information of all the patients being admitted with primary PSD to the surgical departments of three hospitals of the German Armed Forces between 1980 and 1996 was collected and analyzed, 500 patients of which were interviewed. RESULTS: Two of the 500 patients were dead, and every one of the rest 498 patients agreed to take part in the interview. The incidence of PSD rose from 0.3/1000 in 1985 to 2.4/1000 in 2007. The recurrence rates were decreasing within 16 years of treatment from 33% in 1981 via 23% in 1986 to 12% in 1996 (P = 0.01). Recurrence rates of primary open wound healing (16.8%) compared to primary suture (31.0%) differ significantly (P < 0.01). While the mean body weight within the army rose 1 kg per decade, population shows an increase of 1.9 kg per decade though not being an influencing factor on the recurrence rate (P = 0.72). Smoking of more than 20 cigarettes per day proved to be a significant factor on the recurrence rate of PSD (P = 0.015). CONCLUSION: While the recurrence rates-especially of primary open wound treatment-decreased, the incidence of PSD rose nearly tenfold.

Preoperative clinically inapparent leucopenia in patients undergoing neoadjuvant chemotherapy for locally advanced gastric cancer is not a risk factor for surgical or general postoperative complications.

BACKGROUND: Since the recent MAGIC trial neoadjuvant chemotherapy has been considered as treatment option for patients with advanced gastric cancer for tumor-downsizing and increasing R0 resection rates. Morbidity was reported in 45% of the patients treated within this randomized trial. Due to myelotoxicity under chemotherapy a part of the patients might undergo surgery with preoperative leucopenia. As leucopenia causes adverse events such as opportunistic infections and fever, it might be considered as a relevant risk factor in the course of surgical treatment. PATIENTS AND METHODS: We analyzed a cohort of neoadjuvantly treated patients (n = 214), which had a clinically inapparent but proven leucopenia (n = 58) before undergoing surgery due to advanced stage gastric cancer. RESULTS: Statistical analysis by Fisher's exact test showed, that there was no significant effect neither on general (P = 0.191) nor on surgery-dependant postoperative complications (P = 0.75). CONCLUSION: Conclusively patients with clinically inapparent leucopenia after neoadjuvant chemotherapy due to advanced stage gastric cancer can be safely operated on without putting them in danger of relevant surgical complications.

Family history of pilonidal sinus predisposes to earlier onset of disease and a 50% long-term recurrence rate.

PURPOSE: It has long been suspected that a family history of pilonidal sinus disease may predispose to higher disease incidence. The influence of family history on recurrence rate has not been investigated. The purpose of this study was to evaluate the recurrence rate in patients with both a personal and a family history of pilonidal sinus disease. METHODS: A standardized telephone interview was used to retrospectively study 578 patients who underwent primary surgery between 1980 and 1996. Differences concerning the long-term recurrence rate between patients with a positive or negative family history were analyzed using Kaplan-Meier statistics. RESULTS: Sixty-eight of 578 patients (12%) had a positive family history with first-degree relatives, in which 28 brothers and 25 fathers were similarly involved. The long-term recurrence rate was significantly elevated when family history was positive (35% vs. 22% after 15 years and 52% vs. 28% after 25 years; P = 0.02). The long-term recurrence rate was elevated if surgery was needed at a younger age (P = 0.03). The body mass index measured at time of admission for surgery did not seem to have any negative influence on recurrence rates (P = 0.31). Although a positive family history predisposes a person to earlier onset of disease, recurrences occur within 5.1 +/- 6.2 years (mean +/- standard deviation) in patients with a positive family history and within 5.3 +/- 5.2 years in patients with a negative family history (P = 0.95). CONCLUSION: Patients with a positive family history need closer surgical monitoring because primary disease will manifest earlier. A remarkable long-term recurrence rate exceeding 50% after 25 years places a much higher disease burden on patients with a positive family history. All available interventions known to reduce recurrence rate should be applied to this group of patients.

Long-term effects of postoperative razor epilation in pilonidal sinus disease.

PURPOSE: To study potential benefits of postoperative epilation after pilonidal sinus surgery, the long-term effect of hair removal on pilonidal recurrence was investigated. METHODS: A total of 1,960 patients with pilonidal sinus treated surgically from 1980 to 1996 in three hospitals of the Deutsche Bundeswehr were eligible for the study. Regular hair removal with a razor was recommended for all patients after surgery. A randomly selected sample of 504 patients was contacted for a follow-up telephone interview. RESULTS: The mean follow-up time was 11.3 (standard deviation, 6.4) years. Overall, pilonidal sinus disease recurred in 111 (22 percent) of the 504 patients. A total of 113 patients followed the recommendation to perform epilation (mean duration, 7.5 months), and 391 patients did not. Recurrence was observed in 30.1 percent (34/113) of patients who performed postoperative epilation and in 19.7 percent (77/391) of patients who did not perform postoperative epilation (P = 0.01). CONCLUSIONS: Razor hair removal increases the rate of long-term recurrence after surgery for pilonidal sinus disease and therefore should not be recommended. However, the rationale for hair removal in pilonidal sinus disease is compelling. Other epilation techniques such as laser hair removal should be investigated in appropriate studies.

