Idiosyncratic Drug-Induced Liver Injury in a Healthy Patient following PCSK9-Inhibitor Injection.

Background: Acute liver injury is a life-threatening condition with disparate aetiology. Swift and adequate interdisciplinary treatment is essential to assure the best possible outcomes in these patients. Investigations to identify the cause of the condition and the implementation of quick and appropriate treatment can be lifesaving. Case Presentation. In October 2022, an otherwise healthy 66-year-old male presented at the University Hospital Essen with acute liver injury following an inclisiran injection for hypercholesterinaemia. Four weeks following admission, the patient fully recovered after initially receiving short-term cortisol therapy and open albumin (OPAL) dialysis, and the indices of liver, kidney, and coagulation function were normal at discharge. Conclusion: This is to our knowledge the first reported acute liver injury due to an inclisiran injection. Cortisol in combination with OPAL dialysis is an effective method for the treatment of acute liver injury caused by inclisiran injury, and in this case, it led to a near-complete reversal of the acute liver injury at the time of discharge.

[Disposition for organ donation: analysis of a survey and trial of 974 respondents]. / Organspendebereitschaft: Interventionsstudie bei 974 Befragten.

BACKGROUND: Due to the lack of donor organs many patients cannot be helped in time with the necessary transplantation in Germany. At the same time, there is an organ donor potential that is not being exploited. A high refusal rate with a low rate of organ donor card holders remains problematic. The objective of this study was to collect the rate of holders of organ donor cards in a collective and to evaluate the collective according to other attributes in the context of a targeted trial. METHODS: In 2009, a three-part questionnaire including an educational text regarding the topic of "organ donation" was sent out to the employees of the Sparkasse Essen (a savings bank). RESULTS: Altogether, 974 out of 1480 (65.8 %) completely answered questionnaires were evaluated. 21.3 % of the respondents had an organ donor card at the time the survey was carried out. A statistically significant association between gender (p value, 0.0438), age (p value, 0.0267) and the possession of a donor card could be determined. 22.1 % of the respondents who participated in sports regularly or donated blood (p value, < 0.0049), were holding an organ donor card. 60 % of the respondents found the brief information to be sufficient, 22.6 % could imagine acquiring an organ donor card for them based on the presented information alone. CONCLUSION: The spread of information and transparency in transplant medicine are essential for the facilitation of "willingness to donate organs". In the framework of this trial, besides data analysis, also fundamental information on "organ donation" could be conveyed. After all, 95.3 % of the respondents have read the information material and hence document the success of the study.

Efficacy and safety of linezolid in liver transplant patients.

Bacterial infections are the main cause of death within the first year after liver transplantation, and the increased incidence of multidrug-resistant gram-positive pathogens has created a major challenge in the treatment of these patients. Linezolid, the first US Food & Drug Administration-approved oxazolidinone, offers a valuable novel treatment option for serious gram-positive infections. Linezolid is relatively non-toxic but prolonged treatment with linezolid was associated with thrombocytopenia. Here we report on the experience of linezolid treatment in adult liver transplant patients, who are at an increased risk for thrombocytopenia because of hypersplenism. From November 2003 until December 2009, we evaluated the clinical course of 46 liver transplant patients (27 male/19 female) in our surgical intensive care unit. For proven or probable gram-positive infection, all patients received linezolid 600 mg intravenously every 12 h. On clinical improvement, treatment was changed to oral linezolid 600 mg twice daily. Treatment duration was 11 ± 7 days. Treatment indications were pneumonia (n = 8), blood stream infection (n = 30), and surgical site/abdominal infection (n = 3). Clinical cure was achieved in 43 out of 46 patients. During the course of treatment, no cases of severe thrombocytopenia occurred and a statistically significant platelet count increase was seen from day 1 (110 ± 73/nL) to day 7 (165 ± 116/nL) and day 14 (180 ± 140/nL). We did not observe any further adverse events, especially no severe neurological complications (e.g., serotonin syndrome) or signs of lactate acidosis. Two patients died from uncontrolled vancomycin-resistant Enterococcus faecium sepsis with septic shock and one due to uncontrolled methicillin-resistant Staphylococcus aureus pneumonia. These deaths were considered to be unrelated to linezolid treatment, and linezolid was regarded as the optimal treatment choice in these patients. A subgroup analysis of patients treated for >14 days revealed no statistically significant differences when compared with patients on shorter treatment. In particular, no cases of thrombocytopenia occurred during longer treatment. In conclusion, linezolid is a safe and effective treatment for adult liver transplant patients with gram-positive infections.

Tumor markers as a diagnostic key for hilar cholangiocarcinoma.

