Case Report: Eculizumab and ECMO Rescue Therapy of Severe ARDS in Goodpasture Syndrome.

Introduction: Goodpasture's syndrome is a life-threatening autoimmune type IV collagen disease characterized by the presence anti-glomerular basement membrane antibodies, rapid progressive glomerulonephritis and/or pulmonary hemorrhage. Methods: Here, we describe new therapeutic options, which take recent advances in unraveling Goodpasture's pathogenesis into account. Results: In a 17-year old male, severe Goodpasture's syndrome resulted in acute respiratory distress syndrome (ARDS). Within 1 day after hospital admission, the patient required extracorporeal membrane oxygenation (ECMO). Despite steroid-pulse and plasmapheresis, ARDS further deteriorated. Eleven days after admission, the patient was in a pre-final stage. At last, we decided to block the complement-driven lung damage by Eculizumab. Three days after, lung-failure has stabilized in a way allowing us to initiate Cyclophosphamide-therapy. As mechanical ventilation further triggers Goodpasture-epitope exposure, the patient was taken from pressure support - breathing spontaneously by the help of maintaining ECMO therapy. After a total of 24 days, ECMO could be stopped and pulmonary function further recovered. Conclusions: In conclusion, our findings suggest that life-threatening organ-damage in Goodpasture's syndrome can be halted by Eculizumab as well as by lung-protective early withdrawal from pressure support by the help of ECMO. Both therapeutic options serve as new tools in otherwise hopeless situations to prevent further organ-damage and to gain time until the established immunosuppressive therapy works in otherwise lethal autoimmune-diseases.

Secretory Leukocyte Protease Inhibitor (SLPI)-A Novel Predictive Biomarker of Acute Kidney Injury after Cardiac Surgery: A Prospective Observational Study.

Acute kidney injury (AKI) is one of the most frequent complications after cardiac surgery and is associated with poor outcomes. Biomarkers of AKI are crucial for the early diagnosis of this condition. Secretory leukocyte protease inhibitor (SLPI) is an alarm anti-protease that has been implicated in the pathogenesis of AKI but has not yet been studied as a diagnostic biomarker of AKI. Using two independent cohorts (development cohort (DC), n = 60; validation cohort (VC), n = 148), we investigated the performance of SLPI as a diagnostic marker of AKI after cardiac surgery. Serum and urinary levels of SLPI were quantified by ELISA. SLPI was significantly elevated in AKI patients compared with non-AKI patients (6 h, DC: 102.1 vs. 64.9 ng/mL, p < 0.001). The area under the receiver operating characteristic curve of serum SLPI 6 h after surgery was 0.87 ((0.76-0.97); DC). The addition of SLPI to standard clinical predictors significantly improved the predictive accuracy of AKI (24 h, VC: odds ratio (OR) = 3.91 (1.44-12.13)). In a subgroup, the increase in serum SLPI was evident before AKI was diagnosed on the basis of serum creatinine or urine output (24 h, VC: OR = 4.89 (1.54-19.92)). In this study, SLPI was identified as a novel candidate biomarker for the early diagnosis of AKI after cardiac surgery.

Pantoprazole Does not Affect Serum Trough Levels of Tacrolimus and Everolimus in Liver Transplant Recipients.

Background: Liver transplant recipients are frequently treated with proton pump inhibitors. Drug interactions have been described especially with respect to omeprazole. Due to the lower binding capacity of pantoprazole to CYP2C19 this drug became preferred and became the most used proton pump inhibitor in Germany. The data on the influence of pantoprazole on immunosuppressive drugs in liver transplant recipients a very scarce. Methods: The authors performed a single center analysis in liver transplant recipients on the effect of pantoprazole on the serum trough levels of different immunosuppressants. The trough levels were compared over a period of 1 year before and after start or stop of a continuous oral co-administration of 40 mg pantoprazole once daily. Results: The serum trough levels of tacrolimus (n = 30), everolimus (n = 7), or sirolimus (n = 3) remain constant during an observation period of at least 1 year before and after co-administration of pantoprazole. None of the included patients needed a change of dosage of the observed immunosuppressants during the observation period. Conclusions: The oral co-administration of pantoprazole is safe in immunosuppressed liver transplant recipients according to the serum trough levels of tacrolimus, everolimus, and sirolimus. This analysis provides first data on the influence of pantoprazole on immunosuppressive drugs in liver transplant recipients.

Does imatinib turn recurrent and/or metastasized gastrointestinal stromal tumors into a chronic disease? - single center experience.

BACKGROUND: Gastrointestinal stromal tumors (GIST) are mesenchymal tumors of the gastrointestinal tract supposed to arise from the cells of Cajal because of gain-of-function mutations of the tyrosine receptor kinases c-kit or platelet-derived growth factor receptor A. Imatinib selectively inhibits the kinase activity of both receptors. Despite this breakthrough in the treatment of GIST, resistance against imatinib has been reported to be as high as 50% after the first 2 years of treatment. AIM: Outcome of 13 consecutive patients with relapsed or metastasized GIST who were treated with imatinib was analyzed. RESULTS: Mean duration of treatment was 53.5 months. Four patients developed progressive disease and died after a mean treatment time of 31 months in spite of increase of imatinib dosages to 800 mg daily. Two patients (23%) developed a progressive disease after 46 months or 52 months of treatment. Two patients had a stable disease and five had a partial response. The overall progression rate was 46%, the mean survival time since primary diagnosis was 85.8 months. CONCLUSION: From our experience, frequency of resistance development to imatinib may be below that given in the literature (50% after 2 years). Individual treatment in specialized centers may improve compliance.

Chemotherapy-induced suppression to adenoma or complete suppression of the primary in patients with stage IV colorectal cancer: report of four cases.

BACKGROUND: Although modern chemotherapy of stage IV advanced colorectal cancer (CRC) has impressively improved overall survival, the response of the primary tumor has not been studied because surgical resection of the primary continues to be the standard procedure in stage IV CRC. AIM: Long-term follow-up of the primary in patients with stage IV CRC under chemotherapy. METHODS AND RESULTS: Here we report on the histological changes in the primary tumor in four patients suffering from stage IV CRC. Systemic chemotherapy was started immediately after endoscopic tumor debulking in three cases. In one case no endoscopic intervention was performed before chemotherapy. Neither macroscopic nor histological evidence for malignant tumor growth was found at the former site of the primary after 6, 23, 26 or 48 months, respectively. Two patients had a complete suppression of the primary, two patients had an adenoma at the former site of the primary. To date, three patients have died because of progression of liver metastases and one patient is still alive with no signs of tumor growth. CONCLUSION: The four cases illustrate that today's chemotherapy may effectively induces suppression of the primary in CRC. The development of CRC may follow different pathways.