Graft preconditioning with low-dose tacrolimus (FK506) and nitric oxide inhibitor aminoguanidine (AGH) reduces ischemia/reperfusion injury after liver transplantation in the rat.

Ischemia/reperfusion (I/R) injury is a main cause of primary dysfunction or non-function after liver transplantation (LTx). Recent evidence indicates that an increase in nitric oxide (NO) production after LTx is associated with I/R injury. The aim of this study was to demonstrate that low-dose FK506 in combination with aminoguanidine (AGH), which leads to a reduction of NO levels, has a protective effect by reducing I/R associated injury after LTx. Fortyone DA-(RT1av1) rats served as donors and recipients for syngenic orthotopic arterialised LTx. They were divided into 4 groups: controls without pre-/treatment (I), pre-/treatment with high-dose FK506 (II), pre-/treatment with AGH only (III), and pre-/treatment with low-dose FK506 in combination with AGH (IV). After LTx the laboratory parameters and liver biopsy were performed. The levels of transaminase (ALT) in groups I, II and III were significantly higher on day 3 after LTx compared to group IV (p = 0.001, p = 0.001, p = 0.000). In group IV the I/R-associated liver necrosis rate was reduced significantly. Our results demonstrated that a combined dual pharmacological pretreatment (group IV) reduced I/R injury of the graft after LTx in a rat model.

The influence of retrograde reperfusion on the ischaemia-/reperfusion injury after liver transplantation in the rat.

Dysfunction of the graft after liver transplantation caused by ischaemia-/reperfusion (I/R) injury is a serious clinical problem. The aim of this study was to evaluate the influence of different kinds of reperfusion on I/R injury in a rat model. Arterialized orthoptic rat liver treatment was performed on male LEWIS-(RT(1))-rats. Three groups (n = 7) were formed. Group I: antegrade reperfusion with a 6-min delayed reperfusion via the hepatic artery. Group II: Antegrade reperfusion, simultaneously, via the portal vein and the hepatic artery. Group III: Retrograde reperfusion via the vena cava. Serum parameters were determined one, 24 and 48 h after operation. Furthermore, after 48 h, the liver was taken for histological assessment. After 48 h, rats of group III showed significantly lower aspartate amino transferase and alanine amino transferase serum levels compared with group I and group II rats. Forty-eight hours after transplantation, glutamate dehydrogenase serum level was significantly lower in group III than in group II. In histology, group III livers showed significantly less necrotic spots than group I and group II livers. Maximum size of the necrotic spots was significantly lower in group III than in group I. Also, significantly more necrotic spots were seen in the 'Rappaport's zone' 1 and 2 of group I than in group III. Our data suggested that the expression of I/R-injury correlates with the type of reperfusion. Furthermore, under standard conditions, this study was able to demonstrate that in a rat model, the retrograde reperfusion leads to a lower expression of I/R-injury than the antegrade reperfusion.

Expression of a metalloproteinase family of ADAMTS in human vulnerable carotid lesions.

AIMS: ADAMTS family of metalloproteases (a disintegrin and metalloprotease with thrombospondin motifs) possesses high proteolytic activity especially regarding proteoglycans. Their expression pattern in carotid plaques is as-yet unknown. The aim of the study was therefore the analysis of expression of ADAMTS1, 4, 5, and 13 and their inhibitors TIMP-1 and TIMP-3 in stable and unstable carotid plaques. METHODS: Atherosclerotic plaques were collected from 40 patients (29 men, 11 women, mean age 70 years) undergoing carotid endarterectomy. The specimens were categorized into two groups (stable/unstable) according to Redgrave und Rothwell (The Oxford Plaque Study, 2008). SYBR Green-based real-time PCR, histology, and immunohistochemistry were performed. RESULTS: All ADAMTS tested in our study were expressed in both stable and unstable plaques, especially in smooth muscle cells (SMCs) and macrophages. Analysis of the expression pattern on mRNA level showed significant higher expression of ADAMTS1 in unstable plaques compared with stable plaques (1.7-fold, P = 0.049). The expression of ADAMTS4 and 5 was also increased in unstable lesions; however, these changes were not statistically significant (1.2-fold, P = 0.667 and 1.6-fold, P = 0.077). Expression of TIMP-1 was significantly reduced in unstable plaques compared with stable ones (1.9-fold, P = 0.014). CONCLUSION: SMCs seem to be an important source of ADAMTS analyzed in our study. Furthermore, expression of ADAMTS1 was found to be increased in unstable carotid lesions and might potentially contribute to plaque vulnerability.

