Gemcitabine-induced thrombotic microangiopathy treated with eculizumab: a case report.

Background: Gemcitabine is a broadly used chemotherapeutic agent that can cause a rare but life-threatening complication called thrombotic microangiopathy (TMA). Early recognition is crucial as therapy options are limited. Case Description: We report the case of a 46-year-old patient with pancreatic adenocarcinoma who presented with severe anemia and thrombocytopenia as well as acute kidney injury. A diagnosis of gemcitabine-induced TMA was made. He became rapidly transfusion and dialysis dependent. Despite discontinuation of gemcitabine and treatment with high-dose corticotherapy as well as plasmapheresis, no improvement in both renal and hematological parameters was seen. Treatment with eculizumab was initiated. One week after the first administration, the patient no longer required packed cells nor platelet transfusions and one month later, dialysis could be discontinued. After five doses, treatment with eculizumab was stopped. Four months later, his serum creatinine was 1 mg/dL. Conclusions: This case report illustrates the promising beneficial effects of eculizumab in gemcitabine-induced TMA, both regarding transfusion dependence as well as improvement in renal function, thereby allowing further therapy options in patients with an active malignancy.

Alfa-1-antitrypsin deficiency: a predisposing factor leading to invasive infections?

This case report highlights for the first time a possible link between the presence of alfa-1-antitrypsin deficiency (AATD) and the susceptibility to invasive infections. The current patient, with known AATD, initially presented with nausea, vomiting and headache secondary to Listeria monocytogenes rhombencephalitis. Further on, he developed respiratory insufficiency due to probable invasive pulmonary aspergillosis. Diagnostic work-up could not show any arguments for an underlying immunodeficiency or malignancy. The consecutive course of two rare invasive infections in a healthy individual posed the hypothesis if the underlying AATD could be considered a possible trigger for infections. Indirect clinical observations in literature indeed support this link and in addition, two possible pathophysiological pathways might explain the higher susceptibility for infections in AATD patients. First, alveolar macrophages are dysfunctional in AATD patients leading to a lower apoptotic clearance of bacteria and other (mostly intracellular) pathogens. Secondly, a lower release and lower function of tumour necrosis factor α (TNFα) is seen in alfa-1-antitrypsin depletion, priming the path to more frequent infections, a mechanism that is similar in anti-TNFα treated patients. This case is the first to report on severe or invasive infections related to AATD in humans.

Statin-induced myopathy: a case report.

BACKGROUND: Statins are one of the most frequently used drug groups among patients with cardiovascular disease. Muscle pain is very frequent among patients using statins. It is important to distinguish patients with benign muscle pain without significant biochemical correlates from patients with serious myopathies. CASE SUMMARY: We present the case of a 68-year-old woman taking atorvastatin in the past 8 months after a coronary bypass grafting, presenting with proximal muscle weakness and pain. Biochemical analysis showed a markedly elevated creatine kinase (CK) (24,159 U/L). Despite discontinuation of the statin and therapy for rhabdomyolysis (IV fluid, mannitol, and sodium bicarbonate), CK levels did not drop as much as expected. Muscle biopsy showed mild inflammatory changes and few necrotic muscle fibres, suggestive for an immune-mediated necrotizing myopathy (IMNM). Serology showed a high anti-HMG-CoA reductase antibody (anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibody) titre, diagnostic for an IMNM induced by statins. The patient was treated with corticosteroids and methotrexate. Creatine kinase levels, muscle weakness, and pain gradually improved over the following months. DISCUSSION: IMNM induced by statins is a relatively new entity. It is important to be recognized because it is not a self-limiting adverse effect such as the frequent benign muscle pains caused by statins. Beside discontinuation of the causative statin, aggressive immunosuppressive therapy is mandatory in IMNM. Therefore, it is important to test for anti-HMGCR antibodies and if necessary perform a muscle biopsy in patients taking statins, presenting with muscle weakness, and CK elevations not improving after discontinuation of the statin.

Epidemiology of acute kidney injury: how big is the problem?

OBJECTIVE: Acute kidney injury (AKI) is a complication that occurs frequently in hospitalized patients. In this article, we provide an overview of the literature on the epidemiology of AKI in hospitalized patients. PATIENTS AND SETTING: The overview is restricted to hospitalized patients, and most emphasis is put on intensive care unit patients. MEASUREMENTS AND MAIN RESULTS: The population incidence of less severe AKI and AKI treated with renal replacement therapy is approximately 2,000-3,000 and 200-300 per million population per year, respectively. These numbers are comparable with the estimates for severe sepsis and acute lung injury. Approximately 4-5% of general intensive care unit patients will be treated with renal replacement therapy, and up to two thirds of intensive care unit patients will develop AKI defined by the RIFLE classification. The incidence of AKI is increasing. Intensive care unit patients with AKI have a longer length of stay and therefore generate greater costs. In addition, AKI is associated with increased mortality, even after correction for covariates. Increasing RIFLE class is associated with increasing risk of in-hospital death. Patients with AKI who are treated with renal replacement therapy still have a mortality rate of 50-60%. Of surviving patients, 5-20% remain dialysis dependent at hospital discharge. CONCLUSION: AKI has a high incidence, comparable with acute lung injury and severe sepsis, and is associated with higher hospital mortality.