OBJECTIVE: Hilar cholangiocarcinoma is the fourth most common gastrointestinal malignancy. CA19-9 and CEA are helpful devices in the management of gastrointestinal malignancies and belong to clinical routine in surgical oncology. But the validity of these parameters in terms of tumor extension and prognosis of bile duct malignancies still remains unclear. METHODS: From 1998 to 2008, we obtained preoperative CA19-9 and CEA serum levels in 136 patients with hilar cholangiocarcinoma. We correlated tumor stage, resectability rate and survival with preoperative CA 19-9 and CEA serum levels. RESULTS: CA19-9 (UICC I: 253 ± 561U/ml; UICC II: 742 ± 1572 U/ml; UICC III: 906 ± 1708 U/ml; UICC IV: 1707 ± 3053U/ml) and CEA levels (UICC I: 2.9 ± 3.8U/ml; UICC II: 4.6 ± 6.5 U/ml; UICC III: 18.1 ± 29.6 U/ml; UICC IV: 22.7 ± 53.9 U/ml) increase significantly with rising tumor stage. Patients with pre?operative serum levels of CA19-9 (>1000U/ml) and CEA (>14.4ng/ml) showed a significant poorer resectability rate and survival than patients with lower CA19-9 and CEA serum levels respectively. CONCLUSION: CA19-9 and CEA serum levels are associated with the tumor stage. If preoperatively obtained CA19-9 and CEA serum levels are highly elevated patients have an even worse survival and the frequency of irresectability is significantly higher.

One-year Allograft and Patient Survival in Renal Transplant Recipients Receiving Antiplatelet Therapy at the Time of Transplantation.

BACKGROUND: Antiplatelet therapy is common in patients on the waiting list for kidney transplantation. OBJECTIVE: To evaluate the incidence of post-operative bleeding in patients with antiplatelet therapy undergoing kidney transplantation and analyze the impact on the outcome. METHODS: We studied all patients with concomitant antiplatelet therapy undergoing kidney transplantation in our center from January 2007 to June 2012. Data were collected by chart review. Univariate and multivariate logistic regression and Cox proportional hazard model were used to identify risk factors for the long-term outcome. RESULTS: Of 744 kidney transplant recipients during the study period, 161 received oral antiplatelet therapy and were included in the study. One-third of the patients demonstrated signs of bleeding, half of which requiring surgical treatment. Coronary artery disease, deceased donor kidney transplantation, and dual antiplatelet medication were independent risk factors for post-operative bleeding. One-year allograft survival was significantly better in the non-bleeding group (91.4% vs 75.9%, p=0.023). Multivariable analysis found that post-operative bleeding, recipient age, and biopsy-proven rejection were independent risk factors for graft survival. Recipient age and biopsy-proven rejection were also identified as independent risk factors for patient survival. CONCLUSION: This analysis indicated a high risk for post-operative bleeding in renal transplant patients under antiplatelet therapy. The associated negative effect on allograft survival underscored the need to reduce any risk factors for post-operative bleeding.

Organ donation: new hope through the expected amendment in Germany?

INTRODUCTION: The current organ donor shortage in Germany results in the death of 1000 patients on the transplant waiting list every year. In response, a recent amendment to the German Transplant Act aiming to increase donor rates was passed. Among a number of other measures, Germans are asked to decide whether they choose to donate organs or not in the event of a brain death or whether they would like to designate someone who should decide for them in this situation. The objective of this study was to collect and evaluate data on the public's attitude toward organ donation before the expected amendment. METHODS: A survey on the subject of organ donation was conducted in 2011 among clients of a public pharmacy in a major city in the federal state North Rhine-Westphalia, Germany. Data regarding sex, age, health behavior, and attitude toward the amendment were collected and association organ donor card possession was analyzed. RESULTS: A total of 1485 questionnaires were evaluated. Of those surveyed, only 14.1% had an organ donor card. No statistically significant associations between sex (P value .3045), age (P value .1453) and the possession of a donor card were observed. We found that 72.5% of respondents stated that they appreciated the expected amendment, and in the case of implementation, the majority would obtain an organ donor card. DISCUSSION: The future success of transplantation medicine relies on an increase in the public's overall willingness to donate organs. Educating the public and ensuring transparency in transplantation medicine are vital to achieving higher donation rates. The new German transplantation act may be an important step to increase society's awareness and participation in organ donation.

In-house coordination for organ donation--single-center experience in a pilot project in Germany (2006 to 2013).