Evaluation of an ADVanced Organ Support (ADVOS) system in a two-hit porcine model of liver failure plus endotoxemia.

BACKGROUND: Novel extracorporeal procedures are constantly being developed and evaluated for use in patients with sepsis. Preclinical evaluation of such procedures usually requires testing in large animal models. In the present work, the safety and efficacy of a recently developed ADVanced Organ Support (ADVOS) system in a newly developed large animal two-hit model of liver failure combined with endotoxemia were tested. METHODS: After establishing the model in more than 50 animals, a randomized study was performed. An inflammatory cholestatic liver injury was initially provoked in pigs. Three days after surgery, endotoxin was gradually administered during 7½ h. Animals were randomized to receive standard medical treatment either with (ADVOS group, n = 5) or without ADVOS (control group, n = 5). The ADVOS treatment was started 2½ h after endotoxemia and continued for 7 h. Survival, cardiovascular, respiratory, renal, liver, coagulation, and cerebral parameters were analyzed. RESULTS: Three days after surgery, cholestatic injury resulted in hyperbilirubinemia [5.0 mg/dl (IQR 4.3-5.9 mg/dl)], hyperammonemia [292 µg/dl (IQR 291-296 µg/dl)], leukocytosis [20.2 103/µl (IQR 17.7-21.8 103/µl)], and hyperfibrinogenemia [713 mg/dl (IQR 654-803 mg/dl)]. After endotoxemia, the ADVOS procedure stabilized cardiovascular, respiratory, and renal parameters and eliminated surrogate markers as bilirubin [2.3 (IQR 2.3-3.0) vs. 5.5 (IQR 4.6-5.6) mg/dl, p = 0.001] and creatinine [1.4 (IQR 1.1-1.7) vs. 2.3 (IQR 2.1-3.1) mg/dl, p = 0.01]. Mortality: All animals in the ADVOS group survived, while all animals in the control group expired during the 10-h observation period (p = 0.002). No adverse events related to the procedure were observed. CONCLUSIONS: The ADVOS procedure showed a promising safety and efficacy profile and improved survival in a sepsis-like animal model with dysfunction of multiple organs. An amelioration of major organ functions (heart and lung) combined with removal of markers for kidney and liver function was observed.

Primary Cytomegalovirus Infection in Seronegative Kidney Transplant Patients Is Associated with Protracted Cold Ischemic Time of Seropositive Donor Organs.

Human Cytomegalovirus (CMV) can lead to primary infection or reactivation in CMV-seronegative or -seropositive kidney transplant recipients, respectively. Complications comprise severe end-organ diseases and acute or chronic transplant rejection. Risk for CMV manifestation is stratified according to the CMV-IgG-serostatus, with donor+/recipient- (D+/R-) patients carrying the highest risk for CMV-replication. However, risk factors predisposing for primary infection in CMV-seronegative recipients are still not fully elucidated. Therefore, we monitored D+/R- high-risk patients undergoing kidney transplantation in combination with antiviral prophylaxis for the incidence of CMV-viremia for a median follow-up time of 784 days (156-1155 days). In this period, we analyzed the functional CMV-specific T cell response by intracellular cytokine staining and CMV-serology by ELISA. Only four of eight D+/R- patients developed clinically relevant CMV-viremia followed by seroconversion. Viremia triggered expansion of functional CMV-specific T cells correlating with protection against secondary CMV-reactivations. In contrast, all other patients remained permanently aviremic and showed no immunological correlate of infection after discontinuation of antiviral prophylaxis for up to three years. Comparing cold ischemic times (CIT) of viremic (median = 1020 min; 720-1080 min) and aviremic patients (median = 335 min; 120-660 min) revealed significantly (p = 0.0286) protracted CIT in patients with primary CMV-infection. Taken together, primary CMV-infection affects only a subgroup of D+/R- patients correlating with length of CIT. Therefore, patients with extended CIT should be thoroughly monitored for CMV-replication well beyond discontinuation of antiviral prophylaxis. In contrast, patients with short CIT remained permanently uninfected and might benefit from shorter prophylactic treatment.