A challenge for solid organ transplantation in Germany is the shortage of organs. In an effort to increase donation rates, some federal states mandated hospitals to install transplantation officers to coordinate, evaluate, and enhance the donation and transplantation processes. In 2009 the German Foundation for Organ Transplantation (DSO) implemented the In-House Coordination Project, which includes retrospective, quarterly, information technology-based case analyses of all deceased patients with primary or secondary brain injury in regard to the organ donation process in maximum care hospitals. From 2006 to 2008 an analysis of potential organ donors was performed in our hospital using a time-consuming, complex method using questionnaires, hand-written patient files, and the hospital IT documentation system (standard method). Analyses in the In-House Coordination Project are instead carried out by a proprietary semiautomated IT tool called Transplant Check, which uses easily accessible standard data records of the hospital controlling and accounting unit. The aim of our study was to compare the results of the standard method and Transplant Check in detecting and evaluating potential donors. To do so, the same period of time (2006 to 2008) was re-evaluated using the IT tool. Transplant Check was able to record significantly more patients who fulfilled the criteria for inclusion than the standard method (641 vs 424). The methods displayed a wide overlap, apart from 22 patients who were only recorded by the standard method. In these cases, the accompanying brain injury diagnosis was not recorded in the controlling and accounting unit data records due to little relative clinical significance. None of the 22 patients fulfilled the criteria for brain death. In summary, Transplant Check is an easy-to-use, reliable, and valid tool for evaluating donor potential in a maximum care hospital. Therefore from 2010 on, analyses were performed exclusively with Transplant Check at our university hospital.

Neuromonitoring in a porcine model of acute hepatic failure.

Cerebral oedema has been noted to occur frequently in patients dying of fulminant hepatic failure. Therefore, in the present study, multimodal neuromonitoring was evaluated in an animal model of hepatectomy. Acute liver failure was surgically induced in swine by complete hepatectomy (n = 8). Intracranial pressure monitoring via a ventricular drainage system, electroencephalogram and recording of visually evoked potentials were used to establish a continuous neuromonitoring system. Measurements of liquor and serum ammonia (NH(3)) levels were taken at later stages of the trial in an approach to widen monitoring. Serial monitoring of the electroencephalogram revealed progressive slowing of the frequency with decreasing amplitude. Monitoring of the intracranial pressure with a subdural pressure transducer demonstrated a progressive and reproducible elevation. Increase in blood NH(3) was observed. Anaesthesia was terminal. In all cases death was caused by cardiocirculatory insufficiency, confirmed by autopsy. At autopsy, brain tissue of the animals was found to be swollen showing flattened cortical gyri. In conclusion, the technique of extended neuromonitoring offers an advanced option for monitoring animal models of fulminant hepatic failure for further developments and investigations.

Attitude of health care professionals to organ donation: two surveys among the staff of a German university hospital.

The persistent shortage of organs for transplantation could be minimized by increasing the number of potential donors. The opinion of the staff of a university hospital toward organ donation is of special interest because they are directly involved in solid organ transplantation. In 2007, we conducted a first voluntary survey concerning organ donation among the staff of the university hospital of Essen. A short information campaign and further opinion poll among staff as well as visitors was performed in 2009 to compare professional and public attitudes toward organ donation. The first poll comprised 242 questionnaires showing 55% of the hospital staff carrying organ donor cards, particularly more women (60%) than men (46%). After this survey, an additional 19% of the hospital staff imagined they might carrying an organ donor card in the future. In the second survey, we analyzed 151 questionnaires, showing 66% of staff members carrying an organ donor card, an incidence significantly greater than among visitors (48%). The need for information regarding organ donation was greater among visitors (35%). However, 21% of the hospital staff still also need education concerning organ donation. More education and increased transparency of transplantation practice are necessary for hospital staff to act successfully as initiators. Hospital staff with positive attitudes toward organ donation may have a positive impact on the attitudes of the general public toward organ donation.

[Process of organ donation at a maximum care hospital]. / Organspendeprozess an einem Krankenhaus mit Maximalversorgung.

BACKGROUND: A chronic shortage of organs for transplantation has developed due to the disparity between the demand for solid organs and the current supply. Improved processes for identifying potential donors could expand the pool of available organs. PATIENTS AND METHODS: All patients who died between January 1, 2006 and December 31, 2008 in the University hospital of Essen suffering from a primary or secondary cerebral injury were assessed retrospectively. Age, date of death, duration of stay in the intensive care unit, main and additional diagnoses and diagnostic test for assessing brain death as well as discussions with relatives were recorded anonymously. RESULTS: 424 deaths with primary or secondary cerebral injury (group A) were identified during the study period. 267 deaths (62.9 %) (group B) were further evaluated for organ donation after excluding absolute medical contraindications, e. g. malignancies, multiple organ failure. In 68 cases (16.0 %), diagnostic test of brain death had been completed (group C). Despite a high refusal rate, 36 (8.5 %) organ procurements were realized (group D) resulting in 140 transplanted organs (3.9 per organ donor). CONCLUSION: The first crucial step to improve the rate of organ donation is to identify any potential donor. In 8.5 % of intensive care unit deaths with primary or secondary cerebral damage, organ procurement was realized. In addition, education regarding transplant medicine and a positive attitude to organ donation among the general public as well as medical personnel is necessary to minimize the high refusal rates.